common multifactorial disorders: Topics by Science.gov

Sample records for common multifactorial disorders

Is Depression Simply a Nonspecific Response to Brain Injury?

PubMed Central

Strakowski, Stephen M.; Adler, Caleb M.; DelBello, Melissa P.

2013-01-01

Depressive disorders are among the most common ailments affecting humankind and some of the world’s leading causes of medical disability. Despite being common, disabling and a major public health problem, the etiology of depression is unknown. Indeed, investigators have suggested that the causes of depression are multiple and multi-factorial. With these considerations in mind, in this article we examine the hypothesis that our inability to identify the causes of depressive disorders is because depression is a nonspecific epiphenomenon of brain injury or insult arising through multiple pathways. PMID:23943470
[Perioperative disorders of mental functions].

PubMed

Tonković, Dinko; Adam, Visnja Nesek; Kovacević, Marko; Bogović, Tajana Zah; Drvar, Zeljko; Baronica, Robert

2012-03-01

Mental disorders are characterized by disturbances of thought, perception, affect and behavior, which occur as a result of brain damage. Recognizing and treating these conditions is necessary not only for psychiatrists but for all physicians. Disorder of mental function is one of the most common associated conditions in intensive care unit (ICU) patients. However, disturbances of mental function often remain unrecognized. In ICU patients, different types of mental function disorders may develop. They range from sleep disorders, severe depression, anxiety, posttraumatic stress disorder (PTSD) to cognitive disorders including delirium. The causes of mental dysfunction in ICU patients can be divided into environmental and medical. Cognitive disorders are related to mental processes such as learning ability, memory, perception and problem solving. Cognitive disorders are usually not prominent in the early postoperative period and in many cases are discovered after hospital discharge because of difficulties in performing everyday activities at home or at work. The etiology of postoperative cognitive impairment is unclear. Older age, previous presence of cognitive dysfunction, severity of disease, and polypharmacy with more than four drugs are some of the risk factors identified. Delirium is a multifactorial disorder. It is an acute confusional state characterized by alteration of consciousness with reduced ability to focus, sustain, or shift attention. It is considered as the most common form of mental distress in ICU patients. Nearly 30% of all hospitalized patients pass through deliriant phase during their hospital stay. Delirium can last for several days to several weeks. Almost always it ends with complete withdrawal of psychopathological symptoms. Sometimes it can evolve into a chronic brain syndrome (dementia). The causes are often multifactorial and require a number of measures to ease the symptoms. Delirious patient is at risk of complications of immobility and confusion, leading to a high prevalence of irreversible functional decline. An interdisciplinary approach to delirium should also include family or other caregivers. In the diagnosis of delirium, several tests are used to complement clinical assessment. Among the most commonly used are the Confusion Assessment Method (CAM-ICU) and Clinical Dementia Rating (CDR) test. Depression is a common disorder among patients treated at ICU and occurs due to the impact of the disease on the body and the quality of life, independence, employment and other aspects of life. Depression can interfere with the speed of recovery, affects the postoperative quality of life, and in a certain number of patients may lead to suicidal thoughts and intentions. Phobias and generalized anxiety are the most common anxiety disorders. Generalized anxiety disorder is characterized by strong, excessive anxiety and worry about everyday life events. PTSD is delayed and/or protracted response to a stressful event or situation, extremely threatening or catastrophic nature, which is outside the common experience of people and would hit or traumatize almost all people. Treatment of delirium and other disorders is causal. The causes of psychosis are often multifactorial and require a number of measures to ease symptoms. The primary objective of prevention is appropriate therapy and correction of potential imbalances possibly underlying disturbances, stabilization of vital functions as well as early return to daily activities. Doctors and other medical staff must be aware of the importance and consequences of behavioral and emotional disorders in critically ill patients. Additional research is needed to discover the ways to prevent and/ or reduce the frequency and severity of the consequences and treatment of cognitive and emotional disorders.
Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

PubMed Central

KIM, S. E.; CHANG, L.

2013-01-01

Background Irritable bowel syndrome and other gastrointestinal (GI) and non-GI disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint disorder, interstitial cystitis/painful bladder syndrome, and chronic fatigue syndrome are known as functional pain syndromes. They commonly coexist within the same individual. The pathophysiologic mechanisms of these disorders are not well understood, but it has been hypothesized that they share a common pathogenesis. Purpose The objective of this review is to discuss the proposed pathophysiologic mechanisms, which have been similarly studied in these conditions. These mechanisms include enhanced pain perception, altered regional brain activation, infectious etiologies, dysregulations in immune and neuroendocrine function, and genetic susceptibility. Studies suggest that these functional disorders are multifactorial, but factors which increase the vulnerability of developing these conditions are shared. PMID:22863120
HUGO urges genetic benefit-sharing.

PubMed

2000-01-01

In view of the fact that for-profit enterprise exceeds public expenditures on genetic research and that benefits from the Human Genome Project may accrue only to rich people in rich nations, the HUGO Ethics Committee discussed the necessity of benefit-sharing. Discussions involved case examples ranging from single-gene to multi-factorial disorders and included the difficulties of defining community, especially when multifactorial diseases are involved. The Committee discussed arguments for benefit-sharing, including common heritage, the genome as a common resource, and three types of justice: compensatory, procedural, and distributive. The Committee also discussed the importance of community participation in defining benefit, agreed that companies involved in health have special obligations beyond paying taxes, and recommended they devote 1-3% of net profits to healthcare infrastructure or humanitarian efforts.
Development and Validation of a Multifactorial Treatment Outcome Measure for Eating Disorders.

ERIC Educational Resources Information Center

Anderson, Drew A.; Williamson, Donald A.; Duchmann, Erich G.; Gleaves, David H.; Barbin, Jane M.

1999-01-01

Developed a brief self-report inventory to evaluate treatment outcome for anorexia and bulimia nervosa, the Multifactorial Assessment of Eating Disorders, and evaluated the instrument in a series of studies involving 1,054 women. Results support a stable factor structure and satisfactory reliability and validity, and establish normative data. (SLD)
Ethical considerations in the prevention and management of genetic disorders with special emphasis on religious considerations.

PubMed

Albar, Mohammed A

2002-06-01

Genetic diseases include not only single gene disorders, but multifactorial, somatic cell genetic disorders, mitochondrial and even chromosomal. One in 4 adults will suffer from a multifactorial or a somatic cell genetic disease. The common diseases in the community have a hereditary component namely diabetes mellitus, hypertension, ischemic heart diseases and many types of cancer. Even monogenic diseases which affect a small number of the newborns (2%-3%), have a greater impact on childhood diseases up to age 15 years. Therefore, it is imperative to scrutinize the available methods of prevention and management of genetic disorders, their ethical implications, and since east Mediterranean region is mainly occupied by Arabs and muslims, religious considerations become of paramount importance. Islam differs from many other religions in providing a complete code of life, which encompasses the secular with spiritual, the mundane with the celestial and hence forms the basis of the ethical, moral and even juridical attitudes and laws towards any problem or situation. Islamic teachings carry a great deal of instructions for health promotion and disease prevention including hereditary and genetic disorders. This review discusses how the Islamic teachings play an important role in the prevention and management of genetic disorders and the type of ethical implications involved in such management namely premarital medical examination, the question of consanguinity, the genetic counseling, the question of preimplantation diagnosis, the question of abortion and the offering of alternative ways of reproduction.
Nutraceuticals against Neurodegeneration: A Mechanistic Insight.

PubMed

Dadhania, Vivekkumar P; Trivedi, Priyanka P; Vikram, Ajit; Tripathi, Durga Nand

2016-01-01

The mechanisms underlying neurodegenerative disorders are complex and multifactorial; however, accumulating evidences suggest few common shared pathways. These common pathways include mitochondrial dysfunction, intracellular Ca2+ overload, oxidative stress and inflammation. Often multiple pathways co-exist, and therefore limit the benefits of therapeutic interventions. Nutraceuticals have recently gained importance owing to their multifaceted effects. These food-based approaches are believed to target multiple pathways in a slow but more physiological manner without causing severe adverse effects. Available information strongly supports the notion that apart from preventing the onset of neuronal damage, nutraceuticals can potentially attenuate the continued progression of neuronal destruction. In this article, we i) review the common pathways involved in the pathogenesis of the toxicants-induced neurotoxicity and neurodegenerative disorders with special emphasis on Alzheimer`s disease (AD), Parkinson`s disease (PD), Huntington`s disease (HD), Multiple sclerosis (MS) and Amyotrophic lateral sclerosis (ALS), and ii) summarize current research advancements on the effects of nutraceuticals against these detrimental pathways.
Nutraceuticals against Neurodegeneration: A Mechanistic Insight

PubMed Central

Dadhania, Vivekkumar P.; Trivedi, Priyanka P.; Vikram, Ajit; Tripathi, Durga Nand

2016-01-01

The mechanisms underlying neurodegenerative disorders are complex and multifactorial; however, accumulating evidences suggest few common shared pathways. These common pathways include mitochondrial dysfunction, intracellular Ca2+ overload, oxidative stress and inflammation. Often multiple pathways co-exist, and therefore limit the benefits of therapeutic interventions. Nutraceuticals have recently gained importance owing to their multifaceted effects. These food-based approaches are believed to target multiple pathways in a slow but more physiological manner without causing severe adverse effects. Available information strongly supports the notion that apart from preventing the onset of neuronal damage, nutraceuticals can potentially attenuate the continued progression of neuronal destruction. In this article, we i) review the common pathways involved in the pathogenesis of the toxicants-induced neurotoxicity and neurodegenerative disorders with special emphasis on Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS) and Amyotrophic lateral sclerosis (ALS), and ii) summarize current research advancements on the effects of nutraceuticals against these detrimental pathways. PMID:26725888
[Advance of genetics and genomics in neurology].

PubMed

Ginter, E K; Illarioshkin, S N

2012-01-01

Studies of genomic background of neurological disorders are very actual in view of their high population prevalence, severe course, serious impact on patients' disability and progressive mental and physical de-adaptation. In the paper, problems of genetic heterogeneity of hereditary neurological disorders and character of the respective genetic burden in the regions of Russian Federation are discussed in detail, a 'dynamic' type of mutations (increase in number of microsatellite repeats copies) attributable to many neurodegenerative diseases is analyzed, and achievements of Russian researchers in the identification of genes for hereditary neurological disorders and in the realization of pilot protocols of gene therapy are presented. Problems related to studies of genetic predisposition to common multifactorial diseases of the nervous system are discussed.
Fluid Retention and Rostral Fluid Shift in Sleep-Disordered Breathing.

PubMed

Kasai, Takatoshi

2016-01-01

Sleep-disordered breathing (SDB) is common and adversely affects cardiovascular morbidity and mortality. Despite multifactorial pathogenesis, SDB is prevalent in patients with fluid retention disorders, such as drug-resistant hypertension, end-stage renal disease, and heart failure, suggesting that fluid retention may play a role in the pathogenesis of SDB. During the day, fluid is likely to accumulate in the legs, and upon lying down at night is displaced from the legs. Many data suggest that some of this fluid displaced from the legs may redistribute to the upper body and predispose to SDB. This review article will highlight evidence for a relationship between SDB and fluid retention or rostral fluid shift, and discuss mechanisms that link them.
Muscle Deoxygenation Causes Muscle Fatigue

NASA Technical Reports Server (NTRS)

Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

1999-01-01

Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.
Stem Cell Technology for (Epi)genetic Brain Disorders.

PubMed

Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

2017-01-01

Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).
Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders

PubMed Central

Burrage, Lindsay C.; Nagamani, Sandesh C.S.; Campeau, Philippe M.; Lee, Brendan H.

2014-01-01

Branched-chain amino acid (BCAA) metabolism plays a central role in the pathophysiology of both rare inborn errors of metabolism and the more common multifactorial diseases. Although deficiency of the branched-chain ketoacid dehydrogenase (BCKDC) and associated elevations in the BCAAs and their ketoacids have been recognized as the cause of maple syrup urine disease (MSUD) for decades, treatment options for this disorder have been limited to dietary interventions. In recent years, the discovery of improved leucine tolerance after liver transplantation has resulted in a new therapeutic strategy for this disorder. Likewise, targeting the regulation of the BCKDC activity may be an alternative potential treatment strategy for MSUD. The regulation of the BCKDC by the branched-chain ketoacid dehydrogenase kinase has also been implicated in a new inborn error of metabolism characterized by autism, intellectual disability and seizures. Finally, there is a growing body of literature implicating BCAA metabolism in more common disorders such as the metabolic syndrome, cancer and hepatic disease. This review surveys the knowledge acquired on the topic over the past 50 years and focuses on recent developments in the field of BCAA metabolism. PMID:24651065
Mitochondria: A Common Target for Genetic Mutations and Environmental Toxicants in Parkinson’s Disease

PubMed Central

Helley, Martin P.; Pinnell, Jennifer; Sportelli, Carolina; Tieu, Kim

2017-01-01

Parkinson’s disease (PD) is a devastating neurological movement disorder. Since its first discovery 200 years ago, genetic and environmental factors have been identified to play a role in PD development and progression. Although genetic studies have been the predominant driving force in PD research over the last few decades, currently only a small fraction of PD cases can be directly linked to monogenic mutations. The remaining cases have been attributed to other risk associated genes, environmental exposures and gene–environment interactions, making PD a multifactorial disorder with a complex etiology. However, enormous efforts from global research have yielded significant insights into pathogenic mechanisms and potential therapeutic targets for PD. This review will highlight mitochondrial dysfunction as a common pathway involved in both genetic mutations and environmental toxicants linked to PD. PMID:29204154
New developments in the pharmacotherapy of neuropathic chronic pelvic pain

PubMed Central

Carey, Erin T; As-Sanie, Sawsan

2016-01-01

Advancements in further understanding the pathophysiology of chronic pelvic pain syndromes continue to direct therapy. The mechanisms of chronic pelvic pain are often multifactorial and therefore require a multidisciplinary approach. The final treatment plan is often an accumulation of organ-specific treatment and chronic pain medications directed to the CNS and PNS. This article is a review of commonly used medications for chronic pelvic neuropathic pain disorders as well as an introduction to recent innovative developments in pain medicine. PMID:28116131
How Stuttering Develops: The Multifactorial Dynamic Pathways Theory

PubMed Central

Weber, Christine

2017-01-01

Purpose We advanced a multifactorial, dynamic account of the complex, nonlinear interactions of motor, linguistic, and emotional factors contributing to the development of stuttering. Our purpose here is to update our account as the multifactorial dynamic pathways theory. Method We review evidence related to how stuttering develops, including genetic/epigenetic factors; motor, linguistic, and emotional features; and advances in neuroimaging studies. We update evidence for our earlier claim: Although stuttering ultimately reflects impairment in speech sensorimotor processes, its course over the life span is strongly conditioned by linguistic and emotional factors. Results Our current account places primary emphasis on the dynamic developmental context in which stuttering emerges and follows its course during the preschool years. Rapid changes in many neurobehavioral systems are ongoing, and critical interactions among these systems likely play a major role in determining persistence of or recovery from stuttering. Conclusion Stuttering, or childhood onset fluency disorder (Diagnostic and Statistical Manual of Mental Disorders, 5th edition; American Psychiatric Association [APA], 2013), is a neurodevelopmental disorder that begins when neural networks supporting speech, language, and emotional functions are rapidly developing. The multifactorial dynamic pathways theory motivates experimental and clinical work to determine the specific factors that contribute to each child's pathway to the diagnosis of stuttering and those most likely to promote recovery. PMID:28837728
How Stuttering Develops: The Multifactorial Dynamic Pathways Theory.

PubMed

Smith, Anne; Weber, Christine

2017-09-18

We advanced a multifactorial, dynamic account of the complex, nonlinear interactions of motor, linguistic, and emotional factors contributing to the development of stuttering. Our purpose here is to update our account as the multifactorial dynamic pathways theory. We review evidence related to how stuttering develops, including genetic/epigenetic factors; motor, linguistic, and emotional features; and advances in neuroimaging studies. We update evidence for our earlier claim: Although stuttering ultimately reflects impairment in speech sensorimotor processes, its course over the life span is strongly conditioned by linguistic and emotional factors. Our current account places primary emphasis on the dynamic developmental context in which stuttering emerges and follows its course during the preschool years. Rapid changes in many neurobehavioral systems are ongoing, and critical interactions among these systems likely play a major role in determining persistence of or recovery from stuttering. Stuttering, or childhood onset fluency disorder (Diagnostic and Statistical Manual of Mental Disorders, 5th edition; American Psychiatric Association [APA], 2013), is a neurodevelopmental disorder that begins when neural networks supporting speech, language, and emotional functions are rapidly developing. The multifactorial dynamic pathways theory motivates experimental and clinical work to determine the specific factors that contribute to each child's pathway to the diagnosis of stuttering and those most likely to promote recovery.
Lower urinary tract symptoms and metabolic disorders: ICI-RS 2014.

PubMed

Denys, Marie-Astrid; Anding, Ralf; Tubaro, Andrea; Abrams, Paul; Everaert, Karel

2016-02-01

To investigate the link between lower urinary tract symptoms (LUTS) and metabolic disorders. This report results from presentations and subsequent discussions about LUTS and metabolic disorders at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, 2014. There are common pathophysiological determinants for the onset of LUTS and the metabolic syndrome (MetS). Both conditions are multifactorial, related to disorders in circadian rhythms and share common risk factors. As in men with erectile dysfunction, these potentially modifiable lifestyle factors may be novel targets to prevent and treat LUTS. The link between LUTS and metabolic disorders is discussed by using sleep, urine production and bladder function as underlying mechanisms that need to be further explored during future research. Recent findings indicate a bidirectional relationship between LUTS and the MetS. Future research has to explore underlying mechanisms to explain this relationship, in order to develop new preventive and therapeutic recommendations, such as weight loss and increasing physical activity. The second stage is to determine the effect of these new treatment approaches on the severity of LUTS and each of the components of the MetS. © 2016 Wiley Periodicals, Inc.
Craniofacial Syndromes and Sleep-Related Breathing Disorders

PubMed Central

Tan, Hui-Leng; Kheirandish-Gozal, Leila; Abel, François; Gozal, David

2015-01-01

Summary Children with craniofacial syndromes are at risk of sleep disordered breathing, the most common being obstructive sleep apnea. Midface hypoplasia in children with craniosynostosis and glossoptosis in children with Pierre Robin syndrome are well recognized risk factors, but the etiology is often multifactorial and many children have multilevel airway obstruction. We examine the published evidence and explore the current management strategies in these complex patients. Some treatment modalities are similar to those used in otherwise healthy children such as as adenotonsillectomy, positive pressure ventilation and in the refractory cases, tracheostomy. However, there are some distinct approaches such as nasopharyngeal airways, tongue lip adhesion, mandibular distraction osteogenesis in children with Pierre Robin sequence, and midface advancement in children with craniosynostoses. Clinicians should have a low threshold for referral for evaluation of sleep-disordered-breathing in these patients. PMID:26454241
Preventing intensive care unit delirium: a patient-centered approach to reducing sleep disruption.

PubMed

Stuck, Amy; Clark, Mary Jo; Connelly, Cynthia D

2011-01-01

Delirium in the intensive care unit is a disorder with multifactorial causes and is associated with poor outcomes. Sleep-wake disturbance is a common experience for patients with delirium. Care processes that disrupt sleep can lead to sleep deprivation, contributing to delirium. Patient-centered care is a concept that considers what is best for each individual. How can clinicians use a patient-centered approach to alter processes to decrease patient disruptions and improve sleep and rest? Could timing of blood draws and soothing music work to promote sleep?

Fibromyalgia in Primary Care.

PubMed

Higgs, Jay B

2018-06-01

Fibromyalgia is a common disorder and has substantial impact on quality of life. The cause remains unknown, but current evidence points to multifactorial involvement of pain processing. Clinical diagnosis is aided by evidence-based diagnostic criteria with subscores for widespread pain and symptom severity. Nonpharmacologic treatments, including cognitive behavioral therapy, sleep hygiene, and regular aerobic exercise, form the cornerstone of management. Pharmacologic intervention is an important adjunct, but benefit is variable. There is no cure for fibromyalgia at this time, but persistence and patience in management may lead to a satisfactory lifestyle. Published by Elsevier Inc.
Uric acid as one of the important factors in multifactorial disorders – facts and controversies

PubMed Central

Pasalic, Daria; Marinkovic, Natalija; Feher-Turkovic, Lana

2012-01-01

With considering serum concentration of the uric acid in humans we are observing hyperuricemia and possible gout development. Many epidemiological studies have shown the relationship between the uric acid and different disorders such are obesity, metabolic syndrome, hypertension and coronary artery disease. Clinicians and investigators recognized serum uric acid concentration as very important diagnostic and prognostic factor of many multifactorial disorders. This review presented few clinical conditions which are not directly related to uric acid, but the concentrations of uric acid might have a great impact in observing, monitoring, prognosis and therapy of such disorders. Uric acid is recognized as a marker of oxidative stress. Production of the uric acid includes enzyme xanthine oxidase which is involved in producing of radical-oxigen species (ROS). As by-products ROS have a significant role in the increased vascular oxidative stress and might be involved in atherogenesis. Uric acid may inhibit endothelial function by inhibition of nitric oxide-function under conditions of oxidative stress. Down regulation of nitric oxide and induction of endothelial dysfunction might also be involved in pathogenesis of hypertension. The most important and well evidenced is possible predictive role of uric acid in predicting short-term outcome (mortality) in acute myocardial infarction (AMI) patients and stroke. Nephrolithiasis of uric acid origin is significantly more common among patients with the metabolic syndrome and obesity. On contrary to this, uric acid also acts is an “antioxidant”, a free radical scavenger and a chelator of transitional metal ions which are converted to poorly reactive forms. PMID:22384520
Uric acid as one of the important factors in multifactorial disorders--facts and controversies.

PubMed

Pasalic, Daria; Marinkovic, Natalija; Feher-Turkovic, Lana

2012-01-01

With considering serum concentration of the uric acid in humans we are observing hyperuricemia and possible gout development. Many epidemiological studies have shown the relationship between the uric acid and different disorders such are obesity, metabolic syndrome, hypertension and coronary artery disease. Clinicians and investigators recognized serum uric acid concentration as very important diagnostic and prognostic factor of many multifactorial disorders. This review presented few clinical conditions which are not directly related to uric acid, but the concentrations of uric acid might have a great impact in observing, monitoring, prognosis and therapy of such disorders. Uric acid is recognized as a marker of oxidative stress. Production of the uric acid includes enzyme xanthine oxidase which is involved in producing of radical-oxigen species (ROS). As by-products ROS have a significant role in the increased vascular oxidative stress and might be involved in atherogenesis. Uric acid may inhibit endothelial function by inhibition of nitric oxide-function under conditions of oxidative stress. Down regulation of nitric oxide and induction of endothelial dysfunction might also be involved in pathogenesis of hypertension. The most important and well evidenced is possible predictive role of uric acid in predicting short-term outcome (mortality) in acute myocardial infarction (AMI) patients and stroke. Nephrolithiasis of uric acid origin is significantly more common among patients with the metabolic syndrome and obesity. On contrary to this, uric acid also acts is an "antioxidant", a free radical scavenger and a chelator of transitional metal ions which are converted to poorly reactive forms.
Burning mouth syndrome: an enigmatic disorder.

PubMed

Javali, M A

2013-01-01

Burning mouth syndrome (BMS) is a chronic oral pain or burning sensation affecting the oral mucosa, often unaccompanied by mucosal lesions or other evident clinical signs. It is observed principally in middle-aged patients and postmenopausal women and may be accompanied by xerostomia and altered taste. Burning mouth syndrome is characterized by an intense burning or stinging sensation, preferably on the tongue or in other areas of mouth. This disorder is one of the most common, encountered in the clinical practice. This condition is probably of multifactorial origin; however the exact underlying etiology remains uncertain. This article discusses several aspects of BMS, updates current knowledge about the etiopathogenesis and describes the clinical features as well as the diagnosis and management of BMS patients.
Biology and genetics of oculocutaneous albinism and vitiligo - common pigmentation disorders in southern Africa.

PubMed

Manga, Prashiela; Kerr, Robyn; Ramsay, Michèle; Kromberg, Jennifer G R

2013-07-29

Pigmentation disorders span the genetic spectrum from single-gene autosomal recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA connotes a group of disorders that result in hypopigmented skin due to decreased melanin production in melanocytes and loss of visual acuity. There are four non-syndromic forms, OCA1-4, which are classified based on the gene that is mutated (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively). Despite the fact that multiple genes account for the various forms of OCA, the phenotypes of all four forms result from disruption in the maturation and trafficking of the enzyme tyrosinase. OCA2 is the most prevalent autosomal recessive disorder among southern African blacks, affecting 1/3 900 individuals; while OCA3, although rare, is most prevalent in southern Africa. Another common pigmentation disorder in southern Africa is vitiligo, which affects 1 - 2% of people worldwide. Vitiligo is a complex, acquired disorder in which melanocytes are destroyed due to an autoimmune response. The aetiology underlying this disorder is poorly understood, although recent genetic association studies have begun to shed light on the contributing factors. Pigmentation disorders have significant psychosocial implications and co-morbidities, yet therapies are still lacking. Recent progress in our understanding of the pathobiology of both albinism and vitiligo may herald novel treatment strategies for these disorders.
Parents Psychopathology of Children with Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Margari, Francesco; Craig, Francesco; Petruzzelli, Maria Giuseppina; Lamanna, Annalinda; Matera, Emilia; Margari, Lucia

2013-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder with extremely complex etiology, not yet well defined but certainly multi-factorial. This study investigated the possible etiopathogenetic role of ADHD symptoms and psychopathology disorders in parents of children with ADHD. We present a case-control study of parents of 50 children…
Complications of Cushing's syndrome: state of the art.

PubMed

Pivonello, Rosario; Isidori, Andrea M; De Martino, Maria Cristina; Newell-Price, John; Biller, Beverly M K; Colao, Annamaria

2016-07-01

Cushing's syndrome is a serious endocrine disease caused by chronic, autonomous, and excessive secretion of cortisol. The syndrome is associated with increased mortality and impaired quality of life because of the occurrence of comorbidities. These clinical complications include metabolic syndrome, consisting of systemic arterial hypertension, visceral obesity, impairment of glucose metabolism, and dyslipidaemia; musculoskeletal disorders, such as myopathy, osteoporosis, and skeletal fractures; neuropsychiatric disorders, such as impairment of cognitive function, depression, or mania; impairment of reproductive and sexual function; and dermatological manifestations, mainly represented by acne, hirsutism, and alopecia. Hypertension in patients with Cushing's syndrome has a multifactorial pathogenesis and contributes to the increased risk for myocardial infarction, cardiac failure, or stroke, which are the most common causes of death; risks of these outcomes are exacerbated by a prothrombotic diathesis and hypokalaemia. Neuropsychiatric disorders can be responsible for suicide. Immune disorders are common; immunosuppression during active disease causes susceptibility to infections, possibly complicated by sepsis, an important cause of death, whereas immune rebound after disease remission can exacerbate underlying autoimmune diseases. Prompt treatment of cortisol excess and specific treatments of comorbidities are crucial to prevent serious clinical complications and reduce the mortality associated with Cushing's syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.
[Restless Legs Syndrome : A Threat to the quality of life].

PubMed

Castaño-Cárcamo, Mauricio; Escobar-Cordoba, Franklin; Rey de Castro, Jorge

2014-01-01

Restless legs syndrome is a disorder associated with the imperative need to move the legs, starting at different times of day and it gets worse at night, relieved by activity, affecting the quality of life and sleep who sufferers it. Despite being a common disorder at any age, in adults with a prevalence of up to 10%, is not diagnosed by doctors and first level specialists that is why diagnostic and therapeutic interventions get delayed contributing to the perpetuation of symptoms and worsening quality of life. Since its diagnosis is purely clinical, getting familiar with this disorder is essential to ensure proper focus and thus rule out other diseases commonly confused with this one. Restless legs syndrome has a multi-factorial etiology that ranges from a genetic and hereditary, which are called primary restless legs syndrome, to its association with multiple pathologies, known as secondary restless legs syndrome. As for its management, drug therapy and non-drug therapy is aimed at symptom control, as its cure is not possible, although occasionally the condition can refer to later repeat in months or years.
Sleep Disturbances Associated with Parkinson's Disease

PubMed Central

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Iwanami, Masaoki; Hirata, Koichi

2011-01-01

Sleep disturbances are common problems affecting the quality life of Parkinson's disease (PD) patients and are often underestimated. The causes of sleep disturbances are multifactorial and include nocturnal motor disturbances, nocturia, depressive symptoms, and medication use. Comorbidity of PD with sleep apnea syndrome, restless legs syndrome, rapid eye movement sleep behavior disorder, or circadian cycle disruption also results in impaired sleep. In addition, the involvement of serotoninergic, noradrenergic, and cholinergic neurons in the brainstem as a disease-related change contributes to impaired sleep structures. Excessive daytime sleepiness is not only secondary to nocturnal disturbances or dopaminergic medication but may also be due to independent mechanisms related to impairments in ascending arousal system and the orexin system. Notably, several recent lines of evidence suggest a strong link between rapid eye movement sleep behavior disorder and the risk of neurodegenerative diseases such as PD. In the present paper, we review the current literature concerning sleep disorders in PD. PMID:21876839
Docosahexaenoic acid supplementation for children with attention deficit hyperactivity disorder: A comprehensive review of the evidence.

PubMed

Ramalho, Renata; Pereira, Ana Colaço; Vicente, Filipa; Pereira, Paula

2018-06-01

Attention deficit hyperactivity disorder (ADHD) is considered the most common behavioural disorder in school-age children. ADHD is a complex and multifactorial disorder characterised by a variety of symptoms, including concentration problems, excessive motor activity and impulsivity which interferes with execution of simple school tasks. Diagnosis has been essentially subjective, since no specific laboratory tests are available. However, ADHD remains overdiagnosed, probably due to social pressures for children to be successful in school from an early age, which leads parents to seek medical support. Although therapeutic approaches for ADHD have been essentially pharmacologic, in recent years several studies were performed to investigate the role of nutrition, especially omega 3 polyunsaturated fatty acid (omega 3-PUFA), in the development and treatment of this disorder. In this review, the authors gathered the most relevant evidence regarding omega 3-PUFA, mainly docosahexaenoic acid, as coadjutant or as a single therapy, in the management of ADHD symptoms. The authors also reviewed this disorder's current medical and therapeutic features. Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
Stem Cells and the Pathogenesis of Endometriosis

PubMed Central

Sasson, Isaac E.; Taylor, Hugh S.

2011-01-01

Endometriosis is a common gynecological disorder that is defined by the presence of endometrial tissue outside the uterine cavity. This disease often results in extensive morbidity, including chronic pelvic pain and infertility. The pathogenesis of endometriosis is likely multifactorial, and extensive investigation has explored the role of genetics, environmental factors, and the immune system in predisposing patients to developing endometriosis. A series of recent publications have described the identification of endometrial stem/progenitor cells. Such cells have long been speculated to function in the cyclic regeneration of the endometrium during the menstrual cycle and in the pathogenesis of several gynecological disorders. This narrative review will (i) examine the evidence for endometrial stem cells, (ii) examine their potential role in the pathogenesis of endometriosis, and (iii) identify important unanswered questions with suggestions for future investigation. PMID:18443337
Burning mouth syndrome

PubMed Central

Jimson, Sudha; Rajesh, E.; Krupaa, R. Jayasri; Kasthuri, M.

2015-01-01

Burning mouth syndrome (BMS) is a complex disorder that is characterized by warm or burning sensation in the oral mucosa without changes on physical examination. It occurs more commonly in middle-aged and elderly women and often affects the tip of the tongue, lateral borders, lips, hard and soft palate. This condition is probably of multi-factorial origin, often idiopathic, and its etiopathogensis is unknown. BMS can be classified into two clinical forms namely primary and secondary BMS. As a result, a multidisciplinary approach is required for better control of the symptoms. In addition, psychotherapy and behavioral feedback may also help eliminate the BMS symptoms. PMID:26015707
Sleep in the Aging Population.

PubMed

Miner, Brienne; Kryger, Meir H

2017-03-01

There are normal changes to sleep architecture throughout the lifespan. There is not, however, a decreased need for sleep and sleep disturbance is not an inherent part of the aging process. Sleep disturbance is common in older adults because aging is associated with an increasing prevalence of multimorbidity, polypharmacy, psychosocial factors affecting sleep, and certain primary sleep disorders. It is also associated with morbidity and mortality. Because many older adults have several factors from different domains affecting their sleep, these complaints are best approached as a multifactorial geriatric health condition, necessitating a multifaceted treatment approach. Copyright © 2016 Elsevier Inc. All rights reserved.
From Genes to Environment: Using Integrative Genomics to Build a "Systems-Level" Understanding of Autism Spectrum Disorders

ERIC Educational Resources Information Center

Hu, Valerie W.

2013-01-01

Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders that affect an estimated 1 in 110 individuals. Although there is a strong genetic component associated with these disorders, this review focuses on the multifactorial nature of ASD and how different genome-wide (genomic) approaches contribute to our understanding of autism.…
Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging.

PubMed

Brosh, Robert M; Bellani, Marina; Liu, Yie; Seidman, Michael M

2017-01-01

Fanconi Anemia (FA) is a rare autosomal genetic disorder characterized by progressive bone marrow failure (BMF), endocrine dysfunction, cancer, and other clinical features commonly associated with normal aging. The anemia stems directly from an accelerated decline of the hematopoietic stem cell compartment. Although FA is a complex heterogeneous disease linked to mutations in 19 currently identified genes, there has been much progress in understanding the molecular pathology involved. FA is broadly considered a DNA repair disorder and the FA gene products, together with other DNA repair factors, have been implicated in interstrand cross-link (ICL) repair. However, in addition to the defective DNA damage response, altered epigenetic regulation, and telomere defects, FA is also marked by elevated levels of inflammatory mediators in circulation, a hallmark of faster decline in not only other hereditary aging disorders but also normal aging. In this review, we offer a perspective of FA as a monogenic accelerated aging disorder, citing the latest evidence for its multi-factorial deficiencies underlying its unique clinical and cellular features. Published by Elsevier B.V.
Eating disorders in women

PubMed Central

Sharan, Pratap; Sundar, A. Shyam

2015-01-01

Eating disorders, especially anorexia nervosa and bulimia nervosa have been classically described in young females in Western population. Recent research shows that they are also seen in developing countries including India. The classification of eating disorders has been expanded to include recently described conditions like binge eating disorder. Eating disorders have a multifactorial etiology. Genetic factor appear to play a major role. Recent advances in neurobiology have improved our understanding of these conditions and may possibly help us develop more effective treatments in future. Premorbid personality appears to play an important role, with differential predisposition for individual disorders. The role of cultural factors in the etiology of these conditions is debated. Culture may have a pathoplastic effect leading to non-conforming presentations like the non fat-phobic form of anorexia nervosa, which are commonly reported in developing countries. With rapid cultural transformation, the classical forms of these conditions are being described throughout the world. Diagnostic criteria have been modified to accommodate for these myriad presentations. Treatment of eating disorders can be quite challenging, given the dearth of established treatments and poor motivation/insight in these conditions. Nutritional rehabilitation and psychotherapy remains the mainstay of treatment, while pharmacotherapy may be helpful in specific situations. PMID:26330646
Gait and balance disorders in older adults.

PubMed

Salzman, Brooke

2010-07-01

Gait and balance disorders are common in older adults and are a major cause of falls in this population. They are associated with increased morbidity and mortality, as well as reduced level of function. Common causes include arthritis and orthostatic hypotension; however, most gait and balance disorders involve multiple contributing factors. Most changes in gait are related to underlying medical conditions and should not be considered an inevitable consequence of aging. Physicians caring for older patients should ask at least annually about falls, and should ask about or examine for difficulties with gait and balance at least once. For older adults who report a fall, physicians should ask about difficulties with gait and balance, and should observe for any gait or balance dysfunctions. The Timed Up and Go test is a fast and reliable diagnostic tool. Persons who have difficulty or demonstrate unsteadiness performing the Timed Up and Go test require further assessment, usually with a physical therapist, to help elucidate gait impairments and related functional limitations. The most effective strategy for falls prevention involves a multifactorial evaluation followed by targeted interventions for identified contributing factors. Evidence on the effectiveness of interventions for gait and balance disorders is limited because of the lack of standardized outcome measures determining gait and balance abilities. However, effective options for patients with gait and balance disorders include exercise and physical therapy. (c) 2010 American Academy of Family Physicians.
Learning disorders in children with epilepsy.

PubMed

Pavlou, Evangelos; Gkampeta, Anastasia

2011-03-01

Learning Disorders (LD) are defined as disorders that interfere with academic performance or with daily activities that require reading, writing or mathematical skills in subjects with a normal intelligence quotient (IQ). The prevalence of LD in the general population has been found to be 2-10%, and reading disorders are the most frequent subtype. Epilepsy is one of the most common serious neurological disorders in childhood. LD are more common in children with epilepsy than in the general population. As a consequence, the risk of cognitive impairment in children with epilepsy is high, and a review of the literature needs to be fully presented. Narrative review including articles regarding LD in children with various epileptic syndromes published in the international medical literature. LD are more frequent among children with epilepsy. The etiology is multifactorial, being affected by the type of epileptic syndrome, the age of onset and the antiepileptic treatment being selected. LD can be either permanent or state-dependent. Each category has different treatment protocols and prognosis. Despite the fact that the findings of the studies discussed in our article support the evidence that epilepsy in childhood impairs the cognitive function, we should not underestimate the role of demographic and psychosocial factors on academic performance of children with epilepsy. Despite the high prevalence of LD, a healthy family and school environment can help reduce its impact on the patient's quality of life. © Springer-Verlag 2010
Mood disorders and Gilles de la Tourette's syndrome: An update on prevalence, etiology, comorbidity, clinical associations, and implications.

PubMed

Robertson, Mary May

2006-09-01

Gilles de la Tourette's syndrome (GTS) consists of multiple motor tics and one or more phonic tics. Psychopathology occurs in approximately 90% of GTS patients, with attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) being common. Depression is common, with a lifetime risk of 10% and a prevalence of between 1.8% and 8.9%. Depression and depressive symptoms are found to occur in 13% and 76% of GTS patients attending specialist clinics, respectively. In controlled studies embracing over 700 GTS patients, the patients were significantly more depressed than controls in all but one instance. In community and epidemiological studies, depression in GTS individuals was evident in two of five investigations. Clinical correlates of depression in people with GTS appear to be: tic severity and duration, the presence of echophenomena and coprophenomena, premonitory sensations, sleep disturbances, obsessive-compulsive behaviors/OCD, self-injurious behaviors, aggression, conduct disorder (CD) in childhood, and, possibly, ADHD. Depression in people with GTS has been shown to result in a lower quality of life, potentially leading to hospitalization and suicide. The etiology of depression appears to be multifactorial. Bipolar affective disorder (BAD) and GTS may be related in some individuals. However, it is noted that sample sizes in most of these studies were small, and it is unclear at the present time as to why BAD may be overrepresented among GTS patients.
METAGENOMICS AND PERSONALIZED MEDICINE

PubMed Central

Virgin, Herbert W.; Todd, John A.

2015-01-01

The microbiome is a complex community of Bacteria, Archaea, Eukarya and viruses that infect humans and live in our tissues. It contributes the majority of genetic information to our metagenome, and consequently, to our resistance and susceptibility to diseases, especially common inflammatory diseases, such as type 1 diabetes, ulcerative colitis, and Crohn's disease. Here we discuss how host-gene-microbial interactions are major determinants for the development of these multifactorial chronic disorders and thus, for the relationship between genotype and phenotype. We also explore how genome-wide association studies (GWAS) on autoimmune and inflammatory diseases are uncovering mechanism-based sub-types for these disorders. Applying these emerging concepts will permit a more complete understanding of the etiologies of complex diseases and underpin the development of both next generation animal models and new therapeutic strategies for targeting personalized disease phenotypes. PMID:21962506

Preventing musculoskeletal disorders in clinical dentistry: strategies to address the mechanisms leading to musculoskeletal disorders.

PubMed

Valachi, Bethany; Valachi, Keith

2003-12-01

The authors reviewed studies to identify methods for dental operators to use to prevent the development of musculoskeletal disorders, or MSDs. The authors reviewed studies that related to the prevention of MSDs among dental operators. Some studies investigated the relationship between the biomechanics of seated working postures and physiological damage or pain. Other studies suggested that repeated unidirectional twisting of the trunk can lead to low back pain, while yet other studies examined the detrimental effects of working in one position for prolonged periods. Additional studies confirmed the roles that operators' flexibility and core strength can play in balanced musculoskeletal health and the need for operators to know how to properly adjust ergonomic equipment. This review indicates that strategies to prevent the multifactorial problem of dental operators' developing MSDs exist. These strategies address deficiencies in operator position, posture, flexibility, strength and ergonomics. Education and additional research are needed to promote an understanding of the complexity of the problem and to address the problem's multifactorial nature. A comprehensive approach to address the problem of MSDs in dentistry represents a paradigm shift in how operators work. New educational models that incorporate a multifactorial approach can be developed to help dental operators manage and prevent MSDs effectively.
Mining Internet search and social media for epidemiology

EPA Science Inventory

Many pervasive and multifactorial disorders of modern non-communicable and non-infectious diseases (i.e. obesity, asthma, migraine, autism) need to be better understood and explored. The cost of these disorders to the healthcare system and the general public’s quality of life are...
Inflammatory Bowel Disease: Pathophysiology and Current Therapeutic Approaches.

PubMed

Abraham, Bincy P; Ahmed, Tasneem; Ali, Tauseef

2017-01-01

Inflammatory bowel diseases, most commonly categorized as Crohn's disease and ulcerative colitis, are immune mediated chronic inflammatory disorders of the gastrointestinal tract. The etiopathogenesis is multifactorial with different environmental, genetic, immune mediated, and gut microbial factors playing important role. The current goals of therapy are to improve clinical symptoms, control inflammation, prevent complications, and improve quality of life. Different therapeutic agents, with their indications, mechanisms of action, and side effects are discussed in this chapter. Anti-integrin therapy, a newer therapeutic class, with its potential beneficial role in both Crohn's disease and ulcerative colitis is also mentioned. In the end, therapeutic algorithms for both diseases are reviewed.
PREVENTION AND MANAGEMENT OF LIMB CONTRACTURES IN NEUROMUSCULAR DISEASES

PubMed Central

Skalsky, Andrew J.; McDonald, Craig M.

2012-01-01

Synopsis Limb contractures are a common impairment in neuromuscular diseases (NMD). They contribute to increased disability due to decreased motor performance, mobility limitations, reduced functional range of motion, loss of function for activities of daily living (ADL), and increased pain. The pathogenesis of contractures is multifactorial. Myopathic conditions are associated with more severe limb contractures in comparison to neuropathic disorders. Although the evidence supporting the efficacy of multiple interventions to improve ROM in NMD in a sustained manner is lacking, there are generally accepted principles with regard to splinting, bracing, stretching, and surgery that help minimize the impact or disability from the contractures. PMID:22938881
Autism Spectrum Disorders and Epigenetics

ERIC Educational Resources Information Center

Grafodatskaya, Daria; Chung, Brian; Szatmari, Peter; Weksberg, Rosanna

2010-01-01

Objective: Current research suggests that the causes of autism spectrum disorders (ASD) are multifactorial and include both genetic and environmental factors. Several lines of evidence suggest that epigenetics also plays an important role in ASD etiology and that it might, in fact, integrate genetic and environmental influences to dysregulate…
Autism Spectrum Disorders Associated with Chromosomal Abnormalities

ERIC Educational Resources Information Center

Lo-Castro, Adriana; Benvenuto, Arianna; Galasso, Cinzia; Porfirio, Cristina; Curatolo, Paolo

2010-01-01

Autism spectrum disorders (ASDs) constitute a class of severe neurodevelopmental conditions with complex multifactorial and heterogeneous etiology. Despite high estimates of heritability, genetic causes of ASDs remain elusive, due to a high degree of genetic and phenotypic heterogeneity. So far, several "monogenic" forms of autism have been…
Loss of delta catenin function in severe autism

PubMed Central

Turner, Tychele N.; Sharma, Kamal; Oh, Edwin C.; Liu, Yangfan P.; Collins, Ryan L.; Sosa, Maria X.; Auer, Dallas R.; Brand, Harrison; Sanders, Stephan J.; Moreno-De-Luca, Daniel; Pihur, Vasyl; Plona, Teri; Pike, Kristen; Soppet, Daniel R.; Smith, Michael W.; Cheung, Sau Wai; Martin, Christa Lese; State, Matthew W.; Talkowski, Michael E.; Cook, Edwin; Huganir, Richard; Katsanis, Nicholas; Chakravarti, Aravinda

2015-01-01

SUMMARY Autism is a multifactorial neurodevelopmental disorder affecting more males than females; consequently, under a multifactorial genetic hypothesis, females are affected only when they cross a higher biological threshold. We hypothesize that deleterious variants at conserved residues are enriched in severely affected patients arising from FEMFs (female-enriched multiplex families) with severe disease, enhancing the detection of key autism genes in modest numbers of cases. We show the utility of this strategy by identifying missense and dosage sequence variants in the gene encoding the adhesive junction-associated delta catenin protein (CTNND2) in FEMFs and demonstrating their loss-of-function effect by functional analyses in zebrafish embryos and cultured hippocampal neurons from wildtype and Ctnnd2 null mouse embryos. Finally, through gene expression and network analyses, we highlight a critical role for CTNND2 in neuronal development and an intimate connection to chromatin biology. Our data contribute to the understanding of the genetic architecture of autism and suggest that genetic analyses of phenotypic extremes, such as FEMFs, are of innate value in multifactorial disorders. PMID:25807484
Models of comorbidity for multifactorial disorders.

PubMed Central

Neale, M C; Kendler, K S

1995-01-01

We develop several formal models for comorbidity between multifactorial disorders. Based on the work of D. N. Klein and L. P. Riso, the models include (i) alternate forms, where the two disorders have the same underlying continuum of liability; (ii) random multiformity, in which affection status on one disorder abruptly increases risk for the second; (iii) extreme multiformity, where only extreme cases have an abruptly increased risk for the second disorder; (iv) three independent disorders, in which excess comorbid cases are due to a separate, third disorder; (v) correlated liabilities, where the risk factors for the two disorders correlate; and (vi) direct causal models, where the liability for one disorder is a cause of the other disorder. These models are used to make quantitative predictions about the relative proportions of pairs of relatives who are classified according to whether each relative has neither disorder, disorder A but not B, disorder B but not A, or both A and B. For illustration, we analyze data on major depression (MD) and generalized anxiety disorder (GAD) assessed in adult female MZ and DZ twins, which enable estimation of the relative impact of genetic and environmental factors. Several models are rejected--that comorbid cases are due to chance; multiformity of GAD; a third independent disorder; and GAD being a cause of MD. Of the models that fit the data, correlated liabilities, MD causes GAD, and reciprocal causation seem best. MD appears to be a source of liability for GAD. Possible extensions to the models are discussed. PMID:7573055
Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer's disease.

PubMed

Iturria-Medina, Yasser; Carbonell, Félix M; Sotero, Roberto C; Chouinard-Decorte, Francois; Evans, Alan C

2017-05-15

Generative models focused on multifactorial causal mechanisms in brain disorders are scarce and generally based on limited data. Despite the biological importance of the multiple interacting processes, their effects remain poorly characterized from an integrative analytic perspective. Here, we propose a spatiotemporal multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention that accounts for local causal interactions, effects propagation via physical brain networks, cognitive alterations, and identification of optimum therapeutic interventions. In this article, we focus on describing the model and applying it at the population-based level for studying late onset Alzheimer's disease (LOAD). By interrelating six different neuroimaging modalities and cognitive measurements, this model accurately predicts spatiotemporal alterations in brain amyloid-β (Aβ) burden, glucose metabolism, vascular flow, resting state functional activity, structural properties, and cognitive integrity. The results suggest that a vascular dysregulation may be the most-likely initial pathologic event leading to LOAD. Nevertheless, they also suggest that LOAD it is not caused by a unique dominant biological factor (e.g. vascular or Aβ) but by the complex interplay among multiple relevant direct interactions. Furthermore, using theoretical control analysis of the identified population-based multifactorial causal network, we show the crucial advantage of using combinatorial over single-target treatments, explain why one-target Aβ based therapies might fail to improve clinical outcomes, and propose an efficiency ranking of possible LOAD interventions. Although still requiring further validation at the individual level, this work presents the first analytic framework for dynamic multifactorial brain (dis)organization that may explain both the pathologic evolution of progressive neurological disorders and operationalize the influence of multiple interventional strategies. Copyright © 2017 Elsevier Inc. All rights reserved.
Acute and chronic effects of transportation stress in the honey bee, Apis mellifera

USDA-ARS?s Scientific Manuscript database

Owing to the continued impact of colony collapse disorder (CCD) on the beekeeping industry, numerous stressors including nutrition, pests and pathogens and biocides are being investigated as potential contributors to what appears to be a multi-factorial disorder. Because honey bee hives are transpo...
Association of Autism Spectrum Disorders and Inflammatory Bowel Disease

ERIC Educational Resources Information Center

Lee, Maunoo; Krishnamurthy, Jayasree; Susi, Apryl; Sullivan, Carolyn; Gorman, Gregory H.; Hisle-Gorman, Elizabeth; Erdie-Lalena, Christine R.; Nylund, Cade M.

2018-01-01

Autism spectrum disorders (ASD) and inflammatory bowel disease (IBD) both have multifactorial pathogenesis with an increasing number of studies demonstrating gut-brain associations. We aim to examine the association between ASD and IBD using strict classification criteria for IBD. We conducted a retrospective case-cohort study using records from…
Deep Dyspareunia in Endometriosis: A Proposed Framework Based on Pain Mechanisms and Genito-Pelvic Pain Penetration Disorder.

PubMed

Yong, Paul J

2017-10-01

Endometriosis is a common chronic disease affecting 1 in 10 women of reproductive age, with half of women with endometriosis experiencing deep dyspareunia. A review of research studies on endometriosis indicates a need for a validated question or questionnaire for deep dyspareunia. Moreover, placebo-controlled randomized trials have yet to demonstrate a clear benefit for traditional treatments of endometriosis for the outcome of deep dyspareunia. The reason some patients might not respond to traditional treatments is the multifactorial nature of deep dyspareunia in endometriosis, which can include comorbid conditions (eg, interstitial cystitis and bladder pain syndrome) and central sensitization underlying genito-pelvic pain penetration disorder. In general, there is a lack of a framework that integrates these multifactorial causes to provide a standardized approach to deep dyspareunia in endometriosis. To propose a clinical framework for deep dyspareunia based on a synthesis of pain mechanisms with genito-pelvic pain penetration disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Narrative review after literature search with the terms (endometriosis AND dyspareunia) OR (dyspareunia AND deep) and after analysis of placebo-controlled randomized trials. Deep dyspareunia presence or absence or deep dyspareunia severity on a numeric rating scale or visual analog scale. Four types of deep dyspareunia are proposed in women with endometriosis: type I that is directly due to endometriosis; type II that is related to a comorbid condition; type III in which genito-pelvic pain penetration disorder is primary; and type IV that is secondary to a combination of types I to III. Four types of deep dyspareunia in endometriosis are proposed, which can be used as a framework in research studies and in clinical practice. Research trials could phenotype or stratify patients by each type. The framework also could give rise to more personalized care for patients by targeting appropriate treatments to each deep dyspareunia type. Yong PJ. Deep Dyspareunia in Endometriosis: A Proposed Framework Based on Pain Mechanisms and Genito-Pelvic Pain Penetration Disorder. Sex Med Rev 2017;5:495-507. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
[Gait disorders in geriatric patients. Classification and therapy].

PubMed

Jahn, K; Heinze, C; Selge, C; Heßelbarth, K; Schniepp, R

2015-04-01

Slow walking with reduced body dynamics is a characteristic feature of locomotion in the elderly. Impaired mobility and falls associated with gait disorders significantly contribute to a reduced quality of life in the elderly. A gait disorder is not an inevitable consequence of aging. This article shows that it is worth recognizing specific deficits and differentiating specific aspects in multifactorial disorders because many causes can be well treated. Also provided are the bases for clinical classification and therapeutic principles. Review of recent literature and clinical review based on own experience and own scientific results. Common causes of disturbed gait in the elderly are neurological deficits, including sensory deficits (e.g. peripheral neuropathy and vestibulopathy), neurodegeneration (e.g. cerebellar ataxia and parkinsonian syndromes, cognitive impairment (e.g. degenerative dementia), degeneration of joints (e.g. coxarthrosis) and general loss of muscle mass (sarcopenia). Furthermore, a fear of falling also contributes to the gait disorder. Multimodal therapies are often necessary and the principles are presented. Identification of deficits is a prerequisite for specific therapy. As physical activity protects against cognitive impairment, reduces the risk of falling and improves overall quality of life, a structured assessment of causes for gait impairment is crucial.
Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome.

PubMed

O'Malley, Dervla

2016-11-01

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain, bloating, and disturbed bowel habit, symptoms that impact the quality of life of sufferers. The pathophysiological changes underlying this multifactorial condition are complex and include increased sensitivity to luminal and mucosal factors, resulting in altered colonic transit and visceral pain. Moreover, dysfunctional communication in the bidirectional signaling axis between the brain and the gut, which involves efferent and afferent branches of the peripheral nervous system, circulating endocrine hormones, and local paracrine and neurocrine factors, including immune and perhaps even microbial signaling molecules, has a role to play in this disorder. This minireview will examine recent advances in our understanding of the pathophysiology of IBS and assess how cross talk between hormones, immune, and microbe-derived factors and their neuromodulatory effects on peripheral nerves may underlie IBS symptomatology. Copyright © 2016 the American Physiological Society.
Cat-Map: putting cataract on the map

PubMed Central

Bennett, Thomas M.; Hejtmancik, J. Fielding

2010-01-01

Lens opacities, or cataract(s), may be inherited as a classic Mendelian disorder usually with early-onset or, more commonly, acquired with age as a multi-factorial or complex trait. Many genetic forms of cataract have been described in mice and other animal models. Considerable progress has been made in mapping and identifying the genes and mutations responsible for inherited forms of cataract, and genetic determinants of age-related cataract are beginning to be discovered. To provide a convenient and accurate summary of current information focused on the increasing genetic complexity of Mendelian and age-related cataract we have created an online chromosome map and reference database for cataract in humans and mice (Cat-Map). PMID:21042563
Glucose-6-phosphate dehydrogenase a novel hope on a blood-based diagnosis of Alzheimer's disease.

PubMed

Evlice, Ahmet; Ulusu, Nuriye Nuray

2017-03-01

Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder that numerous factors have key properties in the development of this proteopathy. Glucose-6-phosphate dehydrogenase (G6PD) is the most common form of enzymopathy. We have examined G6PD enzyme activity levels in the serum of newly diagnosed AD patients compared with control subjects without dementia from the both sexes. Serum G6PD levels were found to be significantly higher (approximately two times) in AD patients compared to control geriatric subjects in both sexes. We have concluded that G6PD seems to play an integral role in the progress and/or prevention of AD.
Omega-3 and dyslexia

PubMed Central

Zelcer, Michal; Goldman, Ran D.

2015-01-01

Abstract Question In light of the increase in the number of school-aged children diagnosed with dyslexia, what is the role of omega-3 supplements in the management of this condition? Answer Dyslexia is the most common learning disability and is known to have multifactorial causes. Recent evidence suggests that there is a connection between defects in highly unsaturated fatty acid metabolism and neurodevelopmental disorders such as dyslexia. While the benefit of omega-3 supplementation for children with dyslexia has been studied, evidence remains limited. Unified diagnostic criteria for dyslexia, objective measures of fatty acid deficiency, and close monitoring of dietary intake are some of the factors that would improve the quality of research in the field. PMID:26371100
Multifactorial discrimination as a fundamental cause of mental health inequities.

PubMed

Khan, Mariam; Ilcisin, Misja; Saxton, Katherine

2017-03-04

The theory of fundamental causes explains why health disparities persist over time, even as risk factors, mechanisms, and diseases change. Using an intersectional framework, we evaluated multifactorial discrimination as a fundamental cause of mental health disparities. Using baseline data from the Project STRIDE: Stress, Identity, and Mental Health study, we examined the health effects of discrimination among individuals who self-identified as lesbian, gay, or bisexual. We used logistic and linear regression to assess whether multifactorial discrimination met the four criteria designating a fundamental cause, namely that the cause: 1) influences multiple health outcomes, 2) affects multiple risk factors, 3) involves access to resources that can be leveraged to reduce consequences of disease, and 4) reproduces itself in varied contexts through changing mechanisms. Multifactorial discrimination predicted high depression scores, psychological well-being, and substance use disorder diagnosis. Discrimination was positively associated with risk factors for high depression scores: chronic strain and total number of stressful life events. Discrimination was associated with significantly lower levels of mastery and self-esteem, protective factors for depressive symptomatology. Even after controlling for risk factors, discrimination remained a significant predictor for high depression scores. Among subjects with low depression scores, multifactorial discrimination also predicted anxiety and aggregate mental health scores. Multifactorial discrimination should be considered a fundamental cause of mental health inequities and may be an important cause of broad health disparities among populations with intersecting social identities.
EVALUATION OF THE RELATIONSHIP BETWEEN ANDROGENETIC ALOPECIA AND DEMODEX INFESTATION

PubMed Central

Zari, Javidi; Abdolmajid, Fata; Masood, Maleki; Vahid, Mashayekhi; Yalda, Nahidi

2008-01-01

Introduction: Androgenetic alopecia (AGA) is one of the most common dermatologic disorders with a multifactorial etiology. Inflammatory activators such as Demodex infestation may play a role in the pathogenesis of some cases of androgenetic alopecia that do not respond to common treatments such as minoxidil and finasteride. The goal of this study is to evaluate the relationship between Demodex infestation and AGA. Materials and Methods: In this case-control study, 41 patients with AGA referred to the Dermatology Clinic of Imam Reza Hospital and 33 healthy individuals were evaluated as control. All of them were between 20 and 40 years old men. In order to identify Demodex infestation they were referred to the Parasitology laboratory. Results: Demodex was detected in 19.5% of patients and 15.2% of controls; therefore, there was no significant relationship between them statistically (P = 0.0787). Most of patients (85.4%) had greasy hair. The most common pattern of baldness was II degree in Hamilton scale. Conclusion: There is no relation between AGA and Demodex. PMID:19881989
Intrauterine growth restriction and hypospadias: is there a connection?

PubMed Central

2014-01-01

Hypospadias is one of the most common congenital malformations of the genitourinary tract in males. It is an incomplete fusion of urethral folds early in fetal development and may be associated with other malformations of the genital tract. The etiology is poorly understood and may be hormonal, genetic, or environmental, but most often is idiopathic or multifactorial. Among many possible risk factors identified, of particular importance is low birth weight, which is defined in various ways in the literature. No mechanism has been identified for the association of low birth weight and hypospadias, but some authors propose placental insufficiency as a common inciting factor. Currently, there is no standardized approach for evaluating children with hypospadias in the setting of intrauterine growth restriction. We reviewed the available published literature on the association of hypospadias and growth restriction to determine whether it should be considered a separate entity within the category of disorders of sexual differentiation. PMID:25337123

[Cocaine induced psychotic disorders: a review].

PubMed

Karila, L; Petit, A; Phan, O; Reynaud, M

2010-11-01

Cocaine remains the second most used illicit drug in Europe, after cannabis, though levels of use vary between countries. This psychostimulant has become a noticeable part of the European drug scene. Cocaine dependence, a chronic, relapsing and multifactorial disorder, is a significant worldwide public health problem with somatic, legal, social, cognitive and psychological complications. The relationship between clinical psychotic symptoms and use of specific substances other than cannabis has received minimal attention in the literature. Psychotic symptoms and experience of paranoia and suspiciousness are reported during the use and the withdrawal of cocaine. Furthermore, although psychotic symptoms were found to be common among substance users, the risk for development of chronic psychotic disorder was found. In the light of recent epidemiological data stating that there is an increased cocaine use, that there is an increased number of patients entering drug treatment for primary cocaine use in Europe for several years and that cocaine users are an heterogeneous group, we made a review on the specific topic of cocaine-induced psychotic disorders. This review is based on Medline, EMBASE, PsycINFO and Google Scholar searches of English and French-language articles published between 1969 and February, 2010.
[Relations between extraction of wisdom teeth and temporomandibular disorders: a case/control study].

PubMed

Duval, Florian; Leroux, Agathe; Bertaud, Valérie; Meary, Fleur; Le Padellec, Clément; Refuveille, Laura; Lemaire, Arnaud; Sorel, Olivier; Chauvel-Lebret, Dominique

2015-09-01

The aim of this study was to assess the impact of extraction of third molars on the occurrence of temporo-mandibular disorders (TMD). A review of the literature and a case-control study have been conducted. The case-control study compares the frequency of extraction of third molars between the sample with TMD (case) and the sample without TMD (control). The proportion of patients who had undergone extractions of wisdom teeth was higher in the case group than in the control group. The difference was statistically significant when patients had undergone extraction of all four wisdom teeth or when the extraction of four wisdom teeth underwent in one sitting or under general anesthesia. The study of patients in case sample shows that all signs of TMD were more common in patients who had undergone extractions in several sessions and under local anesthesia. The temporomandibular joint sounds are significantly more frequent with local anesthesia. In the case group, 85 to 92% of patients have parafunctions and 5 to 11% have malocclusion. This demonstrates the multifactorial etiology of temporomandibular disorders. © EDP Sciences, SFODF, 2015.
Structure of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Criteria for Obsessive–Compulsive Personality Disorder in Patients With Binge Eating Disorder

PubMed Central

Ansell, Emily B; Pinto, Anthony; Edelen, Maria Orlando; Grilo, Carlos M

2013-01-01

Objective To examine 1-, 2-, and 3-factor model structures through confirmatory analytic procedures for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) obsessive–compulsive personality disorder (OCPD) criteria in patients with binge eating disorder (BED). Method Participants were consecutive outpatients (n = 263) with binge eating disorder and were assessed with semi-structured interviews. The 8 OCPD criteria were submitted to confirmatory factor analyses in Mplus Version 4.2 (Los Angeles, CA) in which previously identified factor models of OCPD were compared for fit, theoretical relevance, and parsimony. Nested models were compared for significant improvements in model fit. Results Evaluation of indices of fit in combination with theoretical considerations suggest a multifactorial model is a significant improvement in fit over the current DSM-IV single-factor model of OCPD. Though the data support both 2- and 3-factor models, the 3-factor model is hindered by an underspecified third factor. Conclusion A multifactorial model of OCPD incorporating the factors perfectionism and rigidity represents the best compromise of fit and theory in modelling the structure of OCPD in patients with BED. A third factor representing miserliness may be relevant in BED populations but needs further development. The perfectionism and rigidity factors may represent distinct intrapersonal and interpersonal attempts at control and may have implications for the assessment of OCPD. PMID:19087485
Structure of diagnostic and statistical manual of mental disorders, fourth edition criteria for obsessive-compulsive personality disorder in patients with binge eating disorder.

PubMed

Ansell, Emily B; Pinto, Anthony; Edelen, Maria Orlando; Grilo, Carlos M

2008-12-01

To examine 1-, 2-, and 3-factor model structures through confirmatory analytic procedures for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) obsessive-compulsive personality disorder (OCPD) criteria in patients with binge eating disorder (BED). Participants were consecutive outpatients (n = 263) with binge eating disorder and were assessed with semi-structured interviews. The 8 OCPD criteria were submitted to confirmatory factor analyses in Mplus Version 4.2 (Los Angeles, CA) in which previously identified factor models of OCPD were compared for fit, theoretical relevance, and parsimony. Nested models were compared for significant improvements in model fit. Evaluation of indices of fit in combination with theoretical considerations suggest a multifactorial model is a significant improvement in fit over the current DSM-IV single- factor model of OCPD. Though the data support both 2- and 3-factor models, the 3-factor model is hindered by an underspecified third factor. A multifactorial model of OCPD incorporating the factors perfectionism and rigidity represents the best compromise of fit and theory in modelling the structure of OCPD in patients with BED. A third factor representing miserliness may be relevant in BED populations but needs further development. The perfectionism and rigidity factors may represent distinct intrapersonal and interpersonal attempts at control and may have implications for the assessment of OCPD.
What factors influence community-dwelling older people’s intent to undertake multifactorial fall prevention programs?

PubMed Central

Hill, Keith D; Day, Lesley; Haines, Terry P

2014-01-01

Purpose To investigate previous, current, or planned participation in, and perceptions toward, multifactorial fall prevention programs such as those delivered through a falls clinic in the community setting, and to identify factors influencing older people’s intent to undertake these interventions. Design and methods Community-dwelling people aged >70 years completed a telephone survey. Participants were randomly selected from an electronic residential telephone listing, but purposeful sampling was used to include equal numbers with and without common chronic health conditions associated with fall-related hospitalization. The survey included scenarios for fall prevention interventions, including assessment/multifactorial interventions, such as those delivered through a falls clinic. Participants were asked about previous exposure to, or intent to participate in, the interventions. A path model analysis was used to identify factors associated with intent to participate in assessment/multifactorial interventions. Results Thirty of 376 participants (8.0%) reported exposure to a multifactorial falls clinic-type intervention in the past 5 years, and 16.0% expressed intention to undertake this intervention. Of the 132 participants who reported one or more falls in the past 12 months, over one-third were undecided or disagreed that a falls clinic type of intervention would be of benefit to them. Four elements from the theoretical model positively influenced intention to participate in the intervention: personal perception of intervention effectiveness, self-perceived risk of falls, self-perceived risk of injury, and inability to walk up/down steps without a handrail (P<0.05). Conclusion Multifactorial falls clinic-type interventions are not commonly accessed or considered as intended fall prevention approaches among community-dwelling older people, even among those with falls in the past 12 months. Factors identified as influencing intention to undertake these interventions may be useful in promoting or targeting these interventions. PMID:25473276
Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome.

