Sample records for acquired microcephaly loss

  1. Hearing Loss in Infants with Microcephaly and Evidence of Congenital Zika Virus Infection - Brazil, November 2015-May 2016.

    PubMed

    Leal, Mariana C; Muniz, Lilian F; Ferreira, Tamires S A; Santos, Cristiane M; Almeida, Luciana C; Van Der Linden, Vanessa; Ramos, Regina C F; Rodrigues, Laura C; Neto, Silvio S Caldas

    2016-09-02

    Congenital infection with Zika virus causes microcephaly and other brain abnormalities (1). Hearing loss associated with other congenital viral infections is well described; however, little is known about hearing loss in infants with congenital Zika virus infection. A retrospective assessment of a series of 70 infants aged 0-10 months with microcephaly and laboratory evidence of Zika virus infection was conducted by the Hospital Agamenon Magalhães in Brazil and partners. The infants were enrolled during November 2015-May 2016 and had screening and diagnostic hearing tests. Five (7%) infants had sensorineural hearing loss, all of whom had severe microcephaly; however, one child was tested after receiving treatment with an ototoxic antibiotic. If this child is excluded, the prevalence of sensorineural hearing loss was 5.8% (four of 69), which is similar to that seen in association with other congenital viral infections. Additional information is needed to understand the prevalence and spectrum of hearing loss in children with congenital Zika virus infection; all infants born to women with evidence of Zika virus infection during pregnancy should have their hearing tested, including infants who appear normal at birth.

  2. Mutations in SPATA5 Are Associated with Microcephaly, Intellectual Disability, Seizures, and Hearing Loss.

    PubMed

    Tanaka, Akemi J; Cho, Megan T; Millan, Francisca; Juusola, Jane; Retterer, Kyle; Joshi, Charuta; Niyazov, Dmitriy; Garnica, Adolfo; Gratz, Edward; Deardorff, Matthew; Wilkins, Alisha; Ortiz-Gonzalez, Xilma; Mathews, Katherine; Panzer, Karin; Brilstra, Eva; van Gassen, Koen L I; Volker-Touw, Catharina M L; van Binsbergen, Ellen; Sobreira, Nara; Hamosh, Ada; McKnight, Dianalee; Monaghan, Kristin G; Chung, Wendy K

    2015-09-03

    Using whole-exome sequencing, we have identified in ten families 14 individuals with microcephaly, developmental delay, intellectual disability, hypotonia, spasticity, seizures, sensorineural hearing loss, cortical visual impairment, and rare autosomal-recessive predicted pathogenic variants in spermatogenesis-associated protein 5 (SPATA5). SPATA5 encodes a ubiquitously expressed member of the ATPase associated with diverse activities (AAA) protein family and is involved in mitochondrial morphogenesis during early spermatogenesis. It might also play a role in post-translational modification during cell differentiation in neuronal development. Mutations in SPATA5 might affect brain development and function, resulting in microcephaly, developmental delay, and intellectual disability. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Microcephaly: general considerations and aids to nosology.

    PubMed

    Opitz, J M; Holt, M C

    1990-01-01

    Microcephaly is defined as an occipito-frontal head circumference (OFC) 2 or more standard deviations below the mean for age and sex using the new Roche et al. [Pediatrics 1987;79:706-712] charts, and corrected for parental OFC by the method of Weaver and Christian [J Pediatr 1980;96:990-994]. "Relative" microcephaly, i.e., a small head on a small child, may be associated with a much better intellectual prognosis than absolute microcephaly, although the average IQ of children with absolute microcephaly ascertained in a normal school system is normal when compared with that of appropriate control children. "Primary" microcephaly means an abnormal OFC at birth (corrected for gestational age and length), and "secondary" microcephaly a normal birth OFC with later, acquired microcephaly due to deceleration of brain growth reflecting infection, trauma, intoxication, metabolic disease, the Rett syndrome, or a true CNS degenerative disease. Some cases of syndromal microcephaly may be associated with normal intelligence including some "primordial dwarfs," children with Dubowitz syndrome, FAS, mild SC-Roberts syndrome, and an occasional Brachmann-de Lange individual. The nosology of (syndromal) microcephaly is extraordinarily complex and requires the assistance of special library resources and information retrieval expertise. At a minimum, it requires McKusick's Catalog of Mendelian Inheritance in Man (MIM); however, we find that our work is greatly enhanced by recently developed electronic databases such as MIM-online (OMIM), POSSUM, SYNDROME, and MEDLINE, as well. Three groups of syndromal and non-syndromal microcephaly are discussed selectively in order to illustrate the marvels of pleiotropy in human development and its abnormalities and the difficulties encountered in splitting and lumping entities with overlapping manifestations.