PubMed

Moloney, Rachel D; Johnson, Anthony C; O'Mahony, Siobhain M; Dinan, Timothy G; Greenwood-Van Meerveld, Beverley; Cryan, John F

2016-02-01

Visceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain. © 2015 John Wiley & Sons Ltd.
Attention Deficit Hyperactivity Disorder in Preschool-Age Children.

PubMed

Tandon, Mini; Pergjika, Alba

2017-07-01

Attention deficit hyperactivity disorder is a neurodevelopmental disorder marked by age-inappropriate deficits in attention or hyperactivity/impulsivity that interfere with functioning or development. It is highly correlated with other disorders, such as oppositional defiant disorder, conduct disorder, and mood symptoms. The etiology is multifactorial, and neuroimaging findings are nonspecific. Although assessment tools exist, there is variability among them, and historically, parent-teacher agreement has not been consistent. Treatment algorithm for attention deficit hyperactivity disorder in preschoolers includes behavioral interventions first followed by psychopharmacologic treatment when behavioral therapies fail. Other nonpharmacologic and nonbehavioral interventions are discussed including the role of exercise and nutrition. Copyright © 2017 Elsevier Inc. All rights reserved.
[Parasitosis and irritable bowel syndrome].

PubMed

Ibarra, Catalina; Herrera, Valentina; Pérez de Arce, Edith; Gil, Luis Carlos; Madrid, Ana María; Valenzuela, Lucía; Beltrán, Caroll J

2016-06-01

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract characterised by multi-factorial aetiology. In IBS physiopathology are involved diverse factors between them biological, psychosocial, and environmental components which affect the immune activation status of gut mucosa. Among these factors is recognized the intestinal parasitosis. Post-infection IBS (PI-IBS) is recognised as a subgroup of functional disorders whose symptoms onset appear after a symptomatic intestinal infection caused by microbial agents. There are few studies regarding of relationship between IBS and intestinal parasitosis in Chile. However, is has been well described a positive association between IBS and Blastocystis hominis infections, one of prevalent parasites in Chile. In other countries, is also described a relationship between IBS and amebiasis and giardiasis. Both, characterized by a common mode of transmission through water as well as contaminated food. Because the high prevalence of parasitosis in our country it is necessary to expand the association studies to clarify the strength of the parasites ethiology in IBS.
Epigenetics and cardiovascular disease

USDA-ARS?s Scientific Manuscript database

Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only...
[Acute inpatient conservative multimodal treatment of complex and multifactorial orthopedic diseases in the ANOA concept].

PubMed

Psczolla, M

2013-10-01

In Germany there is a clear deficit in the non-operative treatment of chronic and complex diseases and pain disorders in acute care hospitals. Only about 20 % of the treatments are carried out in orthopedic hospitals. Hospitals specialized in manual medicine have therefore formed a working group on non-operative orthopedic manual medicine acute care clinics (ANOA). The ANOA has developed a multimodal assessment procedure called the OPS 8-977 which describes the structure and process quality of multimodal and interdisciplinary diagnosis and treatment of the musculoskeletal system. Patients are treated according to clinical pathways oriented on the clinical findings. The increased duration of treatment in the German diagnosis-related groups (DRG) system is compensated for with a supplemental remuneration. Thus, complex and multifactorial orthopedic diseases and pain disorders are conservatively and appropriately treated as inpatient departments of acute care hospitals.
Ghrelin and Eating Disorders

PubMed Central

Atalayer, Deniz; Gibson, Charlisa; Konopacka, Alexandra; Geliebter, Allan

2012-01-01

There is growing evidence supporting a multifactorial etiology that includes genetic, neurochemical, and physiological components for eating disorders above and beyond the more conventional theories based on psychological and sociocultural factors. Ghrelin is one of the key gut signals associated with appetite, and the only known circulating hormone that triggers a positive energy balance by stimulating food intake. This review summarizes recent findings and several conflicting reports on ghrelin in eating disorders. Understanding these findings and inconsistencies may help in developing new methods to prevent and treat patients with these disorders. PMID:22960103
Sleep Disturbances in Neurodevelopmental Disorders.

PubMed

Robinson-Shelton, Althea; Malow, Beth A

2016-01-01

Sleep disturbances are extremely prevalent in children with neurodevelopmental disorders compared to typically developing children. The diagnostic criteria for many neurodevelopmental disorders include sleep disturbances. Sleep disturbance in this population is often multifactorial and caused by the interplay of genetic, neurobiological and environmental overlap. These disturbances often present either as insomnia or hypersomnia. Different sleep disorders present with these complaints and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. This review aims to provide an overview of causes, diagnosis, and treatment of sleep disturbances in neurodevelopmental disorders that present primarily with symptoms of hypersomnia and/or insomnia.
Comparison of energy expenditure, body composition, metabolic disorders, and energy intake between obese children with a history of craniopharyngioma and children with multifactorial obesity.

PubMed

Bomer, Ilanit; Saure, Carola; Caminiti, Carolina; Ramos, Javier Gonzales; Zuccaro, Graciela; Brea, Mercedes; Bravo, Mónica; Maza, Carmen

2015-11-01

Craniopharyngioma is a histologically benign brain malformation with a fundamental role in satiety modulation, causing obesity in up to 52% of patients. To evaluate cardiovascular risk factors, body composition, resting energy expenditure (REE), and energy intake in craniopharyngioma patients and to compare the data with those from children with multifactorial obesity. All obese children and adolescents who underwent craniopharyngioma resection and a control group of children with multifactorial obesity in follow-up between May 2012 and April 2013. Anthropometric measurements, bioelectrical impedance, indirect calorimetry, energy intake, homeostatic model assessment insulin resistance (HOMA-IR), and dyslipidemia were evaluated. Twenty-three patients with craniopharyngioma and 43 controls were included. Children with craniopharyngioma-related obesity had a lower fat-free mass percentage (62.4 vs. 67.5; p=0.01) and a higher fat mass percentage (37.5 vs. 32.5; p=0.01) compared to those with multifactorial obesity. A positive association was found between %REE and %fat-free mass in subjects with multifactorial obesity (68±1% in normal REE vs. 62.6±1% in low REE; p=0.04), but not in craniopharyngioma patients (62±2.7 in normal REE vs. 61.2±1.8% in low REE; p=0.8). No differences were found in metabolic involvement or energy intake. REE was lower in craniopharyngioma patients compared to children with multifactorial obesity regardless of the amount of fat-free mass, suggesting that other factors may be responsible for the lower REE.
Issues in Personality Conceptualizations of Addictive Behaviors.

ERIC Educational Resources Information Center

Sutker, Patricia B.; Allain, Albert N., Jr.

1988-01-01

Describes issues and implications associated with personality conceptualizations of addictive behaviors. Directs attention toward characterizing the sociopolitical climate's effect on identification, evaluation, and management of substance abuse disorders. Explores alcohol and drug use in conceptual schemata encompassing multifactorial,…
Epigenetics lights up the obesity field

USDA-ARS?s Scientific Manuscript database

Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only ...
[Irritable bowel syndrome, levator ani syndrome, proctalgia fugax and chronic pelvic and perineal pain].

PubMed

Watier, Alain; Rigaud, Jérôme; Labat, Jean-Jacques

2010-11-01

To define functional gastrointestinal pain, irritable bowel syndrome (IBS), levator ani syndrome, proctalgia fugax, the pathophysiology of these syndromes and the treatments that can be proposed. Review of articles published on the theme based on a Medline (PubMed) search and consensus conferences selected according to their scientific relevance. IBS is very common. Patients report abdominal pain and/or discomfort, bloating, and abnormal bowel habit (diarrhoea, constipation or both), in the absence of any structural or biochemical abnormalities. IBS has a complex, multifactorial pathophysiology, involving biological and psychosocial interactions resulting in dysregulation of the brain-gut axis associated with disorders of intestinal motility, hyperalgesia, immune disorders and disorders of the intestinal bacterial microflora and autonomic and hormonal dysfunction. Many treatments have been proposed, ranging from diet to pharmacology and psychotherapy. Patients with various types of chronic pelvic and perineal pain, especially those seen in urology departments, very often report associated IBS. This syndrome is also part of a global and integrated concept of pelviperineal dysfunction, avoiding a rigorous distinction between the posterior segment and the midline and anterior segments of the perineum. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Genetics and Genomics of Acute Neurologic Disorders.

PubMed

Maserati, Megan; Alexander, Sheila A

2018-01-01

Neurologic diseases and injuries are complex and multifactorial, making risk prediction, targeted treatment modalities, and outcome prognostication difficult and elusive. Genetics and genomics have affected clinical practice in many aspects in medicine, particularly cancer treatment. Advancements in knowledge of genetic and genomic variability in neurologic disease and injury are growing rapidly. Although these data are not yet ready for use in clinical practice, research continues to progress and elucidate information that eventually will provide answers to complex neurologic questions and serve as a platform to provide individualized care plans aimed at improving outcomes. This article provides a focused review of relevant literature on genetics, genomics, and common complex neurologic disease and injury likely to be seen in the acute care setting. ©2018 American Association of Critical-Care Nurses.
Triggers for Autism: Genetic and Environmental Factors

PubMed Central

Matsuzaki, Hideo; Iwata, Keiko; Manabe, Takayuki; Mori, Norio

2012-01-01

This report reviews the research on the factors that cause autism. In several studies, these factors have been verified by reproducing them in autistic animal models. Clinical research has demonstrated that genetic and environmental factors play a major role in the development of autism. However, most cases are idiopathic, and no single factor can explain the trends in the pathology and prevalence of autism. At the time of this writing, autism is viewed more as a multi-factorial disorder. However, the existence of an unknown factor that may be common in all autistic cases cannot be ruled out. It is hoped that future biological studies of autism will help construct a new theory that can interpret the pathology of autism in a coherent manner. To achieve this, large-scale epidemiological research is essential. PMID:23650465
Gastrointestinal disorders associated with migraine: A comprehensive review

PubMed Central

Cámara-Lemarroy, Carlos R; Rodriguez-Gutierrez, Rene; Monreal-Robles, Roberto; Marfil-Rivera, Alejandro

2016-01-01

Migraine is a recurrent and commonly disabling primary headache disorder that affects over 17% of women and 5%-8% of men. Migraine susceptibility is multifactorial with genetic, hormonal and environmental factors all playing an important role. The physiopathology of migraine is complex and still not fully understood. Many different neuropeptides, neurotransmitters and brain pathways have been implicated. In connection with the myriad mechanisms and pathways implicated in migraine, a variety of multisystemic comorbidities (e.g., cardiovascular, psychiatric and other neurological conditions) have been found to be closely associated with migraine. Recent reports demonstrate an increased frequency of gastrointestinal (GI) disorders in patients with migraine compared with the general population. Helicobacter pylori infection, irritable bowel syndrome, gastroparesis, hepatobiliary disorders, celiac disease and alterations in the microbiota have been linked to the occurrence of migraine. Several mechanisms involving the gut-brain axis, such as a chronic inflammatory response with inflammatory and vasoactive mediators passing to the circulatory system, intestinal microbiota modulation of the enteric immunological milieu and dysfunction of the autonomic and enteric nervous system, have been postulated to explain these associations. However, the precise mechanisms and pathways related to the gut-brain axis in migraine need to be fully elucidated. In this review, we survey the available literature linking migraine with GI disorders. We discuss the possible physiopathological mechanisms, and clinical implications as well as several future areas of interest for research. PMID:27688656
Gastrointestinal disorders associated with migraine: A comprehensive review.

PubMed

Cámara-Lemarroy, Carlos R; Rodriguez-Gutierrez, Rene; Monreal-Robles, Roberto; Marfil-Rivera, Alejandro

2016-09-28

Migraine is a recurrent and commonly disabling primary headache disorder that affects over 17% of women and 5%-8% of men. Migraine susceptibility is multifactorial with genetic, hormonal and environmental factors all playing an important role. The physiopathology of migraine is complex and still not fully understood. Many different neuropeptides, neurotransmitters and brain pathways have been implicated. In connection with the myriad mechanisms and pathways implicated in migraine, a variety of multisystemic comorbidities (e.g., cardiovascular, psychiatric and other neurological conditions) have been found to be closely associated with migraine. Recent reports demonstrate an increased frequency of gastrointestinal (GI) disorders in patients with migraine compared with the general population. Helicobacter pylori infection, irritable bowel syndrome, gastroparesis, hepatobiliary disorders, celiac disease and alterations in the microbiota have been linked to the occurrence of migraine. Several mechanisms involving the gut-brain axis, such as a chronic inflammatory response with inflammatory and vasoactive mediators passing to the circulatory system, intestinal microbiota modulation of the enteric immunological milieu and dysfunction of the autonomic and enteric nervous system, have been postulated to explain these associations. However, the precise mechanisms and pathways related to the gut-brain axis in migraine need to be fully elucidated. In this review, we survey the available literature linking migraine with GI disorders. We discuss the possible physiopathological mechanisms, and clinical implications as well as several future areas of interest for research.

Evaluation and management of crouch gait.

PubMed

Kedem, Paz; Scher, David M

2016-02-01

Crouch gait is defined as excessive ankle dorsiflexion, knee and hip flexion during the stance phase. This gait disorder is common among patients with cerebral palsy. The present article brings an up-to-date literature review on the pathoanatomy, natural history, and treatment of this frequent gait abnormality. Hamstrings are often not shortened in patients with crouch. Patella alta must be addressed if surgery is performed. Surgical correction of joint contractures and lever arm dysfunction can be effectively achieved through a single-event multilevel surgery. Crouch gait is a common gait deviation, often seen among ambulatory diplegic and quadriplegic patients, once they reach the pubertal spurt, when weak muscles can no longer support a toe walking pattern because of rapidly increased weight. This form of gait is highly ineffective and might compromise walking ability over time. The anterior knee is overloaded; pain, extensor mechanism failure, and arthritis might develop. Its progressive nature often requires surgical intervention. The cause of crouch gait is multifactorial, and surgery should be tailored to meet the individual's specific anatomic and physiologic abnormalities.
Honey and Diabetes: The Importance of Natural Simple Sugars in Diet for Preventing and Treating Different Type of Diabetes

PubMed Central

Dezmirean, Daniel S.

2018-01-01

Diabetes is a metabolic disorder with multifactorial and heterogeneous etiologies. Two types of diabetes are common among humans: type 1 diabetes that occurs when the immune system attacks and destroys insulin and type 2 diabetes, the most common form, that may be caused by several factors, the most important being lifestyle, but also may be determined by different genes. Honey was used in folk medicine for a long time, but the health benefits were explained in the last decades, when the scientific world was concerned in testing and thus explaining the benefits of honey. Different studies demonstrate the hypoglycemic effect of honey, but the mechanism of this effect remains unclear. This review presents the experimental studies completed in the recent years, which support honey as a novel antidiabetic agent that might be of potential significance for the management of diabetes and its complications and also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. PMID:29507651
A case of coffee-ground emesis in an elderly patient

PubMed Central

De Palma, Giovanni D; Persico, Marcello; Forestieri, Pietro

2014-01-01

Key Clinical Message Black esophagus is an exceeding rare disorder with a multifactorial etiology. Clinical presentation is generally related to upper gastrointestinal bleeding. Diagnosis is based on endoscopic images. Overall mortality is largely related to the underlying medical condition. PMID:25356232
Current knowledge on psoriasis and autoimmune diseases

PubMed Central

Ayala-Fontánez, Nilmarie; Soler, David C; McCormick, Thomas S

2016-01-01

Psoriasis is a prevalent, chronic inflammatory disease of the skin, mediated by crosstalk between epidermal keratinocytes, dermal vascular cells, and immunocytes such as antigen presenting cells (APCs) and T cells. Exclusive cellular “responsibility” for the induction and maintenance of psoriatic plaques has not been clearly defined. Increased proliferation of keratinocytes and endothelial cells in conjunction with APC/T cell/monocyte/macrophage inflammation leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin. Despite the identification of numerous susceptibility loci, no single genetic determinant has been identified as responsible for the induction of psoriasis. Thus, numerous other triggers of disease, such as environmental, microbial and complex cellular interactions must also be considered as participants in the development of this multifactorial disease. Recent advances in therapeutics, especially systemic so-called “biologics” have provided new hope for identifying the critical cellular targets that drive psoriasis pathogenesis. Recent recognition of the numerous co-morbidities and other autoimmune disorders associated with psoriasis, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus suggest common signaling elements and cellular mediators may direct disease pathogenesis. In this review, we discuss common cellular pathways and participants that mediate psoriasis and other autoimmune disorders that share these cellular signaling pathways. PMID:29387591
Treatment of hyperpigmentation.

PubMed

Rossi, Anthony M; Perez, Maritza I

2011-05-01

Disorders of hyperpigmentation encompass a plethora of pigmentary problems that can range from inherited to acquired. This article focuses on two prevalent disorders of hyperpigmentation and their treatment: melasma and postinflammatory hyperpigmentation. Each represents an acquired disorder of dyspigmentation with multifactorial etiology, which preferentially affects darker phototypes. Treatment can require a combination of medical, surgical, and laser modalities, as well as patience by both physician and patient. Treatment is limited mainly by the skin phototype of the patient, as darker skin types are more susceptible to adverse effects of treatment. Copyright © 2011 Elsevier Inc. All rights reserved.
Copy number variability in Parkinson's disease: assembling the puzzle through a systems biology approach.

PubMed

La Cognata, Valentina; Morello, Giovanna; D'Agata, Velia; Cavallaro, Sebastiano

2017-01-01

Parkinson's disease (PD), the second most common progressive neurodegenerative disorder of aging, was long believed to be a non-genetic sporadic origin syndrome. The proof that several genetic loci are responsible for rare Mendelian forms has represented a revolutionary breakthrough, enabling to reveal molecular mechanisms underlying this debilitating still incurable condition. While single nucleotide polymorphisms (SNPs) and small indels constitute the most commonly investigated DNA variations accounting for only a limited number of PD cases, larger genomic molecular rearrangements have emerged as significant PD-causing mutations, including submicroscopic Copy Number Variations (CNVs). CNVs constitute a prevalent source of genomic variations and substantially participate in each individual's genomic makeup and phenotypic outcome. However, the majority of genetic studies have focused their attention on single candidate-gene mutations or on common variants reaching a significant statistical level of acceptance. This gene-centric approach is insufficient to uncover the genetic background of polygenic multifactorial disorders like PD, and potentially masks rare individual CNVs that all together might contribute to disease development or progression. In this review, we will discuss literature and bioinformatic data describing the involvement of CNVs on PD pathobiology. We will analyze the most frequent copy number changes in familiar PD genes and provide a "systems biology" overview of rare individual rearrangements that could functionally act on commonly deregulated molecular pathways. Assessing the global genome-wide burden of CNVs in PD patients may reveal new disease-related molecular mechanisms, and open the window to a new possible genetic scenario in the unsolved PD puzzle.
Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

PubMed

Zhao, Lu; Liu, Sha; Wang, Yin; Zhang, Qiaoyan; Zhao, Wenjuan; Wang, Zejian; Yin, Ming

2015-01-01

Alzheimer's disease (AD) and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.
Elucidating the Links Between Endocrine Disruptors and Neurodevelopment

PubMed Central

Blawas, Ashley M.; Gray, Kimberly; Heindel, Jerrold J.; Lawler, Cindy P.

2015-01-01

Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes. PMID:25714811
Structural genomic variations and Parkinson's disease.

PubMed

Bandrés-Ciga, Sara; Ruz, Clara; Barrero, Francisco J; Escamilla-Sevilla, Francisco; Pelegrina, Javier; Vives, Francisco; Duran, Raquel

2017-10-01

Parkinson's disease (PD) is the second most common neurodegenerative disease, whose prevalence is projected to be between 8.7 and 9.3 million by 2030. Until about 20 years ago, PD was considered to be the textbook example of a "non-genetic" disorder. Nowadays, PD is generally considered a multifactorial disorder that arises from the combination and complex interaction of genes and environmental factors. To date, a total of 7 genes including SNCA, LRRK2, PARK2, DJ-1, PINK 1, VPS35 and ATP13A2 have been seen to cause unequivocally Mendelian PD. Also, variants with incomplete penetrance in the genes LRRK2 and GBA are considered to be strong risk factors for PD worldwide. Although genetic studies have provided valuable insights into the pathogenic mechanisms underlying PD, the role of structural variation in PD has been understudied in comparison with other genomic variations. Structural genomic variations might substantially account for such genetic substrates yet to be discovered. The present review aims to provide an overview of the structural genomic variants implicated in the pathogenesis of PD.
Protein quality control system in neurodegeneration: a healing company hard to beat but failure is fatal.

PubMed

Chhangani, Deepak; Mishra, Amit

2013-08-01

A common feature in most neurodegenerative diseases and aging is the progressive accumulation of damaged proteins. Proteins are essential for all crucial biological functions. Under some notorious conditions, proteins loss their three dimensional native conformations and are converted into disordered aggregated structures. Such changes rise into pathological conditions and eventually cause serious protein conformation disorders. Protein aggregation and inclusion bodies formation mediated multifactorial proteotoxic stress has been reported in the progression of Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Prion disease. Ongoing studies have been remarkably informative in providing a systematic outlook for better understanding the concept and fundamentals of protein misfolding and aggregations. However, the precise role of protein quality control system and precursors of this mechanism remains elusive. In this review, we highlight recent insights and discuss emerging cytoprotective strategies of cellular protein quality control system implicated in protein deposition diseases. Our current review provides a clear, understandable framework of protein quality control system that may offer the more suitable therapeutic strategies for protein-associated diseases.
Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders.

PubMed

Nebbioso, Marcella; Del Regno, Paola; Gharbiya, Magda; Sacchetti, Marta; Plateroti, Rocco; Lambiase, Alessandro

2017-08-13

The tear film represents the interface between the eye and the environment. The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome. Despite having a multifactorial origin, the main risk factors are female gender and advanced age. Likewise, morphological changes in several glands and in the chemical composition of their secretions, such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors that maintain a steady ocular surface. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic inflammation that involves the ocular surface. DE syndrome is one of the most commonly encountered diseases in clinical practice, and many other causes related to daily life and the increase in average life expectancy will contribute to its onset. This review will consider the disorders of the ocular surface that give rise to such a widespread pathology. At the end, the most recent therapeutic options for the management of DE will be briefly discussed according to the specific underlying pathology.
Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

PubMed Central

Del Regno, Paola; Sacchetti, Marta; Plateroti, Rocco

2017-01-01

The tear film represents the interface between the eye and the environment. The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome. Despite having a multifactorial origin, the main risk factors are female gender and advanced age. Likewise, morphological changes in several glands and in the chemical composition of their secretions, such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors that maintain a steady ocular surface. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic inflammation that involves the ocular surface. DE syndrome is one of the most commonly encountered diseases in clinical practice, and many other causes related to daily life and the increase in average life expectancy will contribute to its onset. This review will consider the disorders of the ocular surface that give rise to such a widespread pathology. At the end, the most recent therapeutic options for the management of DE will be briefly discussed according to the specific underlying pathology. PMID:28805710
Enrichment of deleterious variants of mitochondrial DNA polymerase gene (POLG1) in bipolar disorder.

PubMed

Kasahara, Takaoki; Ishiwata, Mizuho; Kakiuchi, Chihiro; Fuke, Satoshi; Iwata, Nakao; Ozaki, Norio; Kunugi, Hiroshi; Minabe, Yoshio; Nakamura, Kazuhiko; Iwata, Yasuhide; Fujii, Kumiko; Kanba, Shigenobu; Ujike, Hiroshi; Kusumi, Ichiro; Kataoka, Muneko; Matoba, Nana; Takata, Atsushi; Iwamoto, Kazuya; Yoshikawa, Takeo; Kato, Tadafumi

2017-08-01

Rare missense variants, which likely account for a substantial portion of the genetic 'dark matter' for a common complex disease, are challenging because the impacts of variants on disease development are difficult to substantiate. This study aimed to examine the impacts of amino acid substitution variants in the POLG1 found in bipolar disorder, as an example and proof of concept, in three different modalities of assessment: in silico predictions, in vitro biochemical assays, and clinical evaluation. We then tested whether deleterious variants in POLG1 contributed to the genetics of bipolar disorder. We searched for variants in the POLG1 gene in 796 Japanese patients with bipolar disorder and 767 controls and comprehensively investigated all 23 identified variants in the three modalities of assessment. POLG1 encodes mitochondrial DNA polymerase and is one of the causative genes for a Mendelian-inheritance mitochondrial disease, which is occasionally accompanied by mood disorders. The healthy control data from the Tohoku Medical Megabank Organization were also employed. Although the frequency of carriers of deleterious variants varied from one method to another, every assessment achieved the same conclusion that deleterious POLG1 variants were significantly enriched in the variants identified in patients with bipolar disorder compared to those in controls. Together with mitochondrial dysfunction in bipolar disorder, the present results suggested deleterious POLG1 variants as a credible risk for the multifactorial disease. © 2016 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.
From Genes to Environment: Using integrative genomics to build a “systems level” understanding of autism spectrum disorders

PubMed Central

Hu, Valerie W.

2012-01-01

Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders that affect an estimated 1 in 110 individuals. Although there is a strong genetic component associated with these disorders, this review focuses on the multi-factorial nature of ASD and how different genome-wide (genomic) approaches contribute to our understanding of autism. Emphasis is placed on the need to study defined ASD phenotypes as well as to integrate large-scale ‘omics’ data in order to develop a “systems level” perspective of ASD which, in turn, is necessary to allow predictions regarding responses to specific perturbations and interventions. PMID:22497667
The clinical evaluation of infantile nystagmus: What to do first and why

PubMed Central

Bertsch, Morgan; Floyd, Michael; Kehoe, Taylor; Pfeifer, Wanda; Drack, Arlene V.

2017-01-01

Introduction Infantile nystagmus has many causes, some life threatening. We determined the most common diagnoses in order to develop a testing algorithm. Methods Retrospective chart review. Exclusion criteria were no nystagmus, acquired after 6 months, or lack of examination. Data collected: pediatric eye examination findings, ancillary testing, order of testing, referral, and final diagnoses. Final diagnosis was defined as meeting published clinical criteria and/or confirmed by diagnostic testing. Patients with a diagnosis not meeting the definition were “unknown.” Patients with incomplete testing were “incomplete.” Patients with multiple plausible etiologies were “multifactorial.” Patients with negative complete workup were “motor.” Results 284 charts were identified; 202 met inclusion criteria. The 3 most common causes were Albinism(19%), Leber Congenital Amaurosis(LCA)(14%) and Non-LCA retinal dystrophy (13%). Anatomic retinal disorders comprised 10%, motor another 10%. The most common first test was MRI (74/202) with a diagnostic yield of 16%. For 28 MRI-first patients, nystagmus alone was the indication; for 46 MRI-first patients other neurologic signs were present. 0/28 nystagmus-only patients had a diagnostic MRI while 14/46 (30%) with neurologic signs did. Yield of ERG as first test was 56%, OCT 55%, and molecular genetic testing 47%. 90% of patients had an etiology identified. Conclusion The most common causes of infantile nystagmus were retinal disorders (56%), however the most common first test was brain MRI. For patients without other neurologic stigmata complete pediatric eye examination, ERG, OCT and molecular genetic testing had a higher yield than MRI scan. If MRI is not diagnostic, a complete ophthalmologic workup should be pursued. PMID:28177849
[Metabolic Syndrome and Bipolar Affective Disorder: A Review of the Literature].

PubMed

Jaramillo, Carlos López; Mejía, Adelaida Castaño; Velásquez, Alicia Henao; Restrepo Palacio, Tomás Felipe; Zuluaga, Julieta Osorio

2013-09-01

Bipolar disorder (BD) is a chronic psychiatric disorder that is found within the first ten causes of disability and premature mortality. The metabolic syndrome (MS) is a group of risk factors (RF) that predispose to cardiovascular disease (CV), diabetes and early mortality. Both diseases generate high costs to the health system. Major studies have shown that MS has a higher prevalence in patients with mental disorders compared to the general population. The incidence of MS in BD is multifactorial, and due to iatrogenic, genetic, economic, psychological, and behavioral causes related to the health system. The most common RF found is these patients was an increased abdominal circumference, and it was found that the risk of suffering this disease was greater in women and Hispanic patients. As regards the increase in RF to develop a CV in patients with BD, there have been several explanations based on the risky behavior of patients with mental illness, included tobacco abuse, physical inactivity and high calorie diets. An additional explanation described in literature is the view of BD as a multisystemic inflammatory illness, supported by the explanation that inflammation is a crucial element in atherosclerosis, endothelial dysfunction, platelet rupture, and thrombosis. The pathophysiology of MS and BD include factors such as adrenal, thyroid and sympathetic nervous system dysfunction, as well as poor lifestyle and medication common in these patients. This article attempts to give the reader an overall view of the information published in literature to date, as regards the association between BD and MS. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.
Primer in Genetics and Genomics, Article 4-Inheritance Patterns.

PubMed

Aiello, Lisa B; Chiatti, Beth Desaretz

2017-07-01

Since the completion of the Human Genome Project, much has been uncovered about inheritance of various illnesses and disorders. There are two main types of inheritance: Mendelian and non-Mendelian. Mendelian inheritance includes autosomal dominant, autosomal recessive, X-linked, and Y-linked inheritance. Non-Mendelian inheritance includes mitochondrial and multifactorial inheritance. Nurses must understand the types of inheritance in order to identify red flags that may indicate the possibility of a hereditary disorder in a patient or family.
Chronic kidney disease-mineral and bone disorder: Guidelines for diagnosis, treatment, and management.

PubMed

Moschella, Carla

2016-07-01

Chronic kidney disease affects 23 million Americans and is associated with many complications, one of the most complex of which is mineral and bone disorder. Pathophysiologic mechanisms begin to occur early in CKD but when the glomerular filtration rate declines to <50% of normal, biochemical and bone matrix abnormalities, which vary and are multifactorial, begin to be clinically apparent. Mainstays of treatment remain management of hyperphosphatemia and prevention or treatment of secondary hyperparathyroidism.
[Burnout syndrome: diagnosis, principles of treatment, prophylaxis].

PubMed

Ovchinnikov, Yu V; Palchenkova, M V; Kalachev, O V

2015-07-01

Burnout syndrome is a socio-psychological phenomenon of emotional, motivational, and physical exhaustion as a result of chronic occupational stress. It is manifested as long-term emotional exhaustion, depersonalization and diminished personal and professional achievements. Burnout syndrome is common among health care workers, 'due to their high dedication, empathy for suffering patients, and decision-making related to life and health of patients. Personal, role and organizational factors influence on development of burnout. The clinical picture of burnout is multifactorial and can be described as a set of psychosomatic and somatic disorders, symptoms of social dysfunction. Diversity and non-specific symptoms of burnout syndrome determine the need for an interdisciplinary approach to its diagnosis. The leading role in solving problems related to stress and emotional burnout plays psychotherapy. The paper presents diagnostic criteria, risk factors, and methods of prevention and treatment of emotional burnout.
Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus

PubMed Central

Zhao, Jing-Bo; Frøkjær, Jens Brøndum; Drewes, Asbjørn Mohr; Ejskjaer, Niels

2006-01-01

Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed. PMID:16718808

Risk Assessment for Tooth Wear.

PubMed

Kontaxopoulou, Isavella; Alam, Sonia

2015-08-01

Tooth wear has an increasing prevalence in the UK population. The aetiology is commonly multifactorial, and the aetiopathology is through a combination of erosion, attrition, abrasion and abfraction. Erosion is associated with intrinsic or extrinsic acids, and therefore subjects with reflux disease and eating disorders are at increased risk. Fruit juice, fruits and carbonated drink consumption, frequency of consumption and specific habits are also risk factors. Attrition is more prevalent in bruxists. Other habits need to be considered when defining the risk of tooth wear. Abrasion is usually associated with toothbrushing and toothpastes, especially in an already acidic environment. Patients with extensive lesions that affect dentin may be at higher risk, as well as those presenting with unstained lesions. Monitoring of the progress of tooth wear is recommended to identify those with active tooth wear. Indices for tooth wear are a helpful aid.
Breed-Predispositions to Cancer in Pedigree Dogs

PubMed Central

Dobson, Jane M.

2013-01-01

Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies. PMID:23738139
Increased Serum Levels of Epidermal Growth Factor in Children with Autism

ERIC Educational Resources Information Center

Iseri, Elvan; Guney, Esra; Ceylan, Mehmet F.; Yucel, Aysegul; Aral, Arzu; Bodur, Sahin; Sener, Sahnur

2011-01-01

The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the celluler proliferation and the differentiation of the central and peripheral…
Aetiology of Autism: Findings and Questions

ERIC Educational Resources Information Center

Rutter, M.

2005-01-01

Background Although there is good evidence that autism is a multifactorial disorder, an adequate understanding of the genetic and non-genetic causes has yet to be achieved. Methods Empirical research findings and conceptual reviews are reviewed with respect to evidence on possible causal influences. Results Much the strongest evidence concerns the…
Association between altered lipid profiles and attention deficit hyperactivity disorder in boys.

PubMed

Avcil, Sibelnur

2018-04-24

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder, which is multifactorial, complex, and seen most commonly in childhood. The aim of this study was to examine the hypothesis that altered serum lipid profiles are associated with ADHD. The study inluded 32 boys diagnosed with ADHD according to DSM-IV-R criteria and a control group of 29 healthy subjects. All patients were assessed with The Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version, the Turgay DSM-IV-based Disruptive Behavior Disorders Child and Adolescent Rating and Screening Scale, the Conners Parent Rating Scale-Revised Long Form, and the Conners Teacher Rating Scale. Measurements were taken of fasting plasma total cholesterol (T-Chol), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and 1-day food intake levels, and the groups were compared. The mean TC, LDL, and HDL levels were significantly lower in the ADHD group than the control group (p = .005, p < .001, p = .002, respectively). There was no significant difference between the groups' TG levels (p = .295). No significant differences were determined between the combined-type ADHD patients and the predominantly inattentive subtype of ADHD in respect to the lipid profile. The results of this study add to the growing body of evidence indicating an association between serum cholesterol and ADHD in boys. Further genetic and molecular studies are required to elucidate the biochemical mechanisms underlying this relationship.
Digestive tract neural control and gastrointestinal disorders in cerebral palsy.

PubMed

Araújo, Liubiana A; Silva, Luciana R; Mendes, Fabiana A A

2012-01-01

To examine the neural control of digestive tract and describe the main gastrointestinal disorders in cerebral palsy (CP), with attention to the importance of early diagnosis to an efficient interdisciplinary treatment. Systematic review of literature from 1997 to 2012 from Medline, Lilacs, Scielo, and Cochrane Library databases. The study included 70 papers, such as relevant reviews, observational studies, controlled trials, and prevalence studies. Qualitative studies were excluded. The keywords used were: cerebral palsy, dysphagia, gastroesophageal reflux disease, constipation, recurrent respiratory infections, and gastrostomy. The appropriate control of the digestive system depends on the healthy functioning and integrity of the neural system. Since CP patients have structural abnormalities of the central and peripheral nervous system, they are more likely to develop eating disorders. These range from neurological immaturity to interference in the mood and capacity of caregivers. The disease has, therefore, a multifactorial etiology. The most prevalent digestive tract disorders are dysphagia, gastroesophageal reflux disease, and constipation, with consequent recurrent respiratory infections and deleterious impact on nutritional status. Patients with CP can have neurological abnormalities of digestive system control; therefore, digestive problems are common. The issues raised in the present study are essential for professionals within the interdisciplinary teams that treat patients with CP, concerning the importance of comprehensive anamnesis and clinical examination, such as detailed investigation of gastrointestinal disorders. Early detection of these digestive problems may lead to more efficient rehabilitation measures in order to improve patients' quality of life.
The Evaluation of Head and Craniocervical Posture among Patients with and without Temporomandibular Joint Disorders- A Comparative Study.

PubMed

Saddu, Shweta Channavir; Dyasanoor, Sujatha; Valappila, Nidhin J; Ravi, Beena Varma

2015-08-01

Temporomandibular disorders (TMD) are the most common non-dental cause of orofacial pain with a multifactorial aetiology. To evaluate the head and craniocervical posture between individuals with and without TMD and its sub types by photographic and radiographic method. Thirty four TMD patients diagnosed according to Research Diagnostic Criteria for TMD's (RDC/TMD) and were divided into 2 groups: Group I (muscle disorder), Group II (disc displacement). Control group comprised of 34 age and sex matched subjects without TMD. Lateral view photographs were taken and the head posture angle was measured. Craniocervical posture was assessed on lateral skull radiograph with two angles (Craniocervical Angle, Cervical Curvature Angle) and two distances (Suboccipital Space, Atlas-Axis Distance). To compare the results, t-test was used with significance level of 0.05. Head posture showed no statistical significant difference (p > 0.05) between Group I, II and control group in both photographic and radiographic methods. The cervical curvature angle showed significant difference (p = 0.045) in Group I only. Atlas-Axis Distance was statistically significant in Group II (p = 0.001). The present study confirmed that there is a negative association of head posture and TMD whereas, cervical lordosis was present in Group I only.
The Evaluation of Head and Craniocervical Posture among Patients with and without Temporomandibular Joint Disorders- A Comparative Study

PubMed Central

Saddu, Shweta Channavir; Dyasanoor, Sujatha; Ravi, Beena Varma

2015-01-01

Introduction Temporomandibular disorders (TMD) are the most common non-dental cause of orofacial pain with a multifactorial aetiology. Aim To evaluate the head and craniocervical posture between individuals with and without TMD and its sub types by photographic and radiographic method. Materials and Methods Thirty four TMD patients diagnosed according to Research Diagnostic Criteria for TMD’s (RDC/TMD) and were divided into 2 groups: Group I (muscle disorder), Group II (disc displacement). Control group comprised of 34 age and sex matched subjects without TMD. Lateral view photographs were taken and the head posture angle was measured. Craniocervical posture was assessed on lateral skull radiograph with two angles (Craniocervical Angle, Cervical Curvature Angle) and two distances (Suboccipital Space, Atlas-Axis Distance). To compare the results, t-test was used with significance level of 0.05. Results Head posture showed no statistical significant difference (p > 0.05) between Group I, II and control group in both photographic and radiographic methods. The cervical curvature angle showed significant difference (p = 0.045) in Group I only. Atlas-Axis Distance was statistically significant in Group II (p = 0.001). Conclusion The present study confirmed that there is a negative association of head posture and TMD whereas, cervical lordosis was present in Group I only. PMID:26436048
GARLIC: a bioinformatic toolkit for aetiologically connecting diseases and cell type-specific regulatory maps

PubMed Central

Nikolić, Miloš; Papantonis, Argyris

2017-01-01

Abstract Genome-wide association studies (GWAS) have emerged as a powerful tool to uncover the genetic basis of human common diseases, which often show a complex, polygenic and multi-factorial aetiology. These studies have revealed that 70–90% of all single nucleotide polymorphisms (SNPs) associated with common complex diseases do not occur within genes (i.e. they are non-coding), making the discovery of disease-causative genetic variants and the elucidation of the underlying pathological mechanisms far from straightforward. Based on emerging evidences suggesting that disease-associated SNPs are frequently found within cell type-specific regulatory sequences, here we present GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types), a user-friendly, multi-purpose software with an associated database and online viewer that, using global maps of cis-regulatory elements, can aetiologically connect human diseases with relevant cell types. Additionally, GARLIC can be used to retrieve potential disease-causative genetic variants overlapping regulatory sequences of interest. Overall, GARLIC can satisfy several important needs within the field of medical genetics, thus potentially assisting in the ultimate goal of uncovering the elusive and complex genetic basis of common human disorders. PMID:28007912
Genetic, hormonal and metabolic aspects of PCOS: an update.

PubMed

De Leo, V; Musacchio, M C; Cappelli, V; Massaro, M G; Morgante, G; Petraglia, F

2016-07-16

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10 % of women of reproductive age. It generally manifests with oligo/anovulatory cycles, hirsutism and polycystic ovaries, together with a considerable prevalence of insulin resistance. Although the aetiology of the syndrome is not completely understood yet, PCOS is considered a multifactorial disorder with various genetic, endocrine and environmental abnormalities. Moreover, PCOS patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.
How are information seeking, scanning, and processing related to beliefs about the roles of genetics and behavior in cancer causation?

PubMed Central

Waters, Erika A.; Wheeler, Courtney; Hamilton, Jada G.

2016-01-01

Background Understanding that cancer is caused by both genetic and behavioral risk factors is an important component of genomic literacy. However, a considerable percentage of people in the U.S. do not endorse such multifactorial beliefs. Methods Using nationally representative cross-sectional data from the U.S. Health Information National Trends Survey (N=2,529), we examined how information seeking, information scanning, and key information processing characteristics were associated with endorsing a multifactorial model of cancer causation. Results Multifactorial beliefs about cancer were more common among respondents who engaged in cancer information scanning (p=.001), were motivated to process health information (p=.005), and who reported a family history of cancer (p=.0002). Respondents who reported having previous negative information seeking experiences had lower odds of endorsing multifactorial beliefs (p=.01). Multifactorial beliefs were not associated with cancer information seeking, trusting cancer information obtained from the Internet, trusting cancer information from a physician, self-efficacy for obtaining cancer information, numeracy, or being aware of direct-to-consumer genetic testing (ps>.05). Conclusion Gaining additional understanding of how people access, process, and use health information will be critical for the continued development and dissemination of effective health communication interventions and for the further translation of genomics research to public health and clinical practice. PMID:27661291
How Are Information Seeking, Scanning, and Processing Related to Beliefs About the Roles of Genetics and Behavior in Cancer Causation?

PubMed

Waters, Erika A; Wheeler, Courtney; Hamilton, Jada G

2016-01-01

Understanding that cancer is caused by both genetic and behavioral risk factors is an important component of genomic literacy. However, a considerable percentage of people in the United States do not endorse such multifactorial beliefs. Using nationally representative cross-sectional data from the U.S. Health Information National Trends Survey (N = 2,529), we examined how information seeking, information scanning, and key information-processing characteristics were associated with endorsing a multifactorial model of cancer causation. Multifactorial beliefs about cancer were more common among respondents who engaged in cancer information scanning (p = .001), were motivated to process health information (p = .005), and reported a family history of cancer (p = .0002). Respondents who reported having previous negative information-seeking experiences had lower odds of endorsing multifactorial beliefs (p = .01). Multifactorial beliefs were not associated with cancer information seeking, trusting cancer information obtained from the Internet, trusting cancer information from a physician, self-efficacy for obtaining cancer information, numeracy, or being aware of direct-to-consumer genetic testing (ps > .05). Gaining additional understanding of how people access, process, and use health information will be critical for the continued development and dissemination of effective health communication interventions and for the further translation of genomics research to public health and clinical practice.
Advances in the Management of Meconium Aspiration Syndrome

PubMed Central

Swarnam, Kamala; Soraisham, Amuchou S.; Sivanandan, Sindhu

2012-01-01

Meconium aspiration syndrome (MAS) is a common cause of severe respiratory distress in term infants, with an associated highly variable morbidity and mortality. MAS results from aspiration of meconium during intrauterine gasping or during the first few breaths. The pathophysiology of MAS is multifactorial and includes acute airway obstruction, surfactant dysfunction or inactivation, chemical pneumonitis with release of vasoconstrictive and inflammatory mediators, and persistent pulmonary hypertension of newborn (PPHN). This disorder can be life threatening, often complicated by respiratory failure, pulmonary air leaks, and PPHN. Approaches to the prevention of MAS have changed over time with collaboration between obstetricians and pediatricians forming the foundations for care. The use of surfactant and inhaled nitric oxide (iNO) has led to the decreased mortality and the need for extracorporeal membrane oxygenation (ECMO) use. In this paper, we review the current understanding of the pathophysiology and management of MAS. PMID:22164183
Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction.

PubMed

Yannoutsos, Alexandra; Levy, Bernard I; Safar, Michel E; Slama, Gerard; Blacher, Jacques

2014-02-01

Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.
Full-mouth composite rehabilitation of a mixed erosion and attrition patient: a case report with v-shaped veneers and ultra-thin CAD/CAM composite overlays.

PubMed

Bahillo, Jose; Jané, Luis; Bortolotto, Tissiana; Krejci, Ivo; Roig, Miguel

2014-10-01

Loss of tooth substance has become a common pathology in modern society. It is of multifactorial origin, may be induced by a chemical process or by excessive attrition, and frequently has a combined etiology. Particular care should be taken when diagnosing the cause of dental tissue loss, in order to minimize its impact. Several publications have proposed the use of minimally invasive procedures to treat such patients in preference to traditional full-crown rehabilitation. The use of composite resins, in combination with improvements in dental adhesion, allows a more conservative approach. In this paper, we describe the step-by-step procedure of full-mouth composite rehabilitation with v-shaped veneers and ultra-thin computer-aided design/computer-assisted manufacture (CAD/CAM)- generated composite overlays in a young patient with a combination of erosion and attrition disorder.
Genetic and environmental factors in human osteoporosis.

PubMed

Özbaş, Halil; Tutgun Onrat, Serap; Özdamar, Kazım

2012-12-01

Osteoporosis is a common disorder, with prolongation of the average life span it has become a major public health problem. On the formation of osteoporosis genetic factors and environmental influences could play a role then it is considered as multi-factorial. Because a variety of functions to affect susceptibility to the formation of osteoporosis VDR-F, VDR-B, COL1A1, ESR1X, ESR1P and CTR are thought to be candidate genes. In this study, the aim is to investigate the relationship between these genes polymorphism and bone mineral density (BMD) values of lumbar vertebra and femoral neck in 188 Turkish people. Lumbar spine and femoral neck BMD of the individuals included in the study were measured by the dual X-ray absorptiometry method. The genotyped polymorphisms by simultaneous amplification of five regions of the genome, containing six SNPs of interest and detecting the amplified product, using the kit MetaBone Clinical Arrays(®). Statistical analyses indicated that; VDR-B gene polymorphisms major (P = 0.013), VDR-F polymorphisms have minor (P = 0.082) effect on femur BMD. None of the other genes has any significant effect on spinal BMD. Patient age, body mass index and diet has significant effect on femoral and spinal BMD. Osteoporosis is a multi-factorial disease and many genetic and non-genetic risk factors contribute to the development of osteoporosis. Early detection of a genetic predisposition to osteoporosis should allow delay and/or limit unfavorable changes in the bone tissue.
[Psychosomatic treatment of otorhinolaryngological diseases].

PubMed

Marek, A

2009-11-01

The spectrum of psychosomatic diseases in the field of otorhinolaryngology covers reactive disorders brought on by excessive psychosocial demands, post-traumatic disorders following mental traumatization, purely psychological disorders brought on by personality development deficits or learnt false behavior, and multifactorial diseases with somatic correlatives and mental triggers. Psychosomatic medicine describes the interaction of physical and psychological processes. The central treatment method is psychotherapy. In Germany, the costs of psychodynamic psychotherapies and behavioral therapy are covered by the health insurance companies. The tasks of psychosomatic treatment in the field of otorhinolaryngology comprise differential diagnostics, basic psychosomatic treatment and the determination of differential indications for the respective forms of psychotherapy.
The forgotten cause of stridor in the emergency department.

PubMed

Ng, Tian-Tee

2017-01-01

Paradoxical Vocal Fold Movement Disorder is where the larynx exhibits paradoxical vocal cords closure during respiration, creating partial airway obstruction. Causes of vocal fold movement disorder are multifactorial, and patients describe tightness of throat, difficulty getting air in, have stridor, and do not respond to inhalers. We propose using transnasal laryngoscopy examination, which will show narrowing of vocal cords on inspiration, and The Pittsburgh Vocal Cord Dysfunction Index with a cutoff score of ≥4 to distinguish vocal fold movement disorder from asthma and other causes of stridor. Management of paradoxical vocal fold movement disorder involves a combination of pharmacological, psychological, psychiatric, and speech training. Paradoxical vocal fold movement disorder is a very treatable cause of stridor, so long as it is identified and other organic causes are excluded.
The Epigenetic Landscape of Alcoholism

PubMed Central

Krishnan, Harish R.; Sakharkar, Amul J.; Teppen, Tara L.; Berkel, Tiffani D.M.; Pandey, Subhash C.

2015-01-01

Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure, but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, holds great therapeutic potential in the treatment and prevention of alcoholism. PMID:25131543
Inflammatory pathways in children with insufficient or disordered sleep.

PubMed

Kim, Jinkwan; Hakim, Fahed; Kheirandish-Gozal, Leila; Gozal, David

2011-09-30

Sleep is not only an essential physiological function, but also serves important roles in promoting growth, maturation, and overall health of children and adolescents. There is increasing interest regarding the impact of sleep and its disorders on the regulation of inflammatory processes and end-organ morbidities, particularly in the context of metabolic and cardiovascular diseases (CVD) and their complications. Obstructive sleep apnea syndrome (OSAS) is an increasingly common health problem in children, and in the last decade, the emergence of increasing obesity rates has further led to remarkable increases in the prevalence of OSAS, along with more prominent neurocognitive, behavioral, cardiovascular and metabolic morbidities. Although the underlying mechanisms leading to OSAS-induced morbidities are likely multi-factorial, and remain to be fully elucidated, activation of inflammatory pathways by OSAS has emerged as an important pathophysiological component of the end-organ injury associated with this disorder. To this effect, it would appear that OSAS could be viewed as a chronic, low-grade inflammatory disorder. Furthermore, the concurrent presence of obesity and OSAS poses a theoretically increased risk of OSAS-related complications. In this review, we will critically review the current state of research regarding the impact of insufficient and disrupted sleep and OSAS on the immune processes and inflammatory pathways that underlie childhood OSAS as a distinctive systemic inflammatory condition in children, and will explore potential interactions between OSAS and obesity. Copyright © 2011 Elsevier B.V. All rights reserved.

Interpersonal Stress Regulation and the Development of Anxiety Disorders: An Attachment-Based Developmental Framework

PubMed Central

Nolte, Tobias; Guiney, Jo; Fonagy, Peter; Mayes, Linda C.; Luyten, Patrick

2011-01-01

Anxiety disorders represent a common but often debilitating form of psychopathology in both children and adults. While there is a growing understanding of the etiology and maintenance of these disorders across various research domains, only recently have integrative accounts been proposed. While classical attachment history has been a traditional core construct in psychological models of anxiety, contemporary attachment theory has the potential to integrate neurobiological and behavioral findings within a multidisciplinary developmental framework. The current paper proposes a modern attachment theory-based developmental model grounded in relevant literature from multiple disciplines including social neuroscience, genetics, neuroendocrinology, and the study of family factors involved in the development of anxiety disorders. Recent accounts of stress regulation have highlighted the interplay between stress, anxiety, and activation of the attachment system. This interplay directly affects the development of social–cognitive and mentalizing capacities that are acquired in the interpersonal context of early attachment relationships. Early attachment experiences are conceptualized as the key organizer of a complex interplay between genetic, environmental, and epigenetic contributions to the development of anxiety disorders – a multifactorial etiology resulting from dysfunctional co-regulation of fear and stress states. These risk-conferring processes are characterized by hyperactivation strategies in the face of anxiety. The cumulative allostatic load and subsequent “wear and tear” effects associated with hyperactivation strategies converge on the neural pathways of anxiety and stress. Attachment experiences further influence the development of anxiety as potential moderators of risk factors, differentially impacting on genetic vulnerability and relevant neurobiological pathways. Implications for further research and potential treatments are outlined. PMID:21960962
Pregnancy and postpartum bowel changes: constipation and fecal incontinence.

PubMed

Shin, Grace Hewon; Toto, Erin Lucinda; Schey, Ron

2015-04-01

Pregnancy and the postpartum period are often associated with many gastrointestinal complaints, including nausea, vomiting, and heartburn; however, the most troublesome complaints in some women are defecatory disorders such as constipation and fecal incontinence, especially postpartum. These disorders are often multifactorial in etiology, and many studies have looked to see what risk factors lead to these complications. This review discusses the current knowledge of pelvic floor and anorectal physiology, especially during pregnancy, and reviews the current literature on causes and treatments of postpartum bowel symptoms of constipation and fecal incontinence.
Imaging of SHOX-associated anomalies.

PubMed

Gahunia, Harpal K; Babyn, Paul S; Kirsch, Susan; Mendoza-Londono, Roberto

2009-09-01

Human growth is a multifactorial trait influenced by environmental, hormonal, and genetic factors. Although it is clear that multiple factors contribute to an individual's final height and limb development, genetic factors play a crucial role. One such gene is the short stature homeobox ( SHOX) containing gene. Knowledge about the SHOX gene has rapidly increased since its discovery in 1997, and we now know that SHOX haploinsufficiency affects the development of the extremities and is an important cause of short stature. Currently, SHOX mutations occur with an estimated incidence of roughly 1 in 1000 newborns, making mutations of this gene one of the most common genetic defects associated with growth failure and skeletal deformities. Heterozygous mutations of SHOX have been implicated in patients with Madelung's deformity, Leri-Weill dyschondrosteosis (77%), Turner's syndrome (66%), and idiopathic short stature (3%), and homozygous mutations of SHOX gene have been identified in patients with Langer's mesomelic dysplasia (100%). Recognition of the early radiographic features encountered in SHOX haploinsufficiency maybe pivotal for the diagnosis. In this article, we summarize the genetic and clinical features of the various SHOX haploinsufficiency-associated disorders. We present the characteristic imaging features of these disorders and the results of growth hormone treatment trials.
Pectus excavatum and carinatum.

PubMed

Cobben, Jan M; Oostra, Roelof-Jan; van Dijk, Fleur S

2014-08-01

Pectus excavatum and carinatum are the most common morphological chest wall abnormalities. For both pectus excavatum and carinatum the pathogenesis is largely unknown although various hypotheses exist. Usually, exclusion of an underlying syndromal or connective tissue disorder is the reason for referral for genetic evaluation. A detailed anamnesis and family history are needed as well as a complete dysmorphological physical examination. If no features of an underlying disorder are detected, then the pectus excavatum/carinatum can be considered as an isolated abnormality and no further genetic studies seem indicated. Although cases of non-syndromal pectus excavatum/carinatum with a positive family history fitting Mendelian inheritance have been described, it is possible that these pedigrees represent multifactorial inheritance, as no genetic cause for familial isolated pectus excavatum/carinatum has been described yet. The recurrence risk for a non-familial iolated pectus excavatum/carinatum is unknown, but thought to be low. If other symptoms are found then appropriate further diagnostic studies are indicated as pectus excavatum/carinatum can be part of many syndromes. However, the most important and most frequently observed monogenic syndromes with pectus excavatum/carinatum are Marfan Syndrome and Noonan Syndrome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Genetics Home Reference: esophageal atresia/tracheoesophageal fistula

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes Isolated EA/TEF is considered to be a multifactorial condition, which means that multiple gene variations and environmental factors likely contribute to its occurrence. ...
Genetic architecture for human aggression: A study of gene-phenotype relationship in OMIM.

PubMed

Zhang-James, Yanli; Faraone, Stephen V

2016-07-01

Genetic studies of human aggression have mainly focused on known candidate genes and pathways regulating serotonin and dopamine signaling and hormonal functions. These studies have taught us much about the genetics of human aggression, but no genetic locus has yet achieved genome-significance. We here present a review based on a paradoxical hypothesis that studies of rare, functional genetic variations can lead to a better understanding of the molecular mechanisms underlying complex multifactorial disorders such as aggression. We examined all aggression phenotypes catalogued in Online Mendelian Inheritance in Man (OMIM), an Online Catalog of Human Genes and Genetic Disorders. We identified 95 human disorders that have documented aggressive symptoms in at least one individual with a well-defined genetic variant. Altogether, we retrieved 86 causal genes. Although most of these genes had not been implicated in human aggression by previous studies, the most significantly enriched canonical pathways had been previously implicated in aggression (e.g., serotonin and dopamine signaling). Our findings provide strong evidence to support the causal role of these pathways in the pathogenesis of aggression. In addition, the novel genes and pathways we identified suggest additional mechanisms underlying the origins of human aggression. Genome-wide association studies with very large samples will be needed to determine if common variants in these genes are risk factors for aggression. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
Birth Origin Differentially Affects Depressive-Like Behaviours: Are Captive-Born Cynomolgus Monkeys More Vulnerable to Depression than Their Wild-Born Counterparts?

PubMed Central

Camus, Sandrine MJ.; Rochais, Céline; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

2013-01-01

Background Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder) in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild. Methods The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses. Results We identified 10 distinct profiles (groups A to J) that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J) present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment. Conclusions Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups. PMID:23861787
Reaching Future Scientists, Consumers, & Citizens: What Do Secondary School Textbooks Say about Genomics & Its Impact on Health?

ERIC Educational Resources Information Center

Hicks, Melissa A.; Cline, Rebecca J.; Trepanier, Angela M.

2014-01-01

An understanding of how genomics information, including information about risk for common, multifactorial disease, can be used to promote personal health (personalized medicine) is becoming increasingly important for the American public. We undertook a quantitative content analysis of commonly used high school textbooks to assess how frequently…
Syndromes, disorders and maternal risk factors associated with neural tube defects (I).

PubMed

Chen, Chih-Ping

2008-03-01

Fetuses with neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization ( Ds )-like human malformations, isolated hemihyperplasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.
Genetic basis of human left-right asymmetry disorders.

PubMed

Deng, Hao; Xia, Hong; Deng, Sheng

2015-01-27

Humans and other vertebrates exhibit left-right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, including situs inversus and heterotaxy. Situs inversus is complete mirror-imaged arrangement of the internal organs along LR axis, whereas heterotaxy is abnormal arrangement of the internal thoraco-abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved in situs inversus and heterotaxy have been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders.
Attentional but not pre-attentive neural measures of auditory discrimination are atypical in children with developmental language disorder.

PubMed

Kornilov, Sergey A; Landi, Nicole; Rakhlin, Natalia; Fang, Shin-Yi; Grigorenko, Elena L; Magnuson, James S

2014-01-01

We examined neural indices of pre-attentive phonological and attentional auditory discrimination in children with developmental language disorder (DLD, n = 23) and typically developing (n = 16) peers from a geographically isolated Russian-speaking population with an elevated prevalence of DLD. Pre-attentive phonological MMN components were robust and did not differ in two groups. Children with DLD showed attenuated P3 and atypically distributed P2 components in the attentional auditory discrimination task; P2 and P3 amplitudes were linked to working memory capacity, development of complex syntax, and vocabulary. The results corroborate findings of reduced processing capacity in DLD and support a multifactorial view of the disorder.
Autistic enterocolitis: fact or fiction?

PubMed

Galiatsatos, Polymnia; Gologan, Adrian; Lamoureux, Esther

2009-02-01

Autism spectrum disorder refers to syndromes of varying severity, typified by impaired social interactions, communicative delays and restricted, repetitive behaviours and interests. The prevalence of autism spectrum disorders has been on the rise, while the etiology remains unclear and most likely multifactorial. There have been several reports of a link between autism and chronic gastrointestinal symptoms. Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia and focally enhanced gastritis compared with controls. Postulated mechanisms include aberrant immune responses to some dietary proteins, abnormal intestinal permeability and unfavourable gut microflora. Two autism spectrum disorder patients with chronic intestinal symptoms and abnormal endoscopic findings are described, followed by a review of this controversial topic.
Cardiac cachexia: hic et nunc: "hic et nunc" - here and now.

PubMed

Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram; Lainscak, Mitja

2015-12-15

Cardiac cachexia (CC) is the clinical entity at the end of chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. Better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick-up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF.
Cardiac cachexia: hic et nunc

PubMed Central

Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram

2016-01-01

Abstract Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID:27386168
The epigenetic landscape of alcoholism.

PubMed

Krishnan, Harish R; Sakharkar, Amul J; Teppen, Tara L; Berkel, Tiffani D M; Pandey, Subhash C

2014-01-01

Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, hold great therapeutic potential in the treatment and prevention of alcoholism. © 2014 Elsevier Inc. All rights reserved.
Risk Assessment and Communication Tools for Genotype Associations with Multifactorial Phenotypes: The Concept of “Edge Effect” and Cultivating an Ethical Bridge between Omics Innovations and Society

PubMed Central

Suarez-Kurtz, Guilherme; Stenne, Raphaëlle; Somogyi, Andrew A.; Someya, Toshiyuki; Kayaalp, S. Oğuz; Kolker, Eugene

2009-01-01

Abstract Applications of omics technologies in the postgenomics era swiftly expanded from rare monogenic disorders to multifactorial common complex diseases, pharmacogenomics, and personalized medicine. Already, there are signposts indicative of further omics technology investment in nutritional sciences (nutrigenomics), environmental health/ecology (ecogenomics), and agriculture (agrigenomics). Genotype–phenotype association studies are a centerpiece of translational research in omics science. Yet scientific and ethical standards and ways to assess and communicate risk information obtained from association studies have been neglected to date. This is a significant gap because association studies decisively influence which genetic loci become genetic tests in the clinic or products in the genetic test marketplace. A growing challenge concerns the interpretation of large overlap typically observed in distribution of quantitative traits in a genetic association study with a polygenic/multifactorial phenotype. To remedy the shortage of risk assessment and communication tools for association studies, this paper presents the concept of edge effect. That is, the shift in population edges of a multifactorial quantitative phenotype is a more sensitive measure (than population averages) to gauge the population level impact and by extension, policy significance of an omics marker. Empirical application of the edge effect concept is illustrated using an original analysis of warfarin pharmacogenomics and the VKORC1 genetic variation in a Brazilian population sample. These edge effect analyses are examined in relation to regulatory guidance development for association studies. We explain that omics science transcends the conventional laboratory bench space and includes a highly heterogeneous cast of stakeholders in society who have a plurality of interests that are often in conflict. Hence, communication of risk information in diagnostic medicine also demands attention to processes involved in production of knowledge and human values embedded in scientific practice, for example, why, how, by whom, and to what ends association studies are conducted, and standards are developed (or not). To ensure sustainability of omics innovations and forecast their trajectory, we need interventions to bridge the gap between omics laboratory and society. Appreciation of scholarship in history of omics science is one remedy to responsibly learn from the past to ensure a sustainable future in omics fields, both emerging (nutrigenomics, ecogenomics), and those that are more established (pharmacogenomics). Another measure to build public trust and sustainability of omics fields could be legislative initiatives to create a multidisciplinary oversight body, at arm's length from conflict of interests, to carry out independent, impartial, and transparent innovation analyses and prospective technology assessment. PMID:19290811
Risk assessment and communication tools for genotype associations with multifactorial phenotypes: the concept of "edge effect" and cultivating an ethical bridge between omics innovations and society.

PubMed

Ozdemir, Vural; Suarez-Kurtz, Guilherme; Stenne, Raphaëlle; Somogyi, Andrew A; Someya, Toshiyuki; Kayaalp, S Oğuz; Kolker, Eugene

2009-02-01

Applications of omics technologies in the postgenomics era swiftly expanded from rare monogenic disorders to multifactorial common complex diseases, pharmacogenomics, and personalized medicine. Already, there are signposts indicative of further omics technology investment in nutritional sciences (nutrigenomics), environmental health/ecology (ecogenomics), and agriculture (agrigenomics). Genotype-phenotype association studies are a centerpiece of translational research in omics science. Yet scientific and ethical standards and ways to assess and communicate risk information obtained from association studies have been neglected to date. This is a significant gap because association studies decisively influence which genetic loci become genetic tests in the clinic or products in the genetic test marketplace. A growing challenge concerns the interpretation of large overlap typically observed in distribution of quantitative traits in a genetic association study with a polygenic/multifactorial phenotype. To remedy the shortage of risk assessment and communication tools for association studies, this paper presents the concept of edge effect. That is, the shift in population edges of a multifactorial quantitative phenotype is a more sensitive measure (than population averages) to gauge the population level impact and by extension, policy significance of an omics marker. Empirical application of the edge effect concept is illustrated using an original analysis of warfarin pharmacogenomics and the VKORC1 genetic variation in a Brazilian population sample. These edge effect analyses are examined in relation to regulatory guidance development for association studies. We explain that omics science transcends the conventional laboratory bench space and includes a highly heterogeneous cast of stakeholders in society who have a plurality of interests that are often in conflict. Hence, communication of risk information in diagnostic medicine also demands attention to processes involved in production of knowledge and human values embedded in scientific practice, for example, why, how, by whom, and to what ends association studies are conducted, and standards are developed (or not). To ensure sustainability of omics innovations and forecast their trajectory, we need interventions to bridge the gap between omics laboratory and society. Appreciation of scholarship in history of omics science is one remedy to responsibly learn from the past to ensure a sustainable future in omics fields, both emerging (nutrigenomics, ecogenomics), and those that are more established (pharmacogenomics). Another measure to build public trust and sustainability of omics fields could be legislative initiatives to create a multidisciplinary oversight body, at arm's length from conflict of interests, to carry out independent, impartial, and transparent innovation analyses and prospective technology assessment.
A Review of Body Dysmorphic Disorder and Its Presentation in Different Clinical Settings

PubMed Central

Mufaddel, Amir; Osman, Ossama T.; Almugaddam, Fadwa

2013-01-01

Objective: Body dysmorphic disorder (BDD) is a relatively common psychiatric disorder characterized by preoccupations with perceived defects in physical appearance. This review aimed to explore epidemiology, clinical features, comorbidities, and treatment options for BDD in different clinical settings. Data Source and Study Selection: A search of the literature from 1970 to 2011 was performed using the MEDLINE search engine. English-language articles, with no restriction regarding the type of articles, were identified using the search terms body dysmorphic disorder, body dysmorphic disorder clinical settings, body dysmorphic disorder treatment, and body dysmorphic disorder & psychodermatology. Results: BDD occurs in 0.7% to 2.4% of community samples and 13% of psychiatric inpatients. Etiology is multifactorial, with recent findings indicating deficits in visual information processing. There is considerable overlap between BDD and obsessive-compulsive disorder (OCD) in symptom etiology and response to treatment, which has led to suggestions that BDD can be classified with anxiety disorders and OCD. A recent finding indicated genetic overlap between BDD and OCD. Over 60% of patients with BDD had a lifetime anxiety disorder, and 38% had social phobia, which tends to predate the onset of BDD. Studies reported a high level of comorbidity with depression and social phobia occurring in > 70% of patients with BDD. Individuals with BDD present frequently to dermatologists (about 9%–14% of dermatologic patients have BDD). BDD co-occurs with pathological skin picking in 26%–45% of cases. BDD currently has 2 variants: delusional and nondelusional, and both variants respond similarly to serotonin reuptake inhibitors (SRIs), which may have effect on obsessive thoughts and rituals. Cognitive-behavioral therapy has the best established treatment results. Conclusions: A considerable overlap exists between BDD and other psychiatric disorders such as OCD, anxiety, and delusional disorder, and this comorbidity should be considered in evaluation, management, and long-term follow-up of the disorder. Individuals with BDD usually consult dermatologists and cosmetic surgeons rather than psychiatrists. Collaboration between different specialties (such as primary care, dermatology, cosmetic surgery, and psychiatry) is required for better treatment outcome. PMID:24392251
Dental ergonomics to combat musculoskeletal disorders: a review.

PubMed

Gupta, Arpit; Ankola, Anil V; Hebbal, Mamata

2013-01-01

Musculoskeletal disorders (MSDs) are significant workplace problems affecting occupational health, productivity and the careers of dental professionals. The prevalence of MSDs is on the rise for all types of dental workers. In spite of different patterns of work culture, there are parallel levels of symptoms in dentists across nations. Risk factors for MSDs are multifactorial. Symptoms appear very early in careers, with higher prevalence of MSDs even during educational training. Ergonomics improvements, health promotion and organizational interventions are necessary to reduce the risk. An interdisciplinary approach with progressive efforts should be taken to address MSDs in dental professionals.
Etiology of ejaculation and pathophysiology of premature ejaculation.

PubMed

Donatucci, Craig F

2006-09-01

Ejaculation is comprised of three stages of the male sexual response cycle, namely emission, ejection, and orgasm; however, in comparison with erection, which is a well-understood component of male sexual response, the pathophysiology of ejaculation has yet to be fully delineated. Premature ejaculation (PE), the most common sexual disorder in men, while believed to have a multifactorial etiology, is even less well understood. This article reviews the physiology of ejaculation, and the multifactorial pathophysiology of PE. The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24-26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. There were 16 invited presenters and discussants; the group focused on several educational objectives. Data were obtained by extensive examination of published peer-reviewed literature. Evidence supports that biologic mechanisms associated with neurotransmitters such as norepinephrine, serotonin, oxytocin, Gamma-amino-butyric acid, and nitric oxide (NO) as well as the hormone estrogen play central roles in ejaculation, and subsequently may mediate PE. There is also emerging evidence to show that hyperthyroidism may be a causal factor in PE. Recent data also suggest that psychogenic factors include high level of any experience by some men with PE. The pathophysiology of both lifelong and acquired PE appears to be both neurobiogenic and psychogenic. While psychogenic factors appear to be contributory to PE, pharmacologic intervention of PE can modify intravaginal ejaculatory latency time (IELT), which suggests that IELT is a biological variable, and is likely biologically dependent upon neurotransmitters and hormones.

Genetic bases of the nutritional approach to migraine.

PubMed

De Marchis, Maria Laura; Guadagni, Fiorella; Silvestris, Erica; Lovero, Domenica; Della-Morte, David; Ferroni, Patrizia; Barbanti, Piero; Palmirotta, Raffaele

2018-03-08

Migraine is a common multifactorial and polygenic neurological disabling disorder characterized by a genetic background and associated to environmental, hormonal and food stimulations. A large series of evidence suggest a strong correlation between nutrition and migraine and indicates several commonly foods, food additives and beverages that may be involved in the mechanisms triggering the headache attack in migraine-susceptible persons. There are foods and drinks, or ingredients of the same, that can trigger the migraine crisis as well as some foods play a protective function depending on the specific genetic sensitivity of the subject. The recent biotechnological advances have enhanced the identification of some genetic factors involved in onset diseases and the identification of sequence variants of genes responsible for the individual sensitivity to migraine trigger-foods. Therefore many studies are aimed at the analysis of polymorphisms of genes coding for the enzymes involved in the metabolism of food factors in order to clarify the different ways in which people respond to foods based on their genetic constitution. This review discusses the latest knowledge and scientific evidence of the role of gene variants and nutrients, food additives and nutraceuticals interactions in migraine.
Carrier-Based Drug Delivery System for Treatment of Acne

PubMed Central

Vyas, Amber; Kumar Sonker, Avinesh

2014-01-01

Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376
A developmental, biopsychosocial model for the treatment of children with gender identity disorder.

PubMed

Zucker, Kenneth J; Wood, Hayley; Singh, Devita; Bradley, Susan J

2012-01-01

This article provides a summary of the therapeutic model and approach used in the Gender Identity Service at the Centre for Addiction and Mental Health in Toronto. The authors describe their assessment protocol, describe their current multifactorial case formulation model, including a strong emphasis on developmental factors, and provide clinical examples of how the model is used in the treatment.
The Impact of an Ergonomics Intervention on Psychosocial Factors and Musculoskeletal Symptoms among Thai Hospital Orderlies.

PubMed

Chanchai, Withaya; Songkham, Wanpen; Ketsomporn, Pranom; Sappakitchanchai, Punnarat; Siriwong, Wattasit; Robson, Mark Gregory

2016-05-03

(1) BACKGROUND: Musculoskeletal disorders have a multifactorial etiology that is not only associated with physical risk factors, but also psychosocial risk factors; (2) OBJECTIVE: This study evaluated the effects of an ergonomic intervention on musculoskeletal disorders and psychosocial risk factors; (3) MATERIAL AND METHODS: This study took a participatory ergonomic (PE) approach with a randomized controlled trial (RCT) conducted at tertiary care hospitals during July to December 2014. A group of hospital orderlies in Thailand were randomly selected for examination. Fifty orderlies were placed in a case group and another 50 orderlies were placed in the control group. The Nordic Musculoskeletal Disorders Questionnaire (NMQ) and the Copenhagen Psychosocial Questionnaire (COPSOQ) were used for data collection before and after the intervention program; (4) RESULTS: The most commonly reported problem among hospital orderlies was found to be lower back symptoms (82%). The study found significant differences in prevalence rates of reported musculoskeletal conditions in the arm, upper back, and lower back regions before and after intervention. Findings showed that psychosocial risk factors were affected by the intervention. COPSOQ psychosocial risk factors were significantly different pre/post intervention. These variables included: work pace, influence at work, meaning of work, predictability, rewards, role conflicts, and social support from supervisors. No other psychosocial risk factors were found to be significant; (5) CONCLUSIONS: Positive results were observed following the intervention in the work environment, particularly in terms of reducing physical work environment risk factors for musculoskeletal disorders and increasing promotion factors of the psychosocial work environment.
The Impact of an Ergonomics Intervention on Psychosocial Factors and Musculoskeletal Symptoms among Thai Hospital Orderlies

PubMed Central

Chanchai, Withaya; Songkham, Wanpen; Ketsomporn, Pranom; Sappakitchanchai, Punnarat; Siriwong, Wattasit; Robson, Mark Gregory

2016-01-01

(1) Background: Musculoskeletal disorders have a multifactorial etiology that is not only associated with physical risk factors, but also psychosocial risk factors; (2) Objective: This study evaluated the effects of an ergonomic intervention on musculoskeletal disorders and psychosocial risk factors; (3) Material and Methods: This study took a participatory ergonomic (PE) approach with a randomized controlled trial (RCT) conducted at tertiary care hospitals during July to December 2014. A group of hospital orderlies in Thailand were randomly selected for examination. Fifty orderlies were placed in a case group and another 50 orderlies were placed in the control group. The Nordic Musculoskeletal Disorders Questionnaire (NMQ) and the Copenhagen Psychosocial Questionnaire (COPSOQ) were used for data collection before and after the intervention program; (4) Results: The most commonly reported problem among hospital orderlies was found to be lower back symptoms (82%). The study found significant differences in prevalence rates of reported musculoskeletal conditions in the arm, upper back, and lower back regions before and after intervention. Findings showed that psychosocial risk factors were affected by the intervention. COPSOQ psychosocial risk factors were significantly different pre/post intervention. These variables included: work pace, influence at work, meaning of work, predictability, rewards, role conflicts, and social support from supervisors. No other psychosocial risk factors were found to be significant; (5) Conclusions: Positive results were observed following the intervention in the work environment, particularly in terms of reducing physical work environment risk factors for musculoskeletal disorders and increasing promotion factors of the psychosocial work environment. PMID:27153076
Functional disorders of the temporomandibular joints: Internal derangement of the temporomandibular joint.

PubMed

Chang, Chih-Ling; Wang, Ding-Han; Yang, Mu-Chen; Hsu, Wun-Eng; Hsu, Ming-Lun

2018-04-01

Temporomandibular joint (TMJ) is one of the most complex joints of the human body. Due to its unique movement, in terms of combination of rotation and translator movement, disc of the joint plays an important role to maintain its normal function. In order to sustain the normal function of the TMJ, disc must be kept in proper position as well as maintain normal shape in all circumstances. Once the disc is not any more in its normal position during function of the joint, disturbance of the joint can be occurred which will lead to subsequent distortion of the disc. Shape of the disc can be influenced by many factors i.e.: abnormal function or composition of the disc itself. Etiology of the internal derangement of the disc remains controversial. Multifactorial theory has been postulated in most of previous manuscripts. Disc is composed of mainly extracellular matrix. Abnormal proportion of collagen type I & III may also leads to joint hypermobility which may be also a predisposing factor of this disorder. Thus it can be recognized as local manifestation of a systemic disorder. Different treatment modalities with from conservative treatment to surgical intervention distinct success rate have been reported. Recently treatment with extracellular matrix injection becomes more and more popular to strengthen the joint itself. Since multifactorial in character, the best solution of the treatment modalities should be aimed to resolve possible etiology from different aspects. Team work may be indication to reach satisfied results. Copyright © 2018. Published by Elsevier Taiwan.
Attentional but not Pre-Attentive Neural Measures of Auditory Discrimination are Atypical in Children with Developmental Language Disorder

PubMed Central

Kornilov, Sergey A.; Landi, Nicole; Rakhlin, Natalia; Fang, Shin-Yi; Grigorenko, Elena L.; Magnuson, James S.

2015-01-01

We examined neural indices of pre-attentive phonological and attentional auditory discrimination in children with developmental language disorder (DLD, n=23) and typically developing (n=16) peers from a geographically isolated Russian-speaking population with an elevated prevalence of DLD. Pre-attentive phonological MMN components were robust and did not differ in two groups. Children with DLD showed attenuated P3 and atypically distributed P2 components in the attentional auditory discrimination task; P2 and P3 amplitudes were linked to working memory capacity, development of complex syntax, and vocabulary. The results corroborate findings of reduced processing capacity in DLD and support a multifactorial view of the disorder. PMID:25350759
Oxidative damage to macromolecules in human Parkinson’s disease and the rotenone model

PubMed Central

Sanders, Laurie H.; Greenamyre, J. Timothy

2013-01-01

Parkinson’s disease (PD), the most common neurodegenerative movement disorder, is associated with selective degeneration of nigrostriatal dopamine neurons. While the underlying mechanisms contributing to neurodegeneration in PD appear to be multifactorial, mitochondrial impairment and oxidative stress are widely considered to be central to many forms of the disease. Whether oxidative stress is a cause or consequence of dopaminergic death, there is substantial evidence for oxidative stress in both human PD patients and in animal models of PD, especially using rotenone, a complex I inhibitor. There are many indices of oxidative stress, but this review covers the recent evidence for oxidative damage to nucleic acids, lipids and proteins in both the brain and peripheral tissues in human PD and in the rotenone model. Limitations of the existing literature and future perspectives are discussed. Understanding how each particular macromolecule is damaged by oxidative stress and the interplay of secondary damage to other biomolecules may help design better targets for treatment of PD. PMID:23328732
An introduction to DARC technology.

PubMed

Ahmad, Syed Shoeb

2017-01-01

Glaucoma is a multi-factorial neurodegenerative disorder. The common denominator in all types of glaucomas is retinal ganglion cell death through apoptosis. However, this cellular demise in glaucoma is detected late by structural or functional analyses. There can be a 10-year delay prior to the appearance of visual field defects and pre-perimetric glaucoma is an issue still being addressed. However, a new cutting-edge technology called detection of apoptosing retinal cells (DARC) is being developed. This technique is capable of non-invasive, real-time visualization of apoptotic changes at the cellular level. It can detect glaucomatous cell damage at a very early stage, at the moment apoptosis starts, and thus management can be initiated even prior to development of visual field changes. In future, this technique will also be able to provide conclusive evidence of the effectiveness of treatment protocol and the need for any modifications which may be required. This article aims to provide a concise review of DARC technology.
A Cybrid Cell Model for the Assessment of the Link Between Mitochondrial Deficits and Sporadic Parkinson’s Disease

PubMed Central

Arduíno, Daniela M.; Esteves, A. Raquel; Swerdlow, Russell H.; Cardoso, Sandra M.

2015-01-01

Parkinson’s disease (PD) is a multifactorial and clinically complex age-related movement disorder. The cause of its most common form (sporadic PD, sPD) is unknown, but one prominent causal factor is mitochondrial dysfunction. Although several genetic- and toxin-based models have been developed along the last decades to mimic the pathological cascade of PD, cellular models that reliably recapitulate the pathological features of the neurons that degenerate in PD are scarce. We describe here the generation of cytoplasmic hybrid cells (or cybrids) as a cellular model of sPD. This approach consists on the fusion of platelets harboring mtDNA from sPD patients with cells in which the endogenous mtDNA has been depleted (Rho0 cells). The sPD cybrid model has been successful in recapitulating most of the hallmarks of sPD, constituting now a validated model for addressing the link between mitochondrial dysfunction and sPD pathology. PMID:25634293
A cybrid cell model for the assessment of the link between mitochondrial deficits and sporadic Parkinson's disease.

PubMed

Arduíno, Daniela M; Esteves, A Raquel; Swerdlow, Russell H; Cardoso, Sandra M

2015-01-01

Parkinson's disease (PD) is a multifactorial and clinically complex age-related movement disorder. The cause of its most common form (sporadic PD, sPD) is unknown, but one prominent causal factor is mitochondrial dysfunction. Although several genetic- and toxin-based models have been developed along the last decades to mimic the pathological cascade of PD, cellular models that reliably recapitulate the pathological features of the neurons that degenerate in PD are scarce.We describe here the generation of cytoplasmic hybrid cells (or cybrids) as a cellular model of sPD. This approach consists on the fusion of platelets harboring mtDNA from sPD patients with cells in which the endogenous mtDNA has been depleted (Rho0 cells).The sPD cybrid model has been successful in recapitulating most of the hallmarks of sPD, constituting now a validated model for addressing the link between mitochondrial dysfunction and sPD pathology.
Anesthesia and Tau Pathology

PubMed Central

Whittington, Robert A.; Bretteville, Alexis; Dickler, Maya F.; Planel, Emmanuel

2013-01-01

Alzheimer’s disease (AD) is the most common form of dementia and remains a growing worldwide health problem. As life expectancy continues to increase, the number of AD patients presenting for surgery and anesthesia will steadily rise. The etiology of sporadic AD is thought to be multifactorial, with environmental, biological and genetic factors interacting together to influence AD pathogenesis. Recent reports suggest that general anesthetics may be such a factor and may contribute to the development and exacerbation of this neurodegenerative disorder. Intra-neuronal neurofibrillary tangles (NFT), composed of hyperphosphorylated and aggregated tau protein are one of the main neuropathological hallmarks of AD. Tau pathology is important in AD as it correlates very well with cognitive dysfunction. Lately, several studies have begun to elucidate the mechanisms by which anesthetic exposure might affect the phosphorylation, aggregation and function of this microtubule-associated protein. Here, we specifically review the literature detailing the impact of anesthetic administration on aberrant tau hyperphosphorylation as well as the subsequent development of neurofibrillary pathology and degeneration. PMID:23535147
Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases--a mechanistic approach.

PubMed

Baltazar, Maria Teresa; Dinis-Oliveira, Ricardo Jorge; de Lourdes Bastos, Maria; Tsatsakis, Aristidis M; Duarte, José Alberto; Carvalho, Félix

2014-10-15

The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low-dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pesticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Amyotrophic lateral sclerosis: A 40-year personal perspective.

PubMed

Eisen, Andrew

2009-04-01

Amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) shares with other neurodegenetrative disorders of the aging nervous system a polygenic, multifactorial aetiology. Less than 10% are familial and these too probably are associated with several interactive genes. The onset of ALS predates development of clinical symptoms by an unknown interval which may extend several years. The cause of neurodegeneration remains unknown but a common end-point is protein misfolding which in turn causes cell function failure. The complex nature of ALS has hindered therapeutic advances. In recent years longer survival is attributable largely to institution of non-invasive ventilation with BiPAP and timely implementation of percutaneous endoscopic gastrostomy (PEG) feeding. Symptomatic treatment has advanced improving quality of life. Several encouraging avenues of therapy for ALS are beginning to be emerge raising hope for real benefit. They include protective autoimmunity, vaccines against misfolded protein epitopes and other deleterious species, new drug delivery systems employing nanotechnology and the potential of stem cell therapy.
Understanding alcohol use disorders with neuroelectrophysiology

PubMed Central

RANGASWAMY, MADHAVI; PORJESZ, BERNICE

2015-01-01

Neurocognitive deficits associated with impairments in various brain regions and neural circuitries, particularly involving frontal lobes, have been associated with chronic alcoholism, as well as with a predisposition to develop alcohol use and related disorders (AUDs). AUD is a multifactorial disorder caused by complex interactions between behavioral, genetic, and environmental liabilities. Neuroelectrophysiological techniques are instrumental in understanding brain and behavior relationships and have also proved very useful in evaluating the genetic diathesis of alcoholism. This chapter describes findings from neuroelectrophysiological measures (electroencephalogram, event-related potentials, and event-related oscillations) related to acute and chronic effects of alcohol on the brain and those that reflect underlying deficits related to a predisposition to develop AUDs and related disorders. The utility of these measures as effective endophenotypes to identify and understand genes associated with brain electrophysiology, cognitive networks, and AUDs has also been discussed. PMID:25307587
Management of female sexual pain disorders.

PubMed

Boyer, Stéphanie C; Goldfinger, Corrie; Thibault-Gagnon, Stéphanie; Pukall, Caroline F

2011-01-01

Our understanding of the sexual pain disorders vaginismus and dyspareunia has been fundamentally altered over the past two decades due to increased attention and empirically sound research in this domain. This increased knowledge base has included a shift from a dualistic view of the etiology of painful and/or difficult vaginal penetration being due to either psychological or physiological causes, to a multifactorial perspective. The present chapter reviews current classification and prevalence rates, including ongoing definitional debates. Research regarding the etiology, assessment and management of sexual pain disorders is discussed from a biopsychosocial perspective. Cyclical theories of the development and maintenance of sexual pain disorders, which highlight the complex interplay among physiological, psychological and social factors, are described. Medical/surgical treatment options, pelvic floor rehabilitation and psychological approaches are reviewed, as well as future directions in treatment research. Copyright © 2011 S. Karger AG, Basel.
Who says this is a modern disorder? The early history of attention deficit hyperactivity disorder

PubMed Central

Martinez-Badía, Jose; Martinez-Raga, Jose

2015-01-01

Attention-deficit hyperactivity disorder (ADHD) is a complex, heterogeneous and multifactorial neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity and impulsivity. Although the first clinical description of a constellation of symptoms highly resembling to what currently could be diagnosed as ADHD is generally attributed to George F Still in 1902, there are scattered but significant published historical medical, scientific and non-scientific reports, much prior to Still’s lectures, of what is currently conceptualized as ADHD. The present report aimed at exploring the early history of ADHD, prior to the 20th century in the medical literature and in other historical sources, to provide clinicians, researchers and other professionals with a better understanding of the roots and current conceptualization of this disorder. It is possible to find clues and highly suggestive descriptions of individuals presenting symptoms resembling what is currently defined as ADHD in the literature, in paintings or in the Bible. However, the earliest medical reports of individuals with abnormal degrees of inattention, distractibility and overactivity date from the last quarter of the 18th century, included in two of the first textbooks specifically on the subject of mental diseases, published by the German Melchior Adam Weikard and the Scottish Sir Alexander Crichton. During the 19th century some eminent physicians from Germany, France or Great Britain, such as Charles West, Thomas C Albutt, Thomas S Clouston, William W, Ireland, John Haslam, Heinrich Neumann, or Désiré-Magloire Bourneville, among others provided clinical depictions of patients that most likely presently would be diagnosed as having ADHD. Whilst some of the children described by Still and his predecessors may have suffered from a variety of neurological and psychiatric disorders, many of these patients showed clear symptoms of ADHD and may present with comorbid disorders, as it is commonly the case in clinical practice. PMID:26740929
SICK BUILDING SYNDROME: POSSIBLE ASSOCIATIONS WITH EXPOSURE TO MYCOTOXINS FROM INDOOR AIR FUNGI.

EPA Science Inventory

Introduction. Chronic human illness associated with residential or occupational buildings, commonly referred to as sick building syndrome (SBS), may be a multifactorial condition, involving in some cases volatile organic compounds, CO or CO2, pesticides, biologic agents, temperat...
Autism-specific copy number variants further implicate the phosphatidylinositol signaling pathway and the glutamatergic synapse in the etiology of the disorder.

PubMed

Cuscó, Ivon; Medrano, Andrés; Gener, Blanca; Vilardell, Mireia; Gallastegui, Fátima; Villa, Olaya; González, Eva; Rodríguez-Santiago, Benjamín; Vilella, Elisabet; Del Campo, Miguel; Pérez-Jurado, Luis A

2009-05-15

Autism spectrum disorders (ASDs) constitute a group of severe neurodevelopmental conditions with complex multifactorial etiology. In order to explore the hypothesis that submicroscopic genomic rearrangements underlie some ASD cases, we have analyzed 96 Spanish patients with idiopathic ASD after extensive clinical and laboratory screening, by array comparative genomic hybridization (aCGH) using a homemade bacterial artificial chromosome (BAC) array. Only 13 of the 238 detected copy number alterations, ranging in size from 89 kb to 2.4 Mb, were present specifically in the autistic population (12 out of 96 individuals, 12.5%). Following validation by additional molecular techniques, we have characterized these novel candidate regions containing 24 different genes including alterations in two previously reported regions of chromosome 7 associated with the ASD phenotype. Some of the genes located in ASD-specific copy number variants act in common pathways, most notably the phosphatidylinositol signaling and the glutamatergic synapse, both known to be affected in several genetic syndromes related with autism and previously associated with ASD. Our work supports the idea that the functional alteration of genes in related neuronal networks is involved in the etiology of the ASD phenotype and confirms a significant diagnostic yield for aCGH, which should probably be included in the diagnostic workup of idiopathic ASD.
Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential

PubMed Central

Lin, Jenny B.; Phillips, Evan H.; Riggins, Ti’Air E.; Sangha, Gurneet S.; Chakraborty, Sreyashi; Lee, Janice Y.; Lycke, Roy J.; Hernandez, Clarissa L.; Soepriatna, Arvin H.; Thorne, Bradford R. H.; Yrineo, Alexa A.; Goergen, Craig J.

2015-01-01

Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic. PMID:25993289

Common mental disorders and associated factors: a study of women from a rural area.

PubMed

Parreira, Bibiane Dias Miranda; Goulart, Bethania Ferreira; Haas, Vanderlei José; Silva, Sueli Riul da; Monteiro, Juliana Cristina Dos Santos; Gomes-Sponholz, Flávia Azevedo; Parreira, Bibiane Dias Miranda; Goulart, Bethania Ferreira; Haas, Vanderlei José; Silva, Sueli Riul da; Monteiro, Juliana Cristina Dos Santos; Gomes-Sponholz, Flávia Azevedo

2017-05-25

Identifying the prevalence of Common Mental Disorders and analyzing the influence of sociodemographic, economic, behavioral and reproductive health variables on Common Mental Disorders in women of childbearing age living in the rural area of Uberaba-MG, Brazil. An observational and cross-sectional study. Socio-demographic, economic, behavioral and reproductive health instruments were used, along with the Self-Reporting Questionnaire (SRQ-20) to identify common mental disorders. Multiple logistic regression was used for multivariate data analysis. 280 women participated in the study. The prevalence of Common Mental Disorders was 35.7%. In the logistic regression analysis, the variables of living with a partner and education level were associated with Common Mental Disorders, even after adjusting for the other variables. Our findings evidenced an association of social and behavioral factors with Common Mental Disorders among rural women. Identification and individualized care in primary health care are essential for the quality of life of these women. Identificar a prevalência do transtorno mental comum e analisar a influência de variáveis sociodemográficas, econômicas, comportamentais e de saúde reprodutiva sobre o transtorno mental comum em mulheres em idade fértil, residentes na zona rural do município de Uberaba-MG, Brasil. Estudo observacional e transversal. Foram utilizados instrumentos de caracterização sociodemográfica, econômica, comportamental e de saúde reprodutiva, e o Self-Reporting Questionnaire (SRQ-20) para identificar os transtornos mentais comuns. Na análise multivariada dos dados, foi utilizada a regressão logística múltipla. Participaram do estudo 280 mulheres. A prevalência do transtorno mental comum foi de 35,7%. Na análise de regressão logística, as variáveis convivência com o companheiro e escolaridade, associaram-se ao transtorno mental comum, mesmo após o ajuste para as demais variáveis. Os achados evidenciaram a associação de fatores sociais e comportamentais com o transtorno mental comum, entre mulheres rurais. A identificação e a assistência individualizada na atenção primária de saúde são essenciais para a qualidade de vida destas mulheres. Identificar la prevalencia de trastornos mentales comunes y analizar la influencia de las variables socio-demográficas, económicas, de comportamiento y de salud reproductiva en el trastorno mental común en las mujeres en edad fértil, que viven en el municipio rural de Uberaba, Minas Gerais, Brasil. Estudio observacional y transversal. Se usaron instrumentos sociodemográficos, económicos, de comportamiento y salud reproductiva, y el Self-Reporting Questionnaire (SRQ-20) para identificar los trastornos mentales comunes. En el análisis multifactorial de los datos, se utilizó la regresión logística múltiple. El estudio incluyó a 280 mujeres. La prevalencia de los trastornos mentales comunes fue de 35,7%. En el análisis de regresión logística, las variables convivencia con su pareja y la escolarización se asociaron con trastorno mental común, incluso después de ajustar por otras variables. Los resultados muestran la relación entre los factores sociales y de comportamiento con el trastorno mental común entre las mujeres rurales. La identificación y la atención individual en la atención primaria de salud son esenciales para la calidad de vida de las mujeres.
Influence of wavelength on the outcome of the treatment of TMJ disorders: TMDS

NASA Astrophysics Data System (ADS)

Pinheiro, Antônio L. B.; Marques, Aparecida Maria C.; Carvalho, Carolina M.; Cangussú, Maria Cristina T.; Soares, Luiz Guilherme P.

2013-03-01

It is known that wavelength influences the outcome of many clinical protocols. Laser-phototherapy (LPT) and LEDs have been used on the treatment of pain of several origins including temporomandibular disorders - TMDs. TMDs are common painful multifactorial conditions affecting the temporomandibular joint whose treatment depends on the type and symptoms. Initially it requires pain control and for this, drugs, biting plates, oclusal adjustment, physiotherapy or their association are used. This work reports a series of patients of the Center of Biophotonics of the Federal University of Bahia over 10 years. Following standard anamneses, clinical and imaginologic examination and with the diagnosis of any type of TMD, the patients were set for light treatment. Treatment consisted of three sessions a week during six week. Prior irradiation, the patients were asked to score their pain using a VAS. λ780, λ 790, λ 830nm and/or λ660 and λ680nm lasers or LED were used on each session. Most patients were female (~43.6 years old). At the end of the 12 sessions the patients were again examined and score their pain using VAS. No other intervention was carried out during the treatment. The results were statistically analyzed and showed that most patients were asymptomatic or improved after treatment and that the association of wavelengths was very efficient on the symptomatic group. It is concluded that the association of both wavelengths was effective on pain reduction on TMJ disorders of several origins.
The use of phototherapy in the management of TMJ pain: clinical evidence of benefits and limitations

NASA Astrophysics Data System (ADS)

Pinheiro, A. L. B.; Soares, A. P.; Marques, A. M. C.; de Carvalho, F. B.; Soares, L. G. P.; de Oliveira, S. C. P. S.; Cangussú, M. C. T.

2017-02-01

Temporomandibular disorders - TMDs are common painful multifactorial conditions affecting the temporomandibular joint whose treatment depends on the type and symptoms. Initially it requires pain control and for this, drugs, biting plates, occlusal adjustment, physiotherapy or their association are used. Laser-phototherapy (LPT) has been used on the treatment of pain of several origins including TMDs. It is known that wavelength, energy density, frequency of application influences the outcome of many clinical protocols. This work reports a series of patients of the Center of Biophotonics of the Federal University of Bahia over 15 years. Following standard anamneses, clinical and imaginologic examination and with the diagnosis of any type of TMD, the patients were set for light treatment. Treatment consisted of three sessions a week during six week. Prior irradiation, the patients were asked to score their pain using a VAS. IR and/or Red diode lasers were used on each session. The medical records of 432 patients (73 male and 359 female) suffering from TMJ disorders were revised. Most patients were female ( 47.9 years old). At the end of the 12 sessions the patients were again examined and score their pain using VAS. No other intervention was carried out during the treatment. The results were statistically analyzed and showed that 51.16 % of the patients were asymptomatic or improved after treatment. It is concluded that LPT was effective on pain reduction on TMJ disorders of several origins.
Hypertension in children and adolescents: epidemiology and pathogenesis.

PubMed

Raj, Manu; Krishnakumar, R

2013-03-01

High blood pressure is one among the leading contributors to burden of disease globally. Approximately 54 % of stroke and 47 % of ischemic heart disease events worldwide were attributable to high blood pressure in the year 2001. There is deficiency of data on the long-term outcome of hypertension in children. In spite of this, there is sufficient evidence to suspect that the health risks of hypertension in pediatric patients are substantial. Hypertension in childhood is known to result in hypertension in young adulthood. The epidemiology of hypertension in children is well represented from various studies conducted across continents. Factors like methodological issues in measurement, socio demographic differences, adiposity levels and ethnicity appear to influence the distribution of blood pressure as well as prevalence of hypertension in children. The etio-pathogenesis of essential (primary) hypertension is multi-factorial in origin. Obesity, insulin resistance, activation of sympathetic nervous system, alterations in sodium homeostasis, renin-angiotensin system changes, changes in vascular smooth muscle structure and reactivity, high serum uric acid levels, genetic factors and fetal programming have been reported to contribute to this disorder. The causes of secondary hypertension vary with age. Renal disorders and coarctation of the aorta are the most common causes of hypertension in children up to age 6 y. In older children, renal parenchymal disease remains the most frequent cause of increased blood pressure. Other causes of hypertension in children are relatively rare and include systemic arteritis and certain tumours, endocrine dysfunction, and neurologic disorders.
Relationship between psychological factors and symptoms of TMD in university undergraduate students.

PubMed

Pesqueira, Aldiéris A; Zuim, Paulo R J; Monteiro, Douglas R; Ribeiro, Paula Do Prado; Garcia, Alicio R

2010-01-01

Temporomandibular disorders is a collective term used to describe a number of related disorders involving the temporomandibular joints, masticatory muscles and occlusion with common symptoms such as pain, restricted movement, muscle tenderness and intermittent joint sounds. The multifactorial TMD etiology is related to emotional tension, occlusal interferences, tooth loss, postural deviation, masticatory muscular dysfunction, internal and external changes in TMJ structure and the various associations of these factors. The aim of this study was to evaluate the prevalence of the relationship between signs of psychological distress and temporomandibular disorder in university students. A total 150 volunteers participated in this study. They attended different courses in the field of human science at one public university and four private universities. TMD was assessed by the Research Diagnostic Criteria (RDC) questionnaire. Anxiety was measured by means of a self-evaluative questionnaire, Spielberger's Trait-State anxiety inventory, to evaluate students'state and trait anxiety. The results of the two questionnaires were compared to determine the relationship between anxiety levels and severity degrees of chronic TMD pain by means of the chi-square test. The significance level was set at 5%. The statistical analysis showed that the TMD degree has a positive association with state-anxiety (p = 0.008; p < 0.05) and negative with trait-anxiety (p = 0.619; p < 0.05). Moreover a high TMD rate was observed among the students (40%). This study concluded that there is a positive association between TMD and anxiety.
Syndromes, disorders and maternal risk factors associated with neural tube defects (VII).

PubMed

Chen, Chih-Ping

2008-09-01

Neural tube defects (NTDs) may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome), Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher- Zweymller syndrome, parietal foramina (cranium bifidum), Apert syndrome, craniomicromelic syndrome, XXagonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.
Tic disorders.

PubMed

Martino, Davide; Mink, Jonathan W

2013-10-01

Primary tic disorders are complex, multifactorial disorders in which tics are accompanied by other sensory features and an array of comorbid behavioral disorders. Secondary tics are proportionally much less frequent, but their etiology is diverse. This review aims to guide clinicians in the recognition of the phenomenology, pathophysiology, and treatment of these disorders. Advances include greater phenomenologic insights, particularly of nonmotor (sensory) features; increased knowledge of disease mechanisms, particularly coming from neuropsychological, functional imaging, pathologic, and animal model studies; growing evidence on the efficacy of alpha-2 agonists and the newer generation of dopamine-modulating agents; and recent strides in the evaluation of cognitive-behavioral therapy and deep brain stimulation surgery. The correct diagnostic approach to tic disorders requires accurate historical gathering, a thorough neurologic examination, and detailed definition of the patient's psychopathologic profile. Treatment should always begin with individualized psychoeducational strategies. Although pharmacologic treatments remain beneficial for most patients, cognitive-behavioral treatments have thus far shown promising efficacy. Deep brain stimulation surgery should still be limited to adult patients refractory to pharmacotherapy and cognitive-behavioral therapy.
[Sexual disorders in epilepsy. Results of a multidisciplinary evaluation].

PubMed

Silva, H C; Carvalho, M J; Jorge, C L; Cunha Neto, M B; Goes, P M; Yacubian, E M

1999-09-01

Eleven epileptic men who complained of epilepsy and sexual dysfunction were submitted to a multidisciplinary evaluation. Mean age was 27 years (20-34), mean epilepsy duration was 19 years (0.5-32) and the mean seizure frequency was two by week (0-7). Ten patients had partial seizures and one other had myoclonic epilepsy. Ten patients were treated with antiepileptic drugs (phenytoin--1, carbamazepine--8, clonazepam--3, clobazam--2, valproic acid--3, vigabatrin--1). As defined in the DSM III-R, the complaints were: erectile disorder (9), hypoactive sexual desire disorder (4), frotteurism (4), inhibited orgasm (3), premature ejaculation (3), fetishism (2), voyeurism (2), exhibitionism (2), pedophilia (1) and sexual aversion disorder (1). Two patients showed hypogonadotropic hypogonadism on endocrinologic screening. Urological evaluation disclosed organic erectile dysfunction in other two. One patient had a diagnosis of psychogenic sexual disorder. In six patients a conclusive etiologic diagnosis was not reached. This report shows the multifactorial nature of sexual disorder in epilepsy and underlies the need of a multidisciplinar evaluation.
Falls prevention in the elderly: translating evidence into practice.

PubMed

Luk, James K H; Chan, T Y; Chan, Daniel K Y

2015-04-01

Falls are a common problem in the elderly. A common error in their management is that injury from the fall is treated, without finding its cause. Thus a proactive approach is important to screen for the likelihood of fall in the elderly. Fall assessment usually includes a focused history and a targeted examination. Timed up-and-go test can be performed quickly and is able to predict the likelihood of fall. Evidence-based fall prevention interventions include multi-component group or home-based exercises, participation in Tai Chi, environmental modifications, medication review, management of foot and footwear problems, vitamin D supplementation, and management of cardiovascular problems. If possible, these are best implemented in the form of multifactorial intervention. Bone health enhancement for residential care home residents and appropriate community patients, and prescription of hip protectors for residential care home residents are also recommended. Multifactorial intervention may also be useful in a hospital and residential care home setting. Use of physical restraints is not recommended for fall prevention.
Anorexia Nervosa and Bulimia: Problems of “The Pleasing Child”

PubMed Central

McSherry, J. A.

1984-01-01

Widespread media publicity has resulted in increased case findings of eating disorders such as anorexia nervosa and bulimia. The etiology of these conditions is complex and multifactorial, and they may have devastating effects on physical and psychological health. Family physicians have an important role to play in recognizing, evaluating and managing eating disorders. Severe anorexics—those who have lost 25% or more of the average weight for their age and height—require specialist management, but milder forms respond to treatment which can be undertaken by an interested family physician. Most cases of uncomplicated bulimia can be treated successfully in a family practice setting. PMID:21278973
Candida albicans importance to denture wearers. A literature review.

PubMed

Gleiznys, Alvydas; Zdanavičienė, Eglė; Žilinskas, Juozas

2015-01-01

Opportunistic oral fungal infections have spred, especially in denture wearers. Denture stomatitis is a common inflammatory reaction, multifactorial etiology, which is usually associated with Candida species, particularly Candida albicans, due to its high virulence, ability to adhere and form biofilms on oral cavity tissues and denture surfaces. This article highlights the pathogenesis, clinical presentation, and management strategies of Candida-associated denture stomatitis commonly encountered in dental practice.
Do (epi)genetics impact the brain in functional neurologic disorders?

PubMed

Frodl, T

2016-01-01

Advances in neuropsychiatric research are supposed to lead to significant improvements in understanding functional neurologic disorders and their diagnosis. However, epigenetic and genetic research on conversion disorders and somatoform disorders is only at its start. This review demonstrates the current state within this field and tries to bridge a gap from what is known on gene-stress interactions in other psychiatric disorders like depression. The etiology of conversion disorders is hypothesized to be multifactorial. These considerations also suggest that potential etiologic factors lead to alterations in brain function, either episodically or chronically, eventually leading to structural brain changes. In particular, the knowledge of how the environment influences brain structure and function, e.g., via epigenetic regulation, may be interesting for future research in functional neurologic disorders. Reviewing the literature results in evidence that childhood adversities play a role in the development of functional neurologic disorders, whereby at present no reports exist about the interactive effect between childhood adversity and genetic factors or about the impact of epigenetics. © 2016 Elsevier B.V. All rights reserved.
Autism

PubMed Central

Levy, Susan E; Mandell, David S; Schultz, Robert T

2010-01-01

Autism spectrum disorders are characterised by severe deficits in socialisation, communication, and repetitive or unusual behaviours. Increases over time in the frequency of these disorders (to present rates of about 60 cases per 10 000 children) might be attributable to factors such as new administrative classifications, policy and practice changes, and increased awareness. Surveillance and screening strategies for early identification could enable early treatment and improved outcomes. Autism spectrum disorders are highly genetic and multifactorial, with many risk factors acting together. Genes that affect synaptic maturation are implicated, resulting in neurobiological theories focusing on connectivity and neural effects of gene expression. Several treatments might address core and comorbid symptoms. However, not all treatments have been adequately studied. Improved strategies for early identification with phenotypic characteristics and biological markers (eg, electrophysiological changes) might hopefully improve effectiveness of treatment. Further knowledge about early identification, neurobiology of autism, effective treatments, and the effect of this disorder on families is needed. PMID:19819542
Autism.

PubMed

Levy, Susan E; Mandell, David S; Schultz, Robert T

2009-11-07

Autism spectrum disorders are characterised by severe deficits in socialisation, communication, and repetitive or unusual behaviours. Increases over time in the frequency of these disorders (to present rates of about 60 cases per 10,000 children) might be attributable to factors such as new administrative classifications, policy and practice changes, and increased awareness. Surveillance and screening strategies for early identification could enable early treatment and improved outcomes. Autism spectrum disorders are highly genetic and multifactorial, with many risk factors acting together. Genes that affect synaptic maturation are implicated, resulting in neurobiological theories focusing on connectivity and neural effects of gene expression. Several treatments might address core and comorbid symptoms. However, not all treatments have been adequately studied. Improved strategies for early identification with phenotypic characteristics and biological markers (eg, electrophysiological changes) might hopefully improve effectiveness of treatment. Further knowledge about early identification, neurobiology of autism, effective treatments, and the effect of this disorder on families is needed.
Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.

PubMed

Russell, James C; Proctor, Spencer D

2006-01-01

Cardiovascular disease, the leading cause of death in much of the modern world, is the common symptomatic end stage of a number of distinct diseases and, therefore, is multifactorial and polygenetic in character. The two major underlying causes are disorders of lipid metabolism and metabolic syndrome. The ability to develop preventative and ameliorative treatments will depend on animal models that mimic human disease processes. The focus of this review is to identify suitable animal models and insights into cardiovascular disease achieved to date using such models. The ideal animal model of cardiovascular disease will mimic the human subject metabolically and pathophysiologically, will be large enough to permit physiological and metabolic studies, and will develop end-stage disease comparable to those in humans. Given the complex multifactorial nature of cardiovascular disease, no one species will be suitable for all studies. Potential larger animal models are problematic due to cost, ethical considerations, or poor pathophysiological comparability to humans. Rabbits require high-cholesterol diets to develop cardiovascular disease, and there are no rabbit models of metabolic syndrome. Spontaneous mutations in rats provide several complementary models of obesity, hyperlipidemia, insulin resistance, and type 2 diabetes, one of which spontaneously develops cardiovascular disease and ischemic lesions. The mouse, like normal rats, is characteristically resistant to cardiovascular disease, although genetically altered strains respond to cholesterol feeding with atherosclerosis, but not with end-stage ischemic lesions. The most useful and valid species/strains for the study of cardiovascular disease appear to be small rodents, rats, and mice. This fragmented field would benefit from a consensus on well-characterized appropriate models for the study of different aspects of cardiovascular disease and a renewed emphasis on the biology of underlying diseases.
Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

PubMed Central

Marini, Francesca; Cianferotti, Luisella; Brandi, Maria Luisa

2016-01-01

Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles. PMID:27529237
Clinical assessment and crisis intervention for the suicidal bipolar disorder patient.

PubMed

Saunders, Kate E A; Hawton, Keith

2013-08-01

Suicidal behaviour is common in people suffering with bipolar disorder, and suicide is a leading cause of death in this group. Our aim in this review is to provide an overview of key assessment and management strategies, highlight research findings relevant to suicide prevention, and identify important areas for future research. We reviewed the published literature regarding the risk factors for and management of suicida\\l behaviour in individuals with bipolar disorder using the Pubmed and PsychINFO databases. Where available, we focused our search on systematic reviews. Suicide is usually associated with a depressive phase, although mixed affective states also convey increased risk. All individuals with bipolar disorder should have an up-to-date crisis management plan which outlines the action to be taken should suicidal behaviour emerge. Timely clinical assessment is essential in ensuring that those at high risk are identified. This should include mental state examination, consideration of risk factors, and evaluation of issues such as access to means, preparatory acts before suicide, and also protective factors. While pharmacological approaches are the mainstay of management, less specific measures, such as the removal of access to means, are also important in ensuring safety in the acute situation. Intensifying the clinical support of both patients and relatives, and the sharing of risk information with other health agencies are essential in management. Specific psychological treatments are likely to be helpful in preventing crises, although the evidence base is limited. The aetiology of suicidal behaviour in bipolar disorder is multifactorial and requires proactive crisis planning and management. A range of issues need to be addressed in the assessment of at-risk patients. Determining the efficacy of interventions specific to reducing suicidality in bipolar disorder should be a research priority. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Meta-analysis argues for a female-specific role of MAOA-uVNTR in panic disorder in four European populations.

PubMed

Reif, Andreas; Weber, Heike; Domschke, Katharina; Klauke, Benedikt; Baumann, Christian; Jacob, Christian P; Ströhle, Andreas; Gerlach, Alexander L; Alpers, Georg W; Pauli, Paul; Hamm, Alfons; Kircher, Tilo; Arolt, Volker; Wittchen, Hans-Ulrich; Binder, Elisabeth B; Erhardt, Angelika; Deckert, Jürgen

2012-10-01

Panic disorder (PD) is a common mental disorder, ranking highest among the anxiety disorders in terms of disease burden. The pathogenesis of PD is multifactorial with significant heritability, however only a few convincing risk genes have been reported thus far. One of the most promising candidates is the gene encoding monoamine oxidase A (MAOA), due to its key role in monoaminergic neurotransmission, established validity of animal models, and the efficacy of MAO inhibitors in the treatment of PD. A promoter repeat polymorphism in MAOA (MAOA-uVNTR) impacts on gene expression; high-expression alleles have been reported to increase the risk for PD. To further scrutinize the role of this polymorphism, we performed a formal meta-analysis on MAOA-uVNTR and PD using original data from four published European (Estonian, German, Italian, and Polish) samples and genotypes from three hitherto unpublished German PD samples, resulting in the largest (n = 1,115 patients and n = 1,260 controls) genetic study on PD reported to date. In the unpublished samples, evidence for association of MAOA-uVNTR with PD was obtained in one of the three samples. Results of the meta-analysis revealed a significant and female-specific association when calculating an allelic model (OR = 1.23, P = 0.006). This sex-specific effect might be explained by a gene-dose effect causing higher MAOA expression in females. Taken together, our meta-analysis therefore argues that high-expression MAOA-uVNTR alleles significantly increase the risk towards PD in women. However, epigenetic mechanisms might obfuscate the genetic association, calling for ascertainment in larger samples as well as assessment of the MAOA promoter methylation status therein. 2012 Wiley Periodicals, Inc
Sleep disturbances in children with attention-deficit/hyperactivity disorder

PubMed Central

Spruyt, Karen; Gozal, David

2011-01-01

In this article, we advocate the need for better understanding and treatment of children exhibiting inattentive, hyperactive, impulsive behaviors, by in-depth questioning on sleepiness, sleep-disordered breathing or problematic behaviors at bedtime, during the night and upon awakening, as well as night-to-night sleep duration variability. The relationships between sleep and attention-deficit/hyperactivity disorder (ADHD) are complex and are routinely overlooked by practitioners. Motricity and somnolence, the most consistent complaints and objectively measured sleep problems in children with ADHD, may develop as a consequence of multidirectional and multifactorial pathways. Therefore, subjectively perceived or reported restless sleep should be evaluated with specific attention to restless legs syndrome or periodic limb movement disorder, and awakenings should be queried with regard to parasomnias, dyssomnias and sleep-disordered breathing. Sleep hygiene logs detailing sleep onset and offset quantitatively, as well as qualitatively, are required. More studies in children with ADHD are needed to reveal the 24-h phenotype, or its sleep comorbidities. PMID:21469929
The evidence basis for coenzyme Q therapy in oxidative phosphorylation disease.

PubMed

Haas, Richard H

2007-06-01

The evidence supporting a treatment benefit for coenzyme Q10 (CoQ10) in primary mitochondrial disease (mitochondrial disease) whilst positive is limited. Mitochondrial disease in this context is defined as genetic disease causing an impairment in mitochondrial oxidative phosphorylation (OXPHOS). There are no treatment trials achieving the highest Level I evidence designation. Reasons for this include the relative rarity of mitochondrial disease, the heterogeneity of mitochondrial disease, the natural cofactor status and easy 'over the counter availability' of CoQ10 all of which make funding for the necessary large blinded clinical trials unlikely. At this time the best evidence for efficacy comes from controlled trials in common cardiovascular and neurodegenerative diseases with mitochondrial and OXPHOS dysfunction the etiology of which is most likely multifactorial with environmental factors playing on a background of genetic predisposition. There remain questions about dosing, bioavailability, tissue penetration and intracellular distribution of orally administered CoQ10, a compound which is endogenously produced within the mitochondria of all cells. In some mitochondrial diseases and other commoner disorders such as cardiac disease and Parkinson's disease low mitochondrial or tissue levels of CoQ10 have been demonstrated providing an obvious rationale for supplementation. This paper discusses the current state of the evidence supporting the use of CoQ10 in mitochondrial disease.

Dry eye disease: an immune-mediated ocular surface disorder

PubMed Central

Stevenson, William; Chauhan, Sunil K.; Dana, Reza

2013-01-01

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management. PMID:22232476
Systemic sclerosis-scleroderma.

PubMed

Haustein, U-F

2002-06-01

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This review discusses epidemiology and survival, clinical features including subsets and internal organ involvement, pathophysiology and genetics, microvasculature, immunobiology, fibroblasts and connective tissue metabolism and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder, which is treatable, but not curable. Therapy involves immunomodulation as well as the targeting of blood vessel mechanics and fibrosis. Physical therapy and psychotherapy are also important adjunctive therapies in this multifactorial disease.
Segregation analysis reveals evidence of a major gene for Alzheimer disease.

PubMed Central

Farrer, L A; Myers, R H; Connor, L; Cupples, L A; Growdon, J H

1991-01-01

In an attempt to resolve the relative influences of major genes, multifactorial heritability, and cohort effects on the susceptibility to Alzheimer disease (AD), complex segregation analysis was performed on 232 nuclear families. All families were consecutively ascertained through a single proband who was referred for diagnostic evaluation of a memory disorder. The results suggest that susceptibility to AD is determined, in part, by a major autosomal dominant allele with an additional multifactorial component. Single-locus, polygenic, sporadic, and no-transmission models, as well as recessive inheritance of the major effect, were significantly rejected. Excess transmission from the heterozygote was marginally significant and probably reflects the presence of phenocopies or perhaps the existence of two or more major loci for AD. The frequency of the AD susceptibility allele was estimated to be .038, but the major locus accounts for only 24% of the transmission variance, indicating a substantial role for other genetic and nongenetic mechanisms in the causation of AD. PMID:2035523
Ergonomics and dentistry.

PubMed

Murphy, D C

1997-01-01

Since 1992 the Occupational Safety and Health Administration (OSHA) has been preparing Federal legislation concerned with ergonomic hazards in at-risk workplaces. Although multifactorial in nature, there is sufficient evidence in the scientific literature to document an association between the practice of dentistry and a variety of musculoskeletal disorders. There are preventive strategies already known and available to us. Should dentistry be considered an at-risk profession and be required to comply with the forthcoming standard, or is self-monitoring sufficient?
[Air-conditioner disease. Results of an industrial medicine survey (author's transl)].

PubMed

Molina, C; Aiache, J M; Bedu, M; Menaut, P; Wahl, D; Brestowski, J; Grall, Y

1982-07-03

The results of a survey conducted in a company employing 1850 persons working in air-conditioned premises are reported. One hundred and five persons were examined, including 790 who mostly complained of respiratory disorders and 20 controls. Regular check-ups during the last two years have failed to reveal any serious disease. The most frequent complaints were rhinitis and tracheitis, especially among female employees. No alveolitis was observed. The finding of Bacillus subtilis in samples of ambient air and air-conditioner filters in conjunction with the presence of precipitating antibodies against crude extracts from these samples, suggested that the respiratory disorders might have been due to this microorganism. A multifactorial analysis demonstrated a statistically significant correlation between clinical symptoms and immunological disorders. The air-conditioner disease, therefore, may present as a benign condition.
[Selective mutism].

PubMed

Rogoll, J; Petzold, M; Ströhle, A

2018-05-01

Selective mutism was first described in the medical literature 140 years ago. The diagnosis came into the focus of adult psychiatry with the appearance of DSM-5. Henceforth, selective mutism during infancy, adolescence and also adulthood is specified as an independent anxiety disorder. It often begins in early childhood with a kind of speechlessness in certain situations. A diagnostic clarification often only takes place after school enrolment. Very often comorbid anxiety disorders, especially social phobia and depression also occur. The course is very variable and with some affected persons regression of the pathology occurs suddenly and completely and with others there is a slow regression of the symptoms. Equally the disorder can persist until adulthood. Whilst formerly a traumatic genesis was assumed, a multifactorial etiology with genetic, psychological and language-associated effects is nowadays presumed. The therapy is supported through psychotherapy, speech therapy and psychopharmacology.
Contribution of nonprimate animal models in understanding the etiology of schizophrenia

PubMed Central

Lazar, Noah L.; Neufeld, Richard W.J.; Cain, Donald P.

2011-01-01

Schizophrenia is a severe psychiatric disorder that is characterized by positive and negative symptoms and cognitive impairments. The etiology of the disorder is complex, and it is thought to follow a multifactorial threshold model of inheritance with genetic and neurodevelopmental contributions to risk. Human studies are particularly useful in capturing the richness of the phenotype, but they are often limited to the use of correlational approaches. By assessing behavioural abnormalities in both humans and rodents, nonprimate animal models of schizophrenia provide unique insight into the etiology and mechanisms of the disorder. This review discusses the phenomenology and etiology of schizophrenia and the contribution of current nonprimate animal models with an emphasis on how research with models of neurotransmitter dysregulation, environmental risk factors, neurodevelopmental disruption and genetic risk factors can complement the literature on schizophrenia in humans. PMID:21247514
Theories of Memory and Aging: A Look at the Past and a Glimpse of the Future

PubMed Central

Festini, Sara B.

2017-01-01

The present article reviews theories of memory and aging over the past 50 years. Particularly notable is a progression from early single-mechanism perspectives to complex multifactorial models proposed to account for commonly observed age deficits in memory function. The seminal mechanistic theories of processing speed, limited resources, and inhibitory deficits are discussed and viewed as especially important theories for understanding age-related memory decline. Additionally, advances in multivariate techniques including structural equation modeling provided new tools that led to the development of more complex multifactorial theories than existed earlier. The important role of neuroimaging is considered, along with the current prevalence of intervention studies. We close with predictions about new directions that future research on memory and aging will take. PMID:27257229
Autism-specific copy number variants further implicate the phosphatidylinositol signaling pathway and the glutamatergic synapse in the etiology of the disorder

PubMed Central

Cuscó, Ivon; Medrano, Andrés; Gener, Blanca; Vilardell, Mireia; Gallastegui, Fátima; Villa, Olaya; González, Eva; Rodríguez-Santiago, Benjamín; Vilella, Elisabet; Del Campo, Miguel; Pérez-Jurado, Luis A.

2009-01-01

Autism spectrum disorders (ASDs) constitute a group of severe neurodevelopmental conditions with complex multifactorial etiology. In order to explore the hypothesis that submicroscopic genomic rearrangements underlie some ASD cases, we have analyzed 96 Spanish patients with idiopathic ASD after extensive clinical and laboratory screening, by array comparative genomic hybridization (aCGH) using a homemade bacterial artificial chromosome (BAC) array. Only 13 of the 238 detected copy number alterations, ranging in size from 89 kb to 2.4 Mb, were present specifically in the autistic population (12 out of 96 individuals, 12.5%). Following validation by additional molecular techniques, we have characterized these novel candidate regions containing 24 different genes including alterations in two previously reported regions of chromosome 7 associated with the ASD phenotype. Some of the genes located in ASD-specific copy number variants act in common pathways, most notably the phosphatidylinositol signaling and the glutamatergic synapse, both known to be affected in several genetic syndromes related with autism and previously associated with ASD. Our work supports the idea that the functional alteration of genes in related neuronal networks is involved in the etiology of the ASD phenotype and confirms a significant diagnostic yield for aCGH, which should probably be included in the diagnostic workup of idiopathic ASD. PMID:19246517
Hyperbilirubinemia in Neonates: Types, Causes, Clinical Examinations, Preventive Measures and Treatments: A Narrative Review Article

PubMed Central

ULLAH, Sana; RAHMAN, Khaista; HEDAYATI, Mehdi

2016-01-01

Background: Hyperbilirubinemia, or jaundice, is a life threatening disorder in newborns. It is a multifactorial disorder with many symptoms. Generally, the physiological jaundice is the most prevalent type however in some regions pathological jaundice is also common. This review article focuses on a brief introduction to jaundice, its types and causes, measuring the bilirubin level, clinical approaches towards hyperbilirubinemia, different precautionary measures for the parents of babies suffering from hyperbilirubinemia and different remedial therapeutic measures for its treatment. Methods: The main databases including Scopus, Pubmed, MEDLINE, Google scholar and Science Direct were researched to obtain the original papers related to the newborns’ hyperbilirubinemia. The main terms used to literature search were “newborns’ hyperbilirubinemia”, “newborns’ jaundice”, “Physiological Jaundice” and “Patholigical Jaundice”. The timeframe included the obtained articles was from 1952 to 2015. Results: Neonatal jaundice due to breast milk feeding is also sometimes observed. Hemolytic jaundice occurs because of the incompatibility of blood groups with ABO and Rh factors, when the fetus and mother blood groups are not compatible and the fetus blood crosses the barrier of the umbilical cord before birth causing fetus blood hemolysis owing to severe immune response. Conclusion: Jaundice is easily diagnosable however require quick and on the spot treatment. If not treated properly, it leads to many complications. Currently the treatment options for jaundice include photo therapy, chemotherapy, and vaccinations. PMID:27398328
Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders.

PubMed

Rogers, R S

1997-12-01

Recurrent aphthous stomatitis (RAS), commonly known as canker sores, has been reported as recurrent oral ulcers, recurrent aphthous ulcers, or simple or complex aphthosis. RAS is the most common inflammatory ulcerative condition of the oral mucosa in North American patients. One of its variants is the most painful condition of the oral mucosa. Recurrent aphthous stomatitis has been the subject of active investigation along multiple lines of research, including epidemiology, immunology, clinical correlations, and therapy. Clinical evaluation of the patient requires correct diagnosis of RAS and classification of the disease based on morphology (MiAU, MjAU, HU) and severity (simple versus complex). The natural history of individual lesions of RAS is important, because it is the bench mark against which treatment benefits are measured. The lesions of RAS are not caused by a single factor but occur in an environment that is permissive for development of lesions. These factors include trauma, smoking, stress, hormonal state, family history, food hypersensitivity and infectious or immunologic factors. The clinician should consider these elements of a multifactorial process leading to the development of lesions of RAS. To properly diagnose and treat a patient with lesions of RAS, the clinician must identify or exclude associated systemic disorders or "correctable causes." Behçet's disease and complex aphthosis variants, such as ulcus vulvae acutum, mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome, fever, aphthosis, pharyngitis, and adenitis (FAPA) syndrome, and cyclic neutropenia, should be considered. The aphthous-like oral ulcerations of patients with human immunodeficiency virus (HIV) disease represent a challenging differential diagnosis. The association of lesions of RAS with hematinic deficiencies and gastrointestinal diseases provides an opportunity to identify a "correctable cause," which, with appropriate treatment, can result in a remission or substantial lessening of disease activity.
HOW EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE, OUTDOOR AIR POLLUTANTS,AND INCREASED POLLEN BURDENS INFLUENCES THE INCIDENCE OF ASTHMA

EPA Science Inventory

Asthma is a multifactorial airway disease that arises from a relatively common genetic background interphased with exposures to allergens and airborne irritants. The rapid rise in asthma over the past three decades in Western societies has been attributed to numerous diverse fact...
Fatigue and gynecologic cancer.

PubMed

Olt, George J

2003-02-01

Fatigue is common in women with gynecologic cancers and is thought to be multifactorial. Anemia, cachexia, pain, and depression are frequently associated with cancer and treatment-related fatigue and should be evaluated and treated. The National Comprehensive Cancer Network Fatigue Practice Guidelines are helpful in the assessment and treatment of women with gynecologic cancer-related fatigue.
Diverticular Disease: An Update on Pathogenesis and Management

PubMed Central

Rezapour, Mona; Ali, Saima

2018-01-01

Diverticular disease is one of the most common conditions in the Western world and one of the most common findings identified at colonoscopy. Recently, there has been a significant paradigm shift in our understanding of diverticular disease and its management. The pathogenesis of diverticular disease is thought to be multifactorial and include both environmental and genetic factors in addition to the historically accepted etiology of dietary fiber deficiency. Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome. Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some patients with SUDD, although their role(s) in preventing complications remain unclear. Antibiotic use for acute diverticulitis and elective prophylactic resection surgery are considered more individualized treatment modalities that take into account the clinical status, comorbidities and lifestyle of the patient. Our understanding of the pathogenesis of diverticular disease continues to evolve and is likely to be diverse and multifactorial. Paradigm shifts in several areas of the pathogenesis and management of diverticular disease are explored in this review. PMID:28494576
[Esophageal motor function of gastroesophageal reflux disease].

PubMed

Wang, Hong; Tian, Yuan; Ding, Yan

2010-08-01

To study the relationship between esophageal motor functional disorder [decreased lower esophageal sphincter pressure (LESP)and ineffective motility (IEM)] and gastroesophageal reflux disease (GERD). Totally 89 patients with GERD were enrolled in this study. All of them underwent 24-hour pH monitoring with dual-channel probe and stationary esophageal manometry. In addition, 77 of these patients underwent upper endoscopy. IEM and LES, 10 mmHg were common disturbances in patients with GERD (54% and 48%, respectively). The number of the acid reflux events of distal esophagus and prevalence of moderate or severe erosive esophagitis (EE) were significantly higher in patients with low LESP and IEM than patients without low LESP ( P<0.05). The number of the acid reflux events in distal esophagus was significantly correlated with the severity of esophagitis, distal esophagus amplitude, and LESP, while no such correlation was found between IEM and degree of esophageal acid exposure or esophagitis. The pathophysiology of GERD is probably multifactorial. Lower LESP or IEM is not a independent pathophysiological factor for GERD. However,one single factor is insufficient to explain all the pathogenic mechanism of GERD.
Mechanisms and management of dry eye in cataract surgery patients.

PubMed

Sutu, Christine; Fukuoka, Hideki; Afshari, Natalie A

2016-01-01

To provide a summary of the mechanisms that may cause dry eye after cataract surgery and discuss available and upcoming treatment modalities. Development or worsening of dry eye symptoms after cataract surgery is multifactorial with corneal nerve transection, inflammation, goblet cell loss, and meibomian gland dysfunction commonly cited as underlying disorders. With increasing awareness of the prevalence of dry eye disease, current surgical techniques are being analyzed for their contribution to the issue. Although many classic interventions, such as artificial tears and anti-inflammatory drops, remain first-line treatment options, they may not adequately address abnormalities of the tear film. The trend has been to create new drugs and technologies that target meibomian gland deficiencies and restore goblet cell numbers. Therapy for postoperative dry eye symptoms should be determined based on symptom severity and which underlying cause is most prominent at a given time. Patients with high-level risk factors for dry eye should be evaluated preoperatively to determine whether they have preexisting dry eye disease or if they are susceptible to developing disease after surgery.
Connective tissue ulcers.

PubMed

Dabiri, Ganary; Falanga, Vincent

2013-11-01

Connective tissue disorders (CTD), which are often also termed collagen vascular diseases, include a number of related inflammatory conditions. Some of these diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), localized scleroderma (morphea variants localized to the skin), Sjogren's syndrome, dermatomyositis, polymyositis, and mixed connective tissue disease. In addition to the systemic manifestations of these diseases, there are a number of cutaneous features that make these conditions recognizable on physical exam. Lower extremity ulcers and digital ulcers are an infrequent but disabling complication of long-standing connective tissue disease. The exact frequency with which these ulcers occur is not known, and the cause of the ulcerations is often multifactorial. Moreover, a challenging component of CTD ulcerations is that there are still no established guidelines for their diagnosis and treatment. The morbidity associated with these ulcerations and their underlying conditions is very substantial. Indeed, these less common but intractable ulcers represent a major medical and economic problem for patients, physicians and nurses, and even well organized multidisciplinary wound healing centers. Copyright © 2013 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.
A discussion of serum albumin level in advanced-stage hepatocellular carcinoma: a medical oncologist's perspective.

PubMed

Tanriverdi, Ozgur

2014-11-01

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and it is particularly prevalent in East and Southeast Asia. With surgical and/or local interventional treatment methods, survival rates for early-stage hepatocellular cancers have increased. However, it is not yet clear which staging systems are more applicable in hepatocellular carcinoma. Serum albumin level is already being used as a criterion in most staging systems. Albumin is an important serum protein in human bodily functions, but only 5 % of the daily amount needed is synthesized by the liver. The serum albumin level is affected by multifactorial situations, including capillary permeability, drugs, liver insufficiency, inflammation and/or infections, dehydration or overhydration, protein loosing disorders, and decreased nutrition intake in anorexia-malnutrition syndrome and cancer cachexia. Because of this complex situation, serum albumin level may affect many staging systems for hepatocellular carcinoma by leading to false-negative results. In this paper, the statuses of current staging systems are reviewed, and possible negative events regarding the serum albumin levels found in these staging systems are discussed.
Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis.