  4. Microcephaly

    MedlinePlus

    ... possibly even below the first percentile for your baby's age and sex. A child with more severe microcephaly may also have a backward-sloping forehead. When to see a doctor Chances are your doctor will detect microcephaly at the baby's birth or at a regular well-baby checkup. ...

  5. Computational and Organotypic Modeling of Microcephaly ...

    EPA Pesticide Factsheets

    Microcephaly is associated with reduced cortical surface area and ventricular dilations. Many genetic and environmental factors precipitate this malformation, including prenatal alcohol exposure and maternal Zika infection. This complexity motivates the engineering of computational and experimental models to probe the underlying molecular targets, cellular consequences, and biological processes. We describe an Adverse Outcome Pathway (AOP) framework for microcephaly derived from literature on all gene-, chemical-, or viral- effects and brain development. Overlap with NTDs is likely, although the AOP connections identified here focused on microcephaly as the adverse outcome. A query of the Mammalian Phenotype Browser database for ‘microcephaly’ (MP:0000433) returned 85 gene associations; several function in microtubule assembly and centrosome cycle regulated by (microcephalin, MCPH1), a gene for primary microcephaly in humans. The developing ventricular zone is the likely target. In this zone, neuroprogenitor cells (NPCs) self-replicate during the 1st trimester setting brain size, followed by neural differentiation of the neocortex. Recent studies with human NPCs confirmed infectivity with Zika virions invoking critical cell loss (apoptosis) of precursor NPCs; similar findings have been shown with fetal alcohol or methylmercury exposure in rodent studies, leading to mathematical models of NPC dynamics in size determination of the ventricular zone. A key event

  6. Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures.

    PubMed

    Al-Maawali, Almundher; Barry, Brenda J; Rajab, Anna; El-Quessny, Malak; Seman, Ann; Coury, Stephanie Newton; Barkovich, A James; Yang, Edward; Walsh, Christopher A; Mochida, Ganeshwaran H; Stoler, Joan M

    2016-02-01

    Exome sequencing identified homozygous loss-of-function variants in DIAPH1 (c.2769delT; p.F923fs and c.3145C>T; p.R1049X) in four affected individuals from two unrelated consanguineous families. The affected individuals in our report were diagnosed with postnatal microcephaly, early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections. A heterozygous DIAPH1 mutation was originally reported in one family with autosomal dominant deafness. Recently, however, a homozygous nonsense DIAPH1 mutation (c.2332C4T; p.Q778X) was reported in five siblings in a single family affected by microcephaly, blindness, early onset seizures, developmental delay, and bronchiectasis. The role of DIAPH1 was supported using parametric linkage analysis, RNA and protein studies in their patients' cell lines and further studies in human neural progenitors cells and a diap1 knockout mouse. In this report, the proband was initially brought to medical attention for profound metopic synostosis. Additional concerns arose when his head circumference did not increase after surgical release at 5 months of age and he was diagnosed with microcephaly and epilepsy at 6 months of age. Clinical exome analysis identified a homozygous DIAPH1 mutation. Another homozygous DIAPH1 mutation was identified in the research exome analysis of a second family with three siblings presenting with a similar phenotype. Importantly, no hearing impairment is reported in the homozygous affected individuals or in the heterozygous carrier parents in any of the families demonstrating the autosomal recessive microcephaly phenotype. These additional families provide further evidence of the likely causal relationship between DIAPH1 mutations and a neurodevelopmental disorder. © 2016 Wiley Periodicals, Inc.