PubMed

Riancho, J; Gonzalo, I; Ruiz-Soto, M; Berciano, J

2016-02-04

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Although a small proportion of ALS cases are familial in origin and linked to mutations in specific genes, most cases are sporadic and have a multifactorial aetiology. Some recent studies have increased our knowledge of ALS pathogenesis and raised the question of whether this disorder is a proteinopathy, a ribonucleopathy, an axonopathy, or a disease related to the neuronal microenvironment. This article presents a review of ALS pathogenesis. To this end, we have reviewed published articles describing either ALS patients or ALS animal models and we discuss how the main cellular pathways (gene processing, protein metabolism, oxidative stress, axonal transport, relationship with neuronal microenvironment) may be involved in motor neurons degeneration. ALS pathogenesis has not been fully elucidated. Recent studies suggest that although initial triggers may differ among patients, the final motor neurons degeneration mechanisms are similar in most patients once the disease is fully established. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.
Polycystic ovarian syndrome: clinical and biological diagnosis.

PubMed

Bachelot, Anne

2016-12-01

Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. This syndrome leads to clinical hyperandrogenism and/or a biological dysovulation and infertility. Its diagnosis is based on consensual diagnostic criteria, but which are likely to change in the near future with the rise of the interest of new markers such as AMH. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. The exact etiology of PCOS is unknown and is likely multifactorial. Many studies indicate that PCOS results from originally ovarian abnormalities. In some patients, secondary hyperinsulinemia with insulin resistance plays a role in the pathophysiology. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject.

[Obstructive sleep apnea-hypopnea syndrome in children: beyond adenotonsillar hypertrophy].

PubMed

Esteller, Eduard

2015-01-01

The prevalence of obstructive sleep apnea-hypopnea syndrome in the general childhood population is 1-2% and the most common cause is adenotonsillar hypertrophy. However, beyond adenotonsillar hypertrophy, there are other highly prevalent causes of this syndrome in children. The causes are often multifactorial and include muscular hypotonia, dentofacial abnormalities, soft tissue hypertrophy of the airway, and neurological disorders). Collaboration between different specialties involved in the care of these children is essential, given the wide variability of conditions and how frequently different factors are involved in their genesis, as well as the different treatments to be applied. We carried out a wide literature review of other causes of obstructive sleep apnea-hypopnea syndrome in children, beyond adenotonsillar hypertrophy. We organised the prevalence of this syndrome in each pathology and the reasons that cause it, as well as their interactions and management, in a consistent manner. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.
Evaluation of post-surgical cognitive function and protein fingerprints in the cerebro-spinal fluid utilizing surface-enhanced laser Desorption/Ionization time-of-flight mass-spectrometry (SELDI-TOF MS) after coronary artery bypass grafting: review of proteomic analytic tools and introducing a new syndrome.

PubMed

Reis, H J; Wang, L; Verano-Braga, T; Pimenta, A M C; Kálmán, J; Bogáts, G; Babik, B; Vieira, L B; Teixeira, A L; Mukhamedyarov, M A; Zefirov, A L; Kiyasov, A P; Rizvanov, A A; Matin, K; Palotás, M; Guimarães, M M; Ferreira, C N; Yalvaç, M E; Janka, Z; Palotás, A

2011-01-01

Cognitive dysfunction following surgery is a common complication, which increases the incidence of other co-morbid conditions, hospital and health-care costs. The reported rate of the occurrence of post-operative cognitive decline varies with different studies, depending on population profile, type of surgery, definition of cognitive disorder and detection methods, design of study, etc. It remains unclear whether these psychiatric signs and symptoms are direct results of the effects of surgery or general anesthesia. Nonetheless they are more frequent after cardiac surgery and are likely to be multi-factorial, but the patho-mechanisms are not yet fully characterized. This communication provides a synopsis of proteomics tools and delineates novel SELDI-TOF results to evaluate biomarkers in this regard. Presented for the first time is a classification of the clinically relevant forms of post-operative cognitive decline with the advent of a novel subclass.
Burning mouth syndrome

PubMed Central

Gurvits, Grigoriy E; Tan, Amy

2013-01-01

Burning mouth syndrome is a debilitating medical condition affecting nearly 1.3 million of Americans. Its common features include a burning painful sensation in the mouth, often associated with dysgeusia and xerostomia, despite normal salivation. Classically, symptoms are better in the morning, worsen during the day and typically subside at night. Its etiology is largely multifactorial, and associated medical conditions may include gastrointestinal, urogenital, psychiatric, neurologic and metabolic disorders, as well as drug reactions. BMS has clear predisposition to peri-/post menopausal females. Its pathophysiology has not been fully elucidated and involves peripheral and central neuropathic pathways. Clinical diagnosis relies on careful history taking, physical examination and laboratory analysis. Treatment is often tedious and is aimed at correction of underlying medical conditions, supportive therapy, and behavioral feedback. Drug therapy with alpha lipoic acid, clonazepam, capsaicin, and antidepressants may provide symptom relief. Psychotherapy may be helpful. Short term follow up data is promising, however, long term prognosis with treatment is lacking. BMS remains an important medical condition which often places a recognizable burden on the patient and health care system and requires appropriate recognition and treatment. PMID:23429751
Burning mouth syndrome.

PubMed

Gurvits, Grigoriy E; Tan, Amy

2013-02-07

Burning mouth syndrome is a debilitating medical condition affecting nearly 1.3 million of Americans. Its common features include a burning painful sensation in the mouth, often associated with dysgeusia and xerostomia, despite normal salivation. Classically, symptoms are better in the morning, worsen during the day and typically subside at night. Its etiology is largely multifactorial, and associated medical conditions may include gastrointestinal, urogenital, psychiatric, neurologic and metabolic disorders, as well as drug reactions. BMS has clear predisposition to peri-/post menopausal females. Its pathophysiology has not been fully elucidated and involves peripheral and central neuropathic pathways. Clinical diagnosis relies on careful history taking, physical examination and laboratory analysis. Treatment is often tedious and is aimed at correction of underlying medical conditions, supportive therapy, and behavioral feedback. Drug therapy with alpha lipoic acid, clonazepam, capsaicin, and antidepressants may provide symptom relief. Psychotherapy may be helpful. Short term follow up data is promising, however, long term prognosis with treatment is lacking. BMS remains an important medical condition which often places a recognizable burden on the patient and health care system and requires appropriate recognition and treatment.
Holistic approach to prevention and management of type 2 diabetes mellitus in a family setting.

PubMed

Ofori, Sandra N; Unachukwu, Chioma N

2014-01-01

Diabetes mellitus (DM) is a chronic, progressive metabolic disorder with several complications that affect virtually all the systems in the human body. Type 2 DM (T2DM) is a major risk factor for cardiovascular disease (CVD). The management of T2DM is multifactorial, taking into account other major modifiable risk factors, like obesity, physical inactivity, smoking, blood pressure, and dyslipidemia. A multidisciplinary team is essential to maximize the care of individuals with DM. DM self-management education and patient-centered care are the cornerstones of management in addition to effective lifestyle strategies and pharmacotherapy with individualization of glycemic goals. Robust evidence supports the effectiveness of this approach when implemented. Individuals with DM and their family members usually share a common lifestyle that, not only predisposes the non-DM members to developing DM but also, increases their collective risk for CVD. In treating DM, involvement of the entire family, not only improves the care of the DM individual but also, helps to prevent the risk of developing DM in the family members.
JBP485 promotes tear and mucin secretion in ocular surface epithelia

PubMed Central

Nakamura, Takahiro; Hata, Yuiko; Nagata, Maho; Yokoi, Norihiko; Yamaguchi, Shumpei; Kaku, Taiichi; Kinoshita, Shigeru

2015-01-01

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES. PMID:25996902
JBP485 promotes tear and mucin secretion in ocular surface epithelia.

PubMed

Nakamura, Takahiro; Hata, Yuiko; Nagata, Maho; Yokoi, Norihiko; Yamaguchi, Shumpei; Kaku, Taiichi; Kinoshita, Shigeru

2015-05-21

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES.
Flavonoids with gastroprotective activity.

PubMed

Mota, Kelly Samara de Lira; Dias, Guilherme Eduardo Nunes; Pinto, Meri Emili Ferreira; Luiz-Ferreira, Anderson; Souza-Brito, Alba Regina Monteiro; Hiruma-Lima, Clélia Akiko; Barbosa-Filho, José Maria; Batista, Leônia Maria

2009-03-03

Peptic ulcers are a common disorder of the entire gastrointestinal tract that occurs mainly in the stomach and the proximal duodenum. This disease is multifactorial and its treatment faces great difficulties due to the limited effectiveness and severe side effects of the currently available drugs. The use of natural products for the prevention and treatment of different pathologies is continuously expanding throughout the world. This is particularly true with regards to flavonoids, which represent a highly diverse class of secondary metabolites with potentially beneficial human health effects that is widely distributed in the plant kingdom and currently consumed in large amounts in the diet. They display several pharmacological properties in the gastroprotective area, acting as anti-secretory, cytoprotective and antioxidant agents. Besides their action as gastroprotectives, flavonoids also act in healing of gastric ulcers and additionally these polyphenolic compounds can be new alternatives for suppression or modulation of peptic ulcers associated with H. pylori. In this review, we have summarized the literature on ninety-five flavonoids with varying degrees of antiulcerogenic activity, confirming that flavonoids have a therapeutic potential for the more effective treatment of peptic ulcers.
Dry eye disease: pathophysiology, classification, and diagnosis.

PubMed

Perry, Henry D

2008-04-01

Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface that results in eye discomfort, visual disturbance, and often ocular surface damage. Although recent research has made progress in elucidating DED pathophysiology, currently there are no uniform diagnostic criteria. This article discusses the normal anatomy and physiology of the lacrimal functional unit and the tear film; the pathophysiology of DED; DED etiology, classification, and risk factors; and DED diagnosis, including symptom assessment and the roles of selected diagnostic tests.
[Genetic factors in pathogenesis, course and treatment of inflammatory bowel diseases].

PubMed

Zatorski, Hubert; Sałaga, Maciej; Zielińska, Marta; Fichna, Jakub

2015-03-17

Inflammatory bowel diseases (IBD) are a group of chronic gastrointestinal disorders with alternating relapses and remissions. Two main types within IBD can be distinguished: Crohn's disease and ulcerative colitis. Considering the epidemiological, immunological and genetic data, it was concluded that IBD possess multifactorial etiology, where genetic and environmental factors form the immunological background for the disease. In this review we discuss the most important genes and their protein products in IBD etiology and their impact on IBD pharmacotherapy.
[Fetal programming and the etiology of osteoporosis].

PubMed

Pieńkowski, Wojciech; Wolski, Hubert; Drews, Krzysztof; Seremak-Mrozikiewicz, Agnieszka

2015-08-01

Osteoporosis is a multifactorial skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. Peak bone mass is an important predictor of later risk of osteoporosis. Epidemiological studies revealed that the risk of osteoporosis might be modified by exposure to environmental factors during intrauterine life and early postnatal period. This review summarizes the influence of fetal programming on the development of osteoporosis based on the epidemiological studies and potential mechanisms of epigenetic regulation of gene expression.
Impact of Ultraviolet Light on Vitiligo.

PubMed

Singh, Rasnik K

2017-01-01

Vitiligo is a disorder of the melanocytes that results in a dynamic spectrum of skin depigmentation. Its etiology is complex and multifactorial, with data supporting several different hypotheses. Given its prominent phenotype, vitiligo has a significant negative impact on quality of life. Coupled with the chronic and incurable nature of the disease, this presents a formidable treatment challenge. Several treatment modalities have been instituted over the years, with varying efficacy. This chapter focuses on the use of ultraviolet light in vitiligo as an established therapeutic option.
The determination factors of left-right asymmetry disorders- a short review.

PubMed

Catana, Andreea; Apostu, Adina Patricia

2017-01-01

Laterality defects in humans, situs inversus and heterotaxy, are rare disorders, with an incidence of 1:8000 to 1:10 000 in the general population, and a multifactorial etiology. It has been proved that 1.44/10 000 of all cardiac problems are associated with malformations of left-right asymmetry and heterotaxy accounts for 3% of all congenital heart defects. It is considered that defects of situs appear due to genetic and environmental factors. Also, there is evidence that the ciliopathies (defects of structure or function) are involved in development abnormalities. Over 100 genes have been reported to be involved in left-right patterning in model organisms, but only a few are likely to candidate for left-right asymmetry defects in humans. Left-right asymmetry disorders are genetically heterogeneous and have variable manifestations (from asymptomatic to serious clinical problems). The discovery of the right mechanism of left-right development will help explain the clinical complexity and may contribute to a therapy of these disorders.
The molecular mechanism of vitamin D action in attention-deficit/hyperactivity disorder: a review of current evidences.

PubMed

Saedisomeolia, Ahmad; Samadi, Mahsa; Gholami, Fatemeh; Seyedi, Marzieh; Effatpanah, Mohammad; Hashemi, Rezvan; Anvari, Siamand; Abdolahi, Mina; Djalali, Mahmoud; Honarvar, Niyaz Mohammadzadeh

2018-04-30

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder characterized by hyperactivity, impulsivity and inattention. Children with ADHD have challenges with learning, behavior and psychosocial adjustments retaining into adulthood. The exact etiology of ADHD is unknown and the pathophysiology of this disease is complex. Multifactorial hypotheses such as catecholaminergic and serotonergic systems disorders, neurotropic factors, some biological impairment with inflammatory and oxidative stress pathways are considered for ADHD. Some studies have shown that vitamin D level in children with ADHD is lower than healthy children; therefore, it may be involved in the pathogenesis of ADHD. Moreover, vitamin D has important effect on the inflammation, oxidative stress and some of neurotrophic factors and neurotransmitters; therefore, vitamin D supplementation may be effective in these children by facilitating dopaminergic and serotonergic function and some neurotrophic factors, as well as decreasing inflammation and oxidative stress. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
The spectrosome of occupational health problems

PubMed Central

de Gaudemaris, Régis; Bicout, Dominique J.

2018-01-01

Given the increased prevalence of cancer, respiratory diseases, and reproductive disorders, for which multifactorial origins are strongly suspected, the impact of the environment on the population represents a substantial public health challenge. Surveillance systems have become an essential public health decision-making tool. Networks have been constructed to facilitate the development of analyses of the multifactorial aspects of the relationships between occupational contexts and health. The aim of this study is to develop and present an approach for the optimal exploitation of observational databases to describe and improve the understanding of the (occupational) environment–health relationships, taking into account key multifactorial aspects. We have developed a spectral analysis (SA) approach that takes into account both the multi-exposure and dynamic natures of occupational health problems (OHPs) and related associations. The main results of this paper are to present the construction method of the “spectrum” and “spectrosome” of OHPs (range and structured list of occupational exposures) and describe the information contained therein with an illustrative example. The approach is illustrated using the case of non-Hodgkin lymphoma (NHL) from the French National Occupational Diseases Surveillance and Prevention Network database as a working example of an occupational disease. We found that the NHL spectrum includes 40 sets of occupational exposures characterized by important multi-exposures, especially solvent combinations or pesticide combinations, but also specific exposures such as polycyclic aromatic hydrocarbons, formaldehyde and ionizing radiation. These findings may be useful for surveillance and the assessment of occupational exposure related to health risks. PMID:29304043
Markers of Oxidative Stress and Neuroprogression in Depression Disorder

PubMed Central

Vaváková, Magdaléna; Trebatická, Jana

2015-01-01

Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed. PMID:26078821
Animal models of gene-environment interaction in schizophrenia: a dimensional perspective

PubMed Central

Ayhan, Yavuz; McFarland, Ross; Pletnikov, Mikhail V.

2015-01-01

Schizophrenia has long been considered as a disorder with multifactorial origins. Recent discoveries have advanced our understanding of the genetic architecture of the disease. However, even with the increase of identified risk variants, heritability estimates suggest an important contribution of non-genetic factors. Various environmental risk factors have been proposed to play a role in the etiopathogenesis of schizophrenia. These include season of birth, maternal infections, obstetric complications, adverse events at early childhood, and drug abuse. Despite the progress in identification of genetic and environmental risk factors, we still have a limited understanding of the mechanisms whereby gene-environment interactions (GxE) operate in schizophrenia and psychoses at large. In this review we provide a critical analysis of current animal models of GxE relevant to psychotic disorders and propose that dimensional perspective will advance our understanding of the complex mechanisms of these disorders. PMID:26510407
[Autism spectrum disorder: Etiological, diagnostic and therapeutic aspects].

PubMed

Reynoso, César; Rangel, María José; Melgar, Virgilio

2017-01-01

Autism spectrum disorder (ASD) was described for the first time in 1943 by Leo Kanner, and since 2004, 18 490 articles in the subject have been published, which in turn have been cited 48 416 times.1 Almost half of these publications come from the United States of America and the vast maority of the efforts to improve the quality of life of these patients have taken place in developed countries. This disorder consists of an inability to acquire social and emotional skills during early development that progressively results in variable degrees of social adaptation discapacity. The etiology is multifactorial and includes functional and structural neurological abnormalities, some of them with putative genetic and/or epigenetic origin. There is an alarming lack of knowledge in the subject among health care professionals. The purpose of this systematic review is to summarize the most relevant historical, diagnostic and therapeutic aspects of ASD.
[Female sexual dysfunction: Drug treatment options].

PubMed

Alcántara Montero, A; Sánchez Carnerero, C I

2016-01-01

Many women will likely experience a sexual problem in their lifetime. Female sexual dysfunction is a broad term used to describe 3 categories of disorders of a multifactorial nature. Effective, but limited pharmacotherapeutic options exist to address female sexual dysfunction. The FDA recently approved the first agent for treatment of hypoactive sexual desire disorder in pre-menopausal women. Off-label use of hormonal therapies, particularly oestrogen and testosterone, are the most widely employed for female sexual dysfunction, particularly in post-menopausal women. Other drugs currently under investigation include phosphodiesterase inhibitors and agents that modulate dopamine or melanocortin receptors. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Characterizing Sleep in Adolescents and Adults with Autism Spectrum Disorders.

PubMed

Goldman, S E; Alder, M L; Burgess, H J; Corbett, B A; Hundley, R; Wofford, D; Fawkes, D B; Wang, L; Laudenslager, M L; Malow, B A

2017-06-01

We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (4 weeks), and salivary cortisol and melatonin (4 days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors.

Characterizing Sleep in Adolescents and Adults with Autism Spectrum Disorders

PubMed Central

Goldman, SE; Alder, ML; Burgess, HJ; Corbett, BA; Hundley, R; Wofford, D; Fawkes, DB; Wang, L; Laudenslager, ML; Malow, BA

2017-01-01

We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (four weeks), and salivary cortisol and melatonin (four days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors. PMID:28286917
Temporomandibular Disorders (TMD) in Edentulous Patients: A Review and Proposed Classification (Dr. Bader’s Classification).

PubMed Central

2015-01-01

Temporomandibular disorders (TMD) are a collective term given to a number of clinical problems that involve the masticatory musculature, the temporomandibular joints and associated structures, or both. Although the aetiology of TMD has not been fully understood, in general it is considered to be multifactorial. The signs and symptoms of TMD which present in patients with natural teeth may also occur in edentulous patients. These symptoms may appear in various combinations and degrees. TMD has attained a prominent role within the context of dental care due to its high prevalence. The present paper is a review of the current literature on TMD in edentulous patients; with an attempt to propose a classification for the same. PMID:26023660
Outcome of dysthymic disorder at 5-year follow-up: the effect of familial psychopathology, early adversity, personality, comorbidity, and chronic stress.

PubMed

Hayden, E P; Klein, D N

2001-11-01

This study sought to identify predictors of course and outcome in dysthymic disorder. Eighty-six outpatients with early-onset dysthymic disorder (before age 21) participated in a prospective 5-year follow-up study. Family history of psychopathology, early home environment, axis I and II comorbidity, social support, and chronic stress were assessed at baseline. The Longitudinal Interval Follow-up Evaluation and the Hamilton Depression Rating Scale were used in the follow-up assessments conducted at 30 and 60 months. Comorbid anxiety disorder, cluster C and depressive personality features, and chronic stress were associated with a lower rate of recovery from dysthymic disorder, while family history of bipolar disorder was associated with a higher probability of recovery. Family history of dysthymic disorder, poor childhood maternal and paternal relationships, childhood sexual abuse, cluster C features, neuroticism, a history of anxiety and eating disorders, and chronic stress predicted higher levels of depression at follow-up. Multivariate models indicated that almost all domains contributed to the prediction of course and outcome. The course and outcome of dysthymic disorder is best conceptualized within a multifactorial framework, with family history of psychopathology, early adversity, axis I and II comorbidity, and chronic stress all making important contributions.
Surgical Intervention for Medically Refractory Hyperthyroidism.

PubMed

Knollman, Philip D; Giese, Ann; Bhayani, Mihir K

2016-05-01

Pediatric hyperthyroidism can be multifactorial, with Graves' disease (GD) being the most common etiology. Treatment focuses on identification of the cause of the hyperthyroidism and achieving a biochemical cure with symptom resolution. This article highlights the clinical presentation, diagnosis, and treatment of a pediatric patient with GD. [Pediatr Ann. 2016;45(5):e171-e175.]. Copyright 2016, SLACK Incorporated.
Molecular factors in migraine

PubMed Central

Kowalska, Marta; Prendecki, Michał; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

2016-01-01

Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) – are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1 and GRIA3. It is possible that migraine is a multifactorial disease with polygenic influence. Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack. The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease. PMID:27191890
Polyunsaturated Fatty Acids and Recurrent Mood Disorders: Phenomenology, Mechanisms, and Clinical Application

PubMed Central

Messamore, Erik; Almeida, Daniel M.; Jandacek, Ronald J.; McNamara, Robert K.

2017-01-01

A body of evidence has implicated dietary deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of recurrent mood disorders including major depressive disorder (MDD) and bipolar disorder. Cross-national and cross-sectional evidence suggests that greater habitual intake of n-3 PUFA is associated with reduced risk for developing mood symptoms. Meta-analyses provide strong evidence that patients with mood disorders exhibit low blood n-3 PUFA levels which are associated with increased risk for the initial development of mood symptoms in response to inflammation. While the etiology of this n-3 PUFA deficit may be multifactorial, n-3 PUFA supplementation is sufficient to correct this deficit and may also have antidepressant effects. Rodent studies suggest that n-3 PUFA deficiency during perinatal development can recapitulate key neuropathological, neurochemical, and behavioral features associated with mood disorders. Clinical neuroimaging studies suggest that low n-3 PUFA biostatus is associated with abnormalities in cortical structure and function also observed in mood disorders. Collectively, these findings implicate dietary n-3 PUFA insufficiency, particularly during development, in the pathophysiology of mood dysregulation, and support implementation of routine screening for and treatment of n-3 PUFA deficiency in patients with mood disorders. PMID:28069365
Maturity-onset diabetes of the young as a model for elucidating the multifactorial origin of type 2 diabetes mellitus.

PubMed

Horikawa, Yukio

2018-02-06

Maturity-onset diabetes of the young (MODY) is a form of diabetes classically characterized as having autosomal dominant inheritance, onset before the age of 25 years in at least one family member and partly preserved pancreatic β-cell function. The 14 responsible genes are reported to be MODY type 1~14, of which MODY 2 and 3 might be the most common forms. Although MODY is currently classified as diabetes of a single gene defect, it has become clear that mutations in rare MODYs, such as MODY 5 and MODY 6, have small mutagenic effects and low penetrance. In addition, as there are differences in the clinical phenotypes caused by the same mutation even in the same family, other phenotypic modifying factors are thought to exist; MODY could well have characteristics of type 2 diabetes mellitus, which is of multifactorial origin. Here, we outline the effects of genetic and environmental factors on the known phenotypes of MODY, focusing mainly on the examples of MODY 5 and 6, which have low penetrance, as suggestive models for elucidating the multifactorial origin of type 2 diabetes mellitus. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
Prevalence of sexual desire and satisfaction among patients with screen-detected diabetes and impact of intensive multifactorial treatment: results from the ADDITION-Denmark study.

PubMed

Pedersen, Mette B; Giraldi, Annamaria; Kristensen, Ellids; Lauritzen, Torsten; Sandbæk, Annelli; Charles, Morten

2015-03-01

Sexual problems are common in people with diabetes. It is unknown whether early detection of diabetes and subsequent intensive multifactorial treatment (IT) are associated with sexual health. We report the prevalence of low sexual desire and low sexual satisfaction among people with screen-detected diabetes and compare the impact of intensive multifactorial treatment with the impact of routine care (RC) on these measures. A cross-sectional analysis of the ADDITION-Denmark trial cohort six years post-diagnosis. 190 general practices around Denmark. A total of 968 patients with screen-detected type 2 diabetes. Low sexual desire and low sexual satisfaction. Mean (standard deviation, SD) age was 64.9 (6.9) years. The prevalence of low sexual desire was 53% (RC) and 54% (IT) among women, and 24% (RC) and 25% (IT) among men. The prevalence of low sexual satisfaction was 23% (RC) and 18% (IT) among women, and 27% (RC) and 37% (IT) among men. Among men, the prevalence of low sexual satisfaction was significantly higher in the IT group than in the RC group, p = 0.01. Low sexual desire and low satisfaction are frequent among men and women with screen-detected diabetes, and IT may negatively impact men's sexual satisfaction.
Prevalence of external ear disorders in Belgian stray cats.

PubMed

Bollez, Anouck; de Rooster, Hilde; Furcas, Alessandra; Vandenabeele, Sophie

2018-02-01

Objectives Feline otitis externa is a multifactorial dermatological disorder about which very little is known. The objective of this study was to map the prevalence of external ear canal disorders and the pathogens causing otitis externa in stray cats roaming around the region of Ghent, Belgium. Methods One hundred and thirty stray cats were randomly selected during a local trap-neuter-return programme. All cats were European Shorthairs. This study included clinical, otoscopic and cytological evaluation of both external ears of each cat. Prospective data used as parameters in this study included the sex, age and body condition score of each cat, as well as the presence of nasal and/or ocular discharge, and the results of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) Snap tests. Results Remarkably, very few (sub)clinical problems of the external ear canal were found in the stray cat population. Malassezia species was by far the most common organism found in the external ear canals of the 130 stray cats. A total of 96/130 (74%) cats were found to have Malassezia species organisms present in one or both ears based on the cytological examination. No correlation was found between the parameters of sex, age, body condition score, the presence of nasal and/or ocular discharge and FIV and FeLV status, and the presence of parasites, bacteria or yeasts. Conclusions and relevance This study provides more information about the normal state of the external ear canal of stray cats. The ears of most stray cats are relatively healthy. The presence of Malassezia species organisms in the external ear canal is not rare among stray cats.
Unique aspects of impulsive traits in substance use and overeating: specific contributions of common assessments of impulsivity.

PubMed

Beaton, Derek; Abdi, Hervé; Filbey, Francesca M

2014-11-01

Abstract Background: Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. Identify unique impulsivity traits specific to substance use and overeating. Impulsive Sensation Seeking (ImpSS) and Barratt's Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor analytic technique (discriminant correspondence analysis) to identify group-specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine (n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and CONTROLs (n = 37). A significant overall factor structure revealed three components of impulsivity that explained respectively 50.19% (pperm < 0.0005), 24.18% (pperm < 0.0005), and 15.98% (pperm < 0.0005) of the variance. All groups were significantly different from one another. When analyzed together, the BIS and ImpSS produce a multi-factorial structure that identified the impulsivity traits specific to these groups. The group specific traits are (1) CONTROL: low impulse, avoids thrill-seeking behaviors; (2) Marijuana: seeks mild sensation, is focused and attentive; (3) Marijuana + Nicotine: pursues thrill-seeking, lacks focus and attention; (4) Nicotine: lacks focus and planning; (5) Overeating: lacks focus, but plans (short and long term). Our results reveal impulsivity traits specific to each group. This may provide better criteria to define spectrums and trajectories - instead of categories - of symptoms for substance use and eating disorders. Defining symptomatic spectrums could be an important step forward in diagnostic strategies.
Unique aspects of impulsive traits in substance use and overeating: specific contributions of common assessments of impulsivity

PubMed Central

Beaton, Derek; Abdi, Hervé; Filbey, Francesca M.

2015-01-01

Background Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. Objectives Identify unique impulsivity traits specific to substance use and overeating. Methods Impulsive Sensation Seeking (ImpSS) and Barratt’s Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor analytic technique (discriminant correspondence analysis) to identify group-specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine (n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and Controls (n = 37). Results A significant overall factor structure revealed three components of impulsivity that explained respectively 50.19% (pperm<0.0005), 24.18% (pperm<0.0005), and 15.98% (pperm<0.0005) of the variance. All groups were significantly different from one another. When analyzed together, the BIS and ImpSS produce a multi-factorial structure that identified the impulsivity traits specific to these groups. The group specific traits are (1) Control: low impulse, avoids thrill-seeking behaviors; (2) Marijuana: seeks mild sensation, is focused and attentive; (3) Marijuana + Nicotine: pursues thrill-seeking, lacks focus and attention; (4) Nicotine: lacks focus and planning; (5) Overeating: lacks focus, but plans (short and long term). Conclusions Our results reveal impulsivity traits specific to each group. This may provide better criteria to define spectrums and trajectories – instead of categories – of symptoms for substance use and eating disorders. Defining symptomatic spectrums could be an important step forward in diagnostic strategies. PMID:25115831
Distinct Neuroanatomical Substrates and Cognitive Mechanisms of Figure Copy Performance in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia

ERIC Educational Resources Information Center

Possin, Katherine L.; Laluz, Victor R.; Alcantar, Oscar Z.; Miller, Bruce L.; Kramer, Joel H.

2011-01-01

Figure copy is the most common method of visual spatial assessment in dementia evaluations, but performance on this test may be multifactorial. We examined the neuroanatomical substrates of figure copy performance in 46 patients with Alzheimer's disease (AD) and 48 patients with the behavioral variant of Frontotemporal dementia (bvFTD). A group of…
Do reflex seizures and spontaneous seizures form a continuum? - triggering factors and possible common mechanisms.

PubMed

Irmen, Friederike; Wehner, Tim; Lemieux, Louis

2015-02-01

Recent changes in the understanding and classification of reflex seizures have fuelled a debate on triggering mechanisms of seizures and their conceptual organization. Previous studies and patient reports have listed extrinsic and intrinsic triggers, albeit their multifactorial and dynamic nature is poorly understood. This paper aims to review literature on extrinsic and intrinsic seizure triggers and to discuss common mechanisms among them. Among self-reported seizure triggers, emotional stress is most frequently named. Reflex seizures are typically associated with extrinsic sensory triggers; however, intrinsic cognitive or proprioceptive triggers have also been assessed. The identification of a trigger underlying a seizure may be more difficult if it is intrinsic and complex, and if triggering mechanisms are multifactorial. Therefore, since observability of triggers varies and triggers are also found in non-reflex seizures, the present concept of reflex seizures may be questioned. We suggest the possibility of a conceptual continuum between reflex and spontaneous seizures rather than a dichotomy and discuss evidence to the notion that to some extent most seizures might be triggered. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Value of ultrasonography in the diagnosis of polycystic ovary syndrome - literature review.

PubMed

Bachanek, Michał; Abdalla, Nebil; Cendrowski, Krzysztof; Sawicki, Włodzimierz

2015-12-01

Polycystic ovary syndrome is a multi-factorial disease. Its etiopathogenesis has not been elucidated in detail. It is the most common endocrine disorder in women of child-bearing age. This disease entity is primarily characterized by disrupted ovulation and hyperandrogenism, but the clinical picture can be diversified and symptom intensity can vary. Currently, the sonographic assessment of ovaries is one of the obligatory criteria for the diagnosis of PCOS according to the Rotterdam consensus (2003) and Androgen Excess & PCOS Society (2006). This criterion is determined by the presence of ≥12 follicles within the ovary with a diameter of 2-9 mm and/or ovarian volume ≥10 cm(3). Such an ultrasound image in one gonad only is sufficient to define polycystic ovaries. The coexistence of polycystic ovaries with polycystic ovary syndrome is confirmed in over 90% of cases irrespective of ethnic factors or race. However, because of the commonness of ultrasound features of polycystic ovaries in healthy women, the inclusion of this sign to the diagnostic criteria of polycystic ovary syndrome is still questioned. The development of new technologies has an undoubted influence on the percentage of diagnosed polycystic ovaries. This process has caused an increase in the percentage of polycystic ovary diagnoses since the Rotterdam criteria were published. It is therefore needed to prepare new commonly accepted diagnostic norms concerning the number of ovarian follicles and the standardization of the technique in which they are counted. The assessment of anti-Müllerian hormone levels as an equivalent of ultrasound features of polycystic ovaries is a promising method. However, analytic methods have to be standardized in order to establish commonly accepted diagnostic norms.
Value of ultrasonography in the diagnosis of polycystic ovary syndrome – literature review

PubMed Central

Abdalla, Nebil; Cendrowski, Krzysztof; Sawicki, Włodzimierz

2015-01-01

Polycystic ovary syndrome is a multi-factorial disease. Its etiopathogenesis has not been elucidated in detail. It is the most common endocrine disorder in women of child-bearing age. This disease entity is primarily characterized by disrupted ovulation and hyperandrogenism, but the clinical picture can be diversified and symptom intensity can vary. Currently, the sonographic assessment of ovaries is one of the obligatory criteria for the diagnosis of PCOS according to the Rotterdam consensus (2003) and Androgen Excess & PCOS Society (2006). This criterion is determined by the presence of ≥12 follicles within the ovary with a diameter of 2–9 mm and/or ovarian volume ≥10 cm3. Such an ultrasound image in one gonad only is sufficient to define polycystic ovaries. The coexistence of polycystic ovaries with polycystic ovary syndrome is confirmed in over 90% of cases irrespective of ethnic factors or race. However, because of the commonness of ultrasound features of polycystic ovaries in healthy women, the inclusion of this sign to the diagnostic criteria of polycystic ovary syndrome is still questioned. The development of new technologies has an undoubted influence on the percentage of diagnosed polycystic ovaries. This process has caused an increase in the percentage of polycystic ovary diagnoses since the Rotterdam criteria were published. It is therefore needed to prepare new commonly accepted diagnostic norms concerning the number of ovarian follicles and the standardization of the technique in which they are counted. The assessment of anti-Müllerian hormone levels as an equivalent of ultrasound features of polycystic ovaries is a promising method. However, analytic methods have to be standardized in order to establish commonly accepted diagnostic norms. PMID:26807298
Metabolic bone diseases during long-term total parenteral nutrition.

PubMed

Acca, M; Ragno, A; Francucci, C M; D'Erasmo, E

2007-01-01

Long-term total parenteral nutrition (TPN) is a procedure commonly applied to patients with advanced forms of intestinal malabsorption. Among TPN complications, bone metabolic diseases, such as osteoporosis and osteomalacia, are a common finding. Initially considered to be a manifestation of aluminium toxicity which followed massive contamination with the element of the solutions used in TPN, metabolic osteopathy during TPN is currently considered a multiform syndrome, with a multifactorial pathogenesis, which may manifest itself with vague or clear clinical pictures. In this review, we analyse clinical, pathogenetic, and therapeutic aspects of the most common bone metabolic diseases in patients undergoing long-term TPN.
Immunomodulation of enteric neural function in irritable bowel syndrome.

PubMed

O'Malley, Dervla

2015-06-28

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It's generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory function and pain sensitivity associated with IBS. However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. Anecdotally, IBS patients have noted that periods of stress can result in symptom flares and many patients exhibit co-morbid stress-related mood disorders such as anxiety and depression. However, in addition to psychosocial stressors, infection-related stress has also been linked with the initiation, persistence and severity of symptom flares. Indeed, prior gastrointestinal infection is one of the strongest predictors of developing IBS. Despite a lack of overt morphological inflammation, the importance of immune factors in the pathophysiology of IBS is gaining acceptance. Subtle changes in the numbers of mucosal immune cell infiltrates and elevated levels of circulating pro-inflammatory cytokines have been reproducibly demonstrated in IBS populations. Moreover, these immune mediators directly affect neural signalling. An exciting new area of research is the role of luminal microbiota in the modulation of neuro-immune signalling, resulting in local changes in gastrointestinal function and alterations in central neural functioning. Progress in this area has begun to unravel some of the complexities of neuroimmune and neuroendocrine interactions and how these molecular exchanges contribute to GI dysfunction.
Olfaction in Parkinson's disease and related disorders

PubMed Central

Doty, Richard L.

2012-01-01

Olfactory dysfunction is an early ‘pre-clinical’ sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology,or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances. PMID:22192366
Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research.

PubMed

Paraskevaidi, Maria; Martin-Hirsch, Pierre L; Kyrgiou, Maria; Martin, Francis L

2017-05-01

Mitochondrial diseases have been extensively investigated over the last three decades, but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases but also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat, as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell's functionality. Specifically, we suggest that environmental agents can cause damage in mitochondrial DNA and consequently lead to mutagenesis. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests, towards eliminating these maternally inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. Much effort is needed into further unravelling the relationship between xenobiotics and mitochondria, as the extent of influence in mitochondrial pathogenesis is increasingly recognised. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Celiac disease: From pathophysiology to treatment

PubMed Central

Parzanese, Ilaria; Qehajaj, Dorina; Patrinicola, Federica; Aralica, Merica; Chiriva-Internati, Maurizio; Stifter, Sanja; Elli, Luca; Grizzi, Fabio

2017-01-01

Celiac disease, also known as “celiac sprue”, is a chronic inflammatory disorder of the small intestine, produced by the ingestion of dietary gluten products in susceptible people. It is a multifactorial disease, including genetic and environmental factors. Environmental trigger is represented by gluten while the genetic predisposition has been identified in the major histocompatibility complex region. Celiac disease is not a rare disorder like previously thought, with a global prevalence around 1%. The reason of its under-recognition is mainly referable to the fact that about half of affected people do not have the classic gastrointestinal symptoms, but they present nonspecific manifestations of nutritional deficiency or have no symptoms at all. Here we review the most recent data concerning epidemiology, pathogenesis, clinical presentation, available diagnostic tests and therapeutic management of celiac disease. PMID:28573065

Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics.

PubMed

Cardno, A G; Gottesman, I I

2000-01-01

Twin studies have been vital for establishing an important genetic contribution to the etiology of schizophrenia. The five newest studies since 1995 from Europe and Japan have confirmed earlier findings. They yielded probandwise concordance rates of 41-65% in monozygotic (MZ) pairs and 0-28% in dizygotic (DZ) pairs, and heritability estimates of approximately 80-85%. Twin studies are also valuable for investigating the etiological relationships between schizophrenia and other disorders, and the genetic basis of clinical heterogeneity within schizophrenia. Studies of discordant MZ pairs provide further insights into non-inherited factors that contribute to the multifactorial etiology of this disorder. More recently, twin studies have begun to be used to directly investigate molecular genetic and epigenetic processes underlying schizophrenia. Copyright 2000 Wiley-Liss, Inc.
[The possibility of prenatal diagnosis of autism spectrum disorder].

PubMed

Vanya, Melinda; Szücs, Szabina; Szili, Károly; Vetró, Ágnes; Bártfai, György

2015-01-01

Autism spectrum disorder (ASD) is an idiopathic multifactorial disease. Chromosomal abnormalities could be found only in a few percent (0.3-0.6) of cases. The estimated prevalence is 0.6 in Europe and the prevalence of the disease has been increased in last few decades. ASD have an impact on the quality of life of the patient and his family. The early diagnosis of ASD is most important. There are limited data regarding the measure of biparietal diameter (BPD) of the fetus in the first trimester of pregnancy. These data suggested the BPD is an important screening marker for ASD, but the complex prenatal screening is unresolved. There is a need for further investigations of the genetic background of ASD and to identify potentially first trimester ultrasound markers for ASD.
The office management of ejaculatory disorders

PubMed Central

2016-01-01

Premature ejaculation (PE), delayed ejaculation (DE), anejaculation (AE) and retrograde ejaculation (RE) are four main ejaculatory disorders (EjDs) observed in clinical practice. Despite their high prevalence, EjDs remain underdiagnosed and undertreated. Primary care physicians should incorporate the discussion of sexual health topics into routine visits to facilitate EjD diagnosis and treatment. Because the causes of EjDs are multifactorial, the management of EjDs is etiology-specific and may require a holistic approach. Dapoxetine, a selective serotonin reuptake inhibitor, is the only drug approved for on-demand treatment of lifelong and acquired PE. In clinical practice, scheduled follow-up visits, risk factor treatment, appropriate dose escalation, adequate sexual attempts, patient education, and partner involvement are critical factors responsible for optimal overall management of PE and dapoxetine treatment outcomes. PMID:27652225
The office management of ejaculatory disorders.

PubMed

Jiann, Bang-Ping

2016-08-01

Premature ejaculation (PE), delayed ejaculation (DE), anejaculation (AE) and retrograde ejaculation (RE) are four main ejaculatory disorders (EjDs) observed in clinical practice. Despite their high prevalence, EjDs remain underdiagnosed and undertreated. Primary care physicians should incorporate the discussion of sexual health topics into routine visits to facilitate EjD diagnosis and treatment. Because the causes of EjDs are multifactorial, the management of EjDs is etiology-specific and may require a holistic approach. Dapoxetine, a selective serotonin reuptake inhibitor, is the only drug approved for on-demand treatment of lifelong and acquired PE. In clinical practice, scheduled follow-up visits, risk factor treatment, appropriate dose escalation, adequate sexual attempts, patient education, and partner involvement are critical factors responsible for optimal overall management of PE and dapoxetine treatment outcomes.
Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies.

PubMed

Ahluwalia, Bani; Moraes, Luiza; Magnusson, Maria K; Öhman, Lena

2018-04-01

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with a multifactorial pathophysiology. Full comprehension of IBD pathology is still out of reach and, therefore, treatment is far from ideal. Nevertheless, components involved in IBD pathogenesis including environmental, genetic, microbial, and immunological factors are continuously being investigated and the improved knowledge contributes to the development of new therapies. In this article we review the aspects of the immunopathogenesis of IBD, with focus on mucosal immunity, and discuss mechanisms of action for current and emerging biological therapies.
Molecular mechanisms underlying osteoarthritis development: Notch and NF-κB.

PubMed

Saito, Taku; Tanaka, Sakae

2017-05-15

Osteoarthritis (OA) is a multi-factorial and highly prevalent joint disorder worldwide. Since the establishment of murine surgical knee OA models in 2005, many of the key molecules and signalling pathways responsible for OA development have been identified. Here we review the roles of two multi-functional signalling pathways in OA development: Notch and nuclear factor kappa-light-chain-enhancer of activated B cells. Previous studies have identified various aspects of articular chondrocyte regulation by these pathways. However, comprehensive understanding of the molecular networks regulating articular cartilage homeostasis and OA pathogenesis is needed.
Pregnancy-associated transient osteoporosis of the hip: results of a case-control study.

PubMed

Hadji, Peyman; Boekhoff, Jelena; Hahn, Melitta; Hellmeyer, Lars; Hars, Olaf; Kyvernitakis, Ioannis

2017-12-01

The etiology and underlying mechanisms of transient of osteoporosis of the hip (TOH) during pregnancy are still unclear, since no systematic analyses exist. Our results support the hypothesis that TOH is a multifactorial disease, which is associated with immobility, dental problems, and lack of exercise in childhood. Pregnancy-associated transient osteoporosis of the hip (TOH) is a rare but severe form of osteoporosis, which may affect a subgroup of women in the last trimester of pregnancy or immediately postpartum. Common symptoms include acute pain of the hip(s) due to bone marrow edema or even hip fractures. The exact underlining mechanisms of this disorder are still unknown since no published systematic analyses exist. Out of a total of 52 TOH patients, 33 TOH patients could be matched with 33 healthy controls according to age, region, and gravity. The aim of this retrospective case-control study was to evaluate the risk factors for TOH in a homogenous population of women. The baseline characteristics of the two study groups were similar. Overall, 12.1% of the TOH patients sustained a hip fracture. Expectedly, 90.9% of the TOH patients complained about pain of the hip (p ≤ 0.001). TOH patients suffered more frequently from severe dental problems during childhood (p = 0.023) and performed less often sports before and after puberty (p ≤ 0.001), whereas the frequency of immobilization during pregnancy was threefold higher compared to the control group (p = 0.007). We found a significant increase of the TOH risk in patients with dental problems in childhood (OR 3.7; CI 1.3-10.7) as well as in patients with lack of exercise during childhood (OR 4.2; CI 1.3-12.9). Our results support the hypothesis that pregnancy-associated TOH is a multifactorial disease, to which several individual factors may contribute. Hereby, we found significant associations with immobility, dental problems, and lack of exercise in childhood.
Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3.

PubMed

Williams, Nigel M; Franke, Barbara; Mick, Eric; Anney, Richard J L; Freitag, Christine M; Gill, Michael; Thapar, Anita; O'Donovan, Michael C; Owen, Michael J; Holmans, Peter; Kent, Lindsey; Middleton, Frank; Zhang-James, Yanli; Liu, Lu; Meyer, Jobst; Nguyen, Thuy Trang; Romanos, Jasmin; Romanos, Marcel; Seitz, Christiane; Renner, Tobias J; Walitza, Susanne; Warnke, Andreas; Palmason, Haukur; Buitelaar, Jan; Rommelse, Nanda; Vasquez, Alejandro Arias; Hawi, Ziarih; Langley, Kate; Sergeant, Joseph; Steinhausen, Hans-Christoph; Roeyers, Herbert; Biederman, Joseph; Zaharieva, Irina; Hakonarson, Hakon; Elia, Josephine; Lionel, Anath C; Crosbie, Jennifer; Marshall, Christian R; Schachar, Russell; Scherer, Stephen W; Todorov, Alexandre; Smalley, Susan L; Loo, Sandra; Nelson, Stanley; Shtir, Corina; Asherson, Philip; Reif, Andreas; Lesch, Klaus-Peter; Faraone, Stephen V

2012-02-01

Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. The authors performed a genome-wide analysis of large, rare CNVs (<1% population frequency) in children with ADHD (N=896) and comparison subjects (N=2,455) from the IMAGE II Consortium. The authors observed 1,562 individually rare CNVs >100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology.
Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3

PubMed Central

Franke, Barbara; Mick, Eric; Anney, Richard J.L.; Freitag, Christine M.; Gill, Michael; Thapar, Anita; O'Donovan, Michael C.; Owen, Michael J.; Holmans, Peter; Kent, Lindsey; Middleton, Frank; Zhang-James, Yanli; Liu, Lu; Meyer, Jobst; Nguyen, Thuy Trang; Romanos, Jasmin; Romanos, Marcel; Seitz, Christiane; Renner, Tobias J.; Walitza, Susanne; Warnke, Andreas; Palmason, Haukur; Buitelaar, Jan; Rommelse, Nanda; Vasquez, Alejandro Arias; Hawi, Ziarih; Langley, Kate; Sergeant, Joseph; Steinhausen, Hans-Christoph; Roeyers, Herbert; Biederman, Joseph; Zaharieva, Irina; Hakonarson, Hakon; Elia, Josephine; Lionel, Anath C.; Crosbie, Jennifer; Marshall, Christian R.; Schachar, Russell; Scherer, Stephen W.; Todorov, Alexandre; Smalley, Susan L.; Loo, Sandra; Nelson, Stanley; Shtir, Corina; Asherson, Philip; Reif, Andreas; Lesch, Klaus-Peter

2012-01-01

Objective: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. Method: The authors performed a genome-wide analysis of large, rare CNVs (<1% population frequency) in children with ADHD (N=896) and comparison subjects (N=2,455) from the IMAGE II Consortium. Results: The authors observed 1,562 individually rare CNVs >100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. Conclusions: These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology. PMID:22420048
Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches

PubMed Central

Balmus, Ioana Miruna; Dobrin, Romeo; Timofte, Daniel

2016-01-01

The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context. PMID:27563374
Subthreshold Psychiatric Psychopathology in Functional Gastrointestinal Disorders: Can It Be the Bridge between Gastroenterology and Psychiatry?

PubMed Central

Nisita, Cristiana; Cortopassi, Sonia; Corretti, Giorgio; Gambaccini, Dario; De Bortoli, Nicola; Fani, Bernardo; Simonetti, Natalia; Ricchiuti, Angelo; Dell'Osso, Liliana; Marchi, Santino; Bellini, Massimo

2017-01-01

Background and Aims Functional gastrointestinal disorders (FGDs) are multifactorial disorders of the gut-brain interaction. This study investigated the prevalence of Axis I and spectrum disorders in patients with FGD and established the link between FGDs and psychopathological dimensions. Methods A total of 135 consecutive patients with FGD were enrolled. The symptoms' severity was evaluated using questionnaires, while the psychiatric evaluation by clinical interviews established the presence/absence of mental (Diagnostic and Statistical Manual—4th edition, Axis I Diagnosis) or spectrum disorders. Results Of the 135 patients, 42 (32.3%) had functional dyspepsia, 52 (40.0%) had irritable bowel syndrome, 21 (16.2%) had functional bloating, and 20 (15.4%) had functional constipation. At least one psychiatric disorder was present in 46.9% of the patients, while a suprathreshold panic spectrum was present in 26.2%. Functional constipation was associated with depressive disorders (p < 0.05), while functional dyspepsia was related to the current major depressive episode (p < 0.05). Obsessive-compulsive spectrum was correlated with the presence of functional constipation and irritable bowel syndrome (p < 0.05). Conclusion The high prevalence of subthreshold psychiatric symptomatology in patients with FGD, which is likely to influence the expression of gastrointestinal symptoms, suggested the usefulness of psychological evaluation in patients with FGDs. PMID:29213280
Spinal epidural hematomas: personal experience and literature review of more than 1000 cases.

PubMed

Domenicucci, Maurizio; Mancarella, Cristina; Santoro, Giorgio; Dugoni, Demo Eugenio; Ramieri, Alessandro; Arezzo, Maria Felice; Missori, Paolo

2017-08-01

OBJECTIVE The goal of this study was to identify factors that contribute to the formation of acute spinal epidural hematoma (SEH) by correlating etiology, age, site, clinical status, and treatment with immediate results and long-term outcomes. METHODS The authors reviewed their series of 15 patients who had been treated for SEH between 1996 and 2012. In addition, the authors reviewed the relevant international literature from 1869 (when SEH was first described) to 2012, collecting a total of 1010 cases. Statistical analysis was performed in 959 (95%) cases that were considered valid for assessing the incidence of age, sex, site, and clinical status at admission, correlating each of these parameters with the treatment results. Statistical analysis was also performed in 720 (71.3%) cases to study the incidence of etiological factors that favor SEH formation: coagulopathy, trauma, spinal puncture, pregnancy, and multifactorial disorders. The clinical status at admission and long-term outcome were studied for each group. Clinical status was assessed using the Neuro-Grade (NG) scale. RESULTS The mean patient age was 47.97 years (range 0-91 years), and a significant proportion of patients were male (60%, p < 0.001). A bimodal distribution has been reported for age at onset with peaks in the 2nd and 6th decades of life. The cause of the SEH was not reported in 42% of cases. The etiology concerned mainly iatrogenic factors (18%), such as coagulopathy or spinal puncture, rather than noniatrogenic factors (29%), such as genetic or metabolic coagulopathy, trauma, and pregnancy. The etiology was multifactorial in 11.1% of cases. The most common sites for SEH were C-6 (n = 293, 31%) and T-12 (n = 208, 22%), with maximum extension of 6 vertebral bodies in 720 cases (75%). At admission, 806 (84%) cases had moderate neurological impairment (NG 2 or 3), and only lumbar hematoma was associated with a good initial clinical neurological status (NG 0 or 1). Surgery was performed in 767 (80%) cases. Mortality was greater in patients older than 40 years of age (9%; p < 0.01). Sex did not influence any of these data (p > 0.05). CONCLUSIONS Factors that contribute to the formation of acute SEH are iatrogenic, not iatrogenic, or multifactorial. The treatment of choice is surgery, and the results of treatment are influenced by the patient's clinical and neurological status at admission, age, and the craniocaudal site.
[Sleep bruxism in children and adolescents].

PubMed

Firmani, Mónica; Reyes, Milton; Becerra, Nilda; Flores, Guillermo; Weitzman, Mariana; Espinosa, Paula

2015-01-01

Bruxism is a rhythmic masticatory muscle activity, characterized by teeth grinding and clenching. This is a phenomenon mainly regulated by the central nervous system and peripherally influenced. It has two circadian manifestations, during sleep (sleep bruxism) and awake states (awake bruxism). Bruxism is much more than just tooth wearing. It is currently linked to orofacial pain; headaches; sleep disorders; sleep breathing disorders, such as apnea and hypopnea sleep syndrome; behavior disorders, or those associated with the use of medications. It is also influenced by psycho-social and behavior factors, which means that oromandibular parafunctional activities, temporomandibular disorders, malocclusion, high levels of anxiety and stress, among others, may precipitate the occurrence of bruxism. Nowadays, its etiology is multifactorial. The dentist and the pediatrician are responsible for its early detection, diagnosis, management, and prevention of its possible consequences on the patients. The aim of this review is to update the concepts of this disease and to make health professionals aware of its early detection and its timely management. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
A Network Approach to Environmental Impact in Psychotic Disorder: Brief Theoretical Framework.

PubMed

Isvoranu, Adela-Maria; Borsboom, Denny; van Os, Jim; Guloksuz, Sinan

2016-07-01

The spectrum of psychotic disorder represents a multifactorial and heterogeneous condition and is thought to result from a complex interplay between genetic and environmental factors. In the current paper, we analyze this interplay using network analysis, which has been recently proposed as a novel psychometric framework for the study of mental disorders. Using general population data, we construct network models for the relation between 3 environmental risk factors (cannabis use, developmental trauma, and urban environment), dimensional measures of psychopathology (anxiety, depression, interpersonal sensitivity, obsessive-compulsive disorder, phobic anxiety, somatizations, and hostility), and a composite measure of psychosis expression. Results indicate the existence of specific paths between environmental factors and symptoms. These paths most often involve cannabis use. In addition, the analyses suggest that symptom networks are more strongly connected for people exposed to environmental risk factors, implying that environmental exposure may lead to less resilient symptom networks. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Rhythm and mood: relationships between the circadian clock and mood-related behavior.

PubMed

Schnell, Anna; Albrecht, Urs; Sandrelli, Federica

2014-06-01

Mood disorders are multifactorial and heterogeneous diseases caused by the interplay of several genetic and environmental factors. In humans, mood disorders are often accompanied by abnormalities in the organization of the circadian system, which normally synchronizes activities and functions of cells and tissues. Studies on animal models suggest that the basic circadian clock mechanism, which runs in essentially all cells, is implicated in the modulation of biological phenomena regulating affective behaviors. In particular, recent findings highlight the importance of the circadian clock mechanisms in neurological pathways involved in mood, such as monoaminergic neurotransmission, hypothalamus-pituitary-adrenal axis regulation, suprachiasmatic nucleus and olfactory bulb activities, and neurogenesis. Defects at the level of both, the circadian clock mechanism and system, may contribute to the etiology of mood disorders. Modification of the circadian system using chronotherapy appears to be an effective treatment for mood disorders. Additionally, understanding the role of circadian clock mechanisms, which affect the regulation of different mood pathways, will open up the possibility for targeted pharmacological treatments. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Cognitive Dysfunction, Affective States, and Vulnerability to Nicotine Addiction: A Multifactorial Perspective

PubMed Central

Besson, Morgane; Forget, Benoît

2016-01-01

Although smoking prevalence has declined in recent years, certain subpopulations continue to smoke at disproportionately high rates and show resistance to cessation treatments. Individuals showing cognitive and affective impairments, including emotional distress and deficits in attention, memory, and inhibitory control, particularly in the context of psychiatric conditions, such as attention-deficit hyperactivity disorder, schizophrenia, and mood disorders, are at higher risk for tobacco addiction. Nicotine has been shown to improve cognitive and emotional processing in some conditions, including during tobacco abstinence. Self-medication of cognitive deficits or negative affect has been proposed to underlie high rates of tobacco smoking among people with psychiatric disorders. However, pre-existing cognitive and mood disorders may also influence the development and maintenance of nicotine dependence, by biasing nicotine-induced alterations in information processing and associative learning, decision-making, and inhibitory control. Here, we discuss the potential forms of contribution of cognitive and affective deficits to nicotine addiction-related processes, by reviewing major clinical and preclinical studies investigating either the procognitive and therapeutic action of nicotine or the putative primary role of cognitive and emotional impairments in addiction-like features. PMID:27708591
Diabetes and the Esophagus.

PubMed

Monreal-Robles, Roberto; Remes-Troche, José M

2017-12-01

Chronic hyperglycemia is a well-known cause of gastrointestinal motility disorders extending from the esophagus to the anorectum. Even though little attention has been paid to esophageal disorders in the context of DM, its prevalence is higher compared to gastroparesis. Heartburn, as a typical symptom of gastroesophageal reflux disease (GERD), is the most prevalent symptom and has been found in 25 to 41% of patients with DM. Furthermore, DM has recently been established as possible independent factor for the development of Barrett's esophagus. The pathophysiology of esophageal disorders in patients with DM is complex and multifactorial, and the mechanisms described include the following: hyperglycemia, autonomic neuropathy, biomechanical and sensory alterations of the esophagus, presbyesophagus, and psychiatric comorbidity. Opportune detection, together with adequate glycemic control, can delay the onset of esophageal dysfunction and slow its progression in diabetic patients. There is limited evidence on patients with DM and esophageal dysfunction, with respect to medical treatment. Lifestyle modifications, prokinetics, and proton pump inhibitors should be indicated on an individual basis in patients that present with DM and esophageal disorders. A greater number of improved studies are needed to develop new therapeutic strategies. This chapter will review esophageal disorders associated with DM and the currently available treatment options.
[Gap junctions: A new therapeutic target in major depressive disorder?].

PubMed

Sarrouilhe, D; Dejean, C

2015-11-01

Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Patellofemoral pain syndrome in female athletes: A review of diagnoses, etiology and treatment options.

PubMed

Vora, Molly; Curry, Emily; Chipman, Amanda; Matzkin, Elizabeth; Li, Xinning

2017-12-14

Patellofemoral pain syndrome (PFPS) is one of the most common causes of knee pain and is present in females disproportionately more relative to males. PFPS causes tend to be multifactorial in nature and are described in this review. From a review of the current literature, it is clear that there needs to be further research on PFPS in order to better understand the complex etiology of this disorder in both males and females. It is known that females with patellofemoral pain syndrome demonstrate a decrease in abduction, external rotation and extension strength of the affected side compared with healthy patients. Conservative management, including optimizing muscle balance between the vastus medialis and lateralis around the patella along with formal therapy should be the first line of treatment in patients presenting with PFPS. Surgery should be reserved for patients in which all conservative management options have failed. This review aims to guide physicians in accurate clinicaldecision making regarding conservative and surgical treatment options when specifically faced with PFPS in a female athlete. Furthermore, we will discuss the anatomic variants, incidence and prevalence, etiology, diagnosis and treatment of PFPS.
Altered E-Cadherin Levels and Distribution in Melanocytes Precede Clinical Manifestations of Vitiligo.

PubMed

Wagner, Roselyne Y; Luciani, Flavie; Cario-André, Muriel; Rubod, Alain; Petit, Valérie; Benzekri, Laila; Ezzedine, Khaled; Lepreux, Sébastien; Steingrimsson, Eirikur; Taieb, A; Gauthier, Yvon; Larue, Lionel; Delmas, Véronique

2015-07-01

Vitiligo is the most common depigmenting disorder resulting from the loss of melanocytes from the basal epidermal layer. The pathogenesis of the disease is likely multifactorial and involves autoimmune causes, as well as oxidative and mechanical stress. It is important to identify early events in vitiligo to clarify pathogenesis, improve diagnosis, and inform therapy. Here, we show that E-cadherin (Ecad), which mediates the adhesion between melanocytes and keratinocytes in the epidermis, is absent from or discontinuously distributed across melanocyte membranes of vitiligo patients long before clinical lesions appear. This abnormality is associated with the detachment of the melanocytes from the basal to the suprabasal layers in the epidermis. Using human epidermal reconstructed skin and mouse models with normal or defective Ecad expression in melanocytes, we demonstrated that Ecad is required for melanocyte adhesiveness to the basal layer under oxidative and mechanical stress, establishing a link between silent/preclinical, cell-autonomous defects in vitiligo melanocytes and known environmental stressors accelerating disease expression. Our results implicate a primary predisposing skin defect affecting melanocyte adhesiveness that, under stress conditions, leads to disappearance of melanocytes and clinical vitiligo. Melanocyte adhesiveness is thus a potential target for therapy aiming at disease stabilization.

[Physiopathology of overactive bladder syndrome].

PubMed

Sacco, Emilio

2012-01-01

The pathophysiology of OAB is complex, multifactorial and still largely unknown. Several pathophysiological mechanisms have been highlighted that may play a different role in different patient groups. There are now experimental evidences that support both the myogenic and neurogenic hypothesis, but in recent years the "integrative" hypothesis has been gaining more and more acceptance, where a disruption in the multiple interactions between different cell types (neurons, urothelium, interstitial cells, myocytes) and network functions represent a central element of lower urinary tract dysfunctions. Of utmost importance, a disorder in the urothelial sensory function and in the urothelial/suburothelial non-neural cholinergic system, favored by age and comorbidities, appears to be crucial for the development of the OAB. Neuroplastic and detrusor changes in OAB are broadly similar to those observed in bladders exposed to outlet obstruction, neuropathies, inflammation or aging, and may be driven by a common urothelial dysfunction. Several signaling substances and their receptors were found to be involved in central pathways of bidirectional communication between the different cell types in the bladder, and were shown to be modified in several animal models of OAB as well as in human models, indicating new potential therapeutic targets.
Use of Integrative Medicine in the United States Military Health System

PubMed Central

Vaughan, Megan; Koehlmoos, Tracey Pérez

2017-01-01

Integrative medicine (IM) is a model of care which uses both conventional and nonconventional therapies in a “whole person” approach to achieve optimum mental, physical, emotional, spiritual, and environmental health, and is increasingly popular among patients and providers seeking to relieve chronic or multifactorial conditions. The US Department of Defense (DoD) shows particular interest in and usage of IM for managing chronic conditions including the signature “polytrauma triad” of chronic pain, traumatic brain injury (TBI), and posttraumatic stress disorder (PTSD) among its beneficiaries in the Military Health System (MHS). These modalities range from conventional nondrug, nonsurgical options such as cognitive-behavioral therapy to nonconventional options such as acupuncture, chiropractic, and mind-body techniques. These are of particular interest for their potential to relieve symptoms without relying on opiates, which impair performance and show high potential for abuse while often failing to provide full relief. This review describes the use of IM in the MHS, including definitions of the model, common therapies and potential for use, and controversy surrounding the practice. More research is needed to build a comprehensive usage analysis, which in turn will inform sound clinical and financial practice for the MHS and its beneficiaries. PMID:28690665
Patellofemoral pain syndrome in female athletes: A review of diagnoses, etiology and treatment options

PubMed Central

Vora, Molly; Curry, Emily; Chipman, Amanda; Matzkin, Elizabeth; Li, Xinning

2018-01-01

Patellofemoral pain syndrome (PFPS) is one of the most common causes of knee pain and is present in females disproportionately more relative to males. PFPS causes tend to be multifactorial in nature and are described in this review. From a review of the current literature, it is clear that there needs to be further research on PFPS in order to better understand the complex etiology of this disorder in both males and females. It is known that females with patellofemoral pain syndrome demonstrate a decrease in abduction, external rotation and extension strength of the affected side compared with healthy patients. Conservative management, including optimizing muscle balance between the vastus medialis and lateralis around the patella along with formal therapy should be the first line of treatment in patients presenting with PFPS. Surgery should be reserved for patients in which all conservative management options have failed. This review aims to guide physicians in accurate clinicaldecision making regarding conservative and surgical treatment options when specifically faced with PFPS in a female athlete. Furthermore, we will discuss the anatomic variants, incidence and prevalence, etiology, diagnosis and treatment of PFPS. PMID:29564075
From Omics to Drug Metabolism and High Content Screen of Natural Product in Zebrafish: A New Model for Discovery of Neuroactive Compound

PubMed Central

Hung, Ming Wai; Zhang, Zai Jun; Li, Shang; Lei, Benson; Yuan, Shuai; Cui, Guo Zhen; Man Hoi, Pui; Chan, Kelvin; Lee, Simon Ming Yuen

2012-01-01

The zebrafish (Danio rerio) has recently become a common model in the fields of genetics, environmental science, toxicology, and especially drug screening. Zebrafish has emerged as a biomedically relevant model for in vivo high content drug screening and the simultaneous determination of multiple efficacy parameters, including behaviour, selectivity, and toxicity in the content of the whole organism. A zebrafish behavioural assay has been demonstrated as a novel, rapid, and high-throughput approach to the discovery of neuroactive, psychoactive, and memory-modulating compounds. Recent studies found a functional similarity of drug metabolism systems in zebrafish and mammals, providing a clue with why some compounds are active in zebrafish in vivo but not in vitro, as well as providing grounds for the rationales supporting the use of a zebrafish screen to identify prodrugs. Here, we discuss the advantages of the zebrafish model for evaluating drug metabolism and the mode of pharmacological action with the emerging omics approaches. Why this model is suitable for identifying lead compounds from natural products for therapy of disorders with multifactorial etiopathogenesis and imbalance of angiogenesis, such as Parkinson's disease, epilepsy, cardiotoxicity, cerebral hemorrhage, dyslipidemia, and hyperlipidemia, is addressed. PMID:22919414
Diet and Inflammation: Possible Effects on Immunity, Chronic Diseases, and Life Span.

PubMed

Ricordi, Camillo; Garcia-Contreras, Marta; Farnetti, Sara

2015-01-01

Chronic inflammation negatively impacts all physiological functions, causing an array of degenerative conditions including diabetes; cancer; cardiovascular, osteo-articular, and neurodegenerative diseases; autoimmunity disorders; and aging. In particular, there is a growing knowledge of the role that gene transcription factors play in the inflammatory process. Obesity, metabolic syndrome, and diabetes represent multifactorial conditions resulting from improper balances of hormones and gene expression. In addition, these conditions have a strong inflammatory component that can potentially be impacted by the diet. It can reduce pro-inflammatory eicosanoids that can alter hormonal signaling cascades to the modulation of the innate immune system and gene transcription factors. Working knowledge of the impact of how nutrients, especially dietary fatty acids and polyphenols, can impact these various molecular targets makes it possible to develop a general outline of an anti-inflammatory diet that offers a unique, nonpharmacological approach in treating obesity, metabolic syndrome, and diabetes. Several important bioactive dietary components can exert their effect through selected inflammatory pathways that can affect metabolic and genetic changes. In fact, dietary components that can modulate glucose and insulin levels, as well as any other mediator that can activate nuclear factor-kB, can also trigger inflammation through common pathway master switches.
Cholinesterase and Prolyl Oligopeptidase Inhibitory Activities of Alkaloids from Argemone platyceras (Papaveraceae).

PubMed

Siatka, Tomáš; Adamcová, Markéta; Opletal, Lubomír; Cahlíková, Lucie; Jun, Daniel; Hrabinová, Martina; Kuneš, Jiří; Chlebek, Jakub

2017-07-14

Alzheimer's disease is an age-related, neurodegenerative disorder, characterized by cognitive impairment and restrictions in activities of daily living. This disease is the most common form of dementia with complex multifactorial pathological mechanisms. Many therapeutic approaches have been proposed. Among them, inhibition of acetylcholinesterase, butyrylcholinesterase, and prolyl oligopeptidase can be beneficial targets in the treatment of Alzheimer's disease. Roots, along with aerial parts of Argemone platyceras , were extracted with ethanol and fractionated on an alumina column using light petrol, chloroform and ethanol. Subsequently, repeated preparative thin-layer chromatography led to the isolation of (+)-laudanosine, protopine, (-)-argemonine, allocryptopine, (-)-platycerine, (-)-munitagine, and (-)-norargemonine belonging to pavine, protopine and benzyltetrahydroisoquinoline structural types. Chemical structures of the isolated alkaloids were elucidated by optical rotation, spectroscopic and spectrometric analysis (NMR, MS), and comparison with literature data. (+)-Laudanosine was isolated from A. platyceras for the first time. Isolated compounds were tested for human blood acetylcholinesterase, human plasma butyrylcholinesterase and recombinant prolyl oligopeptidase inhibitory activity. The alkaloids inhibited the enzymes in a dose-dependent manner. The most active compound (-)-munitagine, a pavine alkaloid, inhibited both acetylcholinesterase and prolyl oligopeptidase with IC 50 values of 62.3 ± 5.8 µM and 277.0 ± 31.3 µM, respectively.
Alzheimer,s Disease Risk and Progression: The Role of Nutritional Supplements and their Effect on Drug Therapy Outcome

PubMed Central

Giulietti, A.; Vignini, A.; Nanetti, L.; Mazzanti, L.; Primio, R. Di; Salvolini, E.

2016-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly population. Despite significant advancements in understanding the genetic and molecular basis of AD, the pathology still lacks treatments that can slow down or reverse the progression of cognitive deterioration. Recently, the relationship between nutrient deficiency and dementia onset has been highlighted. AD is in fact a multifactorial pathology, so that a multi-target approach using combinations of micronutrients and drugs could have beneficial effects on cognitive function in neurodegenerative brain disorders leading to synaptic degeneration. Primarily, this review examines the most recent literature regarding the effects of nutrition on the risk/progression of the disease, focusing attention mostly on antioxidants agents, polyunsaturated fatty acids and metals. Secondly, it aims to figure out if nutritional supplements might have beneficial effects on drug therapy outcome. Even if nutritional supplements showed contrasting evidence of a likely effect of decreasing the risk of AD onset that could be studied more deeply in other clinical trials, no convincing data are present about their usefulness in combination with drug therapies and their effectiveness in slowing down the disease progression. PMID:26415975
Elevated total plasma homocysteine and 667C{r_arrow}T mutation of the 5,10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Franchis, R.; Sebastio, G.; Andria, G.

1996-07-01

Moderate elevation of total plasma homocysteine (tHcy) has been reported as an independent risk factor for thrombotic vascular disease, a well-known multifactorial disorder. Possible genetic causes of elevated tHcy include defects of the sulfur-containing amino acids metabolism due to deficiencies of cystathionine {Beta}-synthase, of 5,10-methylenetetrahydrofolate reductase (MTHFR), and of the enzymes of cobalamin metabolism. An impaired activity of MTHFR due to a thermolabile form of the enzyme has been observed in {le}28% of hyperhomocysteinemic patients with premature vascular disease. More recently, the molecular basis of such enzymatic thermolability has been related to a common mutation of the MTHFR gene, causingmore » a C-to-T substitution at nt 677 (677C{r_arrow}T). This mutation was found in 38% of unselected chromosomes from 57 French Canadian individuals. The homozygous state for the mutation was present in 12% of these subjects and correlated with significantly elevated tHcy. Preliminary evidence indicates that the frequency of homozygotes for the 677C{r_arrow}T mutation may vary significantly in populations from different geographic areas. 5 refs., 2 tabs.« less
Epidemiología genética sobre las teorías causales y la patogénesis de la diabetes mellitus tipo 2.

PubMed

Castro-Juárez, Carlos Jonnathan; Ramírez-García, Sergio Alberto; Villa-Ruano, Nemesio; García-Cruz, Diana

2017-01-01

Diabetes mellitus type 2 (DM2) is a worldwide public health problem. The etiology of the disease is multifactorial and is characterized by great heterogeneity of metabolic disorders. The most common are the insufficient production of insulin, insulin resistance and impaired incretin system. The specialist must understand the multi-causal nature of DM2 in the post-genomic era. This nature is determined by the additive effect of genes and environment, so there is no simple genetic epidemiological model to explain the inheritance pattern. Hence the need to establish the proportion of disease that is determined by genes and the contribution of environmental factors, the combination of which regulates the threshold or tolerance level for diabetes development. Given this complexity in DM2 in this work are discussed the various existing theories of causality of this disease, which will permit us to understand the interaction between the environment and the human genome, and also to know how risk factors or predisposition to this disease influence, laying the grounds that delimit environment interaction with the genome. Copyright: © 2017 SecretarÍa de Salud.
[Experience of a falls prevention unit in an intermediate care hospital].

PubMed

Roca Carbonell, Ferran; Hernandez Ocampo, Erwin Martin; Aragonès Pascual, Jose Maria; Soler, Eulalia; Clapera, Fina; Espaulella Panicot, Joan

2014-01-01

The aim of this study is to determine clinical features and interventions in patients attended in our hospital falls prevention unit. Medical records and evaluation protocols from October 2010 to June 2012 were reviewed. Results are expressed in means and standard deviation. We studied 68 patients: 53 came due to falls (77.9%), and 15 (22%) due to gait disorders. The mean age was 77.6±7.9. Number of women: 63 (92.6%). Previous Barthel Index was 94/100, cognitive impairment 23 (33.8%), polypharmacy 69.1%, orthostatic hypotension 18 (26.4%). Walking speed 0.66± 0.19m/s and Time up and go to (TUG) 16.6±4.5 s. Post-urography detected vestibular dysfunction in 34 patients (77%). Clinical cause of fall and/or gait disorder was multifactorial in 33 (48.5%), Parkinsonism 19 (27.9%), chronic pain/arthropathy 8 (11.4%), and vestibular syndrome 8 (11.4%). Two-thirds (45; 66.1%) of the patients began Physical therapy, and vitamin D was given to 47 (69.1%). Phone calls were made to patients and/or their relatives and noted that after 3 months of the treatment: 48 (70.5%) had no fall; 59 (86.7%) patients followed the recommendations, and 57 (83.8%) were satisfied. In this sample of older patients, mostly female with a good functional and cognitive condition, the causes of the falls were multifactorial in the half of the cases, and the post-urography detected vestibular changes in the half of the patients. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.
The importance of body image concerns in overweight and normal weight individuals with binge eating disorder.

PubMed

Yiu, Angelina; Murray, Susan M; Arlt, Jean M; Eneva, Kalina T; Chen, Eunice Y

2017-09-01

Body image concerns in binge eating disorder (BED) have been examined almost exclusively in overweight individuals with BED. The current study extends past research by including overweight and normal weight BED and non-BED groups to assess the multifactorial construct of body image using subscales of the Eating Disorder Examination 16.0 (EDE-16.0) and a Body Comparison Task. Independent of weight status and when controlling for age and race, women with BED are distinguished from those without BED by significantly greater overvaluation of shape and weight on the EDE-16.0 and significantly reduced weight satisfaction after a Body Comparison Task. Both BED diagnosis and weight status were independently associated with Weight Concern and Shape Concern subscales on the EDE-16.0. Taken together, these data provide further support for the consideration of body image concerns in the diagnostic criteria for BED. Copyright © 2017 Elsevier Ltd. All rights reserved.
Complex biomarker discovery in neuroimaging data: Finding a needle in a haystack☆

PubMed Central

Atluri, Gowtham; Padmanabhan, Kanchana; Fang, Gang; Steinbach, Michael; Petrella, Jeffrey R.; Lim, Kelvin; MacDonald, Angus; Samatova, Nagiza F.; Doraiswamy, P. Murali; Kumar, Vipin

2013-01-01

Neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease are major public health problems. However, despite decades of research, we currently have no validated prognostic or diagnostic tests that can be applied at an individual patient level. Many neuropsychiatric diseases are due to a combination of alterations that occur in a human brain rather than the result of localized lesions. While there is hope that newer imaging technologies such as functional and anatomic connectivity MRI or molecular imaging may offer breakthroughs, the single biomarkers that are discovered using these datasets are limited by their inability to capture the heterogeneity and complexity of most multifactorial brain disorders. Recently, complex biomarkers have been explored to address this limitation using neuroimaging data. In this manuscript we consider the nature of complex biomarkers being investigated in the recent literature and present techniques to find such biomarkers that have been developed in related areas of data mining, statistics, machine learning and bioinformatics. PMID:24179856
Lay perceptions of predictive testing for diabetes based on DNA test results versus family history assessment: a focus group study.

PubMed

Wijdenes-Pijl, Miranda; Dondorp, Wybo J; Timmermans, Danielle Rm; Cornel, Martina C; Henneman, Lidewij

2011-07-05

This study assessed lay perceptions of issues related to predictive genetic testing for multifactorial diseases. These perceived issues may differ from the "classic" issues, e.g. autonomy, discrimination, and psychological harm that are considered important in predictive testing for monogenic disorders. In this study, type 2 diabetes was used as an example, and perceptions with regard to predictive testing based on DNA test results and family history assessment were compared. Eight focus group interviews were held with 45 individuals aged 35-70 years with (n = 3) and without (n = 1) a family history of diabetes, mixed groups of these two (n = 2), and diabetes patients (n = 2). All interviews were transcribed and analysed using Atlas-ti. Most participants believed in the ability of a predictive test to identify people at risk for diabetes and to motivate preventive behaviour. Different reasons underlying motivation were considered when comparing DNA test results and a family history risk assessment. A perceived drawback of DNA testing was that diabetes was considered not severe enough for this type of risk assessment. In addition, diabetes family history assessment was not considered useful by some participants, since there are also other risk factors involved, not everyone has a diabetes family history or knows their family history, and it might have a negative influence on family relations. Respect for autonomy of individuals was emphasized more with regard to DNA testing than family history assessment. Other issues such as psychological harm, discrimination, and privacy were only briefly mentioned for both tests. The results suggest that most participants believe a predictive genetic test could be used in the prevention of multifactorial disorders, such as diabetes, but indicate points to consider before both these tests are applied. These considerations differ with regard to the method of assessment (DNA test or obtaining family history) and also differ from monogenic disorders.
Epidemiology and management of insomnia in children with autistic spectrum disorders.

PubMed

Miano, Silvia; Ferri, Raffaele

2010-04-01

Insomnia is the predominant sleep concern in children with autistic spectrum disorder (ASD), and its nature is most likely multifactorial, with neurochemical (abnormalities in serotonergic transmission or melatonin levels), psychiatric (anxiety), and behavioral (poor sleep habits) etiological factors involved. Children with ASD experience sleep problems similar to those of typically developing children, although the prevalence is markedly higher, occurring in 44-83% of school-aged children with ASD. Caregivers usually report that insomnia is the most frequent sleep disorder, described as disorders of initiating and maintaining sleep, restless sleep, bedtime resistance, co-sleeping, alterations of sleep hygiene, and early awakenings in the morning. Many actigraphic studies have added information on sleep disorders, confirming the questionnaire findings in the majority of cases. There are relatively few polysomnographic data for ASD, compared with questionnaire studies, and most of these studies reported a reduction in total sleep time and more undifferentiated sleep in the youngest patients. These findings were associated with several sleep microstructure alterations during rapid eye movement (REM) sleep, and with non-REM (NREM) sleep microstructure changes that appeared to be related to cognitive impairment rather than to the autistic core. Moreover, few data about other less frequent sleep disorders, such as periodic limb movements disorder and obstructive sleep apnea syndrome, bruxism, and the influence of epilepsy and EEG abnormalities, are available. Both pharmacologic and behavioral interventions have been suggested for the treatment of sleep problems in autistic children. The most common types of behavioral interventions are complete extinction (removing reinforcement to reduce a behavior) and various forms of graduated extinction. Melatonin has shown promising results in the treatment of insomnia in children with ASD. Although controlled studies are limited, there are more data demonstrating the safety and effectiveness of melatonin in ASD than for other sedative/hypnotic drugs. Finally, a dual treatment for insomnia in ASDs with melatonin and behavioral techniques has been suggested. A recent study using a combination of genetic and functional experimental techniques reported evidence that low melatonin concentration caused by a primary deficit in acetylserotonin methyltransferase activity is a risk factor for ASD. Sleep problems usually start at the same age as developmental regression, suggesting a higher vulnerability at this period of life. Further studies, beginning at younger ages, are necessary to better investigate these aspects and the role of melatonin in insomnia in children with ASD.
What kinds of things are psychiatric disorders?

PubMed

Kendler, K S; Zachar, P; Craver, C

2011-06-01

This essay explores four answers to the question 'What kinds of things are psychiatric disorders?' Essentialist kinds are classes whose members share an essence from which their defining features arise. Although elegant and appropriate for some physical (e.g. atomic elements) and medical (e.g. Mendelian disorders) phenomena, this model is inappropriate for psychiatric disorders, which are multi-factorial and 'fuzzy'. Socially constructed kinds are classes whose members are defined by the cultural context in which they arise. This model excludes the importance of shared physiological mechanisms by which the same disorder could be identified across different cultures. Advocates of practical kinds put off metaphysical questions about 'reality' and focus on defining classes that are useful. Practical kinds models for psychiatric disorders, implicit in the DSM nosologies, do not require that diagnoses be grounded in shared causal processes. If psychiatry seeks to tie disorders to etiology and underlying mechanisms, a model first proposed for biological species, mechanistic property cluster (MPC) kinds, can provide a useful framework. MPC kinds are defined not in terms of essences but in terms of complex, mutually reinforcing networks of causal mechanisms. We argue that psychiatric disorders are objectively grounded features of the causal structure of the mind/brain. MPC kinds are fuzzy sets defined by mechanisms at multiple levels that act and interact to produce the key features of the kind. Like species, psychiatric disorders are populations with central paradigmatic and more marginal members. The MPC view is the best current answer to 'What kinds of things are psychiatric disorders?'
Psychiatric considerations in the diagnosis, treatment, and prevention of HIV/AIDS.

PubMed

Ruiz, P; Guynn, R W; Matorin, A A

2000-05-01

HIV/AIDS has the unfortunate distinction of being one of the most devastating epidemics of the twentieth century. By the end of June, 1999, 420,201 deaths in persons with AIDS had been reported in the United States. While HIV/AIDS patients are currently living longer as a result of more effective and complex treatments, no vaccination or cure has yet been discovered. Over the years, the HIV/AIDS epidemic has become multifactorial and currently affects several different special population groups. Individuals who are at high risk for becoming infected with HIV or who already suffer from HIV/AIDS can benefit greatly from the interventions of psychiatrists or other mental health professionals. It is important that psychiatrists collaborate very closely with infectious disease specialists in the management of HIV/AIDS and its psychological sequelae. The authors describe the psychiatric conditions that most often occur in association with HIV/AIDS: mood disorders, anxiety disorders, substance-related disorders, psychotic disorders, insomnia and sleep disorders, delirium, dementia, and pain syndromes. We present guidelines for diagnosis and psychopharmacological and psychotherapeutic treatment of these disorders in patients with HIV/AIDS. The article concludes with a discussion of prevention strategies that can be used in a mental health treatment setting and special issues related to treating HIV/AIDS in certain special population groups.
Surgical management of gingival recession: A clinical update

PubMed Central

Alghamdi, Hamdan; Babay, Nadir; Sukumaran, Anil

2009-01-01

Gingival recession is defined as the apical migration of the junctional epithelium with exposure of root surfaces. It is a common condition seen in both dentally aware populations and those with limited access to dental care. The etiology of the condition is multifactorial but is commonly associated with underlying alveolar morphology, tooth brushing, mechanical trauma and periodontal disease. Given the high rate of gingival recession defects among the general population, it is imperative that dental practitioners have an understanding of the etiology, complications and the management of the condition. The following review describes the surgical techniques to treat gingival recession. PMID:23960465
Excitotoxicity in the pathogenesis of autism.

PubMed

Essa, M M; Braidy, N; Vijayan, K R; Subash, S; Guillemin, G J

2013-05-01

Autism is a debilitating neurodevelopment disorder characterised by stereotyped interests and behaviours, and abnormalities in verbal and non-verbal communication. It is a multifactorial disorder resulting from interactions between genetic, environmental and immunological factors. Excitotoxicity and oxidative stress are potential mechanisms, which are likely to serve as a converging point to these risk factors. Substantial evidence suggests that excitotoxicity, oxidative stress and impaired mitochondrial function are the leading cause of neuronal dysfunction in autistic patients. Glutamate is the primary excitatory neurotransmitter produced in the CNS, and overactivity of glutamate and its receptors leads to excitotoxicity. The over excitatory action of glutamate, and the glutamatergic receptors NMDA and AMPA, leads to activation of enzymes that damage cellular structure, membrane permeability and electrochemical gradients. The role of excitotoxicity and the mechanism behind its action in autistic subjects is delineated in this review.
Multifactor-Dimensionality Reduction Reveals High-Order Interactions among Estrogen-Metabolism Genes in Sporadic Breast Cancer

PubMed Central

Ritchie, Marylyn D.; Hahn, Lance W.; Roodi, Nady; Bailey, L. Renee; Dupont, William D.; Parl, Fritz F.; Moore, Jason H.

2001-01-01

One of the greatest challenges facing human geneticists is the identification and characterization of susceptibility genes for common complex multifactorial human diseases. This challenge is partly due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes and with environmental exposures. We introduce multifactor-dimensionality reduction (MDR) as a method for reducing the dimensionality of multilocus information, to improve the identification of polymorphism combinations associated with disease risk. The MDR method is nonparametric (i.e., no hypothesis about the value of a statistical parameter is made), is model-free (i.e., it assumes no particular inheritance model), and is directly applicable to case-control and discordant-sib-pair studies. Using simulated case-control data, we demonstrate that MDR has reasonable power to identify interactions among two or more loci in relatively small samples. When it was applied to a sporadic breast cancer case-control data set, in the absence of any statistically significant independent main effects, MDR identified a statistically significant high-order interaction among four polymorphisms from three different estrogen-metabolism genes. To our knowledge, this is the first report of a four-locus interaction associated with a common complex multifactorial disease. PMID:11404819
Genetics of gallstone disease.

PubMed

Rebholz, Charlotte; Krawczyk, Marcin; Lammert, Frank

2018-04-10

Gallstone disease (GD) belongs to the most frequent disorders in gastroenterology and causes high costs in our health-care systems. Gallstones are uncommon in children but frequent in adults, in particular in women, and are triggered by exogenous risk factors. Here, we summarize the current knowledge concerning the contribution of inherited predisposition to gallstone risk. In this review, we present the current data and recent research on the genetics of gallstone disease. Several GD-predisposing gene variants have been reported, with most prominent effects being conferred by a common variant (p.D19H) of the hepatic and intestinal cholesterol transporter ABCG5/G8. A smaller group of patients might develop gallstones primarily due low phosphatidylcholine concentrations in bile as a result of loss-of-function mutations of the ABCB4 transporter (low phospholipid-associated cholelithiasis syndrome). Regardless of the origin, the risk factors for gallstones lead to the supersaturation of bile with insoluble compounds, in particular cholesterol. As result, cholesterol stones develop and present the most frequent type of gallstones. Laparoscopic cholecystectomy with low morbidity and mortality is currently the most common and effective method for the therapy of symptomatic gallbladder stones. Gallstone disease represents a multifactorial condition and previous studies have identified the major genetic contributors to gallstone formation. The increasing knowledge about the pathomechanisms of hepatobiliary metabolism and GD as well as the identification of additional risk factors might help to overcome the current invasive therapy by specific lifestyle intervention and precise molecular treatment. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

A review on recent advances in dry eye: Pathogenesis and management

PubMed Central

Bhavsar, Ankita S.; Bhavsar, Samir G.; Jain, Sunita M.

2011-01-01

Keratoconjunctivitis sicca, more commonly known as dry eye, is an extremely common and often unrecognized disease. It is the condition in ophthalmology that in its mild grade of severity will affect most of the population at one time or other. Due to a wide variety of presentations and symptoms, it often frustrates the ophthalmologists as well as patients. Due to multifactorial and elusive etiology, it is often challenging to treat dry eye. Ocular surface disorders are also clinically important to treat especially in terms of visual acuity. Xero-dacryology is therefore becoming a very important branch of ophthalmology. Recent studies have given insight into the inflammatory etiology of dry eye. The conventional and main approach to the treatment of dry eye is providing lubricating eye drops or tear substitutes. However, the newer treatment approach is to target the underlying cause of dry eye instead of conventional symptomatic relief. In light of the above knowledge, the present article focuses on newer theories on pathogenesis of dry eye and their impact on dry eye management. Method of Literature Search: A systematic literature review was performed using PubMed databases in two steps. The first step was oriented to articles published for dry eye. The second step was focused on the role of inflammation and anti-inflammatory therapy for dry eye. The search strategy was not limited by year of publication. A manual literature search was also undertaken from authentic reference books on ocular surface disease. PMID:21897618
Epidemiology of Voice Disorders in Latvian School Teachers.

PubMed

Trinite, Baiba

2017-07-01

The prevalence of voice disorders in the teacher population in Latvia has not been studied so far and this is the first epidemiological study whose goal is to investigate the prevalence of voice disorders and their risk factors in this professional group. A wide cross-sectional study using stratified sampling methodology was implemented in the general education schools of Latvia. The self-administered voice risk factor questionnaire and the Voice Handicap Index were completed by 522 teachers. Two teachers groups were formed: the voice disorders group which included 235 teachers with actual voice problems or problems during the last 9 months; and the control group which included 174 teachers without voice disorders. Sixty-six percent of teachers gave a positive answer to the following question: Have you ever had problems with your voice? Voice problems are more often found in female than male teachers (68.2% vs 48.8%). Music teachers suffer from voice disorders more often than teachers of other subjects. Eighty-two percent of teachers first faced voice problems in their professional carrier. The odds of voice disorders increase if the following risk factors exist: extra vocal load, shouting, throat clearing, neglecting of personal health, background noise, chronic illnesses of the upper respiratory tract, allergy, job dissatisfaction, and regular stress in the working place. The study findings indicated a high risk of voice disorders among Latvian teachers. The study confirmed data concerning the multifactorial etiology of voice disorders. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Prediabetes: Beyond the Borderline.

PubMed

Wilson, Mara Lynn

2017-12-01

Prediabetes is a complex multifactorial metabolic disorder that extends beyond glucose control. Current studies have found that microvascular disease (neuropathy, nephropathy, and retinopathy), macrovascular disease (stroke, coronary artery disease, and peripheral vascular disease), periodontal disease, cognitive dysfunction, blood pressure changes, obstructive sleep apnea, low testosterone level, fatty liver disease, and cancer are some of conditions that are present with the onset of glycemic dysregulation. The presence of prediabetes increases the risk of developing type 2 diabetes 3-fold to 10-fold. The identification and treatment of prediabetes are imperative to prevent or delay the progression to type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.
Tropical myeloneuropathies: the hidden endemias.

PubMed

Román, G C; Spencer, P S; Schoenberg, B S

1985-08-01

Tropical myeloneuropathies include tropical ataxic neuropathy and tropical spastic paraparesis. These disorders occur in geographic isolates in several developing countries and are associated with malnutrition, cyanide intoxication from cassava consumption, tropical malabsorption (TM), vegetarian diets, and lathyrism. TM-malnutrition was a probable cause of myeloneuropathies among Far East prisoners of war in World War II. Clusters of unknown etiology occur in India, Africa, the Seychelles, several Caribbean islands, Jamaica, and Colombia. Treponemal infection (yaws) could be an etiologic factor in the last two. Tropical myeloneuropathies, a serious health problem, are multifactorial conditions that provide unsurpassed opportunities for international cooperation and neurologic research.
[Impaired hypoglycemia awareness in diabetes mellitus].

PubMed

Brož, Jan; Piťhová, Pavlína; Janíčková Žďárská, Denisa

Impaired hypoglycemia awareness is defined at the onset of neuroglycopenia without the appearance of autonomic warning symptoms. Impaired hypoglycemia awareness is disorder which affects aprox. one third of patients with type 1 diabetes mellitus and 8-10 % of patients with type 2 diabetes mellitus who are treated with insulin. The most dangerous consequence is 6 times higher frequency of severe hypoglycemia in patients with Type 1 diabetes mellitus and 17 times higher in Type 2 diabetic patients treated with insulin. Treatment of impaired hypoglycemia awareness is complex, based on a multifactorial intervention of clinical care and structured patient education. diabetes mellitus - hypoglycemia- impaired hypoglycemia awareness.
Sex differences in abdominal aortic aneurysms.

PubMed

Boese, Austin C; Chang, Lin; Yin, Ke-Jie; Chen, Y Eugene; Lee, Jean-Pyo; Hamblin, Milton H

2018-06-01

Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.
MicroRNAs in Neurocognitive Dysfunctions: New Molecular Targets for Pharmacological Treatments?

PubMed Central

Nadim, Wissem Deraredj; Simion, Viorel; Bénédetti, Hélène; Pichon, Chantal; Baril, Patrick; Morisset-Lopez, Séverine

2017-01-01

Background Neurodegenerative and cognitive disorders are multifactorial diseases (i.e., involving neurodevelopmental, genetic, age or environmental factors) characterized by an abnormal development that affects neuronal function and integrity. Recently, an increasing number of studies revealed that the dysregulation of microRNAs (miRNAs) may be involved in the etiology of cognitive disorders as Alzheimer, Parkinson, and Huntington‘s diseases, Schizophrenia and Autism spectrum disorders. Methods From an extensive search in bibliographic databases of peer-reviewed research literature,  we identified relevant published studies related to specific key words such as memory, cognition, neurodegenerative disorders, neurogenesis and miRNA. We then analysed, evaluated and summerized scientific evidences derived from these studies. Results We first briefly summarize the basic molecular events involved in memory, a process inherent to cognitive disease, and then describe the role of miRNAs in neurodevelopment, synaptic plasticity and memory. Secondly, we provide an overview of the impact of miRNA dysregulation in the pathogenesis of different neurocognitive disorders, and lastly discuss the feasibility of miRNA-based therapeutics in the treatment of these disorders. Conclusion This review highlights the molecular basis of neurodegenerative and cognitive disorders by focusing on the impact of miRNAs dysregulation in these pathological phenotypes. Altogether, the published reports suggest that miRNAs-based therapy could be a viable therapeutic alternative to current treatment options in the future. PMID:27396304
How Stuttering Develops: The Multifactorial Dynamic Pathways Theory

ERIC Educational Resources Information Center

Smith, Anne; Weber, Christine

2017-01-01

Purpose: We advanced a multifactorial, dynamic account of the complex, nonlinear interactions of motor, linguistic, and emotional factors contributing to the development of stuttering. Our purpose here is to update our account as the multifactorial dynamic pathways theory. Method: We review evidence related to how stuttering develops, including…
Risk factors for Raynaud's phenomenon among workers in poultry slaughterhouses and canning factories.

PubMed

Kaminski, M; Bourgine, M; Zins, M; Touranchet, A; Verger, C

1997-04-01

Apart from the use of vibrating tools, little is known about risk factors for Raynaud's phenomenon. However, it has been hypothesized that this disorder may have a multifactorial aetiology, involving potential causal or triggering factors which can be found in the workplace. The objective of the study is to identify individual and occupational risk factors of Raynaud's phenomenon in a population of workers not exposed to vibration, but exposed to cold. The survey was carried out in 1987-1988 in 17 poultry slaughterhouses and six canning factories and included 1474 employees. Data were collected at the annual visit to the occupational health physician. Finger sensitivity to cold and Raynaud's phenomenon were identified from a list of symptoms occurring from exposure to cold. The role of potential risk factors was assessed using multiple logistic regression. A high prevalence of symptoms of finger sensitivity to cold was observed. Raynaud's phenomenon was more common in women than in men, was related to family history of the disease but not to smoking or alcohol consumption. After controlling for non-occupational factors, the following working conditions appeared as risk factors for Raynaud's phenomenon: use of plastic gloves, less than four rest breaks, breaks in an unheated place, continual repetition of the same series of operations, exertion of the arm or hand and being able to think of something else while working. The study showed that a number of working conditions were associated with an increased risk of Raynaud's phenomenon and finger sensitivity to cold. Changes in working conditions might reduce the risk of this disorder in the food processing industry.
Chronic prostatitis and comorbid non-urological overlapping pain conditions: A co-twin control study.

PubMed

Gasperi, Marianna; Krieger, John N; Forsberg, Christopher; Goldberg, Jack; Buchwald, Dedra; Afari, Niloofar

2017-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs. Data from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self-reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations. There were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome. CP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities. Published by Elsevier Inc.
Olfaction in Parkinson's disease and related disorders.

PubMed

Doty, Richard L

2012-06-01

Olfactory dysfunction is an early 'pre-clinical' sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology, or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances. Copyright © 2011 Elsevier Inc. All rights reserved.
Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review.

PubMed

Rabago, David; Nourani, Bobby

2017-06-01

Osteoarthritis and overuse tendinopathy are common chronic conditions of high societal and patient burden. The precise etiology of pain and disability in both conditions is multifactorial and not well understood. Patients are often refractory to conservative therapy. The development of new therapeutic options in both conditions is a public health priority. Prolotherapy is an injection-based outpatient regenerative therapy for chronic musculoskeletal conditions, including osteoarthritis and tendinopathy. The authors reviewed the basic science and clinical literature associated with prolotherapy for these conditions. Systematic review, including meta-analysis, and randomized controlled trials suggest that prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and overuse tendinopathy. Although the mechanism of action is not well understood and is likely multifactorial, a growing body of literature suggests that prolotherapy for knee osteoarthritis may be appropriate for the treatment of symptoms associated with knee osteoarthritis in carefully selected patients who are refractory to conservative therapy and deserves further basic and clinical science investigation for the treatment of osteoarthritis and tendinopathy.
Gene regulatory network inference from multifactorial perturbation data using both regression and correlation analyses.

PubMed

Xiong, Jie; Zhou, Tong

2012-01-01

An important problem in systems biology is to reconstruct gene regulatory networks (GRNs) from experimental data and other a priori information. The DREAM project offers some types of experimental data, such as knockout data, knockdown data, time series data, etc. Among them, multifactorial perturbation data are easier and less expensive to obtain than other types of experimental data and are thus more common in practice. In this article, a new algorithm is presented for the inference of GRNs using the DREAM4 multifactorial perturbation data. The GRN inference problem among [Formula: see text] genes is decomposed into [Formula: see text] different regression problems. In each of the regression problems, the expression level of a target gene is predicted solely from the expression level of a potential regulation gene. For different potential regulation genes, different weights for a specific target gene are constructed by using the sum of squared residuals and the Pearson correlation coefficient. Then these weights are normalized to reflect effort differences of regulating distinct genes. By appropriately choosing the parameters of the power law, we constructe a 0-1 integer programming problem. By solving this problem, direct regulation genes for an arbitrary gene can be estimated. And, the normalized weight of a gene is modified, on the basis of the estimation results about the existence of direct regulations to it. These normalized and modified weights are used in queuing the possibility of the existence of a corresponding direct regulation. Computation results with the DREAM4 In Silico Size 100 Multifactorial subchallenge show that estimation performances of the suggested algorithm can even outperform the best team. Using the real data provided by the DREAM5 Network Inference Challenge, estimation performances can be ranked third. Furthermore, the high precision of the obtained most reliable predictions shows the suggested algorithm may be helpful in guiding biological experiment designs.
[Proctalgia fugax. Differential diagnosis and therapy of fleeting anal cramp].

PubMed

Staude, G

1992-05-30

Proctalgia fugax--short-lived anal spasm--is a common, extremely unpleasant, painful condition that occurs completely unexpectedly, often waking the victim at night. Scientific assessment is difficult on account of the functional nature of the condition and its multifactorial genesis. Before the patient is labeled "anal neurotic", however, he/she should be investigated by a specialist. The results of treating the rarely absent pathological organic findings give rise to optimism.
Temporomandibular dysfunction

PubMed

Lomas, Jonathan; Gurgenci, Taylan; Jackson, Christopher; Campbell, Duncan

2018-04-01

Orofacial pain is a common presentation in the primary healthcare setting and temporomandibular dysfunction represents one of the major causes. Its aetiology is multifactorial, caused by both masticatory muscle dysfunction and derangement within the temporomandibular joint. The aim of this article is to provide an overview of temporomandibular dysfunction, its management and referral considerations for general practioners. Temporomandibular joint dysfunction affects a large number of adults. Conservative management involving non-pharmacological and pharmacological therapies is effective in the majority of cases.
A single-center, cross-sectional prevalence study of impulse control disorders in Parkinson disease: association with dopaminergic drugs.

PubMed

Poletti, Michele; Logi, Chiara; Lucetti, Claudio; Del Dotto, Paolo; Baldacci, Filippo; Vergallo, Andrea; Ulivi, Martina; Del Sarto, Simone; Rossi, Giuseppe; Ceravolo, Roberto; Bonuccelli, Ubaldo

2013-10-01

The current study aimed at establishing the prevalence of impulse control disorders (ICDs) in patients with Parkinson disease (PD) and their association with demographic, drug-related, and disease-related characteristics. We performed a single-center cross-sectional study of 805 PD patients. Impulse control disorders were investigated with the Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease; also comorbid neuropsychiatric complications (dementia, delusions, visual hallucinations) were investigated with clinical interviews and ad hoc instruments (Parkinson Psychosis Questionnaire and Neuropsychiatry Inventory). Impulse control disorders were identified in 65 patients (prevalence, 8.1%), with pathological gambling and hypersexuality the most frequent. Impulse control disorders were present in 57 of 593 cognitively preserved patients (prevalence, 9.6%) and in 8 of 212 demented patients (prevalence, 3.8%). Impulse control disorders were significantly associated with dopamine agonists (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.60-12.46; P < 0.0001) and levodopa (OR, 2.43; 95% CI, 1.06-6.35; P = 0.034). Impulse control disorders frequency was similar for pramipexole and ropinirole (16.6% vs 12.5%; OR, 1.45; 95% CI, 0.79-2.74; P = 0.227). Additional variables associated with ICDs were male sex and younger age. These findings suggested that dopaminergic treatments in PD are associated with increased odds of having an ICD, but also other demographic and clinical variables are associated with ICDs, suggesting the multifactorial nature of the ICD phenomenon in PD.
Hypnotherapy for Esophageal Disorders.

PubMed

Riehl, Megan E; Keefer, Laurie

2015-07-01

Hypnotherapy is an evidence based intervention for the treatment of functional bowel disorders, particularly irritable bowel syndrome. While similar in pathophysiology, less is known about the utility of hypnotherapy in the upper gastrointestinal tract. Esophageal disorders, most of which are functional in nature, cause painful and uncomfortable symptoms that impact patient quality of life and are difficult to treat from a medical perspective. After a thorough medical workup and a failed trial of proton pump inhibitor therapy, options for treatment are significantly limited. While the pathophysiology is likely multifactorial, two critical factors are believed to drive esophageal symptoms--visceral hypersensitivity and symptom hypervigilance. The goal of esophageal directed hypnotherapy is to promote a deep state of relaxation with focused attention allowing the patient to learn to modulate physiological sensations and symptoms that are not easily addressed with conventional medical intervention. Currently, the use of hypnosis is suitable for dysphagia, globus, functional chest pain/non-cardiac chest pain, dyspepsia, and functional heartburn. In this article the authors will provide a rationale for the use of hypnosis in these disorders, presenting the science whenever available, describing their approach with these patients, and sharing a case study representing a successful outcome.
Hypnotherapy for Esophageal Disorders

PubMed Central

Riehl, Megan E.; Keefer, Laurie

2015-01-01

Hypnotherapy is an evidence based intervention for the treatment of functional bowel disorders, particularly irritable bowel syndrome. While similar in pathophysiology, less is known about the utility of hypnotherapy in the upper gastrointestinal tract. Esophageal disorders, most of which are functional in nature, cause painful and uncomfortable symptoms that impact patient quality of life and are difficult to treat from a medical perspective. After a thorough medical workup and a failed trial of proton pump inhibitor therapy, options for treatment are significantly limited. While the pathophysiology is likely multifactorial, two critical factors are believed to drive esophageal symptoms—visceral hypersensitivity and symptom hypervigilance. The goal of esophageal directed hypnotherapy is to promote a deep state of relaxation with focused attention allowing the patient to learn to modulate physiological sensations and symptoms that are not easily addressed with conventional medical intervention. Currently, the use of hypnosis is suitable for dysphagia, globus, functional chest pain/non-cardiac chest pain, dyspepsia, and functional heartburn. In this article the authors will provide a rationale for the use of hypnosis in these disorders, presenting the science whenever available, describing their approach with these patients, and sharing a case study representing a successful outcome. PMID:26046715
Developmental dyslexia: the visual attention span deficit hypothesis.

PubMed

Bosse, Marie-Line; Tainturier, Marie Josèphe; Valdois, Sylviane

2007-08-01

The visual attention (VA) span is defined as the amount of distinct visual elements which can be processed in parallel in a multi-element array. Both recent empirical data and theoretical accounts suggest that a VA span deficit might contribute to developmental dyslexia, independently of a phonological disorder. In this study, this hypothesis was assessed in two large samples of French and British dyslexic children whose performance was compared to that of chronological-age matched control children. Results of the French study show that the VA span capacities account for a substantial amount of unique variance in reading, as do phonological skills. The British study replicates this finding and further reveals that the contribution of the VA span to reading performance remains even after controlling IQ, verbal fluency, vocabulary and single letter identification skills, in addition to phoneme awareness. In both studies, most dyslexic children exhibit a selective phonological or VA span disorder. Overall, these findings support a multi-factorial view of developmental dyslexia. In many cases, developmental reading disorders do not seem to be due to phonological disorders. We propose that a VA span deficit is a likely alternative underlying cognitive deficit in dyslexia.
Aetiological profile of acquired anaemia in a paediatric tertiary care setting.

PubMed

Bibi, Saima; Gilani, Syed Yasir Hussain; Shah, Syed Raza Ali; Bibi, Shawana

2011-01-01

Anaemia is the commonest haematological disorder frequently faced by clinicians worldwide. The multi-factorial aetiology of the disorder warrants a comprehensive search for the different causes as management plans differ for different disorders. The objective of this study was to identify the different acquired causes of anaemia in our paediatric population. The study was conducted at the Department of Paediatrics, Ayub Teaching Hospital from April 2009 to April 2010. It was a cross-sectional study. A total of 110 patients were included in the study who presented with anaemia secondary to acquired aetiologies and were assessed clinically using general physical and systemic examination. The salient clinical and laboratory data was retrieved in designed protocol. Out of a total of 110 patients, 61 (55.5%) were male and 49 (44.5%) were female. Mean age of the participants was 48 months. Nutritional anaemia comprising iron deficiency anaemia and megaloblastic anaemia was the leading cause being present in 49 (44.5%) patients followed by Visceral Leishmaniasis in 28 (25.5%) patients. Mean haemoglobin was 4.36 g/dl. Anaemia secondary to acquired causes is a disorder with grave consequences ranging from cognitive and psychomotor dysfunction to mortality in severe cases. Identification of the different acquired causes is important in preventing the disorder by guiding appropriate interventions.

Association between bullying at work and mental disorders: gender differences in the Italian people.

PubMed

Nolfe, Giovanni; Petrella, Claudio; Zontini, Gemma; Uttieri, Simona; Nolfe, Giuseppe

2010-11-01

In the last few years the international literature has shown an increasing attention for the work as life-event stressor, for its organizational characteristics as well as for job insecurity and interpersonal conflicts. We have studied 707 subjects who approached the Work Psychopathology Medical Centre of Naples to evaluate the DSM IV diagnoses and the degree of bullying at the workplace according to Leymann's definition. Two groups, with high and with low severity of bullying, were compared, mainly in relation to gender differences. The more frequent diagnoses were anxiety disorders (8.7% of the total), mood disorders (31.5%) and adjustment disorders (58.3%). The patients with higher degree of bullying were 55.7% among the subjects with anxiety disorders, 51.4% among the patients with adjustment disorders and 81.25% in the group with mood disorders. The odds of patients with severe bullying was 1.602 times higher for males than for females. Independently by the gender, the odds of patients being in the group with severe bullying were more than three times higher for subjects with mood disorders than for patients suffering from anxiety and adjustment disorders. In the male gender, the psychiatric disturbances are more correlated to bullying at the workplace and this datum is especially linked to the gender differences found in the relationship between severity of bullying and adjustment disorders. Among female employees the psychopathological dimensions could be linked with a more multifactorial genesis in relation to their psychosocial role in the cultural context we examined (Southern Italy).
Incidence of Hypothyroidism in Meniere’s Disease

PubMed Central

Santosh, U.P.

2016-01-01

Introduction Meniere’s disease is a disorder of the membranous labyrinth of the inner ear manifesting as vertigo, tinnitus, sensory neural hearing loss and aural fullness of known or unknown origin. Some patients may present after years into typical forms. The endocrine disorders, especially hypothyroidism and the factors like inflammation, trauma, otosclerosis, autoimmunity explains the multifactorial causation for the basis of Meniere’s disease. Endolymphatic hydrops is the pathologic term named for the defective regulation of endolymph volume with respect to production and absorption. However, hyper production of endolymph cannot be excluded. The cause of Meniers disease is multifactorial so clinical features of repeated attacks of variable duration cannot be explained satisfactorily based on single causation. Aim To study the incidence of hypothyroidism in Meniere’s disease and to assess the success rate of improvement in subjective symptoms after treatment. Materials and Methods The study was carried out on total 35 out patients who were clinically diagnosed of Meniere’s disease and of these 35 patients, 12 patients were found to have hypothyroidism. All patients with hypothyroidism were treated with oral thyroxin supplements and they were evaluated clinically at 3 weeks, 3 months and 6 months interval for the improvement in subjective symptoms on outpatient basis. Results In our study, the subjective improvement of all symptoms was seen in all cases of Meniere’s disease with hypothyroidism after 12 weeks of treatment. Conclusion The improvement in clinical symptoms after treatment demonstrates an association between Meniere’s disease and hypothyroidism which was found to be significant. Hence, clinicians should consider screening patients with Meniere disease for thyroid dysfunction who are not already taking supplements. PMID:27437251
Dry eye disease as an inflammatory disorder.

PubMed

Calonge, Margarita; Enríquez-de-Salamanca, Amalia; Diebold, Yolanda; González-García, María J; Reinoso, Roberto; Herreras, José M; Corell, Alfredo

2010-08-01

Dry eye disease (DED) is a prevalent inflammatory disorder of the lacrimal functional unit of multifactorial origin leading to chronic ocular surface disease, impaired quality of vision, and a wide range of complications, eventually causing a reduction in quality of life. It still is a frustrating disease because of the present scarcity of therapies that can reverse, or at least stop, its progression. A comprehensive literature survey of English-written scientific publications on the role of inflammation in DED. New investigations have demonstrated that a chronic inflammatory response plays a key role in the pathogenesis of human DED. Additionally, correlations between inflammatory molecules and clinical data suggest that inflammation can be responsible for some of the clinical symptoms and signs. Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.
A systems biology-led insight into the role of the proteome in neurodegenerative diseases.

PubMed

Fasano, Mauro; Monti, Chiara; Alberio, Tiziana

2016-09-01

Multifactorial disorders are the result of nonlinear interactions of several factors; therefore, a reductionist approach does not appear to be appropriate. Proteomics is a global approach that can be efficiently used to investigate pathogenetic mechanisms of neurodegenerative diseases. Here, we report a general introduction about the systems biology approach and mechanistic insights recently obtained by over-representation analysis of proteomics data of cellular and animal models of Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders, as well as of affected human tissues. Expert commentary: As an inductive method, proteomics is based on unbiased observations that further require validation of generated hypotheses. Pathway databases and over-representation analysis tools allow researchers to assign an expectation value to pathogenetic mechanisms linked to neurodegenerative diseases. The systems biology approach based on omics data may be the key to unravel the complex mechanisms underlying neurodegeneration.
LncRNAs: key players and novel insights into diabetes mellitus

PubMed Central

He, Xiaoyun; Ou, Chunlin; Xiao, Yanhua; Han, Qing; Li, Hao; Zhou, Suxian

2017-01-01

Long non-coding RNAs (LncRNAs) are a class of endogenous RNA molecules, which have a transcribing length of over 200 nt, lack a complete functional open reading frame (ORF), and rarely encode a functional short peptide. Recent studies have revealed that disruption of LncRNAs levels correlates with several human diseases, including diabetes mellitus (DM), a complex multifactorial metabolic disorder affecting more than 400 million people worldwide. LncRNAs are emerging as pivotal regulators in various biological processes, in the progression of DM and its associated complications, involving pancreatic β-cell disorder, insulin resistance, and epigenetic regulation, etc. Further investigation into the mechanisms of action of LncRNAs in DM will be of great value in the thorough understanding of pathogenesis. However, prior to successful application of LncRNAs, further search for molecular biomarkers and drug targets to provide a new strategy for DM prevention, early diagnosis, and therapy is warranted. PMID:29050364
Hyperbaric oxygen therapy for children with autism spectrum disorder.

PubMed

Sakulchit, Teeranai; Ladish, Chris; Goldman, Ran D

2017-06-01

Question As autism spectrum disorder (ASD) is a multifactorial condition, with genetic and environmental risk factors contributing to children's unique presentation and symptom severity, a range of treatments have been suggested. Parents of children with ASD in my clinic are asking me about alternative therapies to improve their children's condition. One of those therapies is hyperbaric oxygen therapy (HBOT); commercial advertisement in the past has suggested good results with this approach. Should I recommend the use of HBOT for children with ASD? Answer Hyperbaric oxygen therapy provides a higher concentration of oxygen delivered in a chamber or tube containing higher than sea level atmospheric pressure. Case series and randomized controlled trials show no evidence to support the benefit of HBOT for children with ASD. Only 1 randomized controlled trial reported effectiveness of this treatment, and those results have yet to be repeated. Copyright© the College of Family Physicians of Canada.
Autism, epilepsy, and synaptopathies: a not rare association.

PubMed

Keller, Roberto; Basta, Roberta; Salerno, Luana; Elia, Maurizio

2017-08-01

Autism spectrum disorders (ASD) are neurodevelopmental disorders typically diagnosed in childhood, characterized by core social dysfunction, rigid and repetitive behaviors, restricted interests, and abnormal sensorial sensitivity. ASD belong to multifactorial diseases: both genetic and environmental factors have been considered as potential risk factors for their onset. ASD are often associated with neurological conditions: the co-occurrence of epilepsy is well documented and there is also evidence of a higher prevalence of EEG abnormalities with 4-86% of individuals with ASD presenting epileptiform or not epileptiform EEG abnormalities. The presence of epilepsy in people with ASD may be determined by several structural alterations, genetic conditions, or metabolic dysfunctions, known to play a role in the emergence of both epilepsy and autism. The purpose of this article is to discuss precisely such latter cause of the autism-epilepsy association, focusing specifically on those "synaptic genes," whose mutation predisposes to both the diseases.
Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

PubMed Central

2013-01-01

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches. PMID:24289502
Predictors of infant foster care in cases of maternal psychiatric disorders

PubMed Central

Glangeaud-Freudenthal, Nine M.-C.; Sutter-Dallay, Anne-Laure; Thieulin, Anne-Claire; Dagens, Véronique; Zimmermann, Marie-Agathe; Debourg, Alain; Amzallag, Corinne; Cazas, Odile; Cammas, Rafaële; Klopfert, Marie-Emmanuelle; Rainelli, Christine; Tielemans, Pascale; Mertens, Claudine; Maron, Michel; Nezelof, Sylvie; Poinso, François

2013-01-01

Purpose Our aim was to investigate the factors associated with mother-child separation at discharge, after joint hospitalization in psychiatric mother-baby units (MBUs) in France and Belgium. Because parents with postpartum psychiatric disorders are at risk of disturbed parent-infant interactions, their infants have an increased risk of an unstable early foundation. They may be particularly vulnerable to environmental stress and have a higher risk of developing some psychiatric disorders in adulthood. Methods: This prospective longitudinal study of 1018 women with postpartum psychiatric disorders, jointly admitted with their infant, to 16 French and Belgian psychiatric mother-baby units (MBUs), used multifactorial logistic regression models to assess the risk factors for mother-child separation at discharge from MBUs. Those factors include some infant characteristics associated with personal vulnerability, parents’ pathology and psychosocial context. Results Most children were discharged with their mothers, but 151 (15%) were separated from their mothers at discharge. Risk factors independently associated with separation were: i) neonatal or infant medical problems or complications; ii) maternal psychiatric disorder; iii) paternal psychiatric disorder; iv) maternal lack of good relationships with others; v) mother receipt of disability benefits; vi) low social class. Conclusions This study highlights the existence of factors other than maternal pathology that lead to decisions to separate mother and child for the child’s protection in a population of mentally ill mothers jointly hospitalized with the baby in the postpartum period. PMID:22706788
Predictors of infant foster care in cases of maternal psychiatric disorders.

PubMed

Glangeaud-Freudenthal, Nine M-C; Sutter-Dallay, Anne-Laure; Thieulin, Anne-Claire; Dagens, Véronique; Zimmermann, Marie-Agathe; Debourg, Alain; Amzallag, Corinne; Cazas, Odile; Cammas, Rafaële; Klopfert, Marie-Emmanuelle; Rainelli, Christine; Tielemans, Pascale; Mertens, Claudine; Maron, Michel; Nezelof, Sylvie; Poinso, François

2013-04-01

Our aim was to investigate the factors associated with mother-child separation at discharge, after joint hospitalization in psychiatric mother-baby units (MBUs) in France and Belgium. Because parents with postpartum psychiatric disorders are at risk of disturbed parent-infant interactions, their infants have an increased risk of an unstable early foundation. They may be particularly vulnerable to environmental stress and have a higher risk of developing some psychiatric disorders in adulthood. This prospective longitudinal study of 1,018 women with postpartum psychiatric disorders, jointly admitted with their infant to 16 French and Belgian psychiatric mother-baby units (MBUs), used multifactorial logistic regression models to assess the risk factors for mother-child separation at discharge from MBUs. Those factors include some infant characteristics associated with personal vulnerability, parents' pathology and psychosocial context. Most children were discharged with their mothers, but 151 (15 %) were separated from their mothers at discharge. Risk factors independently associated with separation were: (1) neonatal or infant medical problems or complications; (2) maternal psychiatric disorder; (3) paternal psychiatric disorder; (4) maternal lack of good relationship with others; (5) mother receipt of disability benefits; (6) low social class. This study highlights the existence of factors other than maternal pathology that lead to decisions to separate mother and child for the child's protection in a population of mentally ill mothers jointly hospitalized with the baby in the postpartum period.
Recent developments in the genetics of schizophrenia.

PubMed

Shastry, B S

1999-09-01

Schizophrenia, which is also called "split personality," is a complex and multifactorial mental disorder with variable clinical manifestations. It perhaps represents several diseases and occurs throughout the world. It is a more-prevalent disorder among homeless people and is clinically characterized by hallucinations and delusions. The pathophysiology of schizophrenia is not localized to a single region of the brain and the etiology of this illness is not understood. Because of its complex pattern of inheritance, genetic techniques are not readily applicable in identifying the genes responsible for this disorder. Family, twin, and adoption studies, however, provide strong but indirect support for genetic components in the etiology of schizophrenia. Extensive linkage analyses now suggest that susceptibility genes may be present on chromosomes 5q, 6p, 8p, 13q, 18p, and 22q. Identification and characterization of these and other genes, as well as non-genetic factors, is one of the greatest challenges in biomedicine. This may ultimately lead to the development of a new line of effective and safe drugs or treatments for its prevention or cure.
Gynecological pelvic pain as emergency pathology.

PubMed

Rivera Domínguez, A; Mora Jurado, A; García de la Oliva, A; de Araujo Martins-Romeo, D; Cueto Álvarez, L

Acute pelvic pain is a common condition in emergency. The sources of acute pelvic pain are multifactorial, so it is important to be familiar with this type of pathologies. The purpose of this article is review the main causes of gynecological acute pelvic pain and their radiologic appearances to be able to make an accurate diagnosis and provide objective criteria for patient management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.
Vascular anomalies: classification, imaging characteristics and implications for interventional radiology treatment approaches

PubMed Central

Prajapati, H J S; Martin, L G; Patel, T H

2014-01-01

The term vascular anomaly represents a broad spectrum of vascular pathology, including proliferating vascular tumours and vascular malformations. While the treatment of most vascular anomalies is multifactorial, interventional radiology procedures, including embolic therapy, sclerotherapy and laser coagulation among others, are playing an increasingly important role in vascular anomaly management. This review discusses the diagnosis and treatment of common vascular malformations, with emphasis on the technique, efficacy and complications of different interventional radiology procedures. PMID:24588666
The maturational theory of brain development and cerebral excitability in the multifactorially inherited manic-depressive psychosis and schizophrenia.

PubMed

Saugstad, L F

1994-12-01

An association has been established between the multifactorially inherited rate of physical maturation and the final step in brain development, when some 40% of synapses are eliminated. This may imply that similarly to endocrine disease entities, we have cerebral disease entities at the extremes of the maturational rate continuum. The restriction of prepubertal pruning to excitatory synapses leaving the number of inhibitory ones fairly constant, implies changes in cerebral excitability as a function of rate of maturation (age at puberty). In early maturation there will be an excess in excitatory drive due to prematurely abridged pruning, which compounds a synchronization tendency inherent in excessive synaptic density. Lowering excitatory level with antiepileptics is hypothesized to be a logical treatment in this type of brain dysfunction. In late maturation, a deficit in excitatory drive due to failure to shut down the pruning process associated with a tendency to the breakdown of circuitry and desynchronization, adds to a similar adversity inherent in reduced synaptic density. Raising the excitatory level with convulsants is hypothesized to be the treatment for this type of CNS dysfunction. The maturational theory of Kraepelin's psychoses holds that they are naturally occurring contrasting chemical signaling disorders in the brain at the extremes of the maturational rate continuum: manic depressive psychosis is a disorder of the early maturer and comprises raised cerebral excitability and a raised density of synapses. This is successfully treated with anti-epileptics like sodium valproate and carbamazepin. Schizophrenia is a disorder in late maturation with reduced cerebral excitability and reduced synaptic density. This is accordingly treated with convulsants such as typical and atypical neuroleptics. However, the conventional effective treatments in both disorders act on inhibition only by either lowering or raising inhibitory level. While the neuroleptics drugs are superior anti-psychotics they nevertheless do not affect the deviation in cerebral excitability which would explain why they do not cure. Disturbed circadian rhythms which precede psychotic episodes in manic depressives accord with a primary dysfunction in the CNS, the suprachiasmatic nucleus of the hypothalamus via its direct input the glutamatergic retinohypothalamic tract. The residual deficits in schizophrenia accord with persistently disconnected circuitry and communication which is a consequence of reduced excitatory level and is manifested in insufficient motivation, a reduced drive associated hypofunction, and neuromuscular dysfunction.
Quality of life, anxiety, depression and obsessive-compulsive tendencies in patients with chronic hand eczema.

PubMed

Kouris, Anargyros; Armyra, Kalliopi; Christodoulou, Christos; Katoulis, Alexandros; Potouridou, Irene; Tsatovidou, Revekka; Rigopoulos, Dimitrios; Kontochristopoulos, Georgios

2015-06-01

Chronic hand eczema is a common dermatological disorder of multifactorial aetiology. It affects physical, material, social and psychological aspects of life, thereby impairing health-related quality of life. The aim of the present study was to assess quality of life, anxiety, depression and obsessive-compulsive tendencies in patients with chronic hand eczema. Seventy-one patients with chronic hand eczema were included in the study. Quality of life was evaluated according to the Dermatology Life Quality Index (DLQI). Patients were also assessed for anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), and for compulsive behaviour with the Leyton Trait Scale. The DLQI score was 11.11 ± 1.81 in patients with chronic hand eczema. Scores on the Leyton Trait Scale were significantly higher than those of healthy controls (p < 0.027). As concerns the HADS-Anxiety subscale, patients with hand dermatitis had statistically significantly higher scores than those of volunteers (p = 0.002). In contrast, no statistically significant difference was found between the two groups with regard to the HADS-Depression subscale score and total HADS score. Hand eczema treatment should address the severity of skin lesions as well as the psychological impact of hand eczema. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Ginkgo biloba in the treatment of tinnitus: An updated literature review.

PubMed

Mahmoudian-Sani, Mohammad Reza; Hashemzadeh-Chaleshtori, Morteza; Asadi-Samani, Majid; Yang, Qian

2017-06-01

Tinnitus is one of the common diseases of the ear that is associated with numerous physical and mental disorders. One of the known mechanisms in the tinnitus area with unknown reason is oxidative events. Based on the prevalence and economic costs and physical- psychological side effects caused by tinnitus and the importance of finding a suitable solution for its prevention and treatment, the need for further studies becomes more obvious in this context. This review article aimed to review studies on the effectiveness of Ginkgo biloba as a medicinal plant on patients with tinnitus. Google Scholar, Directory of Open Access Journals (DOAJ), PubMed, LISTA (EBSCO) and Web of Science have been searched. There are many studies on the therapeutic effect of Ginkgo biloba on patients with tinnitus. Most findings are in contrast with each other so that some of studies reported that Ginkgo biloba is effective in the treatment of tinnitus and other studies referred to it as ineffective herbal medicine. Generally, according to the previous studies and the present study, it can mention that the Ginkgo biloba may somewhat improve tinnitus. Since tinnitus is multifactorial, it is recommended to evaluate patients individually based on the cause of tinnitus, treatment formulas, and different doses of Ginkgo biloba at the more extensive level in future studies.
Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation

PubMed Central

Chalah, Moussa A.; Riachi, Naji; Ahdab, Rechdi; Créange, Alain; Lefaucheur, Jean-Pascal; Ayache, Samar S.

2015-01-01

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system (CNS) and the major cause of non-traumatic disability in young adults. Fatigue is a frequent symptom reported by the majority of MS patients during their disease course and drastically affects their quality of life. Despite its significant prevalence and impact, the underlying pathophysiological mechanisms are not well elucidated. MS fatigue is still considered the result of multifactorial and complex constellations, and is commonly classified into “primary” fatigue related to the pathological changes of the disease itself, and “secondary” fatigue attributed to mimicking symptoms, comorbid sleep and mood disorders, and medications side effects. Radiological, physiological, and endocrine data have raised hypotheses regarding the origin of this symptom, some of which have succeeded in identifying an association between MS fatigue and structural or functional abnormalities within various brain networks. Hence, the aim of this work is to reappraise the neural correlates of MS fatigue and to discuss the rationale for the emergent use of noninvasive brain stimulation (NIBS) techniques as potential treatments. This will include a presentation of the various NIBS modalities and a suggestion of their potential mechanisms of action in this context. Specific issues related to the value of transcranial direct current stimulation (tDCS) will be addressed. PMID:26648845
Careful assessment key in managing prostatitis.

PubMed

Gujadhur, Rahul; Aning, Jonathan

2015-04-01

Prostatitis is a common condition estimated to affect up to 30% of men in their lifetime, it is most prevalent in men aged between 35 and 50. Prostatitis is subclassified into: acute bacterial prostatitis, chronic bacterial prostatitis, chronic pelvic pain and asymptomatic inflammatory prostatitis. Acute bacterial prostatitis presents with acute onset pelvic pain which may or may not be related to voiding, lower urinary tract symptoms, sometimes haematuria or haematospermia and systemic symptoms such as fever and rigors. A documented history of recurrent urinary tract infections is the key feature of chronic bacterial prostatitis. Duration of symptoms > 3 months defines chronicity. The key symptom of chronic pelvic pain syndrome is pain. Patients may describe pain during or after ejaculation as their predominant symptom. Clinical assessment includes a thorough history and examination. A digital rectal examination should be performed after a midstream urine (MSU) sample has been collected for urine dipstick, microscopy and culture. The prostate should be checked for nodules. In acute bacterial prostatitis the MSU is the only laboratory investigation required. Chronic pelvic pain syndrome may be multifactorial and part of a more generalised pain disorder. Pelvic floor muscle abnormalities, altered neuroendocrine pathways, chemically induced inflammation, bacterial infection, autoimmune processes, dysfunctional voiding as well intraprostatic ductal reflux mechanisms have all been identified in men with chronic pelvic pain syndrome.
Oxidants and anti-oxidants status in acne vulgaris patients with varying severity.

PubMed

Al-Shobaili, Hani A

2014-01-01

Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls. Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease's activity and to monitor its treatment.
The effect of a knowledge-based ergonomic intervention amongst administrators at Aga Khan University Hospital, Nairobi.

PubMed

Wanyonyi, Nancy; Frantz, Jose; Saidi, Hassan

2015-01-01

Low back pain (LBP) and neck pain are part of the common work-related musculoskeletal disorders with a large impact on the affected person. Despite having a multifactorial aetiology, ergonomic factors play a major role thus necessitating workers' education. To determine the prevalence of ergonomic-related LBP and neck pain, and describe the effect of a knowledge-based ergonomic intervention amongst administrators in Aga Khan University Hospital, Nairobi. This study applied a mixed method design utilizing a survey and two focus group discussions (FGD). A self-administered questionnaire was distributed to 208 participants through systematic sampling. A one hour knowledge-based ergonomic session founded on the survey results was thereafter administered to interested participants, followed by two FGDs a month later with purposive selection of eight participants to explore their experience of the ergonomic intervention. Quantitative data was captured and analyzed using SPSS by means of descriptive and inferential statistics, whereas thematic content analysis was used for qualitative data. Most participants were knowledgeable about ergonomic-related LBP and neck pain with a twelve month prevalence of 75.5% and 67.8% respectively. Continual ergonomic education is necessary for adherence to health-related behaviours that will preventwork-related LBP and neck pain.

Dupuytren's: a systems biology disease

PubMed Central

2011-01-01

Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder of the palm of the hands leading to digital contracture. DD commonly occurs in individuals of northern European extraction. Cellular components and processes associated with DD pathogenesis include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components. Histology has shown increased but varying levels of particular types of collagen, myofibroblasts and myoglobin proteins in DD tissue. Free radicals and localised ischaemia have been suggested to trigger the proliferation of DD tissue. Although the existing available biological information on DD may contain potentially valuable (though largely uninterpreted) information, the precise aetiology of DD remains unknown. Systems biology combines mechanistic modelling with quantitative experimentation in studies of networks and better understanding of the interaction of multiple components in disease processes. Adopting systems biology may be the ideal approach for future research in order to improve understanding of complex diseases of multifactorial origin. In this review, we propose that DD is a disease of several networks rather than of a single gene, and show that this accounts for the experimental observations obtained to date from a variety of sources. We outline how DD may be investigated more effectively by employing a systems biology approach that considers the disease network as a whole rather than focusing on any specific single molecule. PMID:21943049
Psoriasis and Microbiota: A Systematic Review.

PubMed

Benhadou, Farida; Mintoff, Dillon; Schnebert, Benjamin; Thio, Hok Bing

2018-06-02

Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, unaffected skin. Through an extensive review of the literature, we aim to discuss the skin and gut microbiota and redefine their role in the pathogenesis of psoriasis. Unfortunately, the direct link between the skin microbiota and the pathogenesis of psoriasis remains to be clearly established. Apart from improving the course of psoriasis, selective modulation of the microbiota may increase the efficacy of medical treatments as well as attenuate their side effects.
[Urinary tract dysfunction in older patients].