  7. Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update

    PubMed Central

    Huang, Lijia; Vanstone, Megan R.; Hartley, Taila; Osmond, Matthew; Barrowman, Nick; Allanson, Judith; Baker, Laura; Dabir, Tabib A.; Dipple, Katrina M.; Dobyns, William B.; Estrella, Jane; Faghfoury, Hanna; Favaro, Francine P.; Goel, Himanshu; Gregersen, Pernille A.; Gripp, Karen W.; Grix, Art; Guion-Almeida, Maria-Leine; Harr, Margaret H.; Hudson, Cindy; Hunter, Alasdair G.W.; Johnson, John; Joss, Shelagh K.; Kimball, Amy; Kini, Usha; Kline, Antonie D.; Lauzon, Julie; Lildballe, Dorte L.; López-González, Vanesa; Martinezmoles, Johanna; Meldrum, Cliff; Mirzaa, Ghayda M.; Morel, Chantal F.; Morton, Jenny E.V.; Pyle, Louise C.; Quintero-Rivera, Fabiola; Richer, Julie; Scheuerle, Angela E.; Schönewolf-Greulich, Bitten; Shears, Deborah J.; Silver, Josh; Smith, Amanda C.; Temple, I. Karen; van de Kamp, Jiddeke M.; van Dijk, Fleur S.; Vandersteen, Anthony M.; White, Sue M.; Zackai, Elaine H.; Zou, Ruobing; Bulman, Dennis E.; Boycott, Kym M.; Lines, Matthew A.

    2017-01-01

    Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5–116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds. Pathogenic EFTUD2 variants comprise 76 distinct mutations and seven microdeletions. Among point mutations, missense substitutions are infrequent (14 out of 76; 18%) relative to stop-gain (29 out of 76; 38%), and splicing (33 out of 76; 43%) mutations. Where known, mutation origin was de novo in 48 out of 64 individuals (75%), dominantly inherited in 12 out of 64 (19%), and due to proven germline mosaicism in four out of 64 (6%). Highly penetrant clinical features include, microcephaly, first and second arch craniofacial malformations, and hearing loss; esophageal atresia is present in an estimated ~27%. Microcephaly is virtually universal in childhood, with some adults exhibiting late “catch-up” growth and normocephaly at maturity. Occasionally reported anomalies, include vestibular and ossicular malformations, reduced mouth opening, atrophy of cerebral white matter, structural brain malformations, and epibulbar dermoid. All reported EFTUD2 mutations can be found in the EFTUD2 mutation database (http://databases.lovd.nl/shared/genes/EFTUD2). PMID:26507355

  8. Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update.

    PubMed

    Huang, Lijia; Vanstone, Megan R; Hartley, Taila; Osmond, Matthew; Barrowman, Nick; Allanson, Judith; Baker, Laura; Dabir, Tabib A; Dipple, Katrina M; Dobyns, William B; Estrella, Jane; Faghfoury, Hanna; Favaro, Francine P; Goel, Himanshu; Gregersen, Pernille A; Gripp, Karen W; Grix, Art; Guion-Almeida, Maria-Leine; Harr, Margaret H; Hudson, Cindy; Hunter, Alasdair G W; Johnson, John; Joss, Shelagh K; Kimball, Amy; Kini, Usha; Kline, Antonie D; Lauzon, Julie; Lildballe, Dorte L; López-González, Vanesa; Martinezmoles, Johanna; Meldrum, Cliff; Mirzaa, Ghayda M; Morel, Chantal F; Morton, Jenny E V; Pyle, Louise C; Quintero-Rivera, Fabiola; Richer, Julie; Scheuerle, Angela E; Schönewolf-Greulich, Bitten; Shears, Deborah J; Silver, Josh; Smith, Amanda C; Temple, I Karen; van de Kamp, Jiddeke M; van Dijk, Fleur S; Vandersteen, Anthony M; White, Sue M; Zackai, Elaine H; Zou, Ruobing; Bulman, Dennis E; Boycott, Kym M; Lines, Matthew A