PubMed

Verdejo, Carlos; Méndez, Santiago; Salinas, Jesús

2016-11-18

Urinary tract dysfunction in older patients has a multifactorial aetiology and is not a uniform clinical condition. Changes due to physiological ageing as well as comorbidity and polypharmacy, can produce several dynamic conditions such as urinary incontinence and urinary retention. Lower urinary tract symptoms increase with age in both sexes and are a major problem in older patients due to their medical and psychosocial consequences. For these reasons, in assessing urinary dysfunction in older patients, we should consider external circumstances such as polypharmacy, poor mobility, affective and cognitive disorders and also accessibility to housing. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Surgical treatment of a Pattern I Obstructive Sleep Apnea Syndrome individual - clinical case report

PubMed Central

Feitoza, Christiane Cavalcante; da-Silva, Matheus Corrêa; Nascimento, Yasmim Lima; Leite, Elaine Sobral; Pereira, Corintho Viana; Patrocínio, Lucas Gomes

2017-01-01

Obstructive Sleep Apnea Syndrome (OSA) is a multifactorial disease that highly alters a persons quality of life. It is characterized by the repeated interruption of breathing during sleep, due to an obstruction or the collapse of the upper airways. Since it is a multifactorial etiological disorder, it requires a thorough diagnosis and treatment with an interdisciplinary team, which comprises several professionals such as a surgical dentist, phonoaudiologist, otorhinolaryngologist, sleep doctor, neurologist and physiotherapist. The diagnosis and the degree of severity of the syndrome is determined through a polysomnography examination. After that, the best form of treatment is devised depending on the gravity of the case. In cases of moderate to severe apnea, invasive treatment through surgical procedures such as maxillomandibular advancement remains the preferred option as it increases the posterior air space, reducing and/or eliminating the obstruction. Thus, improving the patients respiratory function and, consequently, his quality of life as it is shown in the clinical case at hand. In which the male patient, facial pattern type I, 41 years of age, diagnosed with moderate OSA (Apnea-Hypopnea Index - AHI of 23.19), decided to have a surgical treatment instead of a conservative one, resulting in the cure of apnea (AHI of 0.3). PMID:29410749
Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer’s and Parkinson’s Disease

PubMed Central

Caruana, Mario; Cauchi, Ruben; Vassallo, Neville

2016-01-01

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common age-related neurodegenerative disorders and hence pose remarkable socio-economical burdens to both families and state. Although AD and PD have different clinical and neuropathological features, they share common molecular mechanisms that appear to be triggered by multi-factorial events, such as protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation, ultimately leading to neuronal cell death. Currently, there are no established and validated disease-modifying strategies for either AD or PD. Among the various lifestyle factors that may prevent or slow age-related neurodegenerative diseases, epidemiological studies on moderate consumption of red wine, especially as part of a holistic Mediterranean diet, have attracted increasing interest. Red wine is particularly rich in specific polyphenolic compounds that appear to affect the biological processes of AD and PD, such as quercetin, myricetin, catechins, tannins, anthocyanidins, resveratrol, and ferulic acid. Indeed, there is now a consistent body of in vitro and in vivo data on the neuroprotective effects of red wine polyphenols (RWP) showing that they do not merely possess antioxidant properties, but may additionally act upon, in a multi-target manner, the underlying key mechanisms featuring in both AD and PD. Furthermore, it is important that bioavailability issues are addressed in order for neuroprotection to be relevant in a clinical study scenario. This review summarizes the current knowledge about the major classes of RWP and places into perspective their potential to be considered as nutraceuticals to target neuropathology in AD and PD. PMID:27570766
Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer's and Parkinson's Disease.

PubMed

Caruana, Mario; Cauchi, Ruben; Vassallo, Neville

2016-01-01

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related neurodegenerative disorders and hence pose remarkable socio-economical burdens to both families and state. Although AD and PD have different clinical and neuropathological features, they share common molecular mechanisms that appear to be triggered by multi-factorial events, such as protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation, ultimately leading to neuronal cell death. Currently, there are no established and validated disease-modifying strategies for either AD or PD. Among the various lifestyle factors that may prevent or slow age-related neurodegenerative diseases, epidemiological studies on moderate consumption of red wine, especially as part of a holistic Mediterranean diet, have attracted increasing interest. Red wine is particularly rich in specific polyphenolic compounds that appear to affect the biological processes of AD and PD, such as quercetin, myricetin, catechins, tannins, anthocyanidins, resveratrol, and ferulic acid. Indeed, there is now a consistent body of in vitro and in vivo data on the neuroprotective effects of red wine polyphenols (RWP) showing that they do not merely possess antioxidant properties, but may additionally act upon, in a multi-target manner, the underlying key mechanisms featuring in both AD and PD. Furthermore, it is important that bioavailability issues are addressed in order for neuroprotection to be relevant in a clinical study scenario. This review summarizes the current knowledge about the major classes of RWP and places into perspective their potential to be considered as nutraceuticals to target neuropathology in AD and PD.
Rodent Hypoxia–Ischemia Models for Cerebral Palsy Research: A Systematic Review

PubMed Central

Rumajogee, Prakasham; Bregman, Tatiana; Miller, Steven P.; Yager, Jerome Y.; Fehlings, Michael G.

2016-01-01

Cerebral palsy (CP) is a complex multifactorial disorder, affecting approximately 2.5–3/1000 live term births, and up to 22/1000 prematurely born babies. CP results from injury to the developing brain incurred before, during, or after birth. The most common form of this condition, spastic CP, is primarily associated with injury to the cerebral cortex and subcortical white matter as well as the deep gray matter. The major etiological factors of spastic CP are hypoxia/ischemia (HI), occurring during the last third of pregnancy and around birth age. In addition, inflammation has been found to be an important factor contributing to brain injury, especially in term infants. Other factors, including genetics, are gaining importance. The classic Rice–Vannucci HI model (in which 7-day-old rat pups undergo unilateral ligation of the common carotid artery followed by exposure to 8% oxygen hypoxic air) is a model of neonatal stroke that has greatly contributed to CP research. In this model, brain damage resembles that observed in severe CP cases. This model, and its numerous adaptations, allows one to finely tune the injury parameters to mimic, and therefore study, many of the pathophysiological processes and conditions observed in human patients. Investigators can recreate the HI and inflammation, which cause brain damage and subsequent motor and cognitive deficits. This model further enables the examination of potential approaches to achieve neural repair and regeneration. In the present review, we compare and discuss the advantages, limitations, and the translational value for CP research of HI models of perinatal brain injury. PMID:27199883
How are multifactorial beliefs about the role of genetics and behavior in cancer causation associated with cancer risk cognitions and emotions in the US population?

PubMed

Hamilton, Jada G; Waters, Erika A

2018-02-01

People who believe that cancer has both genetic and behavioral risk factors have more accurate mental models of cancer causation and may be more likely to engage in cancer screening behaviors than people who do not hold such multifactorial causal beliefs. This research explored possible health cognitions and emotions that might produce such differences. Using nationally representative cross-sectional data from the US Health Information National Trends Survey (N = 2719), we examined whether endorsing a multifactorial model of cancer causation was associated with perceptions of risk and other cancer-related cognitions and affect. Data were analyzed using linear regression with jackknife variance estimation and procedures to account for the complex survey design and weightings. Bivariate and multivariable analyses indicated that people who endorsed multifactorial beliefs about cancer had higher absolute risk perceptions, lower pessimism about cancer prevention, and higher worry about harm from environmental toxins that could be ingested or that emanate from consumer products (Ps < .05). Bivariate analyses indicated that multifactorial beliefs were also associated with higher feelings of risk, but multivariable analyses suggested that this effect was accounted for by the negative affect associated with reporting a family history of cancer. Multifactorial beliefs were not associated with believing that everything causes cancer or that there are too many cancer recommendations to follow (Ps > .05). Holding multifactorial causal beliefs about cancer are associated with a constellation of risk perceptions, health cognitions, and affect that may motivate cancer prevention and detection behavior. Copyright © 2017 John Wiley & Sons, Ltd.
Multiple tendon ruptures of unknown etiology.

PubMed

Axibal, Derek P; Anderson, John G

2013-10-01

Tendon ruptures are common findings in foot and ankle practice. The etiology of tendon ruptures tends to be multifactorial-usually due to a combination of trauma, effects of systemic diseases, adverse effects of medications, and obesity. We present an unusual case of right Achilles tendinitis, left Achilles tendon rupture, bilateral peroneus longus tendon rupture, and left peroneus brevis tendon rupture of unknown etiology. This case report highlights the need for research for other possible, lesser known etiologies of tendon pathology. Therapeutic, Level IV, Case Study.
Genes and inheritance.

PubMed

Middelton, L A; Peters, K F

2001-10-01

The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are introduced and the biochemistry of genetic errors is described.
Death by acid rain: VAP or EXIT?

PubMed

Thorburn, Kentigern; Darbyshire, Andrew

2009-01-01

Ventilator-associated pneumonia (VAP) is a new (nosocomial) lower respiratory tract infection diagnosed in mechanically ventilated patients 48 or more hours after intubation. There is no gold standard for establishing the diagnosis and its pathogenesis is iatrogenic and multifactorial. Gastro-oesophageal reflux is common in mechanically ventilated children, but its role in VAP remains speculative. VAP is associated with increased mortality and morbidity, prolonged duration of ventilation and hospital stay, and escalated costs of hospitalisation. VAP 'bundles' are championed as the antidote.
Assessment of copy number variations in 120 patients with Poland syndrome.

PubMed

Vaccari, Carlotta Maria; Tassano, Elisa; Torre, Michele; Gimelli, Stefania; Divizia, Maria Teresa; Romanini, Maria Victoria; Bossi, Simone; Musante, Ilaria; Valle, Maura; Senes, Filippo; Catena, Nunzio; Bedeschi, Maria Francesca; Baban, Anwar; Calevo, Maria Grazia; Acquaviva, Massimo; Lerone, Margherita; Ravazzolo, Roberto; Puliti, Aldamaria

2016-11-25

Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown. To investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic and array-CGH analyses were performed in 120 PS patients. Following the application of stringent filter criteria, 14 rare copy number variations (CNVs) were identified in 14 PS patients in different regions outside known common copy number variations: seven genomic duplications and seven genomic deletions, enclosing the two previously reported PS associated chromosomal deletions. These CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA binding and apoptosis processes. The analysis also provided a number of candidate genes possibly causing the developmental defects observed in PS patients, among others REV3L, a gene coding for an error-prone DNA polymerase previously associated with Möbius Syndrome with variable phenotypes including pectoralis muscle agenesis. A number of rare CNVs were identified in PS patients, and these involve genes that represent candidates for further evaluation. Rare inherited CNVs may contribute to, or represent risk factors of PS in a multifactorial mode of inheritance.
Sex, stress and sleep apnoea: Decreased susceptibility to upper airway muscle dysfunction following intermittent hypoxia in females.

PubMed

O'Halloran, Ken D; Lewis, Philip; McDonald, Fiona

2017-11-01

Obstructive sleep apnoea syndrome (OSAS) is a devastating respiratory control disorder more common in men than women. The reasons for the sex difference in prevalence are multifactorial, but are partly attributable to protective effects of oestrogen. Indeed, OSAS prevalence increases in post-menopausal women. OSAS is characterized by repeated occlusions of the pharyngeal airway during sleep. Dysfunction of the upper airway muscles controlling airway calibre and collapsibility is implicated in the pathophysiology of OSAS, and sex differences in the neuro-mechanical control of upper airway patency are described. It is widely recognized that chronic intermittent hypoxia (CIH), a cardinal feature of OSAS due to recurrent apnoea, drives many of the morbid consequences characteristic of the disorder. In rodents, exposure to CIH-related redox stress causes upper airway muscle weakness and fatigue, associated with mitochondrial dysfunction. Of interest, in adults, there is female resilience to CIH-induced muscle dysfunction. Conversely, exposure to CIH in early life, results in upper airway muscle weakness equivalent between the two sexes at 3 and 6 weeks of age. Ovariectomy exacerbates the deleterious effects of exposure to CIH in adult female upper airway muscle, an effect partially restored by oestrogen replacement therapy. Intriguingly, female advantage intrinsic to upper airway muscle exists with evidence of substantially greater loss of performance in male muscle during acute exposure to severe hypoxic stress. Sex differences in upper airway muscle physiology may have relevance to human OSAS. The oestrogen-oestrogen receptor α axis represents a potential therapeutic target in OSAS, particularly in post-menopausal women. Copyright © 2016 Elsevier B.V. All rights reserved.
The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision as an appropriate diagnostic for premature ejaculation.

PubMed

Shabsigh, Ridwan; Rowland, David

2007-09-01

The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) criteria for premature ejaculation (PE) are multifactorial, and include concepts of latency, perceived control over ejaculation, and personal distress and interpersonal difficulty related to the condition. Recent publications have suggested that these criteria are not supported by empirical evidence, leading to the proposal that a PE diagnosis should be based solely on intravaginal ejaculatory latency time (IELT), while the presence of other factors (such as perceived lack of control over ejaculation) may be used to guide treatment decisions. To examine the evidence supporting the elements of the DSM-IV-TR criteria for PE. Literature searches on IELT, perceived control over ejaculation, and personal distress and interpersonal difficulty related to ejaculation. From a historical perspective, there has been a lack of large observational studies that evaluated the contributions of the DSM-IV-TR components in men with PE. However, recently performed large observational studies have generated data supporting the inclusion of perceived control over ejaculation and personal distress related to ejaculation in the definition of PE. Furthermore, emerging evidence indicates that a perceived lack of control over ejaculation is directly associated with elevated personal distress related to ejaculation and decreased satisfaction with sexual intercourse, while the effects of IELT on these parameters are indirect, and mediated by perceived control over ejaculation. A key advantage of the DSM-IV-TR approach to the diagnosis of PE is that it firmly links PE to a negative outcome for the patient, which is an element common to diagnostic criteria for other conditions, including depression, hypertension, and osteoporosis. This new evidence strongly suggests that the DSM-IV-TR criteria for PE encompass aspects of the condition that patients describe as important.
A systematic review of musculoskeletal disorders among school teachers

PubMed Central

2011-01-01

Background Musculoskeletal disorders (MSD) represent one of the most common and most expensive occupational health problems in both developed and developing countries. School teachers represent an occupational group among which there appears to be a high prevalence of MSD. Given that causes of MSD have been described as multi-factorial and prevalence rates vary between body sites and location of study, the objective of this systematic review was to investigate the prevalence and risk factors for MSD among teaching staff. Methods The study involved an extensive search of MEDLINE and EMBASE databases in 2011. All studies which reported on the prevalence and/or risk factors for MSD in the teaching profession were initially selected for inclusion. Reference lists of articles identified in the original search were then examined for additional publications. Of the 80 articles initially located, a final group of 33 met the inclusion criteria and were examined in detail. Results This review suggests that the prevalence of self-reported MSD among school teachers ranges between 39% and 95%. The most prevalent body sites appear to be the back, neck and upper limbs. Nursery school teachers appear to be more likely to report suffering from low back pain. Factors such as gender, age, length of employment and awkward posture have been associated with higher MSD prevalence rates. Conclusion Overall, this study suggests that school teachers are at a high risk of MSD. Further research, preferably longitudinal, is required to more thoroughly investigate the issue of MSD among teachers, with a greater emphasis on the possible wider use of ergonomic principles. This would represent a major step forward in the prevention of MSD among teachers, especially if easy to implement control measures could be recommended. PMID:22087739
[Features of cranio-cerebral trauma in victims of road accidents].

PubMed

Ogleznev, K Ia; Stankevich, P V

2001-01-01

The paper deals with the specific features of brain injury (BI) in victims of road traffic accidents (RTA). RTA victims are most commonly pedestrians (62.6%) and less commonly drivers (17.5%). In over half the cases (62.6%), BI due to RTA is associated with extracranial lesions, leading to diagnostic problems. The pattern and site of lesions are related to the type of a transport vehicle and to the role of a victim as a traffic participant. Multiple extracranial lesions are mostly frequently encountered in victim pedestrians (30.3%), BI concurrent with chest damage is common in drivers (12.8%), BI concurrent with "whip" injury of the cervical spine is found in drivers and passengers though such combinations may also seen in pedestrians (1.5%--5 cases). The most severe form of brain compression is multifactorial compression (27.6%) and its most common form is compression with subdural hematoma (35.3%).
Acute esophageal necrosis and low-flow state

PubMed Central

Burtally, Ahmad; Gregoire, Philippe

2007-01-01

Acute esophageal necrosis (AEN), also called black esophagus, is quite exceptional. Endoscopic findings show circumferential black discolouration of the esophagus with or without exudates. The etiology of AEN is presently unknown and is assumed to be multifactorial. Distal esophageal involvement with proximal extension ending sharply at the gastroesophageal junction is the most common presentation. The present case report describes the clinical and endoscopic evolution of black esophagus observed in a patient with significant peripheral vascular disease, who was presented to the intensive care unit at the Hopital Saint-Francois d’Assise (Quebec City, Quebec). Through an extensive review of the literature, common underlying clinical conditions of patients diagnosed with AEN have been identified. PMID:17431514
Clinical management of sleep disturbances in Alzheimer’s disease: current and emerging strategies

PubMed Central

Urrestarazu, Elena; Iriarte, Jorge

2016-01-01

Sleep and circadian disorders in Alzheimer’s disease (AD) are more frequent than in the general population and appear early in the course of the disease. Quality of sleep and quality of life are parallel in these patients, and such disorders also represent a heavy burden for caregivers. Although alterations in melatonin and hypocretins (orexins) seem to play a key role in the origin of these disturbances, the etiology of these disorders is multifactorial, including many factors such as environment, behavior, treatments, and comorbidities, among others. A comprehensive evaluation of sleep in each patient is essential in the design of the treatment that includes nonpharmacological and pharmacological approaches. One particularly interesting point is the possibility of a role of sleep disorders in the pathogenesis of AD, raising the possibility that treating the sleep disorder may alter the course of the disease. In this review, we present an update on the role of sleep disorders in AD, the bidirectional influence of sleep problems and AD, and treatment options. Behavioral measures, bright light therapy (BLT), melatonin, and other drugs are likely well known and correctly managed by the physicians in charge of these patients. In spite of the multiple treatments used, evidence of efficacy is scarce and more randomized double-blind placebo-controlled studies are needed. Future directions for treatment are the establishment of BLT protocols and the development of drugs with new mechanisms of action, especially hypocretin receptor antagonists, melatonin receptor agonists, and molecules that modulate the circadian clock. PMID:26834500
Multifactorial intervention for children with asthma and overweight (Mikado): study design of a randomised controlled trial.

PubMed

Willeboordse, Maartje; van de Kant, Kim D G; de Laat, Maroeska N; van Schayck, Onno C P; Mulkens, Sandra; Dompeling, Edward

2013-05-21

In children, the prevalence's of both obesity and asthma are disconcertingly high. Asthmatic children with obesity are characterised by less asthma control and a high need for asthma medication. As the obese asthmatic child is becoming more common in the clinical setting and the disease burden of the asthma-obesity phenotype is high, there is an increasing need for effective treatment in these children. In adults, weight reduction resulted in improved lung function, better asthma control and less need for asthma medication. In children this is hardly studied. The Mikado study aims to evaluate the effectiveness of a long term multifactorial weight reduction intervention, on asthma characteristics in children with asthma and a high body weight. The Mikado study is a two-armed, randomised controlled trial. In total, 104 participants will be recruited via online questionnaires, pulmonary paediatricians, the youth department of the Municipal Health Services and cohorts of existing studies. All participants will be aged 6-16 years, will have current asthma, a Body Mass Index in the overweight or obesity range, and no serious comorbidities (such as diabetes, heart diseases). Participants in the intervention arm will receive a multifactorial intervention of 18 months consisting of sessions concerning sports, parental involvement, individual counselling and lifestyle advices including dietary advices and cognitive behavioural therapy. The control group will receive usual care. The primary outcome variables will include Forced Expiratory Volume in one second and Body Mass Index - Standard Deviation Score. Secondary outcomes will include other lung function parameters (including dynamic and static lung function parameters), asthma control, asthma-specific quality of life, use of asthma medication and markers of systemic inflammation and airway inflammation. In this randomised controlled trial we will study the potential of a multifactorial weight reduction intervention to improve asthma-related outcome measures in asthmatic children with overweight. Moreover, it will provide information about the underlying mechanisms in the relationship between asthma and a high body weight in children. These findings can contribute to optimal management programs and better clinical guidelines for children with asthma and overweight. Clinicaltrial.gov NCT00998413.
Manic depressive psychosis and schizophrenia are neurological disorders at the extremes of CNS maturation and nutritional disorders associated with a deficit in marine fat.

PubMed

Saugstad, L F

2001-12-01

The maturational theory of brain development comprises manic depressive psychosis and schizophrenia. It holds that the disorders are part of human diversity in growth and maturation, which explains their ubiquity, shared susceptibility genes and multifactorial inheritance. Rate of maturation and age at puberty are the genotype; the disorders are localized at the extremes with normality in between. This is based on the association between onset of puberty and the final regressive event, with pruning of 40% of excitatory synapses leaving the inhibitory ones fairly unchanged. This makes excitability, a fundamental property of nervous tissue, a distinguishing factor: the earlier puberty, the greater excitability--the later puberty, the greater deficit. Biological treatment supports deviation from the norm: neuroleptics are convulsant; antidepressives are anti-epiletogenic. There is an association between onset of puberty and body-build: early maturers are pyknic broad-built, late ones linearly leptosomic. This discrepancy is similar to that in the two disorders, supporting the theory that body-build is the phenotype. Standard of living is the environmental factor, which affects pubertal age and shifts the panorama of mental illness accordingly. Unnatural death has increased with antipsychotics. Other treatment is needed. PUFA deficit has been observed in RBC in both disorders and striking improvements with addition of minor amounts of PUFA. This supports that dietary deficit might cause psychotic development and that prevention is possible. Other neurological disorders also profit from PUFA, underlining a general deficit in the diet.

Animal models of tic disorders: A translational perspective

PubMed Central

Godar, Sean C.; Mosher, Laura J.; Di Giovanni, Giuseppe; Bortolato, Marco

2014-01-01

Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. PMID:25244952
Menopause, obesity and inflammation: interactive risk factors for Alzheimer’s disease

PubMed Central

Christensen, Amy; Pike, Christian J.

2015-01-01

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder, the development of which is regulated by several environmental and genetic risk factors. Two factors theorized to contribute to the initiation and/or progression of AD pathogenesis are age-related increases in inflammation and obesity. These factors may be particularly problematic in women. The onset of menopause in mid-life elevates the vulnerability of women to AD, an increased risk that is likely associated with the depletion of estrogens. Menopause is also linked with an abundance of additional changes, including increased central adiposity and inflammation. Here, we review the current literature to explore the interactions between obesity, inflammation, menopause and AD. PMID:26217222
Genetics and child psychiatry: I Advances in quantitative and molecular genetics.

PubMed

Rutter, M; Silberg, J; O'Connor, T; Simonoff, E

1999-01-01

Advances in quantitative psychiatric genetics as a whole are reviewed with respect to conceptual and methodological issues in relation to statistical model fitting, new genetic designs, twin and adoptee studies, definition of the phenotype, pervasiveness of genetic influences, pervasiveness of environmental influences, shared and nonshared environmental effects, and nature-nurture interplay. Advances in molecular genetics are discussed in relation to the shifts in research strategies to investigate multifactorial disorders (affected relative linkage designs, association strategies, and quantitative trait loci studies); new techniques and identified genetic mechanisms (expansion of trinucleotide repeats, genomic imprinting, mitochondrial DNA, fluorescent in-situ hybridisation, behavioural phenotypes, and animal models); and the successful localisation of genes.
Clinical features and pathophysiology of Complex Regional Pain Syndrome – current state of the art

PubMed Central

Marinus, Johan; Moseley, G. Lorimer; Birklein, Frank; Baron, Ralf; Maihöfner, Christian; Kingery, Wade S.; van Hilten, Jacobus J.

2017-01-01

That a minor injury can trigger a complex regional pain syndrome (CRPS) - multiple system dysfunction, severe and often chronic pain and disability - has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently increased our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Varying susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS. PMID:21683929
Hear ye? Hear ye! Successful auditory aging.

PubMed Central

Gates, G A; Rees, T S

1997-01-01

Age-related hearing loss (presbycusis) is a multifactorial process that affects nearly all people in their senior years. Most cases are due to a loss of cochlear hair cell function and are well mediated by communication courtesy and modern amplification technology. Severe hearing loss is generally due to cochlear problems or age-related diseases and may require speech reading, assistive listening devices, and cochlear implants, depending on the degree of loss. Presbycusis may seriously impair communication and contribute to isolation, depression, and possibly dementia. Accurate diagnosis and prompt remediation are widely available but are frequently underused. Geriatric health care and well-being is enhanced by the detection and remediation of communication disorders. PMID:9348755
Chronic progressive lymphoedema in draught horses.

PubMed

de Keyser, K; Janssens, S; Buys, N

2015-05-01

The objective of this review was to summarise and evaluate the current state of knowledge about chronic progressive lymphoedema in draught horses. Clinical signs of this multifactorial disorder are mainly restricted to the lower limbs, comprising progressively deteriorating skin, swelling and deformation. Although typical lesions were first reported at the beginning of the 20th century, chronic progressive lymphoedema was recognised as a specific syndrome only in 2003, and since then research has driven forward. Despite the high prevalence in some breeds and the serious economic impact, the pathogenesis is not fully understood, and the available treatment options remain symptomatic and noncurative. There is a need to improve diagnostic techniques and to develop selection tools. © 2014 EVJ Ltd.
Review of the mechanisms and therapeutic avenues for retinal and choroidal vascular dysfunctions in retinopathy of prematurity.

PubMed

Rivera, José Carlos; Madaan, Ankush; Zhou, Tianwei Ellen; Chemtob, Sylvain

2016-12-01

Retinopathy of prematurity (ROP) is a multifactorial disease and the main cause of visual impairment and blindness in premature neonates. The inner retina has been considered the primary region affected in ROP, but choroidal vascular degeneration and progressive outer retinal dysfunctions have also been observed. This review focuses on observations regarding neurovascular dysfunctions in both the inner and outer immature retina, the mechanisms and the neuronal-derived factors implicated in the development of ROP, as well potential therapeutic avenues for this disorder. Alterations in the neurovascular integrity of the inner and outer retina contribute to the development of ROP. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Summary of Recommendations.

PubMed

Barberà, Joan Albert; Román, Antonio; Gómez-Sánchez, Miguel Ángel; Blanco, Isabel; Otero, Remedios; López-Reyes, Raquel; Otero, Isabel; Pérez-Peñate, Gregorio; Sala, Ernest; Escribano, Pilar

2018-04-01

Pulmonary hypertension is a hemodynamic disorder defined by abnormally high pulmonary artery pressure that can occur in numerous diseases and clinical situations. The causes of pulmonary hypertension are classified into 5 major groups: arterial, due to left heart disease, due to lung disease and/or hypoxemia, chronic thromboembolic, with unclear and/or multifactorial mechanisms. This is a brief summary of the Guidelines on the Diagnostic and Treatment of Pulmonary Hypertension of the Spanish Society of Pulmonology and Thoracic Surgery. These guidelines describe the current recommendations for the diagnosis and treatment of the different pulmonary hypertension groups. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.
Clinical and manometric characteristics of patients with Parkinson's disease and esophageal symptoms.

PubMed

Su, A; Gandhy, R; Barlow, C; Triadafilopoulos, G

2017-04-01

Dysphagia is a common problem in patients with Parkinson's disease (PD); its etiology is multifactorial and its management is challenging. In this retrospective cohort analysis using prospectively collected data, we aimed to objectively characterize dysphagia and/or other esophageal symptoms in patients with PD, assess the prevalence of outflow obstruction as well as major or minor disorders of esophageal peristalsis leading to impaired esophageal clearance and highlight objective parameters that can help in the current management algorithm. Thirty-three consecutive patients with PD presenting with dysphagia, odynophagia, heartburn, regurgitation, chest pain, and weight loss underwent clinical and functional evaluation by high-resolution manometry (HRM). Esophagogastric junction (EGJ) outflow obstruction and major as well as minor disorders of peristalsis were then assessed using the Chicago classification (v3). Thirty-three PD patients with esophageal symptoms were enrolled in the study; 12 of them reported weight loss that was considered as potentially reflecting underlying esophageal dysfunction. The median age of the patients was 70 years (range: 53-89 years), 24 (75%) were men. The majority (62%) experienced dysphagia, likely contributing to weight loss in 41% of patients. Odynophagia was rare (6%) while GER symptoms, such as heartburn, regurgitation, and chest pain were noted in 37%, 31%, and 28% of patients, respectively. Using the hierarchy of the Chicago classification, 12 patients (39%) exhibited EGJ outflow obstruction, 16 (48%) diffuse esophageal spasm (DES), 18 (55%), ineffective esophageal peristalsis (IEM), 16 (48%) fragmented peristalsis, and only 2 patients (6%) had normal HRM tracings. There were no patients with HRM features of achalasia. Dysphagia is common in patients with PD and is associated with a high prevalence of underlying motility disturbances as identified by HRM. The exact impact of these motility abnormalities on symptom induction and their role in influencing clinical management are unclear and will require further study. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
The Latent Structure of Attention Deficit/Hyperactivity Disorder in an Adult Sample

PubMed Central

Marcus, David K.; Norris, Alyssa L.; Coccaro, Emil F.

2012-01-01

The vast majority of studies that have examined the latent structure of attention deficit/hyperactivity disorder (ADHD) in children and adolescents have concluded that ADHD has a dimensional latent structure. In other words, ADHD symptomatology exists along a continuum and there is no natural boundary or qualitative distinction (i.e., taxon) separating youth with ADHD from those with subclinical inattention or hyperactivity/impulsivity problems. Although adult ADHD appears to be less prevalent than ADHD in youth (which could suggest a more severe adult ADHD taxon), researchers have yet to examine the latent structure of ADHD in adults. The present study used a sample (N = 600) of adults who completed a self-report measure of ADHD symptoms. The taxometric analyses revealed a dimensional latent structure for inattention, hyperactivity/impulsivity, and ADHD. These findings are consistent with previous taxometric studies that examined ADHD in children and adolescents, and with contemporary polygenic and multifactorial models of ADHD. PMID:22480749
Feeding problems of infants and toddlers

PubMed Central

Bernard-Bonnin, Anne-Claude

2006-01-01

OBJECTIVE To propose a diagnostic and therapeutic approach to feeding problems in early childhood. QUALITY OF EVIDENCE Articles were retrieved through a MEDLINE search from January 1990 to December 2005 using the MeSH terms eating disorders, infant, and child. Recommended practice is based mainly on levels II and III evidence. MAIN MESSAGE Feeding problems are classified under structural abnormalities, neurodevelopmental disabilities, and behavioural disorders, with overlap between categories. A medical approach also needs an evaluation of diet and an assessment of the interaction between parent and child. Treating medical or surgical conditions, increasing caloric intake, and counseling about general nutrition can alleviate mild to moderate problems. More complicated cases should be referred to multidisciplinary teams. Behavioural therapy aims to foster appropriate behaviour and discourage maladaptive behaviour. CONCLUSION Feeding problems in early childhood often have multifactorial causes and a substantial behavioural component. Family physicians have a key role in detecting problems, offering advice, managing mildly to moderately severe cases, and referring more complicated cases to multidisciplinary teams. PMID:17279184
Hyperthyroidism and pulmonary hypertension: an important association.

PubMed

Vallabhajosula, Sailaja; Radhi, Saba; Cevik, Cihan; Alalawi, Raed; Raj, Rishi; Nugent, Kenneth

2011-12-01

Pulmonary hypertension is a complex disorder with multiple etiologies. The World Health Organization Group 5 (unclear multifactorial mechanisms) includes patients with thyroid disorders. The authors reviewed the literature on the association between hyperthyroidism and pulmonary hypertension and identified 20 publications reporting 164 patients with treatment outcomes. The systolic pulmonary artery (PA) pressures in these patients ranged from 28 to 78 mm Hg. They were treated with antithyroid medications, radioactive iodine and surgery. The mean pretherapy PA systolic pressure was 39 mm Hg; the mean posttreatment pressure was 30 mm Hg. Pulmonary hypertension should be considered in hyperthyroid patients with dyspnea. All patients with pulmonary hypertension should be screened for hyperthyroidism, because the treatment of hyperthyroidism can reduce PA pressures, potentially avoid the side-effects and costs with current therapies for pulmonary hypertension and limit the consequences of untreated hyperthyroidism. However, the long-term outcome in these patients is uncertain, and this issue needs more study. Changes in the pulmonary circulation and molecular regulators of vascular remodeling likely explain this association.
Corneal thickness in dry eyes in an Iraqi population.

PubMed

Ali, Noora Mauwafak; Hamied, Furkaan M; Farhood, Qasim K

2017-01-01

Dry eye disorder is a multifactorial disease of the tears and ocular surface that results in discomfort and visual disturbance. Corneal pachymetry becomes increasingly important in refractive surgery, for the accurate assessment of intraocular pressure, and in the preoperative assessment of other ocular surgeries. To assess the effect of dry eye disorder on the central corneal thickness (CCT) by comparing with CCT of normal eyes of age-matched individuals. The total number of eyes examined was 280 (140 dry eyes from 70 patients and 140 normal eyes from 70 individuals). Pentacam (Scheimpflug imaging system) was used for measuring the CCT of all eyes. Patients with dry eye syndrome had significantly lower CCT compared to the control group ( P <0.01). Its mean was 536.5 versus 561.3, respectively. CCT of dry eyes was significantly reduced when compared with age- and gender-matched population. This result can be attributed to chronic desiccation by the inflammatory mediators in dry eyes, leading to corneal thinning.
The latent structure of attention deficit/hyperactivity disorder in an adult sample.

PubMed

Marcus, David K; Norris, Alyssa L; Coccaro, Emil F

2012-06-01

The vast majority of studies that have examined the latent structure of attention deficit/hyperactivity disorder (ADHD) in children and adolescents have concluded that ADHD has a dimensional latent structure. In other words, ADHD symptomatology exists along a continuum and there is no natural boundary or qualitative distinction (i.e., taxon) separating youth with ADHD from those with subclinical inattention or hyperactivity/impulsivity problems. Although adult ADHD appears to be less prevalent than ADHD in youth (which could suggest a more severe adult ADHD taxon), researchers have yet to examine the latent structure of ADHD in adults. The present study used a sample (N = 600) of adults who completed a self-report measure of ADHD symptoms. The taxometric analyses revealed a dimensional latent structure for inattention, hyperactivity/impulsivity, and ADHD. These findings are consistent with previous taxometric studies that examined ADHD in children and adolescents, and with contemporary polygenic and multifactorial models of ADHD. Copyright © 2012 Elsevier Ltd. All rights reserved.
Potential of nor-Ursodeoxycholic Acid in Cholestatic and Metabolic Disorders.

PubMed

Trauner, Michael; Halilbasic, Emina; Claudel, Thierry; Steinacher, Daniel; Fuchs, Claudia; Moustafa, Tarek; Pollheimer, Marion; Krones, Elisabeth; Kienbacher, Christian; Traussnigg, Stefan; Kazemi-Shirazi, Lili; Munda, Petra; Hofer, Harald; Fickert, Peter; Paumgartner, Gustav

2015-01-01

24-nor-ursodeoxycholic acid (norUDCA) is a side-chain shortened derivate of ursodeoxycholic acid (UDCA). Since norUDCA is only ineffectively conjugated with glycine or taurine, it has specific physicochemical and therapeutic properties distinct from UDCA. Nonamidated norUDCA undergoes cholehepatic shunting enabling 'ductular targeting' and inducing a bicarbonate-rich hypercholeresis, with cholangioprotective effects. At the same time it has direct anti-inflammatory, antilipotoxic, anti fibrotic, and antiproliferative properties targeting various liver cell populations. norUDCA appears to be one of the most promising novel treatment approaches targeting the liver and the bile duct system at multifactorial and multicellular levels. This review article is a summary of a lecture given at the XXIII International Bile Acid Meeting (Falk Symposium 194) on 'Bile Acids as Signal Integrators and Metabolic Modulators' held in Freiburg, October 8-9, 2014, and summarizes the recent progress with norUDCA as a novel therapeutic approach in cholestatic and metabolic (liver) disorders. 2015 S. Karger AG, Basel.
Current views on the mechanisms of immune responses to trauma and infection

PubMed Central

Michalak, Grzegorz; Słotwiński, Robert

2015-01-01

According to the World Health Organization, post-traumatic mortality rates are still very high and show an increasing tendency. Disorders of innate immune response that may increase the risk of serious complications play a key role in the immunological system response to trauma and infection. The mechanism of these disorders is multifactorial and is still poorly understood. The changing concepts of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) early inflammatory response, presented in this work, have been extended to genetic studies. Overexpression of genes and increased production of immune response mediators are among the main causes of multiple organ dysfunction syndrome (MODS). Changes in gene expression detected early after injury precede the occurrence of subsequent complications with a typical clinical picture. Rapid depletion of energy resources leads to immunosuppression and persistent inflammation and immune suppression catabolism syndrome (PICS). Early diagnosis of immune disorders and appropriate nutritional therapy can significantly reduce the incidence of complications, length of hospital stay, and mortality. The study presents the development of knowledge and current views explaining the mechanisms of the immune response to trauma and infection. PMID:26557036
[Attention deficit syndrome. Basic aspects of its diagnosis and treatment].

PubMed

Arriada-Mendicoa, N; Otero-Siliceo, E

The attention deficit syndrome is one of the commonest behavior disorders of infancy, although it is considerably underestimated. The aetiology of attention deficit syndrome is multifactorial since genetic, environmental, nutritional and psychosocial factors have been found to be associated with its development. Diagnosis depends mainly on the identification of behavior changes especially of inattention, impulsiveness and hyperactivity: it should be made at home and at school and based on the exclusion of severe organic and neurological disorders which also present initially with similar characteristics. Electrophysiological studies may be useful since multiple electroencephalographic changes have been reported, as have prolonged latency of III and V waves of brain stem evoked potentials, The best management requires educational therapy combined with controlled medical treatment. Use of stimulants should be carefully considered and the tricyclic drugs are preferably the first pharmacological option. Current findings regarding the repercussions of attention deficit syndrome in adults shows the need for early diagnosis and treatment of the condition so as to avoid severe personality disorders including antisocial and criminal behavior. It is essential that the parents and the child himself understand the condition in order to achieve satisfactory results of long term treatment.
Posttransplant Lymphoproliferative Disorders

PubMed Central

Ibrahim, Hazem A. H.; Naresh, Kikkeri N.

2012-01-01

Posttransplant lymphoproliferative disorders (PTLDs) are a group of diseases that range from benign polyclonal to malignant monoclonal lymphoid proliferations. They arise secondary to treatment with immunosuppressive drugs given to prevent transplant rejection. Three main pathologic subsets/stages of evolution are recognised: early, polymorphic, and monomorphic lesions. The pathogenesis of PTLDs seems to be multifactorial. Among possible infective aetiologies, the role of EBV has been studied in depth, and the virus is thought to play a central role in driving the proliferation of EBV-infected B cells that leads to subsequent development of the lymphoproliferative disorder. It is apparent, however, that EBV is not solely responsible for the “neoplastic” state. Accumulated genetic alterations of oncogenes and tumour suppressor genes (deletions, mutations, rearrangements, and amplifications) and epigenetic changes (aberrant hypermethylation) that involve tumour suppressor genes are integral to the pathogenesis. Antigenic stimulation also plays an evident role in the pathogenesis of PTLDs. Plasmacytoid dendritic cells (PDCs) that are critical to fight viral infections have been thought to play a pathogenetically relevant role in PTLDs. Furthermore, regulatory T cells (Treg cells), which are modulators of immune reactions once incited, seem to have an important role in PTLDs where antigenic stimulation is key for the pathogenesis. PMID:22570658
Altered heavy metals and transketolase found in autistic spectrum disorder.

PubMed

Obrenovich, Mark E; Shamberger, Raymond J; Lonsdale, Derrick

2011-12-01

Autism and autism spectrum disorder (ASD) are developmental brain disorders with complex, obscure, and multifactorial etiology. Our recent clinical survey of patient records from ASD children under the age of 6 years and their age-matched controls revealed evidence of abnormal markers of thiol metabolism, as well as a significant alteration in deposition of several heavy metal species, particularly arsenic, mercury, copper, and iron in hair samples between the groups. Altered thiol metabolism from heavy metal toxicity may be responsible for the biochemical alterations in transketolase, and are mechanisms for oxidative stress production, dysautonomia, and abnormal thiamine homeostasis. It is unknown why the particular metals accumulate, but we suspect that children with ASD may have particular trouble excreting thiol-toxic heavy metal species, many of which exist as divalent cations. Accumulation or altered mercury clearance, as well as concomitant oxidative stress, arising from redox-active metal and arsenic toxicity, offers an intriguing component or possible mechanism for oxidative stress-mediated neurodegeneration in ASD patients. Taken together, these factors may be more important to the etiology of this symptomatically diverse disease spectrum and may offer insights into new treatment approaches and avenues of exploration for this devastating and growing disease.
Case-control study of risk factors for spasmodic dysphonia: A comparison with other voice disorders.

PubMed

Tanner, Kristine; Roy, Nelson; Merrill, Ray M; Sauder, Cara; Houtz, Daniel R; Smith, Marshall E

2012-05-01

This epidemiology study examined risk factors uniquely associated with spasmodic dysphonia (SD). Case-control. A questionnaire was administered to 150 patients with SD (with and without coexisting vocal tremor) and 136 patients with other structural, neurological, and functional voice disorders (excluding SD and vocal tremor). Questions included personal and family medical histories, environmental exposures, trauma, illnesses, voice use habits, and the Short Form 36. Several factors were uniquely associated with SD (α = .05), including: 1) a personal history of cervical dystonia, sinus and throat illnesses, mumps, rubella, dust exposure, and frequent volunteer voice use, 2) a family history of voice disorders, 3) an immediate family history of vocal tremor and meningitis, and 4) an extended family history of head and neck tremor, ocular disease, and meningitis. Vocal tremor coexisted with SD in 29% of cases. Measles and mumps vaccines were protective for SD. SD is likely multifactorial and associated with several endogenous and exogenous factors. Certain viral exposures, voice use patterns, and familial neurological conditions may contribute to the onset of SD later in life. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Phenotypic approaches to gene mapping in platelet function disorders - identification of new variant of P2Y12, TxA2 and GPVI receptors.

PubMed

Watson, S; Daly, M; Dawood, B; Gissen, P; Makris, M; Mundell, S; Wilde, J; Mumford, A

2010-01-01

Platelet number or function disorders cause a range of bleeding symptoms from mild to severe. Patients with platelet dysfunction but normal platelet number are the most prevalent and typically have mild bleeding symptoms. The study of this group of patients is particularly difficult because of the lack of a gold-standard test of platelet function and the variable penetrance of the bleeding phenotype among affected individuals. The purpose of this short review is to discuss the way in which this group of patients can be investigated through platelet phenotyping in combination with targeted gene sequencing. This approach has been used recently to identify patients with mutations in key platelet activation receptors, namely those for ADP, collagen and thromboxane A2 (TxA2). One interesting finding from this work is that for some patients, mild bleeding is associated with heterozygous mutations in platelet proteins that are co-inherited with other genetic disorders of haemostasis such as type 1 von Willebrand's disease. Thus, the phenotype of mild bleeding may be multifactorial in some patients and may be considered to be a complex trait.
Autism in 2016: the need for answers.

PubMed

Posar, Annio; Visconti, Paola

Autism spectrum disorders are lifelong and often devastating conditions that severely affect social functioning and self-sufficiency. The etiopathogenesis is presumably multifactorial, resulting from a very complex interaction between genetic and environmental factors. The dramatic increase in autism spectrum disorder prevalence observed during the last decades has led to placing more emphasis on the role of environmental factors in the etiopathogenesis. The objective of this narrative biomedical review was to summarize and discuss the results of the most recent and relevant studies about the environmental factors hypothetically involved in autism spectrum disorder etiopathogenesis. A search was performed in PubMed (United States National Library of Medicine) about the environmental factors hypothetically involved in the non-syndromic autism spectrum disorder etiopathogenesis, including: air pollutants, pesticides and other endocrine-disrupting chemicals, electromagnetic pollution, vaccinations, and diet modifications. While the association between air pollutants, pesticides and other endocrine-disrupting chemicals, and risk for autism spectrum disorder is receiving increasing confirmation, the hypothesis of a real causal relation between them needs further data. The possible pathogenic mechanisms by which environmental factors can lead to autism spectrum disorder in genetically predisposed individuals were summarized, giving particular emphasis to the increasingly important role of epigenetics. Future research should investigate whether there is a significant difference in the prevalence of autism spectrum disorder among nations with high and low levels of the various types of pollution. A very important goal of the research concerning the interactions between genetic and environmental factors in autism spectrum disorder etiopathogenesis is the identification of vulnerable populations, also in view of proper prevention. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
Potential common factors associated with predisposition to common cold in middle-aged and elderly Japanese: A community-based cross-sectional study.

PubMed

Shibata, Michi; Iwane, Taizo; Higuchi, Ryoko; Suwa, Kaname; Nakajima, Kei

2018-05-01

People worldwide frequently catch a common cold, which occasionally develops into secondary severe conditions such as pneumonia. However, it is unclear whether predisposition to the common cold is associated with the individual's characteristics including age, body weight, lifestyles, diets, and intestinal functions, besides exposure to a responsible pathogen. We addressed this issue epidemiologically considering many relevant clinical factors.We reviewed data from a cross-sectional study consisting of 39,524 apparently healthy Japanese aged 40 to 79 years (26,975 men and 12,549 women) who underwent a checkup in 2007. Self-reported predisposition to common cold (SPCC) and relevant clinical conditions and parameters were considered.We observed no significant difference in most clinical parameters including age, body mass index (BMI), glycated hemoglobin (HbA1c), and prevalence of men and current smokers between subjects with and without SPCC. In univariate analysis, circulating white blood cell (WBC) count and serum alanine-aminotransferase (ALT) were significantly higher in subjects with SPCC than in those without, whereas serum high-density lipoprotein cholesterol (HDL-C) and duration of sleep were lower. In logistic regression analysis after full adjustment for relevant confounding factors, BMI categories except BMI of ≥27.0 kg/m were significantly associated with SPCC compared with BMI of 23.0 to 24.9 kg/m. Short duration of sleep (≤5 hours), occasional alcohol drinking, and no-exercise were significantly associated with SPCC compared with 7 hours sleep duration, no-drinking alcohol, and low frequent exercise (twice per month), respectively. All gastrointestinal disorders (gastric complaints, constipation, and diarrhea) were independently associated with SPCC. Imbalanced diet and taking a snack were also associated with SPCC in a degree dependent manner. Furthermore, WBC count, serum ALT, and HDL-C (as continuous variables) were associated with SPCC (HDL-C was inversely), whereas no significant association was observed between SPCC and age, smoking, HbA1c, and pharmacotherapy for diabetes, hypertension, and dyslipidemia.Our results demonstrated that multifactorial conditions and parameters might be simultaneously associated with the predisposition to common cold. Prospective studies including detailed common cold questionnaire and measurements are needed to confirm currently suspected causative and protective factors.
A MULTI-CENTER CLUSTER-RANDOMIZED TRIAL OF A MULTI-FACTORIAL INTERVENTION TO IMPROVE ANTIHYPERTENSIVE MEDICATION ADHERENCE AND BLOOD PRESSURE CONTROL AMONG PATIENTS AT HIGH CARDIOVASCULAR RISK (The COM99 study)*

PubMed Central

Pladevall, Manel; Brotons, Carlos; Gabriel, Rafael; Arnau, Anna; Suarez, Carmen; de la Figuera, Mariano; Marquez, Emilio; Coca, Antonio; Sobrino, Javier; Divine, George; Heisler, Michele; Williams, L Keoki

2010-01-01

Background Medication non-adherence is common and results in preventable disease complications. This study assesses the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. Methods and Results In this multi-center, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients’ pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end-point of all cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62; 95% confidence interval [CI] 0.50–0.78) and were more likely to be adherent (OR 1.91; 95% CI 1.19–3.05) when compared with control group patients at 6 months. After five years 16% of the patients in the intervention group and 19% in the control group met the composite end-point (hazard ratio 0.97; 95% CI 0.67–1.39). Conclusions A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events. PMID:20823391
Design and statistical problems in prevention.

PubMed

Gullberg, B

1996-01-01

Clinical and epidemiological research in osteoporosis can benefit from using the methods and techniques established in the area of chronic disease epidemiology. However, attention has to be given to the special characteristics such as the multifactorial nature and the fact that the subjects usually are of high ages. In order to evaluate prevention it is of course first necessary to detect and confirm reversible risk factors. The advantage and disadvantage of different design (cross-sectional, cohort and case-control) are well known. The effects of avoidable biases, e.g. selection, observation and confounding have to be balanced against practical conveniences like time, expenses, recruitment etc. The translation of relative risks into population attributable risks (etiologic fractions, prevented fractions) are complex and are usually performed under unrealistic, simplified assumptions. The consequences of interactions (synergy) between risk factors are often neglected. The multifactorial structure requires application of more advanced multi-level statistical techniques. The common strategy in prevention to target a cluster of risk factors in order to avoid the multifactorial nature implies that in the end it is impossible to separate each unique factor. Experimental designs for evaluating prevention like clinical trials and intervention have to take into account the distinction between explanatory and pragmatic studies. An explanatory approach is similar to an idealized laboratory trial while the pragmatic design is more realistic, practical and has a general public health perspective. The statistical techniques to be used in osteoporosis research are implemented in easy available computer-packages like SAS, SPSS, BMDP and GLIM. In addition to the traditional logistic regression methods like Cox analysis and Poisson regression also analysis of repeated measurement and cluster analysis are relevant.
Physiology of Hyperuricemia and Urate-Lowering Treatments.

PubMed

Benn, Caroline L; Dua, Pinky; Gurrell, Rachel; Loudon, Peter; Pike, Andrew; Storer, R Ian; Vangjeli, Ciara

2018-01-01

Gout is the most common form of inflammatory arthritis and is a multifactorial disease typically characterized by hyperuricemia and monosodium urate crystal deposition predominantly in, but not limited to, the joints and the urinary tract. The prevalence of gout and hyperuricemia has increased in developed countries over the past two decades and research into the area has become progressively more active. We review the current field of knowledge with emphasis on active areas of hyperuricemia research including the underlying physiology, genetics and epidemiology, with a focus on studies which suggest association of hyperuricemia with common comorbidities including cardiovascular disease, renal insufficiency, metabolic syndrome and diabetes. Finally, we discuss current therapies and emerging drug discovery efforts aimed at delivering an optimized clinical treatment strategy.
Universal etiology, multifactorial diseases and the constitutive model of disease classification.

PubMed

Fuller, Jonathan

2018-02-01

Infectious diseases are often said to have a universal etiology, while chronic and noncommunicable diseases are said to be multifactorial in their etiology. It has been argued that the universal etiology of an infectious disease results from its classification using a monocausal disease model. In this article, I will reconstruct the monocausal model and argue that modern 'multifactorial diseases' are not monocausal by definition. 'Multifactorial diseases' are instead defined according to a constitutive disease model. On closer analysis, infectious diseases are also defined using the constitutive model rather than the monocausal model. As a result, our classification models alone cannot explain why infectious diseases have a universal etiology while chronic and noncommunicable diseases lack one. The explanation is instead provided by the Nineteenth Century germ theorists. Copyright © 2017 Elsevier Ltd. All rights reserved.
Medical genetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorde, L.B.; Carey, J.C.; White, R.L.

This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.
Hepatitis C virus infection and type 1 and type 2 diabetes mellitus.

PubMed

Antonelli, Alessandro; Ferrari, Silvia Martina; Giuggioli, Dilia; Di Domenicantonio, Andrea; Ruffilli, Ilaria; Corrado, Alda; Fabiani, Silvia; Marchi, Santino; Ferri, Clodoveo; Ferrannini, Ele; Fallahi, Poupak

2014-10-15

Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients.
[Consensus document about the nutritional evaluation and management of eating disorders: anorexia nervosa].

PubMed

Gómez-Candela, Carmen; Palma Milla, Samara; Miján-de-la-Torre, Alberto; Rodríguez Ortega, Pilar; Matía Martín, Pilar; Loria Kohen, Viviana; Campos Del Portillo, Rocío; Martín-Palmero, Ángela; Virgili Casas, M ª Nuria; Martínez Olmos, Miguel Á; Mories Álvarez, M ª Teresa; Castro Alija, M ª José; Martín-Palmero, Ángela

2018-03-07

Anorexia nervosa is the most common psychiatric disease among young women and it is assumed to be of multifactorial origin. Diagnostic criteria have recently been modified; therefore amenorrhea has ceased to be a part of them. This disease shows a large variability in its presentation and severity which conditions different therapeutic approaches and the need to individualize the treatment, thus it is indispensable a multidisciplinary approach. The goals are to restore nutritional status (through an individualized diet plan based on a healthy consumption pattern), treat complications and comorbidities, nutritional education (based on healthy eating and nutritional patterns), correction of compensatory behaviors and relapse prevention. The treatment will vary according to the patient's clinical situation, and it may be performed in outpatient clinics (when there is clinical stability), in a day hospital or ambulatory clinic (intermediate mode between traditional outpatient treatment and hospitalization) or hospitalization (when there is outpatient management failure or presence of serious medical or psychiatric complications). Artificial nutrition using oral nutritional supplements, enteral nutrition and exceptionally parenteral nutrition may be necessary in certain clinical settings. In severely malnourished patients the refeeding syndrome should be avoided. Anorexia nervosa is associated with numerous medical complications which determines health status, life quality, and is closely related to mortality. There is little clinical evidence to assess the results of different treatments in anorexia nervosa, when most of the recommendations are being based on expert consensus.
Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

PubMed Central

Antonelli, Alessandro; Ferrari, Silvia Martina; Giuggioli, Dilia; Di Domenicantonio, Andrea; Ruffilli, Ilaria; Corrado, Alda; Fabiani, Silvia; Marchi, Santino; Ferri, Clodoveo; Ferrannini, Ele; Fallahi, Poupak

2014-01-01

Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients. PMID:25317237
Gastroesophageal reflux disease: Update on inflammation and symptom perception.

PubMed

Altomare, Annamaria; Guarino, Michele Pier Luca; Cocca, Silvia; Emerenziani, Sara; Cicala, Michele

2013-10-21

Although gastroesophageal reflux disease (GERD) is a common disorder in Western countries, with a significant impact on quality of life and healthcare costs, the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated. GERD symptoms and complications may result from a multifactorial mechanism, in which acid and acid-pepsin are the important noxious factors involved. Prolonged contact of the esophageal mucosa with the refluxed content, probably caused by a defective anti-reflux barrier and luminal clearance mechanisms, would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium. Receptors on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity, as suggested in animal models of chronic acid exposure. Meanwhile, specific cytokine and chemokine profiles would appear to underlie the various esophageal phenotypes of GERD, explaining, in part, the genesis of esophagitis in a subset of patients. Despite these findings, which show a significant production of inflammatory mediators and neurotransmitters in the pathogenesis of GERD, the relationship between the hypersensitivity and esophageal inflammation is not clear. Moreover, the large majority of GERD patients (up to 70%) do not develop esophageal erosions, a variant of the condition called non-erosive reflux disease. This summary aims to explore the inflammatory pathway involved in GERD pathogenesis, to better understand the possible distinction between erosive and non-erosive reflux disease patients and to provide new therapeutic approaches.
The TreadWheel: Interval Training Protocol for Gently Induced Exercise in Drosophila melanogaster.

PubMed

Lowman, Kelsey E; Wyatt, Brélahn J; Cunneely, Owen P; Reed, Laura K

2018-06-08

The incidence of complex metabolic diseases has increased as a result of a widespread transition towards lifestyles of increased caloric intake and lowered activity levels. These multifactorial diseases arise from a combination of genetic, environmental, and behavioral factors. One such complex disease is Metabolic Syndrome (MetS), which is a cluster of metabolic disorders, including hypertension, hyperglycemia, and abdominal obesity. Exercise and dietary intervention are the primary treatments recommended by doctors to mitigate obesity and its subsequent metabolic diseases. Exercise intervention, in particular aerobic interval training, stimulates favorable changes in the common risk factors for Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD), and other conditions. With the influx of evidence describing the therapeutic effect exercise has on metabolic health, establishing a system that models exercise in a controlled setting provides a valuable tool for assessing the effects of exercise in an experimental context. Drosophila melanogaster is a great tool for investigating the physiological and molecular changes that result from exercise intervention. The flies have short lifespans and similar mechanisms of metabolizing nutrients when compared to humans. To induce exercise in Drosophila, we developed a machine called the TreadWheel, which utilizes the fly's innate, negative geotaxis tendency to gently induce climbing. This enables researchers to perform experiments on large cohorts of genetically diverse flies to better understand the genotype-by-environment interactions underlying the effects of exercise on metabolic health.
Selection against canine hip dysplasia: success or failure?

PubMed

Wilson, Bethany; Nicholas, Frank W; Thomson, Peter C

2011-08-01

Canine hip dysplasia (CHD) is a multifactorial skeletal disorder which is very common in pedigree dogs and represents a huge concern for canine welfare. Control schemes based on selective breeding have been in operation for decades. The aim of these schemes is to reduce the impact of CHD on canine welfare by selecting for reduced radiographic evidence of CHD pathology as assessed by a variety of phenotypes. There is less information regarding the genotypic correlation between these phenotypes and the impact of CHD on canine welfare. Although the phenotypes chosen as the basis for these control schemes have displayed heritable phenotypic variation in many studies, success in achieving improvement in the phenotypes has been mixed. There is significant room for improvement in the current schemes through the use of estimated breeding values (EBVs), which can combine a dog's CHD phenotype with CHD phenotypes of relatives, other phenotypes as they are proven to be genetically correlated with CHD (especially elbow dysplasia phenotypes), and information from genetic tests for population-relevant DNA markers, as such tests become available. Additionally, breed clubs should be encouraged and assisted to formulate rational, evidenced-based breeding recommendations for CHD which suit their individual circumstances and dynamically to adjust the breeding recommendations based on continuous tracking of CHD genetic trends. These improvements can assist in safely and effectively reducing the impact of CHD on pedigree dog welfare. Copyright © 2011 Elsevier Ltd. All rights reserved.
Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

PubMed

Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

2014-06-01

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.
Epstein-Barr virus and its association with rheumatoid arthritis and oral lichen planus.

PubMed

Adtani, Pooja; Malathi, Narasimhan

2015-01-01

Pathogenesis of autoimmune diseases (AD) is one of a multifactorial milieu. A genetic predisposition, an immune system failure, hormonal imbalance and environmental factors play important roles. Among the many environmental factors, the role of infection is gaining importance in the pathogenesis of various autoimmune disorders; among them, Epstein-Barr virus (EBV) plays a pivotal role. Literature states an association of various AD with EBV namely multiple sclerosis, autoimmune thyroiditis, systemic lupus erythematous, oral lichen planus (OLP), rheumatoid arthritis (RA), autoimmune hepatitis, Sjögren's syndrome and Kawasaki disease; among these, the most commonly occurring are OLP and RA. Considering the frequency of occurrences, our aim was to perform a qualitative analysis of EBV viral capsid antigen (EBV VCA) IgG in the sera of patients with RA, OLP and establish a comparison with normal. In-vitro experiment in a research laboratory. Five-milliliter blood sample was collected from 25 patients diagnosed with RA and OLP. Serum was separated and EBV VCA IgG antibody titer was detected using NovaTec EBV VCA IgG ELISA kit. Chi-square test. Six out of 25 subjects with RA and 4 out of 25 subjects with OLP tested positive for EBV VCA IgG. Both environmental and genetic factors are important contributory components for autoimmune conditions. Screening for viral etiology would improve the efficacy of conventional treatment and reduce the risk of relapses.
Depression is a predictor for balance in people with multiple sclerosis.

PubMed

Alghwiri, Alia A; Khalil, Hanan; Al-Sharman, Alham; El-Salem, Khalid

2018-05-26

Balance impairments are common and multifactorial among people with multiple sclerosis (MS). Depression is the most common psychological disorder in MS population and is strongly correlated with MS disease. Depression might be one of the factors that contribute to balance deficits in this population. However, the relationship between depression and balance impairments has not been explored in people with MS. To investigate the association between depression and balance impairments in people with MS. Cross sectional design was used in patients with MS. The Activities-specific Balance Confidence scale (ABC) and Berg Balance Scale (BBS) was used to assess balance. Beck Depression Inventory (BDI-II) was used to quantify depression and Kurtizki Expanded Disability Status Scale (EDSS) was utilized for the evaluation of MS disability severity. Pearson correlation coefficient was used to examine the association between depression and balance measurements. Multiple linear stepwise regressions were also conducted to find out if depression is a potential predictor for balance deficits. Seventy-five individuals with MS (Female = 69%) with a mean age (SD) of 38.8 (10) and a mean (SD) EDSS score of 3.0 (1.4) were recruited in this study. Depression was present in 53% of the patients. Depression was significantly correlated with balance measurements and EDSS. However, multiple linear stepwise regressions found that only depression and age significantly predict balance. Depression and balance were found frequent and associated in people with MS. Importantly depression was a significant predictor for balance impairments in individuals with MS. Balance rehabilitation may be hindered by depression. Therefore, depression should be evaluated and treated properly in individuals with MS. Copyright © 2018 Elsevier B.V. All rights reserved.
Deregulation of EIF4E: a novel mechanism for autism.

PubMed

Neves-Pereira, M; Müller, B; Massie, D; Williams, J H G; O'Brien, P C M; Hughes, A; Shen, S-B; Clair, David St; Miedzybrodzka, Z

2009-11-01

Autism is a common childhood onset neurodevelopmental disorder, characterised by severe and sustained impairment of social interaction and social communication, as well as a notably restricted repertoire of activities and interests. Its aetiology is multifactorial with a strong genetic basis. EIF4E is the rate limiting component of eukaryotic translation initiation, and plays a key role in learning and memory through its control of translation within the synapse. EIF4E mediated translation is the final common process modulated by the mammalian target of rapamycin (mTOR), PTEN and fragile X mental retardation protein (FMRP) pathways, which are implicated in autism. Linkage of autism to the EIF4E region on chromosome 4q has been found in genome wide linkage studies. The authors present evidence that directly implicates EIF4E in autism. In a boy with classic autism, the authors observed a de novo chromosome translocation between 4q and 5q and mapped the breakpoint site to within a proposed alternative transcript of EIF4E. They then screened 120 autism families for mutations and found two unrelated families where in each case both autistic siblings and one of the parents harboured the same single nucleotide insertion at position -25 in the basal element of the EIF4E promoter. Electrophoretic mobility shift assays and reporter gene studies show that this mutation enhances binding of a nuclear factor and EIF4E promoter activity. These observations implicate EIF4E, and more specifically control of EIF4E activity, directly in autism. The findings raise the exciting possibility that pharmacological manipulation of EIF4E may provide therapeutic benefit for those with autism caused by disturbance of the converging pathways controlling EIF4E activity.
Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease.

PubMed

Eloranta, Jyrki J; Wenger, Christa; Mwinyi, Jessica; Hiller, Christian; Gubler, Christoph; Vavricka, Stephan R; Fried, Michael; Kullak-Ublick, Gerd A

2011-09-01

Inflammatory bowel diseases (IBDs), Crohn's disease, and ulcerative colitis (UC), are multifactorial disorders, characterized by chronic inflammation of the intestine. A number of genetic components have been proposed to contribute to IBD pathogenesis. In this case-control study, we investigated the association between two common vitamin D-binding protein (DBP) genetic variants and IBD susceptibility. These two single nucleotide polymorphisms (SNPs) in exon 11 of the DBP gene, at codons 416 (GAT>GAG; Asp>Glu) and 420 (ACG>AAG; Thr>Lys), have been previously suggested to play roles in the etiology of other autoimmune diseases. Using TaqMan SNP technology, we have genotyped 884 individuals (636 IBD cases and 248 non-IBD controls) for the two DBP variants. On statistical analysis, we observed that the DBP 420 variant Lys is less frequent in IBD cases than in non-IBD controls (allele frequencies, P=0.034; homozygous carrier genotype frequencies, P=0.006). This inverse association between the DBP 420 Lys and the disease remained significant, when non-IBD participants were compared with UC (homozygous carrier genotype frequencies, P=0.022) or Crohn's disease (homozygous carrier genotype frequencies, P=0.016) patients separately. Although the DBP position 416 alone was not found to be significantly associated with IBD, the haplotype DBP_2, consisting of 416 Asp and 420 Lys, was more frequent in the non-IBD population, particularly notably when compared with the UC group (Odds ratio, 4.390). Our study adds DBP to the list of potential genes that contribute to the complex genetic etiology of IBD, and further emphasizes the association between vitamin D homeostasis and intestinal inflammation.
Polycystic ovary syndrome and environmental toxins.