    2016-02-01

    Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5-116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds. Pathogenic EFTUD2 variants comprise 76 distinct mutations and seven microdeletions. Among point mutations, missense substitutions are infrequent (14 out of 76; 18%) relative to stop-gain (29 out of 76; 38%), and splicing (33 out of 76; 43%) mutations. Where known, mutation origin was de novo in 48 out of 64 individuals (75%), dominantly inherited in 12 out of 64 (19%), and due to proven germline mosaicism in four out of 64 (6%). Highly penetrant clinical features include, microcephaly, first and second arch craniofacial malformations, and hearing loss; esophageal atresia is present in an estimated ∼27%. Microcephaly is virtually universal in childhood, with some adults exhibiting late "catch-up" growth and normocephaly at maturity. Occasionally reported anomalies, include vestibular and ossicular malformations, reduced mouth opening, atrophy of cerebral white matter, structural brain malformations, and epibulbar dermoid. All reported EFTUD2 mutations can be found in the EFTUD2 mutation database (http://databases.lovd.nl/shared/genes/EFTUD2). © 2015 WILEY PERIODICALS, INC.

  9. Practice Parameter: Evaluation of the child with microcephaly (an evidence-based review)

    PubMed Central

    Ashwal, Stephen; Michelson, David; Plawner, Lauren; Dobyns, William B.

    2009-01-01

    Objective: To make evidence-based recommendations concerning the evaluation of the child with microcephaly. Methods: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a 4-tiered scheme of evidence classification. Results: Microcephaly is an important neurologic sign but there is nonuniformity in its definition and evaluation. Microcephaly may result from any insult that disturbs early brain growth and can be seen in association with hundreds of genetic syndromes. Annually, approximately 25,000 infants in the United States will be diagnosed with microcephaly (head circumference <−2 SD). Few data are available to inform evidence-based recommendations regarding diagnostic testing. The yield of neuroimaging ranges from 43% to 80%. Genetic etiologies have been reported in 15.5% to 53.3%. The prevalence of metabolic disorders is unknown but is estimated to be 1%. Children with severe microcephaly (head circumference <−3 SD) are more likely (∼80%) to have imaging abnormalities and more severe developmental impairments than those with milder microcephaly (−2 to −3 SD; ∼40%). Coexistent conditions include epilepsy (∼40%), cerebral palsy (∼20%), mental retardation (∼50%), and ophthalmologic disorders (∼20% to ∼50%). Recommendations: Neuroimaging may be considered useful in identifying structural causes in the evaluation of the child with microcephaly (Level C). Targeted and specific genetic testing may be considered in the evaluation of the child with microcephaly who has clinical or imaging abnormalities that suggest a specific diagnosis or who shows no evidence of an acquired or environmental etiology (Level C). Screening for coexistent conditions such as cerebral palsy, epilepsy, and sensory deficits may also be considered (Level C). Further study is needed regarding the yield of diagnostic testing in children with microcephaly. GLOSSARY CP = cerebral palsy; GDD = global developmental delay; HC = head

  10. Microcephaly Information Page

    MedlinePlus

    ... You are here Home » Disorders » All Disorders Microcephaly Information Page Microcephaly Information Page What research is being done? The National ... the U.S. and Worldwide NINDS Clinical Trials Related Information Patient Organizations Birth Defect Research for Children, Inc. ...

  11. Decreased Axon Caliber Underlies Loss of Fiber Tract Integrity, Disproportional Reductions in White Matter Volume, and Microcephaly in Angelman Syndrome Model Mice

    PubMed Central

    Judson, Matthew C.; Burette, Alain C.; Shen, Mark D.; Rumple, Ashley M.; Del Cid, Wilmer A.; Paniagua, Beatriz