PubMed

Rutkowska, Aleksandra Zofia; Diamanti-Kandarakis, Evanthia

2016-09-15

Polycystic ovary syndrome (PCOS) is the most common, heterogeneous, and multifactorial endocrine disorder in premenopausal women. The pathophysiology of this endocrinopathy is still unclear; however, the heterogeneity of its features within ethnic races, geographic location, and families suggests that environment and lifestyle are of prime importance. This work is mainly focused on the possible role of the most common and studied environmental toxins for this syndrome in the pathogenesis of PCOS. Plasticizers, such as bisphenol A (BPA) or phthalates, which belong to the categories of endocrine disrupting chemicals (EDCs) and advanced glycation end products (AGEs), affect humans' health in everyday, industrialized life; therefore special attention should be paid to such exposure. Timing of exposure to EDCs is crucial for the intensity of adverse health effects. It is now evident that fetuses, infants, and/or young children are the most susceptible groups, especially in the early development periods. Prenatal exposure to EDCs that mimic endogenous hormones may contribute to the altered fetal programming and in consequence lead to PCOS and other adverse health effects, potentially transgenerationally. Acute or prolonged exposure to EDCs and AGEs through different life cycle stages may result in destabilization of the hormonal homeostasis and lead to disruption of reproductive functions. They may also interfere with metabolic alterations such as obesity, insulin resistance, and compensatory hyperinsulinemia that can exacerbate the PCOS phenotype and contribute to PCOS consequences such as type 2 diabetes and cardiovascular disease. Since wide exposure to environmental toxins and their role in the pathophysiology of PCOS are supported by extensive data derived from diverse scientific models, protective strategies and strong recommendations should be considered to reduce human exposure to protect present and future generations from their adverse health effects. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Hypermobility, the Ehlers-Danlos syndromes and chronic pain.

PubMed

Syx, Delfien; De Wandele, Inge; Rombaut, Lies; Malfait, Fransiska

2017-01-01

Chronic widespread pain is a common complaint among individuals affected by generalised joint hypermobility. In the absence of other conditions that cause chronic pain, these individuals are usually diagnosed with joint hypermobility syndrome (JHS). JHS is a multifactorial trait with a strong genetic basis, but no specific genetic markers. Clinical overlap of JHS is seen with heritable connective tissue disorders, particularly with the Ehlers-Danlos syndrome, hypermobile type (hEDS). The Ehlers-Danlos syndromes (EDS) comprise a heterogeneous group of rare monogenic conditions that are characterised by joint hypermobility, skin and vascular fragility and generalised connective tissue friability, and are caused by genetic defects in an array of extracellular matrix genes. The genetic basis of hEDS remains however unknown, in contrast to other well-described EDS subtypes. In view of the considerable clinical overlap with JHS, many consider it and hEDS to be a single clinical entity. Clinical experience and a limited number of clinical studies show that chronic pain also is common in EDS patients, especially in hEDS. The specific underlying causes and mechanisms of pain in JHS and EDS remain poorly understood. Factors likely contributing to the generation and chronicity of pain include nociceptive pain, directly based on structural changes in affected joints, muscle and connective tissue; neuropathic pain; impaired proprioception and muscle weakness; and central sensitisation. These mechanisms are not mutually exclusive, and likely more than one mechanism may be present. Furthermore, anxiety, depression, and other variables may influence the phenotype. Chronic pain in JHS and EDS patients often is inadequately controlled by traditional analgesics and physical therapy. In view of the high prevalence of these underrecognised conditions, future studies addressing the nature and mediators of chronic pain are needed in order to potentially identify novel targets for therapeutic intervention and optimise treatment.
Risk factors and antecedent life events in the development of anorexia nervosa: a Portuguese case-control study.

PubMed

Machado, Bárbara C; Gonçalves, Sónia F; Martins, Carla; Hoek, Hans W; Machado, Paulo P

2014-07-01

The aetiology of anorexia nervosa (AN) is considered to be multifactorial. This study aims to identify potential risk factors for AN and whether these factors are specific to AN or precede the development of psychiatric disorders in general and to identify specific life events in the 12 months immediately preceding the onset of eating disorder (ED) symptoms. A case-control design was used to compare a group of women who meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for AN (N = 86) with healthy controls (N = 86) and with a group of controls with other psychiatric disorders (N = 68), each group matched to the AN patients by age and parental socioeconomic status bands. Risk factors were assessed by interviewing each person with the Oxford Risk Factor Interview. Women with AN reported significantly higher rates of perfectionism, negative attitudes toward parents' shape and weight, significant concern about feeling fat and a family history of AN or bulimia nervosa. Critical comments about weight, shape or eating was the most notable event in the year preceding AN onset. Perfectionism and a family history of ED emerged as the most convergent findings in the development of AN, along with being critical toward parents' shape and weight, and feeling fat. Critical comments about appearance and eating seem to be an important precipitating factor in AN onset. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.
[Investigation of sleep patterns and sleep disorders in Uigur and Hui children in Xinjiang].

PubMed

Abuzhare, Tajiguli; Xu, Pei-Ru; Tiemuer, Amanguli; Zhang, Ji-Hong

2011-07-01

To study the sleep quality and quantity and their influencing factors in Uigur and Hui children in Xinjiang Province. From March to December of 2007, 912 Uigur and 1019 Hui school children (6 to 14 years) were randomly sampled from 6 cities of Xinjing Province. The questionnaire on children's sleep states and sleep environments was filled in by children's parents. The mean sleep time of Uigur and Hui children was 10.1±1.4 hrs. The sleep time in Uigur children was significantly less than that in Hui children (9.7±1.2 hrs vs 10.4±1.5 hrs; P<0.05). The mean incidence of sleep disorders was 23.56%. The Uigur children had a lower incidence of sleep disorders compared with the Hui children (18.42% vs 28.16%; P<0.001). Ethnic group, sleep latency, use of a swing bed, family history of snore, watching TV before sleeping, hypertrophy of tonsils, eating before sleeping, feeding patterns and recurrent upper respiratory tract infection were the factors associated with the sleep quality and quantity. The influencing factors of sleep quality and quantity are multifactorial in Uigur and Hui children in Xinjiang Province. Pediatrician, child health care doctors and parents should pay more attention to children's sleep. The incidence of sleep disorders is different between Uigur and Hui children, suggesting that more research for the prevention and treatment of sleep disorders should be performed in different ethic groups.
[Dysthymia in the Clinical Context].

PubMed

Jiménez-Maldonado, Miriam E; Gallardo-Moreno, Geisa B; Villaseñor-Cabrera, Teresita; González-Garrido, Andrés A

2013-06-01

Dysthymia is defined as a chronic mood disorder that persists for at least two years in adults, and one year in adolescents and children. According to DSM IV-TR, Dysthymia is classified into two subtypes: early-onset, when it begins before 21 years-old, and late onset Dysthymia, when it starts after this age. Before age 21, symptoms of conduct disorder, attention deficit disorder and hyperactivity with a few vegetative symptoms are usually present. It is important to distinguish it from other types of depression, as earlier as possible. This would allow providing these patients with the appropriate treatment to attenuate the impact of symptoms, such as poor awareness of self-mood, negative thinking, low self-esteem, and low energy for social and family activities, which progressively deteriorate their life quality. The etiology of Dysthymia is complex and multifactorial, given the various biological, psychological and social factors involved. Several hypotheses attempt to explain the etiology of Dysthymia, highlighting the genetic hypothesis, which also includes environmental factors, and an aminergic hypothesis suggesting a deficiency in serotonin, norepinephrine and dopamine in the central nervous system. From our point of view, dysthymia cannot be conceived as a simple mild depressive disorder. It is a distinct entity, characterized by a chronic depressive disorder which could persist throughout life, with important repercussions on the life quality of both patients and families. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.
Spirituality, religiosity and addiction recovery: current perspectives.

PubMed

Castaldelli-Maia, Joao Mauricio; Beraldo, Livia; Ventriglio, Antonio; de Andrade, Arthur Guerra; da Silva, Antonio Geraldo; Torales, Julio; Goncalves, Priscila Dib; Bhugra, Dinesh

2018-06-11

Substance use disorders are an important public health problem with a multifactorial etiology and limited effective treatment options. Within this context, spirituality-based approaches may provide interesting and useful options in managing substance use disorders. This kind of intervention can have positive effects in alleviating some core symptoms associated with substance use, such as aggressiveness. Improvement in cessation rates for alcohol, cocaine and opioid use disorders have also been described in some clinical studies. However, spirituality may not play a beneficial role in some subgroups, such as among individuals with crack cocaine and cannabis use disorders. A widely available intervention for alcohol use disorders is Alcoholics Anonymous (AA), which can be seen as a spirituality-based intervention. Spirituality also seems to be especially beneficial for minorities such as Latinos, African-Americans and Native-Americans. Moreover, spiritual-based interventions are also helpful alternatives in many rural environments where conventional healthcare for substance use disorders may not be easily available. However, spiritual-based interventions may be considered as a possible adjunctive therapeutic option to conventional treatments. There is a need for prospective studies outside U.S., especially where spiritual-based approaches are available. It may be difficult to carry out randomized controlled trials because of the nature of the spiritual/religious dimensions. However, prospective studies that evaluate mediation effect of spirituality and religiosity on recovery would be helpful. Qualitative studies combined with quantitative design offer excellent options to evaluate the recovery process, especially among special populations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Neighborhood, Socioeconomic, and Racial Influence on Chronic Pain.

PubMed

Maly, Angelika; Vallerand, April Hazard

2018-02-01

The purpose of this review is to highlight the neighborhood, socioeconomic, and racial influences on chronic pain. Negative influences on the experience of chronic pain are explored and defined as any adverse stressor common in low socioeconomic, urban neighborhoods that potentially contributes to health disparity in African Americans experiencing chronic pain. The multifactorial influences on chronic pain disparity in African Americans are explored and expounded upon in this review of existing evidence. Databases used for the search included CINAHL, PubMed, and PsycArticles. The experience of chronic pain is multifaceted, existing with multiple comorbidities and lasting consequences. To improve the burden of chronic pain requires a multifactorial assessment that considers neighborhood risk factors, emphasis on environmental stressors, limitations to support networks, barriers to physical activity, and access to primary care providers with whom communication is open and without bias. A comprehensive assessment of barriers will aid in the development of interventions that reach beyond the physical factors of chronic pain, also considering the psychosocial barriers to improving the burden of chronic pain in African Americans living in impoverished urban neighborhoods. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.
Common mental disorder and obesity: insight from four repeat measures over 19 years: prospective Whitehall II cohort study.

PubMed

Kivimäki, Mika; Lawlor, Debbie A; Singh-Manoux, Archana; Batty, G David; Ferrie, Jane E; Shipley, Martin J; Nabi, Hermann; Sabia, Séverine; Marmot, Michael G; Jokela, Markus

2009-10-06

To examine potential reciprocal associations between common mental disorders and obesity, and to assess whether dose-response relations exist. Prospective cohort study with four measures of common mental disorders and obesity over 19 years (Whitehall II study). Civil service departments in London. 4363 adults (28% female, mean age 44 years at baseline). Common mental disorder defined as general health questionnaire "caseness;" overweight and obesity based on Word Health Organization definitions. In models adjusted for age, sex, and body mass index at baseline, odds ratios for obesity at the fourth screening were 1.33 (95% confidence interval 1.00 to 1.77), 1.64 (1.13 to 2.36), and 2.01 (1.21 to 3.34) for participants with common mental disorder at one, two, or three preceding screenings compared with people free from common mental disorder (P for trend<0.001). The corresponding mean differences in body mass index at the most recent screening were 0.20, 0.31, and 0.50 (P for trend<0.001). These associations remained after adjustment for baseline characteristics related to mental health and exclusion of participants who were obese at baseline. In addition, obesity predicted future risk of common mental disorder, again with evidence of a dose-response relation (P for trend=0.02, multivariable model). However, this association was lost when people with common mental disorder at baseline were excluded (P for trend=0.33). These findings suggest that in British adults the direction of association between common mental disorders and obesity is from common mental disorder to increased future risk of obesity. This association is cumulative such that people with chronic or repeat episodes of common mental disorder are particularly at risk of weight gain.
[The "war neurosis"-- an early model of a pluridimensional outlined trauma-theory in psychiatry].

PubMed

Tölle, Rainer

2005-10-01

The war neurosis, mainly observed during the first World War, caused a lively debate on its origin and etiology. In psychiatric history this debate is often portrayed in a somewhat simplifying manner. Namely Oppenheim was considered as the leading exponent of the organic etiology of traumatic neurosis, while others, with growing interest in psychodynamic theories, were thought to favor exclusively psychogenesis of this condition. However, only discussing matters in this way would be too simple. Rather, the controversy was much more differentiated and led to important insights: First, it turned out to be impossible to explain any psychopathological syndrome exclusively in terms of neuropathological, i. e. structural alterations, in particular, a syndrome presenting with a sudden onset of dissociative and conversion symptoms. Secondly, the psychiatric theory of hysteria of Charcot and Freud was developed and extended further. And, last, the etiology of war neurosis was recognized to be multifactorial. Thus, the discourse on this issue was not one-dimensional and favoring a single explanation for a complex disorder, but revealed "pluridimensional" features. Subsequently psychotherapy, for the first time, was widely introduced into clinical practice with a clear indication and well-defined methodological approach. In summary, war neuroses can be addressed as an early model of traumatic stress disorder, such as acute stress disorder or post-traumatic stress disorder.
Animal breeding and disease

PubMed Central

Nicholas, Frank W

2005-01-01

Single-locus disorders in domesticated animals were among the first Mendelian traits to be documented after the rediscovery of Mendelism, and to be included in early linkage maps. The use of linkage maps and (increasingly) comparative genomics has been central to the identification of the causative gene for single-locus disorders of considerable practical importance. The ‘score-card’ in domestic animals is now more than 100 disorders for which the molecular lesion has been identified and hence for which a DNA test is available. Because of the limited lifespan of any such test, a cost-effective and hence popular means of protecting the intellectual property inherent in a DNA test is not to publish the discovery. While understandable, this practice creates a disconcerting precedent. For multifactorial disorders that are scored on an all-or-none basis or into many classes, the effectiveness of control schemes could be greatly enhanced by selection on estimated breeding values for liability. Genetic variation for resistance to pathogens and parasites is ubiquitous. Selection for resistance can therefore be successful. Because of the technical and welfare challenges inherent in the requirement to expose animals to pathogens or parasites in order to be able to select for resistance, there is a very active search for DNA markers for resistance. The first practical fruits of this research were seen in 2002, with the launch of a national scrapie control programme in the UK. PMID:16048793
Animal models of tic disorders: a translational perspective.

PubMed

Godar, Sean C; Mosher, Laura J; Di Giovanni, Giuseppe; Bortolato, Marco

2014-12-30

Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. Copyright © 2014 Elsevier B.V. All rights reserved.
Syndromology: an updated conceptual overview. VI. Molecular and biochemical aspects of dysmorphology.

PubMed

Cohen, M M

1989-12-01

The role of chance using a stochastic single gene model has been shown to generate a continuous liability curve resembling that obtained from a multifactorial threshold model. Segregation of some malformations may be explained by a single defective gene that predisposes to, but does not necessarily result in, the malformation. Low penetrance and remarkably variable expressivity that characterize a number of presumed autosomal dominant malformation syndromes are possibly reflections of specific stochastic influences that are intrinsic to the embryonic process itself. Gene analysis is discussed and illustrated. Using polymorphic DNA probes to study cleft palate and ankyloglossia in males and ankyloglossia only in females in a large Icelandic family, the responsible gene was found to be located on the long arm of the X chromosome in the Xq21.1 region. In addition to gene analysis, some of the implications of transgenic analysis using mice are discussed. Among disorders of collagen metabolism, both the osteogenesis imperfectas and the Ehlers-Danlos syndromes are shown to represent genetically heterogeneous groups of connective tissue disorders. The days of thinking about osteogenesis imperfecta as one disorder and the Ehlers-Danlos syndrome as another are a thing of the past; persistence of such thinking is erroneous and misleading. Of the many disorders affecting bone mineral, the complexities of hypophosphatasia and pseudohypoparathyroidism are singled out for discussion. For lysosomal storage disorders, an overview of the mucopolysaccharidoses is provided. Finally, the recently delineated peroxisomal disorders--hyperpipecolic acidemia, rhizomelic chondrodysplasia, neonatal adrenoleukodystrophy, Zellweger syndrome, and infantile Refsum disease--are known to share a distinctive biochemical phenotype, although fibroblast complementation analysis suggests that some of these disorders are etiologically distinct.
Prevalence of spinal disorders and their relationships with age and gender

PubMed Central

Alshami, Ali M.

2015-01-01

Objectives: To establish the period prevalence of spinal disorders referred to physical therapy in a university hospital over a 3-year period, and to determine the relationships of common spinal disorders with patients’ age and gender. Methods: This retrospective study was conducted in the Physical Therapy Department, King Fahd Hospital of the University, Dammam, Saudi Arabia. Computer data of all new electronic referrals from January 2011 to December 2013 were retrieved and reviewed. The computer data included demographic information, referring facility, and diagnosis/disorder. Results: One thousand six hundred and sixty-nine (28.1%) of all referred patients (5929) had spinal disorders. The most common disorders affected the lumbar spine (53.1%) and cervical spine (27.1%), and pain was the most common disorder. Neck pain (60.5%) was more common in patients <30 years old (p<0.001). Cervical spondylosis was common (~30%) in the >30 age groups. Spondylosis and low back pain were more prevalent in women (7.8% and 76.2%) than in men (73.9% and 3.3%). Conclusion: Spinal disorders were common compared with other disorders. Low back pain and neck pain were the most common spinal disorders. Age and gender were weakly related to some of the disorders that affected the lumbar and cervical spine. PMID:25987116
Office management of gait disorders in the elderly

PubMed Central

Lam, Robert

2011-01-01

Abstract Objective To provide family physicians with an approach to office management of gait disorders in the elderly. Sources of information Ovid MEDLINE was searched from 1950 to July 2010 using subject headings for gait or neurologic gait disorders combined with physical examination. Articles specific to family practice or family physicians were selected. Relevant review articles and original research were used when appropriate and applicable to the elderly. Main message Gait and balance disorders in the elderly are difficult to recognize and diagnose in the family practice setting because they initially present with subtle undifferentiated manifestations, and because causes are usually multifactorial, with multiple diseases developing simultaneously. To further complicate the issue, these manifestations can be camouflaged in elderly patients by the physiologic changes associated with normal aging. A classification of gait disorders based on sensorimotor levels can be useful in the approach to management of this problem. Gait disorders in patients presenting to family physicians in the primary care setting are often related to joint and skeletal problems (lowest-level disturbances), as opposed to patients referred to neurology specialty clinics with sensory ataxia, myelopathy, multiple strokes, and parkinsonism (lowest-, middle-, and highest-level disturbances). The difficulty in diagnosing gait disorders stems from the challenge of addressing early undifferentiated disease caused by multiple disease processes involving all sensorimotor levels. Patients might present with a nonspecific “cautious” gait that is simply an adaptation of the body to disease limitations. This cautious gait has a mildly flexed posture with reduced arm swing and a broadening of the base of support. This article reviews the focused history (including medication review), practical physical examination, investigations, and treatments that are key to office management of gait disorders. Conclusion Family physicians will find it helpful to classify gait disorders based on sensorimotor level as part of their approach to office management of elderly patients. Managing gait disorders at early stages can help prevent further deconditioning and mobility impairment. PMID:21753097
Office management of gait disorders in the elderly.

PubMed

Lam, Robert

2011-07-01

To provide family physicians with an approach to office management of gait disorders in the elderly. Ovid MEDLINE was searched from 1950 to July 2010 using subject headings for gait or neurologic gait disorders combined with physical examination. Articles specific to family practice or family physicians were selected. Relevant review articles and original research were used when appropriate and applicable to the elderly. Gait and balance disorders in the elderly are difficult to recognize and diagnose in the family practice setting because they initially present with subtle undifferentiated manifestations, and because causes are usually multifactorial, with multiple diseases developing simultaneously. To further complicate the issue, these manifestations can be camouflaged in elderly patients by the physiologic changes associated with normal aging. A classification of gait disorders based on sensorimotor levels can be useful in the approach to management of this problem. Gait disorders in patients presenting to family physicians in the primary care setting are often related to joint and skeletal problems (lowest-level disturbances), as opposed to patients referred to neurology specialty clinics with sensory ataxia, myelopathy, multiple strokes, and parkinsonism (lowest-, middle-, and highest-level disturbances). The difficulty in diagnosing gait disorders stems from the challenge of addressing early undifferentiated disease caused by multiple disease processes involving all sensorimotor levels. Patients might present with a nonspecific "cautious" gait that is simply an adaptation of the body to disease limitations. This cautious gait has a mildly flexed posture with reduced arm swing and a broadening of the base of support. This article reviews the focused history (including medication review), practical physical examination, investigations, and treatments that are key to office management of gait disorders. Family physicians will find it helpful to classify gait disorders based on sensorimotor level as part of their approach to office management of elderly patients. Managing gait disorders at early stages can help prevent further deconditioning and mobility impairment.
Munchausen by proxy syndrome mimicking systemic autoinflammatory disease: case report and review of the literature.

PubMed

Wittkowski, Helmut; Hinze, Claas; Häfner-Harms, Sigrid; Oji, Vinzenz; Masjosthusmann, Katja; Monninger, Martina; Grenzebach, Ulrike; Foell, Dirk

2017-04-05

Systemic autoinflammatory diseases (SAIDs) represent a growing number of monogenic, polygenic or multifactorial disorders that are often difficult to diagnose. Here we report a patient who was initially erroneously diagnosed and treated for SAID. Symptoms consisted of recurrent fever, erythematous and/or blistering skin lesions, angioedema, susceptibility to bleeding, external ear infections and reversible anisocoria in the absence of laboratory evidence of systemic inflammation. After two and a half years of extensive diagnostic work-up and multiple empirical therapies, a final diagnosis of Munchausen by proxy syndrome (MBPS) was established. The diagnosis of SAID needs to be carefully reassessed if measurable systemic inflammation is missing, and MBPS should be included in the differential diagnosis.
Review of and Updates on Hypertension in Obstructive Sleep Apnea

PubMed Central

Ahmad, Masood; Makati, Devan

2017-01-01

Obstructive sleep apnea (OSA) is a prevalent sleep disorder as is hypertension (HTN) in the 21st century with the rising incidence of obesity. Numerous studies have shown a strong association of OSA with cardiovascular morbidity and mortality. There is overwhelming evidence supporting the relationship between OSA and hypertension (HTN). The pathophysiology of HTN in OSA is complex and dependent on various factors such as sympathetic tone, renin-angiotensin-aldosterone system, endothelial dysfunction, and altered baroreceptor reflexes. The treatment of OSA is multifactorial ranging from CPAP to oral appliances to lifestyle modifications to antihypertensive drugs. OSA and HTN both need prompt diagnosis and treatment to help address the growing cardiovascular morbidity and mortality due to these two entities. PMID:29147581
Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

PubMed Central

Kim, Jung Eun; Kim, Jong Sic; Cho, Dae Ho; Park, Hyun Jeong

2016-01-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease resulting from interactions between genetic susceptibility and environmental factors. The pathogenesis of AD is poorly understood, and the treatment of recalcitrant AD is still challenging. There is accumulating evidence for new gene polymorphisms related to the epidermal barrier function and innate and adaptive immunity in patients with AD. Newly-found T cells and dendritic cell subsets, cytokines, chemokines and signaling pathways have extended our understanding of the molecular pathomechanism underlying AD. Genetic changes caused by environmental factors have been shown to contribute to the pathogenesis of AD. We herein present a review of the genetics, epigenetics, barrier dysfunction and immunological abnormalities in AD with a focus on updated molecular biology. PMID:27483258
Update on the therapy of Behçet disease

PubMed Central

Saleh, Zeinab

2014-01-01

Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials. PMID:24790727
Abdominal aortic aneurysms: an autoimmune disease?

PubMed

Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R

2008-12-01

Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. AAAs share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in AAAs is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in AAA formation will allow the development of therapeutic agents for the treatment of AAA.
Endocrine Glands and Hearing: Auditory Manifestations of Various Endocrine and Metabolic Conditions

PubMed Central

Cherian, Kripa Elizabeth; Kapoor, Nitin; Mathews, Suma Susan; Paul, Thomas Vizhalil

2017-01-01

The aetiology of hearing loss in humans is multifactorial. Besides genetic, environmental and infectious causes, several endocrine and metabolic abnormalities are associated with varying degrees of hearing impairment. The pattern of hearing loss may be conductive, sensori-neural or mixed. The neurophysiology of hearing as well as the anatomical structure of the auditory system may be influenced by changes in the hormonal and metabolic milieu. Optimal management of these conditions requires the integrated efforts of the otolaryngologist and the endocrinologist. The presence of hearing loss especially in the young age group should prompt the clinician to explore the possibility of an associated endocrine or metabolic disorder for timely referral and early initiation of treatment. PMID:28553606

Insights into the genetics of gastroesophageal reflux disease (GERD) and GERD-related disorders.

PubMed

Böhmer, A C; Schumacher, J

2017-02-01

Gastroesophageal reflux disease (GERD) is associated with obesity and hiatal hernia, and often precedes the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EA). Epidemiological studies show that the global prevalence of GERD is increasing. GERD is a multifactorial disease with a complex genetic architecture. Genome-wide association studies (GWAS) have provided initial insights into the genetic background of GERD. The present review summarizes current knowledge of the genetics of GERD and a possible genetic overlap between GERD and BE and EA. The review discusses genes and cellular pathways that have been implicated through GWAS, and provides an outlook on how future molecular research will enhance understanding of GERD pathophysiology. © 2017 John Wiley & Sons Ltd.
Optimizing human factors in dentistry.

PubMed

Gupta, Arpit; Ankola, Anil V; Hebbal, Mamata

2013-03-01

Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs.
Sporadic inclusion-body myositis: conformational multifactorial ageing-related degenerative muscle disease associated with proteasomal and lysosomal inhibition, endoplasmic reticulum stress, and accumulation of amyloid-β42 oligomers and phosphorylated tau.

PubMed

Askanas, Valerie; Engel, W King

2011-04-01

The pathogenesis of sporadic inclusion-body myositis (s-IBM), the most common muscle disease of older persons, is complex and multifactorial. Both the muscle fiber degeneration and the mononuclear-cell inflammation are components of the s-IBM pathology, but how each relates to the pathogenesis remains unsettled. We consider that the intramuscle fiber degenerative component plays the primary and the major pathogenic role leading to muscle fiber destruction and clinical weakness. In this article we review the newest research advances that provide a better understanding of the s-IBM pathogenesis. Cellular abnormalities occurring in s-IBM muscle fibers are discussed, including: several proteins that are accumulated in the form of aggregates within muscle fibers, including amyloid-β42 and its oligomers, and phosphorylated tau in the form of paired helical filaments, and we consider their putative detrimental influence; cellular mechanisms leading to protein misfolding and aggregation, including evidence of their inadequate disposal; pathogenic importance of endoplasmic reticulum stress and the unfolded protein response demonstrated in s-IBM muscle fibers; and decreased deacetylase activity of SIRT1. All these factors are combined with, and perhaps provoked by, an ageing intracellular milieu. Also discussed are the intriguing phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer and Parkinson's disease patients, the two most common neurodegenerative diseases associated with ageing. Muscle biopsy diagnostic criteria are also described and illustrated. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Common Mental Disorders among Occupational Groups: Contributions of the Latent Class Model

PubMed Central

Martins Carvalho, Fernando; de Araújo, Tânia Maria

2016-01-01

Background. The Self-Reporting Questionnaire (SRQ-20) is widely used for evaluating common mental disorders. However, few studies have evaluated the SRQ-20 measurements performance in occupational groups. This study aimed to describe manifestation patterns of common mental disorders symptoms among workers populations, by using latent class analysis. Methods. Data derived from 9,959 Brazilian workers, obtained from four cross-sectional studies that used similar methodology, among groups of informal workers, teachers, healthcare workers, and urban workers. Common mental disorders were measured by using SRQ-20. Latent class analysis was performed on each database separately. Results. Three classes of symptoms were confirmed in the occupational categories investigated. In all studies, class I met better criteria for suspicion of common mental disorders. Class II discriminated workers with intermediate probability of answers to the items belonging to anxiety, sadness, and energy decrease that configure common mental disorders. Class III was composed of subgroups of workers with low probability to respond positively to questions for screening common mental disorders. Conclusions. Three patterns of symptoms of common mental disorders were identified in the occupational groups investigated, ranging from distinctive features to low probabilities of occurrence. The SRQ-20 measurements showed stability in capturing nonpsychotic symptoms. PMID:27630999
Anterior Knee Pain in Children and Adolescents: Overview and Management.

PubMed

Slotkin, Steven; Thome, Andrew; Ricketts, Cassandra; Georgiadis, Andrew; Cruz, Aristides I; Seeley, Mark

2018-05-01

Anterior knee pain (AKP) is a common presenting complaint for pediatricians and orthopaedic surgeons and is often seen in young athletes. AKP is multifactorial and has a broad differential diagnosis. The growth changes, biomechanics, and anatomy around the knee add to the complexity of diagnosis and treatment of AKP. Common causes of AKP include Osgood-Schlatter's disease, patellar tendinitis, and patellofemoral instability. In the diagnosis of AKP, it is important to rule out serious and morbid causes of pain, including infection and tumor. It is crucial to complete a detailed history and physical examination and obtain appropriate imaging studies. In general, the majority of patients will respond to nonoperative measures targeted to correct neuromuscular control and kinetic chain dysfunction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Patellofemoral pain in athletes: clinical perspectives

PubMed Central

Halabchi, Farzin; Abolhasani, Maryam; Mirshahi, Maryam; Alizadeh, Zahra

2017-01-01

Patellofemoral pain (PFP) is a very common problem in athletes who participate in jumping, cutting and pivoting sports. Several risk factors may play a part in the pathogenesis of PFP. Overuse, trauma and intrinsic risk factors are particularly important among athletes. Physical examination has a key role in PFP diagnosis. Furthermore, common risk factors should be investigated, such as hip muscle dysfunction, poor core muscle endurance, muscular tightness, excessive foot pronation and patellar malalignment. Imaging is seldom needed in special cases. Many possible interventions are recommended for PFP management. Due to the multifactorial nature of PFP, the clinical approach should be individualized, and the contribution of different factors should be considered and managed accordingly. In most cases, activity modification and rehabilitation should be tried before any surgical interventions. PMID:29070955
Does the Use of Multifactorial Training Methods Increase Practitioners' Competence?

ERIC Educational Resources Information Center

Pittman, Corinthus Omari; Lawdis, Katina

2017-01-01

Skilled therapy practitioners are required by their governing associations to seek professional development per licensure requirements. These requirements facilitate clinical reasoning and confidence during patient care. There are limited online professional development workshops, especially ones that offer multifactorial training as an…
Anxiety Disorders: Recognizing the Symptoms of Six of the Most Common Anxiety Disorders

ERIC Educational Resources Information Center

Cancro, Robert

2007-01-01

This article describes six common types of anxiety disorders: (1) generalized anxiety disorder; (2) panic disorder; (3) obsessive-compulsive disorder; (4) post-traumatic stress disorder; (5) specific phobias; and (6) social phobia. Treatment of anxiety disorders have two components that can be offered separately or in combination. They are…
Mood Disorders in Systemic Lupus Erythematosus

PubMed Central

Hanly, John G.; Su, Li; Urowitz, Murray B.; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; Bernatsky, Sasha; Clarke, Ann E.; Wallace, Daniel J.; Merrill, Joan T.; Isenberg, David A.; Rahman, Anisur; Ginzler, Ellen M.; Petri, Michelle; Bruce, Ian N.; Dooley, M. A.; Fortin, Paul; Gladman, Dafna D.; Sanchez-Guerrero, Jorge; Steinsson, Kristjan; Ramsey-Goldman, Rosalind; Khamashta, Munther A.; Aranow, Cynthia; Alarcón, Graciela S.; Fessler, Barri J.; Manzi, Susan; Nived, Ola; Sturfelt, Gunnar K.; Zoma, Asad A.; van Vollenhoven, Ronald F.; Ramos-Casals, Manuel; Ruiz-Irastorza, Guillermo; Lim, S. Sam; Kalunian, Kenneth C.; Inanc, Murat; Kamen, Diane L.; Peschken, Christine A.; Jacobsen, Soren; Askanase, Anca; Theriault, Chris; Thompson, Kara; Farewell, Vernon

2015-01-01

Objective To determine the frequency, clinical and autoantibody associations and outcome of mood disorders in a multi-ethnic/racial, prospective, inception cohort of SLE patients. Methods Patients were assessed annually for mood disorders (4 types as per DSM-IV) and 18 other neuropsychiatric (NP) events. Global disease activity (SLEDAI-2K), SLICC/ACR damage index (SDI) and SF-36 subscale, mental (MCS) and physical (PCS) component summary scores were collected. Time to event, linear and ordinal regressions and multi-state models were used as appropriate. Results Of 1,827 SLE patients, 88.9% were female, 48.9% Caucasian, mean ± SD age 35.1±13.3 years, disease duration 5.6±4.8 months and follow-up 4.73±3.45 years. Over the study 863 (47.2%) patients had 1,627 NP events. Mood disorders occurred in 232/1827 (12.7%) patients and 98/256 (38.3%) events were attributed to SLE. The estimated cumulative incidence of any mood disorder after 10 years was 17.7% (95%CI=[15.1%,20.2%]). There was a greater risk of mood disorder in patients with concurrent NP events (p ≤ 0.01) and lower risk with Asian race/ethnicity (p=0.01) and immunosuppressive drugs (p=0.003). Mood disorders were associated with lower mental health subscale and MCS scores but not with SLEDAI-2K, SDI scores or lupus autoantibodies. Antidepressants were used in 168/232 (72.4%) patients with depression. 126/256 (49.2%) mood disorders resolved in 117/232 (50.4%) patients. Conclusion Mood disorders, the second most frequent NP event in SLE patients, have a negative impact on HRQoL and improve over time. The lack of association with global SLE disease activity, cumulative organ damage and lupus autoantibodies emphasize their multifactorial etiology and a role for non-lupus specific therapies. PMID:25778456
Is the Relationship between Common Mental Disorder and Adiposity Bidirectional? Prospective Analyses of a UK General Population-Based Study.

PubMed

Fezeu, Léopold K; Batty, G David; Batty, David G; Gale, Catharine R; Kivimaki, Mika; Hercberg, Serge; Czernichow, Sebastien

2015-01-01

The direction of the association between mental health and adiposity is poorly understood. Our objective was to empirically examine this link in a UK study. This is a prospective cohort study of 3 388 people (men) aged ≥ 18 years at study induction who participated in both the UK Health and Lifestyle Survey at baseline (HALS-1, 1984/1985) and the re-survey (HALS-2, 1991/1992). At both survey examinations, body mass index, waist circumference and self-reported common mental disorder (the 30-item General Health Questionnaire, GHQ) were measured. Logistic regression models were used to compute odds ratios (OR) and accompanying 95% confidence intervals (CI) for the associations between (1) baseline common mental disorder (QHQ score > 4) and subsequent general and abdominal obesity and (2) baseline general and abdominal obesity and re-survey common mental disorders. After controlling for a range of covariates, participants with common mental disorder at baseline experienced greater odds of subsequently becoming overweight (women, OR: 1.30, 1.03 - 1.64; men, 1.05, 0.81 - 1.38) and obese (women, 1.26, 0.82 - 1.94; men, OR: 2.10, 1.23 - 3.55) than those who were free of common mental disorder. Similarly, having baseline common mental health disorder was also related to a greater risk of developing moderate (1.57, 1.21 - 2.04) and severe (1.48, 1.09 - 2.01) abdominal obesity (women only). Baseline general or abdominal obesity was not associated with the risk of future common mental disorder. These findings of the present study suggest that the direction of association between common mental disorders and adiposity is from common mental disorder to increased future risk of adiposity as opposed to the converse.
Transgender Associations and Possible Etiology: A Literature Review.

PubMed

Saleem, Fatima; Rizvi, Syed W

2017-12-24

Transgender or gender dysphoria has been defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), as distress resulting from the incongruence between one's experienced gender and one's assigned gender, along with a persistent and strong desire to be of another gender, and accompanied by clinically significant distress. Adolescents referred for evaluation often want hormonal therapy and several among them also express a desire for gender reassignment surgery. Furthermore, evidence shows that adolescents and adults with gender dysphoria without a sex development disorder, before gender reassignments, are at increased risk for suicide. For this review, a search of the English language scientific literature was conducted using the PubMed database. This summary discusses the associations and comorbidities of gender dysphoria and reiterates the evidence that its etiology is multifactorial. Transsexualism involves prenatal neuroanatomical changes, has a psychiatric association, and is found to be more prevalent in conjunction with schizophrenia and autism spectrum disorders. Childhood adversities and neglect are also linked to having a transgender identity. Moreover, the evidence favors a genetic predisposition. Likewise, there seems to be a growing concern with regards to the relationship between endocrine disruptors and transsexuals as well as other gender minority populations. More research needs to be done to understand the exact pathways.
DNA Damage and Repair in Schizophrenia and Autism: Implications for Cancer Comorbidity and Beyond

PubMed Central

Markkanen, Enni; Meyer, Urs; Dianov, Grigory L.

2016-01-01

Schizophrenia and autism spectrum disorder (ASD) are multi-factorial and multi-symptomatic psychiatric disorders, each affecting 0.5%–1% of the population worldwide. Both are characterized by impairments in cognitive functions, emotions and behaviour, and they undermine basic human processes of perception and judgment. Despite decades of extensive research, the aetiologies of schizophrenia and ASD are still poorly understood and remain a significant challenge to clinicians and scientists alike. Adding to this unsatisfactory situation, patients with schizophrenia or ASD often develop a variety of peripheral and systemic disturbances, one prominent example of which is cancer, which shows a direct (but sometimes inverse) comorbidity in people affected with schizophrenia and ASD. Cancer is a disease characterized by uncontrolled proliferation of cells, the molecular origin of which derives from mutations of a cell’s DNA sequence. To counteract such mutations and repair damaged DNA, cells are equipped with intricate DNA repair pathways. Oxidative stress, oxidative DNA damage, and deficient repair of oxidative DNA lesions repair have been proposed to contribute to the development of schizophrenia and ASD. In this article, we summarize the current evidence of cancer comorbidity in these brain disorders and discuss the putative roles of oxidative stress, DNA damage and DNA repair in the aetiopathology of schizophrenia and ASD. PMID:27258260
Modeling anorexia nervosa: transcriptional insights from human iPSC-derived neurons

PubMed Central

Negraes, P D; Cugola, F R; Herai, R H; Trujillo, C A; Cristino, A S; Chailangkarn, T; Muotri, A R; Duvvuri, V

2017-01-01

Anorexia nervosa (AN) is a complex and multifactorial disorder occurring predominantly in women. Despite having the highest mortality among psychiatric conditions, it still lacks robust and effective treatment. Disorders such as AN are most likely syndromes with multiple genetic contributions, however, genome-wide studies have been underpowered to reveal associations with this uncommon illness. Here, we generated induced pluripotent stem cells (iPSCs) from adolescent females with AN and unaffected controls. These iPSCs were differentiated into neural cultures and subjected to extensive transcriptome analysis. Within a small cohort of patients who presented for treatment, we identified a novel gene that appears to contribute to AN pathophysiology, TACR1 (tachykinin 1 receptor). The participation of tachykinins in a variety of biological processes and their interactions with other neurotransmitters suggest novel mechanisms for how a disrupted tachykinin system might contribute to AN symptoms. Although TACR1 has been associated with psychiatric conditions, especially anxiety disorders, we believe this report is its first association with AN. Moreover, our human iPSC approach is a proof-of-concept that AN can be modeled in vitro with a full human genetic complement, and represents a new tool for understanding the elusive molecular and cellular mechanisms underlying the disease. PMID:28291261
Transgender Associations and Possible Etiology: A Literature Review

PubMed Central

Rizvi, Syed W

2017-01-01

Transgender or gender dysphoria has been defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), as distress resulting from the incongruence between one’s experienced gender and one’s assigned gender, along with a persistent and strong desire to be of another gender, and accompanied by clinically significant distress. Adolescents referred for evaluation often want hormonal therapy and several among them also express a desire for gender reassignment surgery. Furthermore, evidence shows that adolescents and adults with gender dysphoria without a sex development disorder, before gender reassignments, are at increased risk for suicide. For this review, a search of the English language scientific literature was conducted using the PubMed database. This summary discusses the associations and comorbidities of gender dysphoria and reiterates the evidence that its etiology is multifactorial. Transsexualism involves prenatal neuroanatomical changes, has a psychiatric association, and is found to be more prevalent in conjunction with schizophrenia and autism spectrum disorders. Childhood adversities and neglect are also linked to having a transgender identity. Moreover, the evidence favors a genetic predisposition. Likewise, there seems to be a growing concern with regards to the relationship between endocrine disruptors and transsexuals as well as other gender minority populations. More research needs to be done to understand the exact pathways. PMID:29503778
The Matrix Metalloproteinase 9 Point-of-Care Test in Dry Eye.

PubMed

Lanza, Nicole L; Valenzuela, Felipe; Perez, Victor L; Galor, Anat

2016-04-01

Dry eye is a common, multifactorial disease currently diagnosed by a combination of symptoms and signs. However, the subjective symptoms of dry eye poorly correlate to the current gold standard for diagnostic tests, reflecting the need to develop better objective tests for the diagnosis of dry eye. This review considers the role of ocular surface matrix metalloproteinase 9 (MMP-9) in dry eye and the implications of a novel point-of-care test that measures MMP-9 levels, InflammaDry (RPS, Sarasota, FL) on choosing appropriate therapeutic treatments. Published by Elsevier Inc.
Oropharyngeal Dysphagia in children: mechanism, source, and management.

PubMed

Durvasula, Venkata S P B; O'Neill, Ashley C; Richter, Gresham T

2014-10-01

Oropharyngeal dysphagia (OPD) is a challenging and relatively common condition in children. Both developmentally normal and delayed children may be affected. The etiology of OPD is frequently multifactorial with neurologic, inflammatory, and anatomic conditions contributing to discoordination of the pharyngeal phase of swallowing. Depending on the severity and source, OPD may persist for several years with significant burden to a patient's health and family. This article details current understanding of the mechanism and potential sources of OPD in children while providing an algorithm for managing it in the acute and chronic setting. Copyright © 2014 Elsevier Inc. All rights reserved.
What are the causes of late-life depression?

PubMed

Aziz, Rehan; Steffens, David C

2013-12-01

Although depression in old age is less common than depression in younger populations, it still affects more than 1 million community-living older adults. Depression in late life has been associated with reduced quality of life and increased mortality from both suicide and illness. Its causes are multifactorial but are prominently related to both biologic and social factors. Psychological factors, although less studied in elders, are also important in understanding its cause. In this article, multiple facets of late-life depression are reviewed, including its clinical presentation, epidemiology, and biopsychosocial causes. Copyright © 2013 Elsevier Inc. All rights reserved.
Probiotic Therapy for Irritable Bowel Syndrome

PubMed Central

Aragon, George; Graham, Deborah B.; Borum, Marie

2010-01-01

The etiology of irritable bowel syndrome (IBS) is thought to be multifactorial, with several factors (including alterations in gut motility, small-bowel bacterial overgrowth, microscopic inflammation, and visceral hypersensitivity) potentially playing a role. Recent studies have suggested that probiotics may be useful in the treatment of IBS. Although the exact mechanism for how probiotics may aid in the reduction of symptoms commonly found in IBS is unknown, the effects of probiotics on alterations in gut bacteria appear to play a part. This review focuses on recent studies examining the role of probiotics in the treatment of IBS. PMID:20567539
Clues to immune tolerance: The monogenic autoimmune syndromes

PubMed Central

Waterfield, Michael; Anderson, Mark S.

2010-01-01

Autoimmune disease affects a significant proportion of the population. The etiology of most autoimmune diseases is largely unknown, but it is thought to be multifactorial with both environmental and genetic influences. Rare monogenic autoimmune diseases, however, offer an invaluable window into potential disease mechanisms. In this review, we will discuss the autoimmune polyglandular syndrome (APS1), the immunedysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), and autoimmune lymphoproliferative syndrome (ALPS). Significantly, the information gained from the study of these diseases has provided new insights into more common autoimmune disease and have yielded new diagnostics and therapeutic opportunities. PMID:20969580
New and emerging pathogens in canine infectious respiratory disease.

PubMed

Priestnall, S L; Mitchell, J A; Walker, C A; Erles, K; Brownlie, J

2014-03-01

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

Genetics and Genomics of Endometriosis

PubMed Central

Hansen, Keith A.; Eyster, Kathleen M.

2015-01-01

Endometriosis is a common cause of morbidity in women with an unknown etiology. Studies have demonstrated the familial nature of endometriosis and suggest that inheritance occurs in a polygenic/multifactorial fashion. Studies have attempted to define the gene or genes responsible for endometriosis through association or linkage studies with candidate genes or DNA mapping technology. A number of genomics studies have demonstrated significant alterations in gene expression in endometriosis. A more thorough understanding of the genetics and genomics of endometriosis will facilitate understanding the basic biology of the disease and open new inroads to diagnosis and treatment of this enigmatic condition. PMID:20436317
[About the heterogeneity in adolescents with gender identity disorder: differential importance of psychiatric comorbidity and considerations of individual psychodynamics].

PubMed

Korte, Alexander; Beier, Klaus M; Vukorepa, Julia; Mersmann, Maik; Albiez, Verena

2014-01-01

Gender identity disorder (GID), gender dysphoria (GD) respectively, is considered a multifactorial disease whose etiology is subject to complex bio-psycho-social conditions, each with different weighting. As a result, therapists, who treat children and adolescents with GID/GD, have to deal with a very heterogeneous group with individually varying causes, differing psychopathology and varying disease progression. In addition to general psychiatric aspects of development, particularly psychiatric comorbidity, but also the different individual psychodynamics--i. e. the specific constellation of conflicts and possible ego deficits and structural deficits in the learning history of the person are of differential importance. In regard to the indication for gender reassignment measures this sometimes is relevant for the decision. The difficulties arising for decision making and the usefulness of a systematic evaluation of case reports as a basis for further optimization of the treatment recommendations are illustrated by two case reports. In the course of this, also the disadvantages and potential dangers of too early diagnostic definition and introduction of gender somato-medical and legal measures are shown exemplarily.
The application of participatory ergonomics in a healthcare setting in Hong Kong.

PubMed

Lee, Edwin W C; Fok, Joan P C; Lam, Augustine T; Law, Rainbow K Y; Szeto, Grace P Y; Li, Philip P K

2014-01-01

Work-related musculoskeletal disorders (WRMDs) are recognized as a major source of significant pain and disability in the healthcare sector. However, they are preventable if appropriate surveillance and intervention programs are implemented. The purpose of this paper is to describe the holistic ergonomic approach that was used to address the multifactorial problems encountered by healthcare workers in their daily work. Using participatory ergonomics, healthcare workers in this study teamed up with management and staff with expertise in ergonomic analysis, design, and implementation of remedies. Selected participatory ergonomic intervention programs targeted at an organizational level are elaborated. Interventions included pre-work stretching, workplace surveillance at a psychiatric department, on-site ergonomic teaching for community nurses, and display screen equipment consultancy. Changes in workplace design, equipment re-arrangement, awareness of proper posture, and adoption of good work practices all play important roles in reducing musculoskeletal disorders among healthcare workers. Prompt occupational medicine and rehabilitation services were also provided to complement the work disability prevention process. The impact of the various intervention programs on staff health, costs and productivity of the organization are simultaneously discussed.
The new insight on the regulatory role of the vitamin D3 in metabolic pathways characteristic for cancerogenesis and neurodegenerative diseases.

PubMed

Kubis, Adriana Maria; Piwowar, Agnieszka

2015-11-01

Apart from the classical function of regulating intestinal, bone and kidney calcium and phosphorus absorption as well as bone mineralization, there is growing evidence for the neuroprotective function of vitamin D3 through neuronal calcium regulation, the antioxidative pathway, immunomodulation and detoxification. Vitamin D3 and its derivates influence directly or indirectly almost all metabolic processes such as proliferation, differentiation, apoptosis, inflammatory processes and mutagenesis. Such multifactorial effects of vitamin D3 can be a profitable source of new therapeutic solutions for two radically divergent diseases, cancer and neurodegeneration. Interestingly, an unusual association seems to exist between the occurrence of these two pathological states, called "inverse comorbidity". Patients with cognitive dysfunctions or dementia have considerably lower risk of cancer, whereas survivors of cancer have lower prevalence of central nervous system (CNS) disorders. To our knowledge, there are few publications analyzing the role of vitamin D3 in biological pathways existing in carcinogenic and neuropathological disorders. Copyright © 2015 Elsevier B.V. All rights reserved.
Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition

PubMed Central

Sterns, J. David; Smith, Colin B.; Steele, John R.; Stevenson, Kimberly L.; Gallicano, G. Ian

2014-01-01

Type II diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance precipitating abnormally high blood glucose levels. While the onset of T2DM is known to be the consequence of a multifactorial interplay with a strong genetic component, emerging research has demonstrated the additional role of a variety of epigenetic mechanisms in the development of this disorder. Heritable epigenetic modifications, such as DNA methylation and histone modifications, play a vital role in many important cellular processes, including pancreatic cellular differentiation and maintenance of normal β-cell function. Recent studies have found possible epigenetic mechanisms to explain observed risk factors, such as altered atherogenic lipid profiles, elevated body mass index (BMI), and impaired glucose tolerance (IGT), for later development of T2DM in children born to mothers experiencing both famine and hyperglycemic conditions. It is suggested that these epigenetic influences happen early during gestation and are less susceptible to the effects of postnatal environmental modification as was previously thought, highlighting the importance of early preventative measures in minimizing the global burden of T2DM. PMID:25364722
Current Perspectives on Physical Activity and Exercise Recommendations for Children and Adolescents With Autism Spectrum Disorders

PubMed Central

Srinivasan, Sudha M.; Pescatello, Linda S.

2014-01-01

Recent evidence suggests that childhood obesity is increasing in children who are developing typically as well as in children with developmental disabilities such as autism spectrum disorders (ASDs). Impairments specific to autism as well as general environmental factors could lead to an imbalance between the intake and expenditure of energy, leading to obesity. In this article, we describe the mechanisms by which autism-specific impairments contribute to obesity. The evidence on exercise interventions to improve physical fitness, address obesity, and reduce autism-specific impairments in children and adolescents with ASDs is discussed. Limited evidence is currently available for exercise interventions in individuals with ASDs. Therefore, literature on other pediatric developmental disabilities and children who are developing typically was reviewed to provide recommendations for clinicians to assess physical activity levels, to promote physical fitness, and to reduce obesity in children and adolescents with ASDs. There is a clear need for further systematic research to develop sensitive assessment tools and holistic multisystem and multifactorial obesity interventions that accommodate the social communication, motor, and behavioral impairments of individuals with ASDs. PMID:24525861
Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases.

PubMed

Migliore, Lucia; Coppedè, Fabio

2009-07-10

In the present review we summarize recent advances in the understanding of the interaction between genetics and environmental factors involved in complex multi-factorial neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). The discovery of several genes responsible for the familial forms has led to a better comprehension of the molecular pathways involved in the selective neuronal degeneration which is specific for each of these disorders. However, the vast majority of the cases occurs as sporadic forms, likely resulting from complex gene-gene and gene-environment interplay. Several environmental factors, including, pesticides, metals, head injuries, lifestyles and dietary habits have been associated with increased disease risk or even with protection. Hundreds of genetic variants have been investigated as possible risk factors for the sporadic forms, but results are often conflicting, not repeated or inconclusive. New approaches to environmental health research are revealing us that at the basis there could be chemically induced changes in gene regulation and emphasise the importance of understanding the susceptibility of the human epigenome to dietary and other environmental effects.
Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease

PubMed Central

Suárez, Manuel; Boqué, Noemí; del Bas, Josep M.; Arola, Lluís; Caimari, Antoni

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of hepatic disorders, from simple steatosis to hepatic necro-inflammation leading to non-alcoholic steatohepatitis (NASH). Although the prevalence of these multifactorial pathologies is continuously increasing in the population, there is still not an established methodology for their treatment other than weight loss and a change in lifestyle habits, such as a hypocaloric diet and physical exercise. In this framework, there is increasing evidence that several food bioactives and dietary patterns are effective for reversing and preventing the onset of these pathologies. Some studies have claimed that better responses are obtained when treatments are performed under a multifaceted approach, using different bioactive compounds that act against complementary targets. Thus, in this work, current strategies for treating NAFLD and NASH based on multi-ingredient-based supplements or the Mediterranean diet, a dietary pattern rich in bioactive compounds, are reviewed. Furthermore, the usefulness of omics techniques to design effective multi-ingredient nutritional interventions and to predict and monitor their response against these disorders is also discussed. PMID:28937599
Correlation between traumatic events and posttraumatic stress disorder among North Korean defectors in South Korea.

PubMed

Jeon, WooTaek; Hong, ChangHyung; Lee, ChangHo; Kim, Dong Kee; Han, Mooyoung; Min, SungKil

2005-04-01

The number of North Korean defectors entering South Korea has been increasing rapidly since 1994. Two hundred North Korean defectors in South Korea were studied to identify their experiences of traumatic events in North Korea and during defection, and the correlation with Posttraumatic Stress Disorder (PTSD). Researchers conducted face-to-face interviews and assisted defectors in performing a self-report assessment of this survey. The study questionnaire consisted of demographic characteristics, the Traumatic Experiences Scale for North Korean Defectors, and the PTSD part of the Structured Clinical Interview for DSM-III-R Korean version. Prevalence rate of PTSD in defectors was 29.5%, with a higher rate for women. In factor analysis, the 25 items of traumatic events experienced in North Korea were divided into three factors: Physical Trauma, Political-Ideological Trauma, and Family-Related Trauma. In addition, the 19 items of traumatic events during defection were grouped into four factors: Physical Trauma, Detection and Capture-Related Trauma, Family-Related Trauma, and Betrayal-Related Trauma. In multifactorial logistic regression analysis, Family-Related Trauma in North Korea had a significant odds ratio.
The role of DNA methylation in the pathophysiology and treatment of bipolar disorder

PubMed Central

Fries, Gabriel Rodrigo; Li, Qiongzhen; McAlpin, Blake; Rein, Theo; Walss-Bass, Consuelo; Soares, Jair C.; de Quevedo, Joao

2016-01-01

Bipolar disorder (BD) is a multifactorial illness thought to result from an interaction between genetic susceptibility and environmental stimuli. Epigenetic mechanisms, including DNA methylation, can modulate gene expression in response to the environment, and therefore might account for part of the heritability reported for BD. This paper aims to review evidence of the potential role of DNA methylation in the pathophysiology and treatment of BD. In summary, several studies suggest that alterations in DNA methylation may play an important role in the dysregulation of gene expression in BD, and some actually suggest their potential use as biomarkers to improve diagnosis, prognosis, and assessment of response to treatment. This is also supported by reports of alterations in the levels of DNA methyltransferases in patients and in the mechanism of action of classical mood stabilizers. In this sense, targeting specific alterations in DNA methylation represents exciting new treatment possibilities for BD, and the ‘plastic’ characteristic of DNA methylation accounts for a promising possibility of restoring environment-induced modifications in patients. PMID:27328785
Work-associated irritable larynx syndrome.

PubMed

Anderson, Jennifer A

2015-04-01

The purpose of this study is to review the relevant literature concerning work-associated irritable larynx syndrome (WILS), a hyperkinetic laryngeal disorder associated with occupational irritant exposure. Clinical symptoms are variable and include dysphonia, cough, dyspnoea and globus pharyngeus. WILS is a clinical diagnosis and can be difficult to differentiate from asthma. Treatment options for WILS include medical and behavioural therapy. Laryngeal-centred upper airway symptoms secondary to airborne irritants have been documented in the literature under a variety of diagnostic labels, including WILS, vocal cord dysfunction (VCD), laryngeal hypersensitivity and laryngeal neuropathy and many others. The underlying pathophysiology is as yet poorly understood; however, the clinical scenario suggests a multifactorial nature to the disorder. More recent literature indicates that central neuronal plasticity, inflammatory processes and psychological factors are all likely contributors. Possible mechanisms for WILS include central neuronal network plasticity after noxious exposure and/or viral infection, inflammation (i.e. reflux disease) and intrinsic patient factors such a psychological state. Treatment is individualized and frequently includes one or more of the following: environmental changes in the workplace, GERD therapy, behavioural/speech therapy, psychotherapy counselling and neural modifiers.
Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues.

PubMed

Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K

2016-03-01

Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets.
[Age-related changes in swallowing. Physiology and pathophysiology].

PubMed

Muhle, P; Wirth, R; Glahn, J; Dziewas, R

2015-04-01

The term presbyphagia refers to all changes of swallowing physiology that are manifested with increasing age. Alterations in the pattern of deglutition that are part of healthy aging are called primary presbyphagia. Primary presbyphagia is not an illness in itself but contributes to a more pervasive naturally diminished functional reserve, making older adults more susceptible to dysphagia. If disorders in swallowing occur in the elderly as a comorbidity of a specific disease, for example stroke or neurodegenerative disorders, this is called secondary presbyphagia. Increasing age has an impact on each stage of deglutition. In the oral preparatory phase a diminished input for smell and taste as well as a usually multifactorial cause of dry mouth are the most important influencing factors. Sarcopenia, the degenerative loss of skeletal muscle mass, strength and quality associated with aging, interferes in particular with the oropharyngeal phase. A decreased sensory feedback from the oropharyngeal mucosa leads to a delayed triggering of the swallowing reflex. Finally, a reduction in connective tissue elasticity and changes of the axial skeleton lead to various modifications of the swallowing pattern with advanced age.
The role of omega-3 and micronutrients in age-related macular degeneration.

PubMed

Querques, Giuseppe; Souied, Eric H

2014-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States, Europe, and other developed countries. Although the pathogenesis of AMD remains unclear, current evidence suggests a multifactorial aetiology. Nutrition may play an important role in the development and progression of AMD. There have been several epidemiological studies suggesting that omega-3 fatty acids could have a protective role in AMD, but a beneficial effect remains to be demonstrated in randomized controlled trials. There also exists a substantial body of evidence suggesting that protection against AMD may be provided by specific micronutrients (vitamins and minerals and antioxidants). The identification of risk factors for the development and progression of AMD is of particular importance for understanding the origins of the disorder and for establishing strategies for its prevention. We examine the relationship between dietary omega-3 intake and the incidence and progression of AMD, as well as the role of omega-3 supplementation in the prevention of the disorder, and also explore the role of other micronutrients in AMD. Copyright © 2014 Elsevier Inc. All rights reserved.
28.1 VARIETIES OF SELF DISORDER: A BIO-PHENO-SOCIAL MODEL OF SCHIZOPHRENIA

PubMed Central

Nelson, Barnaby; Sass, Louis

2018-01-01

Abstract Background The self-disorder model offers a unifying way of conceptualizing schizophrenia’s highly diverse symptoms (positive, negative, disorganized), of capturing their distinctive bizarreness, and of conceiving their longitudinal development. These symptoms are viewed as differing manifestations of an underlying disorder of ‘core-self’: hyperreflexivity/diminished-self presence with accompanying disturbances of “grip” or “hold” on reality. Methods We have recently revised and tested this phenomenological model, in particular distinguishing primary versus-secondary factors, in offering a bio-pheno-social model of schizophrenia spectrum disorders. Results The revised model is consistent with recent empirical findings and offers several advantages: 1) It helps account for the temporal variations of the symptoms or syndrome, including longitudinal progression, but also the shorter-term, situationally-reactive, sometimes defensive, and possibly quasi-agentive variability of symptom-expression that can occur in schizophrenia (consistent with understanding some aspects of self-disturbance as dynamic and mutable, involving shifting attitudes or experiential orientations). 2) It accommodates the overlapping of some key schizophrenic symptoms with certain non-schizophrenia spectrum conditions involving dissociation (depersonalization and derealization), including Depersonalization Disorder and Panic Disorder, thereby acknowledging both shared and distinguishing symptoms. 3) It integrates recent neurocognitive, neurobiological, and psychosocial (e.g., influence of trauma and culture) findings into a coherent but multi-factorial neuropsychological account. Discussion An adequate model of schizophrenia will postulate shared disturbances of core-self experiences that nevertheless can follow several distinct pathways and occur in various forms. Such a model is preferable to uni-dimensional alternatives—whether of schizophrenia or core self disturbance—given its ability to account for distinctive yet varying experiential and neurocognitive abnormalities found in research on schizophrenia, and to integrate these with recent psychosocial as well as neurobiological findings.
Dental attrition models predicting temporomandibular joint disease or masticatory muscle pain versus asymptomatic controls.

PubMed

Seligman, D A; Pullinger, A G

2006-11-01

To determine whether patients with temporomandibular joint disease or masticatory muscle pain can be usefully differentiated from asymptomatic controls using multifactorial classification tree models of attrition severity and/or rates. Measures of attrition severity and rates in patients diagnosed with disc displacement (n = 52), osteoarthrosis (n = 74), or masticatory muscle pain only (n = 43) were compared against those in asymptomatic controls (n = 132). Cross-validated classification tree models were tested for fit with sensitivity, specificity, accuracy and log likelihood accountability. The model for identifying asymptomatic controls only required the three measures of attrition severity (anterior, mediotrusive and laterotrusive posterior) to be differentiated from the patients with a 74.2 +/- 3.8% cross-validation accuracy. This compared with cross-validation accuracies of 69.7 +/- 3.7% for differentiating disc displacement using anterior and laterotrusive attrition severity, 68.7 +/- 3.9% for differentiating disc displacement using anterior and laterotrusive attrition rates, 70.9 +/- 3.3% for differentiating osteoarthrosis using anterior attrition severity and rates, 94.6 +/- 2.1% for differentiating myofascial pain using mediotrusive and laterotrusive attrition severity, and 92.0 +/- 2.1% for differentiating myofascial pain using mediotrusive and anterior attrition rates. The myofascial pain models exceeded the > or =75% sensitivity and > or =90% specificity thresholds recommended for diagnostic tests, and the asymptomatic control model approached these thresholds. Multifactorial models using attrition severity and rates may differentiate masticatory muscle pain patients from asymptomatic controls, and have some predictive value for differentiating intracapsular temporomandibular disorder patients as well.
[Diagnostics and multimodal treatment of depression in old age : New developments].

PubMed

Eschweiler, Gerhard W

2017-02-01

Depressive disorders in elderly persons are frequent and can either first be manifested at a younger age and show a recurrent pattern during later life (ICD 10, F33.*) or have an onset beyond 60 years, which is termed late onset depression (LOD). This LOD has a higher tendency to chronification and implies an increased risk of progression, especially to vascular dementia. The multifactorial genesis of depression in old age includes psychosocial, vascular and metabolic factors and requires multimodal therapy modules at the biological and psychosocial level, which is now increasingly being empirically proven. Depressive disorders with executive and cognitive deficits have to be considered a defined entity with respect to prognosis and treatment. As a first step of treatment watchful waiting is appropriate, especially in depressive adjustment disorders triggered by acute psychosocial stressors (e.g. loss of relatives and conflicts). After 2-4 weeks pharmacological antidepressant therapy should be initiated, at least in a moderate depressive episode. Furthermore, the revised national guidelines for depressive disorders also explicitly recommend psychotherapy as an alternative or supplement to pharmacotherapy in the elderly. Several forms of psychotherapy are emphasized: cognitive behavioral therapy, interpersonal therapy and in particular problem solving, as this is a form of treatment that can also be carried out by other professional groups, thus alleviating the treatment gap caused by the lack of psychotherapists. In summary, a depressive disorder in old age should not induce therapeutic nihilism: after stepped diagnostic assessments, multimodal therapies are individually adapted to the physical, cognitive and social resources of the patients.
Aural symptoms in patients with temporomandibular joint disorders: multiple frequency tympanometry provides objective evidence of changes in middle ear impedance.

PubMed

Riga, Maria; Xenellis, John; Peraki, Eleni; Ferekidou, Elisa; Korres, Stavros

2010-12-01

The association of temporomandibular joint (TMJ) disorders with aural symptoms, such as tinnitus, otic fullness, and subjective decrease of hearing acuity, is a well-established clinical observation. Although several hypotheses have been made about the otic-conductive origin of these complaints, conventional 226-Hz tympanometry has failed to demonstrate any middle ear abnormalities. The aim of this study was to evaluate patients with TMJ disorders with multiple frequency tympanometry (MFT). Prospective clinical study. Outpatient clinic. The population of this study consisted of 40 patients with unilateral TMJ disorders diagnosed for longer than 1 month. After verifying that there were no abnormal otoscopic findings, 226-Hz tympanometry, conventional pure-tone audiometry, brainstem auditory evoked potentials, and MFT were performed. Resonant frequency (RF) values. With the exception of MFT, no abnormal audiologic findings were revealed. The ear ipsilateral to the lesion demonstrated significantly higher (p = 0.002) RF values in comparison to the contralateral ear. The difference in RF values was more obvious in patients aged 45 years or younger. The results of this study imply an increase in the stiffness of the middle ear, which has not been detected by conventional tympanometry. This represents the first concrete documentation of minor alterations in the conductive properties of the middle ear and seems to support the various hypotheses on the middle-ear origin of aural complaints in patients with TMJ disorders. Further studies are needed before a clear insight on the presumably multifactorial pathophysiology of these complaints can finally be reached.
RNAi control of aflatoxins in peanut plants, a multifactorial system

USDA-ARS?s Scientific Manuscript database

RNA-interference (RNAi)-mediated control of aflatoxin contamination in peanut plants is a multifactorial and hyper variable system. The use of RNAi biotechnology to silence single genes in plants has inherently high-variability among transgenic events. Also the level of expression of small interfe...
Risk factors for common mental disorders in women. Population-based longitudinal study.