    2017-01-01

    Angelman syndrome (AS) is a debilitating neurodevelopmental disorder caused by loss of function of the maternally inherited UBE3A allele. It is currently unclear how the consequences of this genetic insult unfold to impair neurodevelopment. We reasoned that by elucidating the basis of microcephaly in AS, a highly penetrant syndromic feature with early postnatal onset, we would gain new insights into the mechanisms by which maternal UBE3A loss derails neurotypical brain growth and function. Detailed anatomical analysis of both male and female maternal Ube3a-null mice reveals that microcephaly in the AS mouse model is primarily driven by deficits in the growth of white matter tracts, which by adulthood are characterized by densely packed axons of disproportionately small caliber. Our results implicate impaired axon growth in the pathogenesis of AS and identify noninvasive structural neuroimaging as a potentially valuable tool for gauging therapeutic efficacy in the disorder. SIGNIFICANCE STATEMENT People who maternally inherit a deletion or nonfunctional copy of the UBE3A gene develop Angelman syndrome (AS), a severe neurodevelopmental disorder. To better understand how loss of maternal UBE3A function derails brain development, we analyzed brain structure in a maternal Ube3a knock-out mouse model of AS. We report that the volume of white matter (WM) is disproportionately reduced in AS mice, indicating that deficits in WM development are a major factor underlying impaired brain growth and microcephaly in the disorder. Notably, we find that axons within the WM pathways of AS model mice are abnormally small in caliber. This defect is associated with slowed nerve conduction, which could contribute to behavioral deficits in AS, including motor dysfunction. PMID:28663201

  12. Microcephaly and Macrocephaly in Autism.

    ERIC Educational Resources Information Center

    Fombonne, Eric; Roge, Bernadette; Claverie, Jacques; Courty, Stephanie; Fremolle, Jeanne

    1999-01-01

    Analysis of data from 126 children with autism found macrocephaly (head circumstance microcephaly (head circumference <3rd centile) was found in 15.1%. Microcephaly was significantly associated with the presence of medical disorders. (Author/DB)

  13. Microcephaly and Zika virus: a clinical and epidemiological analysis of the current outbreak in Brazil.

    PubMed

    Nunes, Magda Lahorgue; Carlini, Celia Regina; Marinowic, Daniel; Neto, Felipe Kalil; Fiori, Humberto Holmer; Scotta, Marcelo Comerlato; Zanella, Pedro Luis Ávila; Soder, Ricardo Bernardi; da Costa, Jaderson Costa

    2016-01-01

    This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases. Experts from Instituto do Cérebro do Rio Grande do Sul performed a critical (nonsystematic) literature review regarding different aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology, diagnostic criteria, and its possible association with the increase of microcephaly reports. The PubMed search using the key word "Zika virus" in February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all publications/guidelines from the Brazilian Ministry of Health, World Health Organization and Centers for Disease Control and Prevention (CDC - United States). Epidemiological data suggest a temporal association between the increased number of microcephaly notifications in Brazil and outbreak of Zika virus, primarily in the Brazil's Northeast. It has been previously documented that many different viruses might cause congenital acquired microcephaly. Still there is no consensus on the best curve to measure cephalic circumference, specifically in preterm neonates. Conflicting opinions regarding the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be used for the notifications were also found in the literature. The development of diagnostic techniques that confirm a cause-effect association and studies regarding the physiopathology of the central nervous system impairment should be prioritized. It is also necessary to strictly define the criteria for the diagnosis of microcephaly to identify cases that should undergo an etiological investigation. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  14. Congenital microcephaly: A diagnostic challenge during Zika epidemics.

    PubMed

    Alvarado-Socarras, Jorge L; Idrovo, Álvaro J; Contreras-García, Gustavo A; Rodriguez-Morales, Alfonso J; Audcent, Tobey A; Mogollon-Mendoza, Adriana C; Paniz-Mondolfi, Alberto

    2018-02-19

    The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Microcephaly and Other Birth Defects: Zika

    MedlinePlus

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Zika and Microcephaly Microcephaly is a birth defect in ... pregnancy or has stopped growing after birth. Congenital Zika Syndrome Congenital Zika syndrome is a unique pattern ...