PubMed

Patel, Vikram; Kirkwood, Betty R; Pednekar, Sulochana; Weiss, Helen; Mabey, David

2006-12-01

The determinants of common mental disorders in women have not been described in longitudinal studies from a low-income country. Population-based cohort study of 2494 women aged 18 to 50 years, in India. The Revised Clinical Interview Schedule was used for the detection of common mental disorders. There were 39 incident cases of common mental disorder in 2166 participants eligible for analysis (12-month rate 1.8%, 95% CI 1.3-2.4%). The following baseline factors were independently associated with the risk for common mental disorder: poverty (low income and having difficulty making ends meet); being married as compared with being single; use of tobacco; experiencing abnormal vaginal discharge; reporting a chronic physical illness; and having higher psychological symptom scores at baseline. Programmes to reduce the burden of common mental disorder in women should target poorer women, women with chronic physical illness and who have gynaecological symptoms, and women who use tobacco.

[Common mental disorders and self-esteem in pregnancy: prevalence and associated factors].

PubMed

Silva, Ricardo Azevedo da; Ores, Liliane da Costa; Mondin, Thaíse Campos; Rizzo, Raquel Nolasco; Moraes, Inácia Gomes da Silva; Jansen, Karen; Pinheiro, Ricardo Tavares

2010-09-01

The aim of this study was to assess the prevalence of common mental disorders and the association with self-esteem and other factors in pregnant women. A nested cross-sectional study was performed in a cohort of pregnant women treated in the public health system in Pelotas, Rio Grande do Sul State, Brazil. The Self-Reporting Questionnaire (SRQ-20) was used to screen for common mental disorders and the Rosenberg's Self-Esteem Scale for self-esteem. The sample consisted of 1,267 pregnant women with a mean age of 25 years (SD = 6.53). Mean self-esteem was 9.3 points (SD = 4.76), and prevalence of common mental disorders was 41.4%. Lower self-esteem was associated with higher odds of common mental disorders (p < 0.001). There was a significant association between higher prevalence of common mental disorders and low self-esteem.
[Movement disorders is psychiatric diseases].

PubMed

Hidasi, Zoltan; Salacz, Pal; Csibri, Eva

2014-12-01

Movement disorders are common in psychiatry. The movement disorder can either be the symptom of a psychiatric disorder, can share a common aetiological factor with it, or can be the consequence of psychopharmacological therapy. Most common features include tic, stereotypy, compulsion, akathisia, dyskinesias, tremor, hypokinesia and disturbances of posture and gait. We discuss characteristics and clinical importance of these features. Movement disorders are frequently present in mood disorders, anxiety disorders, schizophrenia, catatonia, Tourette-disorder and psychogenic movement disorder, leading to differential-diagnostic and therapeutical difficulties in everyday practice. Movement disorders due to psychopharmacotherapy can be classified as early-onset, late-onset and tardive. Frequent psychiatric comorbidity is found in primary movement disorders, such as Parkinson's disease, Wilson's disease, Huntington's disease, diffuse Lewy-body disorder. Complex neuropsychiatric approach is effective concerning overlapping clinical features and spectrums of disorders in terms of movement disorders and psychiatric diseases.
Workplace bullying and common mental disorders: a follow-up study.

PubMed

Lahelma, Eero; Lallukka, Tea; Laaksonen, Mikko; Saastamoinen, Peppiina; Rahkonen, Ossi

2012-06-01

Workplace bullying has been associated with mental health, but longitudinal studies confirming the association are lacking. This study examined the associations of workplace bullying with subsequent common mental disorders 5-7 years later, taking account of baseline common mental disorders and several covariates. Baseline questionnaire survey data were collected in 2000-2002 among municipal employees, aged 40-60 years (n=8960; 80% women; response rate 67%). Follow-up data were collected in 2007 (response rate 83%). The final data amounted to 6830 respondents. Workplace bullying was measured at baseline using an instructed question about being bullied currently, previously or never. Common mental disorders were measured at baseline and at follow-up using the 12-item version of the General Health Questionnaire. Those scoring 3-12 were classified as having common mental disorders. Covariates included bullying in childhood, occupational and employment position, work stress, obesity and limiting longstanding illness. Logistic regression analysis was used. After adjusting for age, being currently bullied at baseline was associated with common mental disorders at follow-up among women (OR 2.34, CI 1.81 to 3.02) and men (OR 3.64, CI 2.13 to 6.24). The association for the previously bullied was weaker. Adjusting for baseline common mental disorders, the association attenuated but remained. Adjusting for further covariates did not substantially alter the studied association. CONCLUSION The study confirms that workplace bullying is likely to contribute to subsequent common mental disorders. Measures against bullying are needed at workplaces to prevent mental disorders.
[Attention Deficit Hyperactivity disorder at schools in Sfax-Tunisia].

PubMed

Khemakhem, Khaoula; Ayadi, Héla; Moalla, Yousr; Yaich, Sourour; Hadjkacem, Imen; Walha, Adel; Damak, Jamel; Ghribi, Farhat

2015-05-01

Frequency, social impact, the negative effects of ADHD on personal development, make it a public health problem. Tunisian existing data confirm its frequency and severity in clinical population. The absence of data in student population has led us to develop this work.The objectives of our study were to study epidemiological profile of ADHD in school population. The analysis involved a cross-sectional descriptive study conducted from April 2008 to October 2008 using a representative randomized multistage sample of schoolchildren between 6 and 12 years old. Measurement was performed in two stages first the parents and teachers of each children filled Conners questionnaire separately then students with the score in subscales inattention, hyperactivity with impulsivity higher than 70 were selected for psychiatric interview. Psychiatric interview was intended to confirm or refute the diagnosis of ADHD. The diagnoses were made according to DSM IV-TR. To study the possible associated factors with the disorder they were compared in children with ADHD and children without the disorder taken as controls. A total of 51 students out of 513 had ADHD. Prevalence was found to be 9,94%. For the study of factors associated with ADHD were found in males, neonatal hospitalization, psychiatric and family history of ADHD and the existence of a family dysfunctionment. Our prevalence is similar to the majority of those reported by studies conducted through the same methodology as ours. The etiology of ADHD is not unequivocal. The disorder appears to be multifactorial.
The role of steroids in the development of post-partum mental disorders.

PubMed

Paskova, Andrea; Jirak, Roman; Mikesova, Michaela; Adamcova, Karolina; Fartakova, Zdenka; Horakova, Vladimira; Koucky, Michal; Hill, Martin; Hruskovicova, Hana; Starka, Luboslav; Duskova, Michaela; Parizek, Antonin

2014-09-01

Unfavorable post-partum changes to mental well-being affect more than half of all women, and are a risk to the health of both mother and baby. Their effects place strains on health and social systems. Currently, no generally accepted theory exists of the causes and mechanisms of post-partum mental disorders. Literature search up to 2012, using PubMed and search words: neuroactive steroids, post-partum mental disorders, depression, corticotropin-releasing hormone and estrogens. There are several theories for post-partum depression. One is that autoimmune diseases are involved. Others revolve around genes responsible or that lead to increased disposition to the disorder. It is likely however that the process is associated with the separation of the placenta and the fetal zone of fetal adrenal gland, the main sources of corticotropin-releasing hormone and sexual and neuroactive steroids during pregnancy, and the ability of the receptor system to adapt to these changes. The central nervous system is able to produce neurosteroids, but the drop in levels of peripheral steroids likely leads to a sudden deficit in neuroinhibitory steroids modulating ionotropic receptors in the brain. Post-partum depression is a multifactorial disease with unknown etiology. It is probably associated with sudden changes in the production of hormones influencing the nervous system, and on the other hand the ability of the receptor system to adapt to these changes. When the relative changes in concentrations of hormones, rather than their absolute levels, is likely more important.
Prevalence and early determinants of common mental disorders in the 1982 birth cohort, Pelotas, Southern Brazil

PubMed Central

Anselmi, Luciana; Barros, Fernando C; Minten, Gicele C; Gigante, Denise P; Horta, Bernardo L; Victora, Cesar G

2009-01-01

OBJECTIVE To estimate the prevalence of common mental disorders and assess its association with risk factors in a cohort of young adults. METHODS Cross-sectional study nested in a 1982 birth cohort study conducted in Pelotas, Southern Brazil. In 2004-5, 4,297 subjects were interviewed during home visits. Common mental disorders were assessed using the Self-Report Questionnaire. Risk factors included socioeconomic, demographic, perinatal, and environmental variables. The analysis was stratified by gender and crude and adjusted prevalence ratios were estimated by Poisson regression. RESULTS The overall prevalence of common mental disorders was 28.0%; 32.8% and 23.5% in women and men, respectively. Men and women who were poor in 2004-5, regardless of their poor status in 1982, had nearly 1.5-fold increased risk for common mental disorders (p≤0.001) when compared to those who have never been poor. Among women, being poor during childhood (p≤0.001) and black/mixed skin color (p=0.002) increased the risk for mental disorders. Low birth weight and duration of breastfeeding were not associated to the risk of these disorders. CONCLUSIONS Higher prevalence of common mental disorders among low-income groups and race-ethnic minorities suggests that social inequalities present at birth have a major impact on mental health, especially common mental disorders. PMID:19142342
The Role of Psychobiological and Neuroendocrine Mechanisms in Appetite Regulation and Obesity

PubMed Central

Paspala, Ioanna; Katsiki, Niki; Kapoukranidou, Dorothea; Mikhailidis, Dimitri P; Tsiligiroglou-Fachantidou, Anna

2012-01-01

Obesity is a multifactorial disease. Among its causes are physical inactivity and overeating. In addition, other factors may play an important role in the development of overweight/obesity. For example, certain hormones including leptin, insulin and ghrelin, may influence appetite and consequently body weight. Obesity frequently co-exists with metabolic disorders including dyslipidemia, hypertension and insulin resistance, thus constituting the metabolic syndrome which is characterized by increased cardiovascular risk. Lack of comprehensive knowledge on obesity-related issues makes both prevention and treatment difficult. This review considers the psychobiological and neuroendocrine mechanisms of appetite and food intake. Whether these factors, in terms of obesity prevention and treatment, will prove to be relevant in clinical practice (including reducing the cardiovas-cular risk associated with obesity) remains to be established. PMID:23346258
Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models

PubMed Central

Marr, Julia; Bock, Gavin; Desbonnet, Lieve; Waddington, John

2016-01-01

The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia. PMID:27725886
Genetics of eosinophilic esophagitis

PubMed Central

Kottyan, LC; Rothenberg, ME

2017-01-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches. PMID:28224995
Genetics of eosinophilic esophagitis.

PubMed

Kottyan, L C; Rothenberg, M E

2017-05-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.
Murine Models of Systemic Lupus Erythematosus

PubMed Central

Perry, Daniel; Sang, Allison; Yin, Yiming; Zheng, Ying-Yi; Morel, Laurence

2011-01-01

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder. The study of diverse mouse models of lupus has provided clues to the etiology of SLE. Spontaneous mouse models of lupus have led to identification of numerous susceptibility loci from which several candidate genes have emerged. Meanwhile, induced models of lupus have provided insight into the role of environmental factors in lupus pathogenesis as well as provided a better understanding of cellular mechanisms involved in the onset and progression of disease. The SLE-like phenotypes present in these models have also served to screen numerous potential SLE therapies. Due to the complex nature of SLE, it is necessary to understand the effect specific targeted therapies have on immune homeostasis. Furthermore, knowledge gained from mouse models will provide novel therapy targets for the treatment of SLE. PMID:21403825
Neck and shoulder disorders in medical secretaries. Part II. Ergonomical work environment and symptom profile.

PubMed

Kamwendo, K; Linton, S J; Moritz, U

1991-01-01

Seventy-nine medical secretaries with neck and shoulder pain were included in a study aimed at an in-depth description of the ergonomical work environment and the participant's symptom profile, as well as analysing relationships between ergonomical factors and symptoms. Data were collected by daily ratings, questionnaires, and direct observation. The symptom profile showed low mean daily ratings of perceived fatigue and pain, a low medicine consumption, and few stress symptoms. A mean number of 2.1 undesirable work postures was observed. The correlations between perceived fatigue, pain, and well-being with number of shifts from sitting to standing and time spent typing, were generally small. This study suggests that risk factors for neck and shoulder pain are individual and multifactorial.
[Postural tachycardia syndrome (PoTS): An up-to-date].

PubMed

Astudillo, L; Laure, A; Fabry, V; Pugnet, G; Maury, P; Labrunée, M; Sailler, L; Pavy-Le Traon, A

2018-06-13

Postural tachycardia syndrome (PoTS) is a multifactorial syndrome defined by an increase in heart rate ≥30bpm, within 10minutes of standing (or during a head up tilt test to at least 60°), in absence of orthostatic hypotension. It is associated with symptoms of cerebral hypoperfusion that are worse when upright and improve in supine position. Patients have an intense fatigue with a high incidence on quality of life. This syndrome can be explained by many pathophysiological mechanisms. It can be associated with Ehlers-Danlos disease and some autoimmune disorders. The treatment is based on nonpharmacological measures and treatment with propranolol, fludrocortisone or midodrine. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.
Optimizing human factors in dentistry

PubMed Central

Gupta, Arpit; Ankola, Anil V.; Hebbal, Mamata

2013-01-01

Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs. PMID:23946745
Assessment of the environmental and genetic factors influencing prevalence of metabolic syndrome in Saudi Arabia

PubMed Central

Gosadi, Ibrahim M.

2016-01-01

Metabolic syndrome (MS) is a combination of factors that increases the risk of cardiovascular atherosclerotic diseases including diabetes, obesity, dyslipidemia, and high blood pressure. Cardiovascular diseases are one of the leading causes of death in the adult Saudi population where the increase in cardiovascular-related mortality is augmented by the rise in the prevalence of MS. Metabolic syndrome is a multi-factorial disorder influenced by interactions between genetic and environmental components. This review aims to provide a comprehensive assessment of studied environmental and genetic factors explaining the prevalence of MS in the Kingdom of Saudi Arabia. Additionally, this review aims to illustrate factors related to the population genetics of Saudi Arabia, which might explain a proportion of the prevalence of MS. PMID:26739969
Water Buffalo (Bubalus bubalis) as a spontaneous animal model of Vitiligo.

PubMed

Singh, Vijay Pal; Motiani, Rajender K; Singh, Archana; Malik, Garima; Aggarwal, Rangoli; Pratap, Kunal; Wani, Mohan R; Gokhale, Suresh B; Natarajan, Vivek T; Gokhale, Rajesh S

2016-07-01

Vitiligo is a multifactorial acquired depigmenting disorder. Recent insights into the molecular mechanisms driving the gradual destruction of melanocytes in vitiligo will likely lead to the discovery of novel therapies, which need to be evaluated in animal models that closely recapitulate the pathogenesis of human vitiligo. In humans, vitiligo is characterized by a spontaneous loss of functional melanocytes from the epidermis, but most animal models of vitiligo are either inducible or genetically programmed. Here, we report that acquired depigmentation in water buffalo recapitulates molecular, histological, immunohistochemical, and ultrastructural changes observed in human vitiligo and hence could be used as a model to study vitiligo pathogenesis and facilitate the discovery and evaluation of therapeutic interventions for vitiligo. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Complex genetics of familial exudative vitreoretinopathy and related pediatric retinal detachments

PubMed Central

Kondo, Hiroyuki

2015-01-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder that can cause various types of retinal detachments. The abnormalities in eyes with FEVR are caused by poor vascularization in the peripheral retina. The genetics of FEVR is highly heterogeneous, and mutations in the genes for Wnt signaling and a transcription factor have been reported to be responsible for FEVR. These factors have been shown to be the regulators of the pathophysiological pathways of retinal vascular development. Studies conducted to identify the causative genes of FEVR have uncovered a diverse and complex relationship between FEVR and other diseases; for example, Norrie disease, a Mendelian-inherited disease; retinopathy of prematurity, a multifactorial genetic disease; and Coats disease, a nongenetic disease, associated with pediatric retinal detachments. PMID:29018668
Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies.

PubMed

Ruocco, Eleonora; Ruocco, Vincenzo; Tornesello, Maria Lina; Gambardella, Alessio; Wolf, Ronni; Buonaguro, Franco M

2013-01-01

Kaposi's sarcoma (KS), an angioproliferative disorder, has a viral etiology and a multifactorial pathogenesis hinged on an immune dysfunction. The disease is multifocal, with a course ranging from indolent, with only skin manifestations to fulminant, with extensive visceral involvement. In the current view, all forms of KS have a common etiology in human herpesvirus (HHV)-8 infection, and the differences among them are due to the involvement of various cofactors. In fact, HHV-8 infection can be considered a necessary but not sufficient condition for the development of KS, because further factors (genetic, immunologic, and environmental) are required. The role of cofactors can be attributed to their ability to interact with HHV-8, to affect the immune system, or to act as vasoactive agents. In this contribution, a survey of the current state of knowledge on many and various factors involved in KS pathogenesis is carried out, in particular by highlighting the facts and controversies about the role of some drugs (quinine analogues and angiotensin-converting enzyme inhibitors) in the onset of the disease. Based on these assessments, it is possible to hypothesize that the role of cofactors in KS pathogenesis can move toward an effect either favoring or inhibiting the onset of the disease, depending on the presence of other agents modulating the pathogenesis itself, such as genetic predisposition, environmental factors, drug intake, or lymph flow disorders. It is possible that the same agents may act as either stimulating or inhibiting cofactors according to the patient's genetic background and variable interactions. Treatment guidelines for each form of KS are outlined, because a unique standard therapy for all of them cannot be considered due to KS heterogeneity. In most cases, therapeutic options, both local and systemic, should be tailored to the patient's peculiar clinical conditions. Copyright © 2013. Published by Elsevier Inc.
Genetics of human hydrocephalus

PubMed Central

Williams, Michael A.; Rigamonti, Daniele

2006-01-01

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus. This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions. PMID:16773266
Rectal intussusception and unexplained faecal incontinence: findings of a proctographic study.

PubMed

Collinson, R; Cunningham, C; D'Costa, H; Lindsey, I

2009-01-01

The aetiology of faecal incontinence is multifactorial, yet there remains an approach to assessment and treatment that focusses on the sphincter. Rectal intussusception (RI) is underdiagnosed and manifests primarily as obstructed defecation. Yet greater than 50% of these patients admit to faecal incontinence on closer questioning. We aimed to evaluate the incidence of RI at evacuation proctography selectively undertaken in the evaluation of patients with faecal incontinence. Patients with faecal incontinence seen in a pelvic floor clinic were evaluated with anorectal physiology and ultrasound. Where the faecal incontinence was not fully explained by physiology and ultrasound, evacuation proctography was undertaken. Studies were classified as 'normal', 'low-grade RI' (recto-rectal), 'high-grade RI' (recto-anal) or 'anismus'. Forty patients underwent evacuation proctography (33 women, 83%). Median age was 63 years (range 34-77 years). Seven patients (17%) had a normal proctogram. Three (8%) had recto-rectal RI. Twenty-five (63%) demonstrated recto-anal RI. Five patients (12%) had anismus. Recto-anal intussusception is common in patients undergoing selective evacuation proctography for investigation of faecal incontinence. The role of recto-anal intussusception in the multifactorial aetiology of faecal incontinence has been largely overlooked. Evacuation proctography should be considered as part of routine work-up of patients with faecal incontinence.

Erectile dysfunction in chronic kidney disease: From pathophysiology to management

PubMed Central

Papadopoulou, Eirini; Varouktsi, Anna; Lazaridis, Antonios; Boutari, Chrysoula; Doumas, Michael

2015-01-01

Chronic kidney disease (CKD) is encountered in millions of people worldwide, with continuously rising incidence during the past decades, affecting their quality of life despite the increase of life expectancy in these patients. Disturbance of sexual function is common among men with CKD, as both conditions share common pathophysiological causes, such as vascular or hormonal abnormalities and are both affected by similar coexisting comorbid conditions such as cardiovascular disease, hypertension and diabetes mellitus. The estimated prevalence of erectile dysfunction reaches 70% in end stage renal disease patients. Nevertheless, sexual dysfunction remains under-recognized and under-treated in a high proportion of these patients, a fact which should raise awareness among clinicians. A multifactorial approach in management and treatment is undoubtedly required in order to improve patients’ quality of life and cardiovascular outcomes. PMID:26167462
Dry Eye Disease and Microbial Keratitis: Is There a Connection?

PubMed Central

Narayanan, Srihari; Redfern, Rachel L.; Miller, William L.; Nichols, Kelly K.; McDermott, Alison M.

2013-01-01

Dry eye is a common ocular surface disease of multifactorial etiology characterized by elevated tear osmolality and inflammation leading to a disrupted ocular surface. The latter is a risk factor for ocular surface infection, yet overt infection is not commonly seen clinically in the typical dry eye patient. This suggests that important innate mechanisms operate to protect the dry eye from invading pathogens. This article reviews the current literature on epidemiology of ocular surface infection in dry eye patients and laboratory-based studies on innate immune mechanisms operating at the ocular surface and their alterations in human dry eye and animal models. The review highlights current understanding of innate immunity in dry eye and identifies gaps in our knowledge to help direct future studies to further unravel the complexities of dry eye disease and its sequelae. PMID:23583043
Is the Relationship between Common Mental Disorder and Adiposity Bidirectional? Prospective Analyses of a UK General Population-Based Study

PubMed Central

Fezeu, Léopold K.; Batty, David G.; Gale, Catharine R.; Kivimaki, Mika; Hercberg, Serge; Czernichow, Sebastien

2015-01-01

The direction of the association between mental health and adiposity is poorly understood. Our objective was to empirically examine this link in a UK study. This is a prospective cohort study of 3 388 people (men) aged ≥ 18 years at study induction who participated in both the UK Health and Lifestyle Survey at baseline (HALS-1, 1984/1985) and the re-survey (HALS-2, 1991/1992). At both survey examinations, body mass index, waist circumference and self-reported common mental disorder (the 30-item General Health Questionnaire, GHQ) were measured. Logistic regression models were used to compute odds ratios (OR) and accompanying 95% confidence intervals (CI) for the associations between (1) baseline common mental disorder (QHQ score > 4) and subsequent general and abdominal obesity and (2) baseline general and abdominal obesity and re-survey common mental disorders. After controlling for a range of covariates, participants with common mental disorder at baseline experienced greater odds of subsequently becoming overweight (women, OR: 1.30, 1.03 – 1.64; men, 1.05, 0.81 – 1.38) and obese (women, 1.26, 0.82 – 1.94; men, OR: 2.10, 1.23 – 3.55) than those who were free of common mental disorder. Similarly, having baseline common mental health disorder was also related to a greater risk of developing moderate (1.57, 1.21 – 2.04) and severe (1.48, 1.09 – 2.01) abdominal obesity (women only). Baseline general or abdominal obesity was not associated with the risk of future common mental disorder. These findings of the present study suggest that the direction of association between common mental disorders and adiposity is from common mental disorder to increased future risk of adiposity as opposed to the converse. PMID:25993130
Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the "end of the road" for renal denervation?

PubMed

Epstein, Murray; de Marchena, Eduardo

2015-02-01

Resistant hypertension is a common medical problem that is increasing with the advent of an increasingly older and heavier population. The etiology of resistant hypertension is almost always multifactorial, but the results of numerous studies indicate that renal sympathetic activation is a particularly common cause of resistance to antihypertensive treatment. Consistent with the belief in a pivotal role of renal sympathetic stimulation, there has been a growing interest in renal denervation (RDN) treatment strategies. The long-awaited results of SYMPLICITY HTN-3 study disclosed that the reduction in blood pressure by the SYMPLICITY device did not differ from that in the sham-procedure arm of the study. In the present article, we identify several factors that explain why the study failed to demonstrate any benefit from the intervention. The reasons are multifactorial and include inadequate screening at entry and frequent medication changes during the study. Additional problems include the lack of experience of many operators with the SYMPLICITY device and procedure variability, as attested to by a diminished number of ablation "quadrants." Also a factor was the inability of the first generation Medtronic device to allow four ablations to be performed simultaneously. We recommend that future RDN studies adhere to more rigorous screening procedures, and utilize newer multi-site denervation systems that facilitate four ablations simultaneously. Drug optimization should be achieved by monitoring adherence throughout the study. Nevertheless, we are optimistic about a future role of RDN. To optimize chances of success, increased efforts are necessary to identify the appropriate patients for RDN and investigators must use second and third generation denervation devices and techniques. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
[Prevalence of common mental disorders in a population covered by the Family Health Program (QUALIS) in São Paulo, Brazil].

PubMed

Maragno, Luciana; Goldbaum, Moisés; Gianini, Reinaldo José; Novaes, Hillegonda Maria Dutilh; César, Chester Luiz Galvão

2006-08-01

The prevalence of common mental disorders has increased in many countries. Cases are often not identified and adequately treated because traditional health care services are rarely prepared to deal with this problem. The Family Health Program (FHP) has been implemented in Brazil since 1995-1996 and provides a new primary health care model with the potential for better care for these patients. This study investigates common mental disorders prevalence according to FHP coverage and associated socio-demographic factors. A large health and health care survey was conducted from January to March 2001 in areas partly covered by the FHP in a peripheral area of the city of Sao Paulo and included common mental disorders screening in 2,337 individuals > 15 years of age. There was no significant difference in common mental disorders prevalence according to FHP. Common mental disorders prevalence was significantly higher among females (PR = 1.34), elderly (PR = 1.56), and individuals with lower income (PR = 2.64) or less schooling (PR = 2.83). Common mental disorders was associated with indicators of social disadvantage, implying the need to focus on specific health problems and risk groups to improve the impact of care.
Public interest in predictive genetic testing, including direct-to-consumer testing, for susceptibility to major depression: preliminary findings.

PubMed

Wilde, Alex; Meiser, Bettina; Mitchell, Philip B; Schofield, Peter R

2010-01-01

The past decade has seen rapid advances in the identification of associations between candidate genes and a range of common multifactorial disorders. This paper evaluates public attitudes towards the complexity of genetic risk prediction in psychiatry involving susceptibility genes, uncertain penetrance and gene-environment interactions on which successful molecular-based mental health interventions will depend. A qualitative approach was taken to enable the exploration of the views of the public. Four structured focus groups were conducted with a total of 36 participants. The majority of participants indicated interest in having a genetic test for susceptibility to major depression, if it was available. Having a family history of mental illness was cited as a major reason. After discussion of perceived positive and negative implications of predictive genetic testing, nine of 24 participants initially interested in having such a test changed their mind. Fear of genetic discrimination and privacy issues predominantly influenced change of attitude. All participants still interested in having a predictive genetic test for risk for depression reported they would only do so through trusted medical professionals. Participants were unanimously against direct-to-consumer genetic testing marketed through the Internet, although some would consider it if there was suitable protection against discrimination. The study highlights the importance of general practitioner and public education about psychiatric genetics, and the availability of appropriate treatment and support services prior to implementation of future predictive genetic testing services.
A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides

PubMed Central

D’Silva, Sheryl; Xiao, Xunjun; Lowe, Mark E.

2013-01-01

Type 2 diabetes mellitus is a multifactorial and polygenic disorder with increasing prevalence. Recently, a polymorphism in the gene encoding procolipase, a cysteine for arginine substitution at position 92, was associated with type 2 diabetes in two human populations. Because procolipase plays a critical role in dietary fat metabolism, polymorphisms that affect the function of procolipase could influence the development of type 2 diabetes. We hypothesized that the Arg92Cys polymorphism has functional consequences. To test our hypothesis, we expressed recombinant cysteine 92 (Cys92) procolipase in a yeast expression system and compared the function and stability of purified Cys92 with that of the more common arginine 92 (Arg92) procolipase. Cys92 fully restored the activity of bile-salt inhibited lipase with short- and medium-chain triglycerides but only had 50% of Arg92 function with long-chain triglycerides. After storage at 4°C, Cys92 lost the ability to restore pancreatic triglyceride lipase activity with medium- and long-chain triglycerides. The loss of function correlated with the inability of Cys92 to anchor lipase on an emulsion surface and oxidation of the cysteine. No detectable degradation or intramolecular disulfide formation occurred in Cys92 after storage. Our findings demonstrate that the Arg92Cys polymorphism decreases the function of Cys92 colipase. This change may contribute to the development of type 2 diabetes. PMID:17715423
Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.
Heritability and phenotypic variation of canine hip dysplasia radiographic traits in a cohort of Australian German shepherd dogs.

PubMed

Wilson, Bethany J; Nicholas, Frank W; James, John W; Wade, Claire M; Tammen, Imke; Raadsma, Herman W; Castle, Kao; Thomson, Peter C

2012-01-01

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14-0.24 (ordinal models), 0.14-0.25 (linear models) and 0.12-0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30 ± 0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals.
Chinese Herbal Medicine Treatment Improves the Overall Survival Rate of Individuals with Hypertension among Type 2 Diabetes Patients and Modulates In Vitro Smooth Muscle Cell Contractility

PubMed Central

Yeh, Yi-Chun; Cheng, Chi-Fung; Shiao, Yi-Tzone; Wang, Chang-Bi; Chien, Wen-Kuei; Chen, Jin-Hua; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Li, Ju-Pi; Lin, Cheng-Wen; Pang, Hao-Yu; Lin, Jaung-Geng; Lan, Yu-Ching; Liu, Yu-Huei; Chen, Shih-Yin; Tsai, Fuu-Jen; Liang, Wen-Miin

2015-01-01

Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients. PMID:26699542
Chinese Herbal Medicine Treatment Improves the Overall Survival Rate of Individuals with Hypertension among Type 2 Diabetes Patients and Modulates In Vitro Smooth Muscle Cell Contractility.

PubMed

Lin, Ying-Ju; Ho, Tsung-Jung; Yeh, Yi-Chun; Cheng, Chi-Fung; Shiao, Yi-Tzone; Wang, Chang-Bi; Chien, Wen-Kuei; Chen, Jin-Hua; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Li, Ju-Pi; Lin, Cheng-Wen; Pang, Hao-Yu; Lin, Jaung-Geng; Lan, Yu-Ching; Liu, Yu-Huei; Chen, Shih-Yin; Tsai, Fuu-Jen; Liang, Wen-Miin

2015-01-01

Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients.
How the visual aspects can be crucial in reading acquisition? The intriguing case of crowding and developmental dyslexia.

PubMed

Gori, Simone; Facoetti, Andrea

2015-01-14

Developmental dyslexia (DD) is the most common neurodevelopmental disorder (about 10% of children across cultures) characterized by severe difficulties in learning to read. According to the dominant view, DD is considered a phonological processing impairment that might be linked to a cross-modal, letter-to-speech sound integration deficit. However, new theories-supported by consistent data-suggest that mild deficits in low-level visual and auditory processing can lead to DD. This evidence supports the probabilistic and multifactorial approach for DD. Among others, an interesting visual deficit that is often associated with DD is excessive visual crowding. Crowding is defined as difficulty in the ability to recognize objects when surrounded by similar items. Crowding, typically observed in peripheral vision, could be modulated by attentional processes. The direct consequence of stronger crowding on reading is the inability to recognize letters when they are surrounded by other letters. This problem directly translates to reading at a slower speed and being more prone to making errors while reading. Our aim is to review the literature supporting the important role of crowding in DD. Moreover, we are interested in proposing new possible studies in order to clarify whether the observed excessive crowding could be a cause rather than an effect of DD. Finally, we also suggest possible remediation and even prevention programs that could be based on reducing the crowding in children with or at risk for DD without involving any phonological or orthographic training. © 2015 ARVO.
Common mental disorders and intimate partner violence in pregnancy.

PubMed

Ludermir, Ana Bernarda; Valongueiro, Sandra; Araújo, Thália Velho Barreto de

2014-02-01

To investigate the association between common mental disorders and intimate partner violence during pregnancy. A cross sectional study was carried out with 1,120 pregnant women aged 18-49 years old, who were registered in the Family Health Program in the city of Recife, Northeastern Brazil, between 2005 and 2006. Common mental disorders were assessed using the Self-Reporting Questionnaire (SRQ-20). Intimate partner violence was defined as psychologically, physically and sexually abusive acts committed against women by their partners. Crude and adjusted odds ratios were estimated for the association studied utilizing logistic regression analysis. The most common form of partner violence was psychological. The prevalence of common mental disorders was 71.0% among women who reported all form of violence in pregnancy and 33.8% among those who did not report intimate partner violence. Common mental disorders were associated with psychological violence (OR 2.49, 95%CI 1.8;3.5), even without physical or sexual violence. When psychological violence was combined with physical or sexual violence, the risk of common mental disorders was even higher (OR 3.45; 95%CI 2.3;5.2). Being assaulted by someone with whom you are emotionally involved can trigger feelings of helplessness, low self-esteem and depression. The pregnancy probably increased women`s vulnerability to common mental disorders.
Falls in elderly people: a multifactorial analysis of risk markers using data from the Swedish general population study 'Good ageing in Skåne'.

PubMed

Stenhagen, Magnus; Nordell, Eva; Elmståhl, Sölve

2013-04-01

The aim of this study was to describe the prevalence of falls in a general older population, especially among the most elderly, and the risk markers associated with falls. This is a cross-sectional study in which 38 fall risk markers were analysed in non-, occasional- and frequent-fallers. The population was 2,865 individuals (aged 60-93), randomly selected from the general population register. The risk of falling was calculated as age-adjusted odds ratios. The relation between the number of risk markers for an individual and falls was also analysed. About one in ten reported falling during the past 6 months, 35% of which were over 90 years old. Twenty-one risk markers were significantly related to falls confirming falling as a multifactorial problem. These included a variety of diseases, symptoms, medical and physical functions, life-style factors and the taking of certain drugs. The five risk markers with the highest odds ratio in frequent fallers were 'tendency to fall' (37.9), 'low walking speed' (12.8), consumption of 'neuroleptics' (10.9), 'impaired mobility' (10.0) and 'dementia' (5.4). Subjects with more than four and seven risk markers showed a 9- respectively 28-fold increase in the risk of falling, especially among frequent fallers and those aged over 90 years. Falls are common in the elderly population and the risk is multifactorial. The results imply that there is an overrepresentation of fallers in a distinct subgroup of the very elderly and those with multiple risk markers. The self-perceived clinical sign 'tendency to fall' seems highly sensitive as indicator of individuals at risk. Several risk markers may be treatable. Fall risk seems to increase in a non-linear, almost exponential way with increasing number of risk markers.
Application of multi-factorial design of experiments to successfully optimize immunoassays for robust measurements of therapeutic proteins.

PubMed

Ray, Chad A; Patel, Vimal; Shih, Judy; Macaraeg, Chris; Wu, Yuling; Thway, Theingi; Ma, Mark; Lee, Jean W; Desilva, Binodh

2009-02-20

Developing a process that generates robust immunoassays that can be used to support studies with tight timelines is a common challenge for bioanalytical laboratories. Design of experiments (DOEs) is a tool that has been used by many industries for the purpose of optimizing processes. The approach is capable of identifying critical factors and their interactions with a minimal number of experiments. The challenge for implementing this tool in the bioanalytical laboratory is to develop a user-friendly approach that scientists can understand and apply. We have successfully addressed these challenges by eliminating the screening design, introducing automation, and applying a simple mathematical approach for the output parameter. A modified central composite design (CCD) was applied to three ligand binding assays. The intra-plate factors selected were coating, detection antibody concentration, and streptavidin-HRP concentrations. The inter-plate factors included incubation times for each step. The objective was to maximize the logS/B (S/B) of the low standard to the blank. The maximum desirable conditions were determined using JMP 7.0. To verify the validity of the predictions, the logS/B prediction was compared against the observed logS/B during pre-study validation experiments. The three assays were optimized using the multi-factorial DOE. The total error for all three methods was less than 20% which indicated method robustness. DOE identified interactions in one of the methods. The model predictions for logS/B were within 25% of the observed pre-study validation values for all methods tested. The comparison between the CCD and hybrid screening design yielded comparable parameter estimates. The user-friendly design enables effective application of multi-factorial DOE to optimize ligand binding assays for therapeutic proteins. The approach allows for identification of interactions between factors, consistency in optimal parameter determination, and reduced method development time.
Management of Dyslipidemia in Patients with Hypertension, Diabetes, and Metabolic Syndrome.

PubMed

Srikanth, Sundararajan; Deedwania, Prakash

2016-10-01

The purpose of this review is to discuss dyslipidemia in the various common clinical conditions including hypertension, diabetes mellitus, and metabolic syndrome and review the current therapeutic strategy in these settings. Dyslipidemias are common in patients with hypertension, diabetes mellitus, and metabolic syndrome. Epidemiologic studies have shown a strong correlation between serum lipid levels and risk of atherosclerotic cardiovascular disease. Multifactorial intervention strategies aimed at controlling lipids, blood pressure, and blood glucose simultaneously achieve maximal reductions in cardiovascular risk. Dyslipidemia and metabolic abnormalities are strongly associated with atherosclerosis and worse cardiovascular outcomes. While pharmacotherapy with statins has been proven to be beneficial for dyslipidemia, lifestyle modification emphasizing weight loss and regular exercise is an essential component of the interventional strategy. The common thread underlying atherosclerosis and metabolic abnormalities is endothelial dysfunction. Improved understanding of the role of endothelium in health and disease can potentially lead to novel therapies that may preempt development of atherosclerosis and its complications.
Hypertension in postmenopausal women: pathophysiology and treatment.

PubMed

Leuzzi, Chiara; Modena, Maria Grazia

2011-03-01

Hypertension is the most common chronic disease in industrialized countries and represents the most common major cardiovascular risk factor after the fifth decade of life in both men and women. The prevalence of hypertension is lower in premenopausal women than men, whereas in postmenopausal women it is higher than in men. Mechanisms responsible for the increase in blood pressure are complex and multifactorial, including loss of estrogen, oxidative stress, endothelial dysfunction, modification in renin-angiotensin system spillover and sympathetic activation. In addition, postmenopausal hypertension can be considered an isolated disease, more typical of elderly women, or part of the metabolic syndrome, which is indeed more common in early postmenopausal women. In particular, metabolic syndrome may be considered a potentially unfavourable prognostic factor in hypertensive postmenopausal women, because it seems to worsen the severity of hypertension and reduce the capacity to respond to specific treatments. This article summarizes the different causes of postmenopausal hypertension and the specific treatment recommended by guidelines for this condition.
Infertility today: the management of female medical causes.

PubMed

Tinneberg, Hans-Rudolf; Gasbarrini, Antonio

2013-12-01

It has to be suspected that some environmentally hazardous substances have genotoxic properties, revealing their reproductive toxicity at a later stage only. Cancer, including childhood cancer, is more common than usually expected. Undesirable side effects of surgery, chemotherapy, and/or radiation can be premature ovarian failure or even premature menopause. In cases of autoimmune disease, autoantibodies can directly affect maturation of oocytes in the follicle, fertilization, and implantation. Spontaneous abortions are more common in patients with autoimmune disease. Thrombophilia is known to display a higher rate of spontaneous abortions as well as pre-eclampsia and intrauterine growth retardation. Infections are a common threat to pregnancy. Metabolic syndrome is increasingly frequent in western countries and often associated with hyperandrogenemia and polycystic disease. Women with inflammatory bowel disease such as Crohn disease or ulcerative colitis usually have no problems conceiving. In conclusion, even though infertility is a multifactorial disease, various medical and non-medical conditions can be attributed to it. © 2013.
Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees.

PubMed

Campbell, Desmond D; Li, Yiming; Sham, Pak C

2018-03-01

Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported methodology based on a liability-threshold model. Multifactorial disease models incorporating all the following features in combination are handled: quantitative risk factors (including polygenic scores), categorical risk factors (including major genetic risk loci), stratified age of onset curves, and the partition of the population variance in disease liability into genetic, shared, and unique environment effects. It allows the application of such models to disease pedigrees. Pedigree-related outputs are (i) individual disease risk for pedigree members, (ii) n year risk for unaffected pedigree members, and (iii) the disease pedigree's joint liability distribution. Risk prediction for each pedigree member is based on using the constructed disease model to appropriately weigh evidence on disease risk available from personal attributes and family history. Evidence is used to construct the disease pedigree's joint liability distribution. From this, lifetime and n year risk can be predicted. Example disease models and pedigrees are provided at the website and are used in accompanying tutorials to illustrate the features available. The website is built on an R package which provides the functionality for pedigree validation, disease model construction, and risk prediction. Website: http://grass.cgs.hku.hk:3838/mdrc/current. © 2017 WILEY PERIODICALS, INC.
The effects of multifactorial fall prevention on depressive symptoms among the aged at increased risk of falling.

PubMed

Sjösten, Noora M; Vahlberg, Tero J; Kivelä, Sirkka-Liisa

2008-05-01

The aim was to determine the effects of multifactorial fall prevention on depressive symptoms among aged Finns at increased risk of falling. This study is part of a multifactorial fall prevention trial with a randomised controlled design implemented in the town of Pori, western Finland. The study population consisted of ambulatory, 65-year-old or older Finns, with moderate or high cognitive and physical abilities who had fallen at least once during the previous 12 months. The participants (n=591) were randomised into a risk-based multifactorial fall prevention programme (intervention group, IG) or into a one-time counselling group (control group, CG). The 1-year intervention included individual geriatric assessment followed by treatment recommendations, individual guidance regarding fall prevention, physical exercise in small groups twice a month, psychosocial group activities and lectures once a month, home-exercises and home hazard assessment. The outcome, depressive symptoms, was measured by the 30-item Geriatric Depression Scale (GDS). The full GDS data with no missing items were available for 464 persons. A significant decrease in depressive symptoms during the 12-month intervention was found both in IG and in CG, but the difference in change was not significant (p=0.110). However, a significant difference in change between the groups was found among men and older subjects (>or=75) in favour of the IG. Multifactorial fall prevention had no effects on depressive symptoms among the community-dwelling aged. However, men and older participants benefited from the intervention.

Psychotic experiences and suicide attempt risk in common mental disorders and borderline personality disorder.

PubMed

Kelleher, I; Ramsay, H; DeVylder, J

2017-03-01

Recent research has demonstrated a strong relationship between psychotic experiences and suicidal behaviour. No research to date, however, has investigated the role of borderline personality disorder (BPD) in this relationship, despite the fact that BPD is highly comorbid with common mental disorders and is associated with both recurrent suicidal behaviour and psychotic experiences. This paper examined the relationship between psychotic experiences and suicide attempts, including interrelationships with BPD and common mental disorders. We used the 2007 Adult Psychiatric Morbidity Study, a stratified, multistage probability sample of households in England, which recruited a nationally representative sample aged 16 years and older. Participants were assessed for common mental disorders, BPD (clinical and subclinical), suicidal behaviour, and psychotic experiences. Approximately 4% of the total sample (n = 323) reported psychotic experiences. Psychotic experiences were associated with increased odds of suicide attempts in individuals with BPD (OR = 2.23, 95% CI = 1.03-4.85), individuals with a common mental disorder (OR = 2.47, 95% CI = 1.37-4.43), individuals without a common mental disorder (OR = 3.99, 95% CI = 2.47-6.43), and individuals with neither a common mental disorder nor BPD (OR = 3.20, 95% CI = 1.71-5.98). Psychotic experiences are associated with high odds of suicidal behaviour in individuals with and without psychopathology. This relationship is not explained by clinical or subclinical BPD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders

PubMed Central

Fonzo, Gregory A.; Ramsawh, Holly J.; Flagan, Taru M.; Sullivan, Sarah G.; Letamendi, Andrea; Simmons, Alan N.; Paulus, Martin P.; Stein, Murray B.

2015-01-01

Background Although evidence exists for abnormal brain function across various anxiety disorders, direct comparison of neural function across diagnoses is needed to elicit abnormalities common across disorders and those distinct to a particular diagnosis. Aims To delineate common and distinct abnormalities within generalised anxiety (GAD), panic and social anxiety disorder (SAD) during affective processing. Method Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and 15 healthy controls) underwent functional magnetic resonance imaging while completing a facial emotion matching task with fearful, angry and happy faces. Results Greater differential right amygdala activation to matching fearful v. happy facial expressions related to greater negative affectivity (i.e. trait anxiety) and was heightened across all anxiety disorder groups compared with controls. Collapsing across emotional face types, participants with panic disorder uniquely displayed greater posterior insula activation. Conclusions These preliminary results highlight a common neural basis for clinical anxiety in these diagnoses and also suggest the presence of disorder-specific dysfunction. PMID:25573399
Segregation analysis of apolipoproteins A-1 and B-100 measured before and after an exercise training program: the HERITAGE Family Study.

PubMed

An, P; Rice, T; Gagnon, J; Borecki, I B; Bergeron, J; Després, J P; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2000-03-01

Complex segregation analyses of apolipoproteins (apo) A-1 and B-100 were performed in a sample of 520 individuals from 99 white families who participated in the HERITAGE Family Study. In these sedentary families, plasma apo A-1 and B-100 concentrations were measured before and after a 20-week endurance exercise training program. Baseline apo A-1 and B-100 were adjusted for the effects of age (age-adjusted baseline apo A-1 and B-100) and for the effects of age and BMI (age-BMI-adjusted baseline apo A-1 and B-100). The change in response to training was computed as a simple Delta (posttraining minus baseline) and was adjusted for age and the baseline (age-baseline-adjusted apo A-1 and B-100 responses to training). In the present study, a major gene could not be inferred for baseline apo A-1. Rather, we found a major effect along with a multifactorial effect accounting for 8% to 9% and 51% to 56% of the variance, respectively. In addition, no clear evidence supported a major-gene effect for its response to training, whereas the transmission of a major effect from parents to offspring was ambiguous, ie, genetic in nature or familial environmental in origin. The major effect accounted for 15% of the variance, with an additional 21% and 58% of the variance being accounted for by a multifactorial effect in parents and offspring, respectively. It is interesting to have obtained evidence of a putative recessive major locus for baseline apo B-100, which accounted for 50% to 56% of the variance, with an additional 25% to 29% of the variance due to a multifactorial effect. In contrast, no major effect for its response to training was identified, although a multifactorial effect was found that accounted for 27% of the variance. The novel findings arising from the present study are summarized as follows. Baseline apo A-1 and its response to training were influenced by a major effect and a multifactorial effect. Baseline apo B-100 was influenced by a putative major recessive gene with a multifactorial component, but its response to training was influenced solely by a multifactorial component in these sedentary families.
Overview of Common Sleep Disorders and Intersection with Dermatologic Conditions.

PubMed

Walia, Harneet K; Mehra, Reena

2016-04-30

Sleep disorders are very common, often under-recognized and therefore undertreated, are associated with a myriad of medical conditions and could lead to significant impairment of quality of life. This review provides an up-to-date synopsis of common sleep disorders encompassing insufficient sleep syndrome, insomnia, circadian rhythm disorders and obstructive sleep apnea with a brief overview of epidemiology, screening, diagnostic testing and treatment. We also emphasize the emerging area of the intersection of sleep disorders and dermatologic conditions and present compelling data regarding underlying mechanisms including sleep dysfunction in relation to disorders of skin inflammation, aging and skin cancer.
[Prevalence of neurological disorders among children with Down syndrome].

PubMed

Gaete, Beatriz; Mellado, Cecilia; Hernández, Marta

2012-02-01

Neurological disturbances are common problems in children with Down Syndrome (DS). To determine the prevalence of neurological disorders affecting children with Down Syndrome. Review of medical records of 253 children aged from 1 day to 23 years affected with DS, attended at a public hospital and a University clinic. The overall prevalence of neurological disorders was 38.7%. The most common problems were ocular motor disorders in 26% of cases and epilepsy in 12%. Neurological disorders are more common in children with DS than in the general population. Motor ocular disorders and epilepsy are the predominant disturbances detected.
The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity.

PubMed

Riesche, Laren; Tardif, Suzette D; Ross, Corinna N; deMartelly, Victoria A; Ziegler, Toni; Rutherford, Julienne N

2018-05-01

Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.
Prevalence of common mental disorders among sugarcane workers.

PubMed

Costa, Polyana Felipe Ferreira da; Santos, Solange Laurentino Dos; Silva, Marcelo Saturnino da; Gurgel, Idê Gomes Dantas

2017-12-11

To estimate the prevalence of common mental disorders and to analyze the associated factors in migrant and sugarcane workers. This is a cross-sectional study carried out with 110 workers. Common mental disorders were evaluated using the Self-Reporting Questionnaire (SRQ-20), and sociodemographic, occupational, and lifestyle variables were studied. The CAGE questionnaire was used to detect the abuse of alcoholic beverages. The prevalence of common mental disorders affected 40% of the workers and the association showed statistical significance for the positive result of the CAGE test, sickness, absence from work, and medical care during the harvest period. The suspected cases of problem drinkers and the control mechanisms used by the mill for workers who miss work or become ill are factors that can cause common mental disorders.
Sub-clinical psychosis symptoms in young adults are risk factors for subsequent common mental disorders.

PubMed

Rössler, Wulf; Hengartner, Michael P; Ajdacic-Gross, Vladeta; Haker, Helene; Gamma, Alex; Angst, Jules

2011-09-01

Not all persons identified in the early stages to be at risk for psychosis eventually cross the threshold for a psychotic illness. However, sub-clinical symptoms may not only indicate a specific risk but also suggest a more general, underlying psychopathology that predisposes one to various common mental disorders. Analyzing data from the prospective Zurich Cohort Study, we used two psychosis subscales - "schizotypal signs" and "schizophrenia nuclear symptoms" - derived from the SCL-90-R checklist that measured sub-clinical psychosis symptoms in 1979. We also assessed 10 different diagnoses of common mental disorders through seven interview waves between 1979 and 2008. This 30-year span, covering participant ages of 19/20 to 49/50, encompasses the period of highest risk for the occurrence of such disorders. Both psychosis scales from 1979, but especially "schizotypal signs", were significantly correlated with most mental disorders over the subsequent test period. Higher values on both subscales were associated with an increasing number of co-occurring disorders. Our data demonstrate that sub-clinical psychosis generally represents a risk factor for the development of common mental disorders and a liability for co-occurring disorders. This refers in particular to dysthymia, bipolar disorder, social phobia, and obsessive-compulsive disorder. Proneness to psychosis could signal a fundamental tendency toward common mental disorders. Copyright © 2011 Elsevier B.V. All rights reserved.
Bedaquiline in the multidrug-resistant tuberculosis treatment: Belarus experience.

PubMed

Skrahina, Alena; Hurevich, Hennadz; Falzon, Dennis; Zhilevich, Liudmila; Rusovich, Valiantsin; Dara, Masoud; Setkina, Svetlana

2016-12-01

Outcomes of treatment for multidrug-resistant tuberculosis (MDR-TB) remain poor worldwide. Among patients with MDR-TB in Belarus who started treatment in 2012, only 54% completed it successfully, with treatment failure reported in 22% of the patients; additionally, 11% died and 13% were lost to follow-up or remained unevaluated. In Belarus, to improve outcomes, bedaquiline was introduced in MDR-TB treatment in June 2015. The national TB program developed measures to monitor safety and effectiveness of bedaquiline-containing regimens in line with the World Health Organization recommendations. After enrollment of patients, clinical, radiological, laboratory, and microbiological data were carefully collected at start, during treatment, and at follow-up. A total of 197 patients were enrolled: male, 140 (71%); female, 57 (29%); new TB cases, 83 (42%); previously treated, 114 (58%); extensively drug-resistant-TB (XDR-TB), 128 (65%), pre-XDR-TB (fluoroquinolone resistant), 34 (17%), pre-XDR-TB (injectables resistant), 25 (13%), and other MDR-TB cases, 10 (5%). According to the intermediate analysis, 186 patients currently are continuing with the treatment, two patients died, and nine patients were lost to follow-up. Sputum culture conversion were observed in 186 patients (94%) at 6months and one (0.5%) of these 197 patients started treatment; six patients (3%) remain sputum culture positive. The safety data were as follows: 135 patients (68%) experienced metabolism and nutrition disorders (hyperuricemia being the most common), 127 patients (64%) experienced hepatobiliary disorders (hepatic functions abnormality being the most common), 93 patients (47%) experienced electrolyte disorders (hypomagnesemia being the most common), 80 patients (41%) experienced cardiac disorders (abnormal electrocardiogram and arrhythmia being the most common), 68 patients (35%) experienced gastrointestinal system disorders (nausea, vomiting, and abdominal pain being the most common disorders), 54 patients (27%) experienced blood and the lymphatic system disorders (low platelet count being the most common), 42 patients (21%) experienced renal and urinary disorders (creatinine clearance decrease being the most common), 40 patients (20%) experienced nervous system disorders (headache, dizziness, and paresthesia being the most common ones), 36 patients (18%) experienced skin and subcutaneous tissue disorders (rush and pruritus being the most common), 35 patients (17%) experienced ear and labyrinth disorders (tinnitus and decreased hearing being the most common ones), 32 patients (15%) experienced psychiatric disorders (insomnia being the most common disorder), and 30 patients (14%) experienced infections and infestations (candidiasis being the most common). The most adverse events were mild or moderate in severity and reversible. One death was possibly related to MDR-TB therapy. Our interim results on safety and effectiveness of bedaquiline-containing regimens in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) patients are encouraging. They will add value to understanding role and place of this new anti-TB drug in M/XDR-TB treatment. Copyright © 2016.
Eating Patterns among Students with Intellectual Disabilities after a Multifactorial School Intervention Using the Plate Model

ERIC Educational Resources Information Center

Wallen, Eva Flygare; Mullerdorf, Maria; Christensson, Kyllike; Marcus, Claude

2013-01-01

Adolescents with intellectual disabilities (ID) have an increased prevalence of being overweight and having cardiometabolic diseases as adults, in part due to poor eating habits with an inadequate intake of vegetables. The aim of this study was to evaluate whether a multifactorial school intervention using the "Plate Model" results in…
Equine Glaucoma.

PubMed

Michau, Tammy Miller

2017-12-01

Glaucoma is a multifactorial neurodegenerative ocular disease leading to progressive loss of retinal ganglion cells and their axons that form the optic nerve, causing blindness. Knowledge of the pathogenesis and development of equine glaucoma is in its infancy compared with human glaucoma. Glaucoma occurs most commonly secondary to uveitis and may be underdiagnosed or misdiagnosed in horses suffering from uveitis. Recognition and clinical diagnosis of glaucoma in the horse is improved with clinician awareness and the availability of handheld tonometers. Therapy for glaucoma is aimed at decreasing aqueous humor production through medical and surgical means. Even with therapy, long-term prognosis for vision is poor. Copyright © 2017 Elsevier Inc. All rights reserved.
Recurrent pregnancy loss: evaluation and treatment.

PubMed

Shahine, Lora; Lathi, Ruth

2015-03-01

Recurrent pregnancy loss (RPL) is a multifactorial condition. Approximately half of patients with RPL will have no explanation for their miscarriages. De novo chromosome abnormalities are common in sporadic and recurrent pregnancy loss. Testing for embryonic abnormalities can provide an explanation for the miscarriage in many cases and prognostic information. Regardless of the cause of RPL, patients should be reassured that the prognosis for live birth with an evidence-based approach is excellent for most patients. The authors review current evidence for the evaluation and treatment of RPL and explore the proposed use of newer technology for patients with RPL. Copyright © 2015 Elsevier Inc. All rights reserved.
Prosthetic rehabilitation in a pediatric patient with hypohidrotic ectodermal dysplasia: a case report.

PubMed

Quintanilha, Luís Eduardo Lavigne Paranhos; Carneiro-Campos, Luís Eduardo; Antunes, Lívia Azeredo Alves; Antunes, Leonardo Santos; Fernandes, Claudio Pinheiro; Abreu, Fernanda Volpe

2017-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare ectodermal disease with a systemic expression. Oral abnormalities are common and may include hypodontia and shape irregularities in the primary and permanent dentitions. Rehabilitation of the dental arches in pediatric patients with HED is a challenge because HED is a multifactorial disease that demands a complicated treatment approach and most dentists have limited experience or training in the necessary treatment. In addition, pediatric patients often lack the patience or ability to cooperate with complex prosthetic treatment. This case report describes a simplified technique used to fabricate complete dentures for a 4-year-old HED patient in 4 sessions.
Anxiety and helplessness in the face of stress predisposes, precipitates, and sustains gastric ulceration.

PubMed

Overmier, J B; Murison, R

2000-06-01

When an organism is subjected to stress, gastric ulcers or ulcerations commonly develop but the vulnerability to and amount of pathology induced varies considerably between individuals. The role of psychological factors in determining the occurrence and severity of these ulcerations is amply demonstrated in the studies reviewed here. The present paper (a) gives a brief history of the search for the causes of gastric ulcer, (b) provides a review of our own research which reveals that vulnerability to gastric ulceration is modulated by psychologically meaningful experiences, and (c) offers a multifactorial perspective on the causes of gastric ulceration and the future of research on it.
Pernicious Anemia: Fundamental and Practical Aspects in Diagnosis.

PubMed

Tun, Aung Myint; Thein, Kyaw Zin; Myint, Zin War; Oo, Thein Hlaing

2017-11-08

Pernicious Anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex environmental and immunological factors. Although it was first reported by Addison in 1849 with subsequent advances in understanding of pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity and diverse clinical presentations. Herein, we provide an overview of PA, mainly focusing on its scientific and practical aspects in diagnosis. We also discuss the limitations of currently available diagnostic tools for the evaluation of cobalamin deficiency and PA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Clinical Findings Documenting Cellular and Molecular Abnormalities of Glia in Depressive Disorders

PubMed Central

Czéh, Boldizsár; Nagy, Szilvia A.

2018-01-01

Depressive disorders are complex, multifactorial mental disorders with unknown neurobiology. Numerous theories aim to explain the pathophysiology. According to the “gliocentric theory”, glial abnormalities are responsible for the development of the disease. The aim of this review article is to summarize the rapidly growing number of cellular and molecular evidences indicating disturbed glial functioning in depressive disorders. We focus here exclusively on the clinical studies and present the in vivo neuroimaging findings together with the postmortem molecular and histopathological data. Postmortem studies demonstrate glial cell loss while the in vivo imaging data reveal disturbed glial functioning and altered white matter microstructure. Molecular studies report on altered gene expression of glial specific genes. In sum, the clinical findings provide ample evidences on glial pathology and demonstrate that all major glial cell types are affected. However, we still lack convincing theories explaining how the glial abnormalities develop and how exactly contribute to the emotional and cognitive disturbances. Abnormal astrocytic functioning may lead to disturbed metabolism affecting ion homeostasis and glutamate clearance, which in turn, affect synaptic communication. Abnormal oligodendrocyte functioning may disrupt the connectivity of neuronal networks, while microglial activation indicates neuroinflammatory processes. These cellular changes may relate to each other or they may indicate different endophenotypes. A theory has been put forward that the stress-induced inflammation—mediated by microglial activation—triggers a cascade of events leading to damaged astrocytes and oligodendroglia and consequently to their dysfunctions. The clinical data support the “gliocentric” theory, but future research should clarify whether these glial changes are truly the cause or simply the consequences of this devastating disorder. PMID:29535607
Varieties of Self Disorder: A Bio-Pheno-Social Model of Schizophrenia.

PubMed

Sass, Louis; Borda, Juan P; Madeira, Luis; Pienkos, Elizabeth; Nelson, Barnaby

2018-06-06

The self-disorder model offers a unifying way of conceptualizing schizophrenia's highly diverse symptoms (positive, negative, disorganized), of capturing their distinctive bizarreness, and of conceiving their longitudinal development. These symptoms are viewed as differing manifestations of an underlying disorder of ipseity or core-self: hyper-reflexivity/diminished-self-presence with accompanying disturbances of "grip" or "hold" on reality. Recent revision to this phenomenological theory, in particular distinguishing primary-vs-secondary factors, offers a bio-pheno-social model that is consistent with recent empirical findings and offers several advantages: (1) It helps account for the temporal variations of the symptoms or syndrome, including longitudinal progression, but also the shorter-term, situationally reactive, and sometimes defensive or quasi-intentional variability of symptom-expression that can occur in schizophrenia (consistent with understanding some aspects of ipseity-disturbance as dynamic and mutable, involving shifting attitudes or experiential orientations). (2) It accommodates the overlapping of some key schizophrenic symptoms with certain nonschizophrenic conditions involving dissociation (depersonalization, derealization), including depersonalization disorder and panic disorder, thereby acknowledging both shared and distinguishing symptoms. (3) It integrates recent neurocognitive and neurobiological as well as psychosocial (eg, influence of trauma and culture) findings into a coherent but multi-factorial neuropsychological account. An adequate model of schizophrenia will postulate shared disturbances of core-self experiences that nevertheless can follow several distinct pathways and occur in various forms. Such a model is preferable to uni-dimensional alternatives-whether of schizophrenia or ipseity-disturbance-given its ability to account for distinctive yet varying experiential and neurocognitive abnormalities found in research on schizophrenia, and to integrate these with recent psychosocial and neurobiological findings.
Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders.

PubMed

Ochoa-Ruiz, Estefanía; Díaz-Ruiz, Rodrigo; Hernández-Vázquez, Alaín de J; Ibarra-González, Isabel; Ortiz-Plata, Alma; Rembao, Daniel; Ortega-Cuéllar, Daniel; Viollet, Benoit; Uribe-Carvajal, Salvador; Corella, José Ahmed; Velázquez-Arellano, Antonio

2015-11-01

Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.
Development and validation of a prediction algorithm for the onset of common mental disorders in a working population.

PubMed

Fernandez, Ana; Salvador-Carulla, Luis; Choi, Isabella; Calvo, Rafael; Harvey, Samuel B; Glozier, Nicholas

2018-01-01

Common mental disorders are the most common reason for long-term sickness absence in most developed countries. Prediction algorithms for the onset of common mental disorders may help target indicated work-based prevention interventions. We aimed to develop and validate a risk algorithm to predict the onset of common mental disorders at 12 months in a working population. We conducted a secondary analysis of the Household, Income and Labour Dynamics in Australia Survey, a longitudinal, nationally representative household panel in Australia. Data from the 6189 working participants who did not meet the criteria for a common mental disorders at baseline were non-randomly split into training and validation databases, based on state of residence. Common mental disorders were assessed with the mental component score of 36-Item Short Form Health Survey questionnaire (score ⩽45). Risk algorithms were constructed following recommendations made by the Transparent Reporting of a multivariable prediction model for Prevention Or Diagnosis statement. Different risk factors were identified among women and men for the final risk algorithms. In the training data, the model for women had a C-index of 0.73 and effect size (Hedges' g) of 0.91. In men, the C-index was 0.76 and the effect size was 1.06. In the validation data, the C-index was 0.66 for women and 0.73 for men, with positive predictive values of 0.28 and 0.26, respectively Conclusion: It is possible to develop an algorithm with good discrimination for the onset identifying overall and modifiable risks of common mental disorders among working men. Such models have the potential to change the way that prevention of common mental disorders at the workplace is conducted, but different models may be required for women.
[Analysis of etiological factors involved in noncarious cervical lesions].

PubMed

Tomasik, Małgorzata

2006-01-01

The etiopathology of noncarious cervical lesions (NCCL) is multifactorial and still not fully understood. Tooth wear is defined as loss of dental hard tissue by a chemical or mechanical process that does not involve bacteria. This form of tooth surface loss includes attrition, abrasion, erosion, and abfraction. Noncarious cervical lesions represent loss of tooth structure at the cementoenamel junction. The purpose of this clinical study of NCCL was to analyze the etiology in relation to age and to identify the most important risk factors associated with cervical lesions, as well as patients and teeth more susceptible to NCCL with a focus on more effective treatment of this condition. The study group comprised 124 patients with NCCL, aged 15-75 years (mean = 44). A questionnaire was distributed addressing medical history--gastric disorders, dietary habits--consumption of acidic drinks, dental history, oral hygiene practices, and parafunctional habits. Clinical examination of tooth wear was performed on four tooth surfaces after air-drying. The distribution and severity of tooth wear was graded using the tooth wear index (TWI) calculated with a computer programme allowing for tooth characteristic to be determined for each decade of life. Depth of the cervical defect was measured with a periodontal probe. TWI was devised to reveal the extent of tooth surface wear irrespective of the cause. Raw scores were compared with the computer using predetermined threshold values which are set to distinguish between acceptable and unacceptable pathological levels of tooth wear for each decade of life and each tooth surface. Dentition status, oral hygiene, periodontal status, gingival recession, number of teeth and their mobility, oral symptoms of parafunction and relationship to lateral and protrusive tooth contact schemes was assessed and analyzed. Statistical analyses were performed with the Stata Statistical Software: release 5. The risk of NCCL formation was estimated with the logistic regression model. Results were presented as odds ratio, 95% confidence interval, and p probability. Tooth wear on all surfaces of the tooth, including cervical, was related to age and the ranges were 25-60%. Older patients were more likely to exhibit NCCL. Frequency, localization, and depth of noncarious cervical lesions in a given group of teeth was related to age, although NCCL was more common in premolars (mean = 85.1%). Associations between oral hygiene, consumption of acidic drinks, status of periodontium, number of teeth, their mobility and etiology of wedge-shaped defects were revealed. A relationship between lateral excursive contact of teeth, bruxism, and formation of cervical lesions was established evidencing a correlation between occlusal and cervical pathology. 1. Cervical lesions were most common in premolars. 2. Early detection of dental erosion is important for prevention of serious irreversible damage to dentition. 3. An understanding of the multifactorial nature of tooth wear and risk factors of erosion, abrasion, and ab-fraction is important in the patient's diagnostic protocol and management strategy.

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