  16. Acquired hearing loss and brain plasticity.

    PubMed

    Eggermont, Jos J

    2017-01-01

    Acquired hearing loss results in an imbalance of the cochlear output across frequency. Central auditory system homeostatic processes responding to this result in frequency specific gain changes consequent to the emerging imbalance between excitation and inhibition. Several consequences thereof are increased spontaneous firing rates, increased neural synchrony, and (in adults) potentially restricted to the auditory thalamus and cortex a reorganization of tonotopic areas. It does not seem to matter much whether the hearing loss is acquired neonatally or in adulthood. In humans, no clear evidence of tonotopic map changes with hearing loss has so far been provided, but frequency specific gain changes are well documented. Unilateral hearing loss in addition makes brain activity across hemispheres more symmetrical and more synchronous. Molecular studies indicate that in the brainstem, after 2-5 days post trauma, the glutamatergic activity is reduced, whereas glycinergic and GABAergic activity is largely unchanged. At 2 months post trauma, excitatory activity remains decreased but the inhibitory one is significantly increased. In contrast protein assays related to inhibitory transmission are all decreased or unchanged in the brainstem, midbrain and auditory cortex. Comparison of neurophysiological data with the molecular findings during a time-line of changes following noise trauma suggests that increases in spontaneous firing rates are related to decreases in inhibition, and not to increases in excitation. Because noise-induced hearing loss in cats resulted in a loss of cortical temporal processing capabilities, this may also underlie speech understanding in humans. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Facts about Microcephaly

    MedlinePlus

    ... input class="button submit" name="commit" type="submit" value="Submit" /> Information For… Media Policy ... and Severe Microcephaly Comparison The images are in the public domain and thus free of any copyright restrictions. As a matter of ...

  18. Genetic Causes of Microcephaly and Lessons for Neuronal Development

    PubMed Central

    Gilmore, Edward C.; Walsh, Christopher A.

    2012-01-01

    The study of human developmental microcephaly is providing important insights into brain development. It has become clear that developmental microcephalies are associated with abnormalities in cellular production, and that the pathophysiology of microcephaly provides remarkable insights into how the brain generates the proper number of neurons that determine brain size. Most of the genetic causes of ‘primary’ developmental microcephaly (i.e., not associated with other syndromic features) are associated with centrosomal abnormalities. In addition to other functions, centrosomal proteins control the mitotic spindle, which is essential for normal cell proliferation during mitosis. However, the brain is often uniquely affected when microcephaly genes are mutated implying special centrosomal related functions in neuronal production. Although models explaining how this could occur have some compelling data, they are not without controversy. Interestingly, some of the microcephaly genes show evidence that they were targets of evolutionary selection in primates and human ancestors, suggesting potential evolutionary roles in controlling neuronal number and brain volume across species. Mutations in DNA repair pathway genes also lead to microcephaly. Double stranded DNA breaks appear to be a prominent type of damage that needs to be repaired during brain development, yet why defects in DNA repair affect the brain preferentially and if DNA repair relates to centrosome function, are not clearly understood. PMID:24014418

  19. Prevalence and Clinical Attributes of Congenital Microcephaly - New York, 2013-2015.

    PubMed

    Graham, Krishika A; Fox, Deborah J; Talati, Achala; Pantea, Cristian; Brady, Laura; Carter, Sondra L; Friedenberg, Eric; Vora, Neil M; Browne, Marilyn L; Lee, Christopher T

    2017-02-10

    Congenital Zika virus infection can cause microcephaly and other severe fetal neurological anomalies (1). To inform microcephaly surveillance efforts and assess ascertainment sources, the New York State Department of Health and the New York City Department of Health and Mental Hygiene sought to determine the prevalence of microcephaly in New York during 2013-2015, before known importation of Zika virus infections. Suspected newborn microcephaly diagnoses were identified from 1) reports submitted by birth hospitals in response to a request and 2) queries of a hospital administrative discharge database for newborn microcephaly diagnoses. Anthropometric measurements, maternal demographics, and pregnancy characteristics were abstracted from newborn records from both sources. Diagnoses were classified using microcephaly case definitions developed by CDC and the National Birth Defects Prevention Network (NBDPN) (2). During 2013-2015, 284 newborns in New York met the case definition for severe congenital microcephaly (prevalence = 4.2 per 10,000 live births). Most newborns with severe congenital microcephaly were identified by both sources; 263 (93%) were identified through hospital requests and 256 (90%) were identified through administrative discharge data. The proportions of newborns with severe congenital microcephaly who were black (30%) or Hispanic (31%) were higher than the observed proportions of black (15%) or Hispanic (23%) infants among New York live births. Fifty-eight percent of newborns with severe congenital microcephaly were born to mothers with pregnancy complications or who had in utero or perinatal infections or teratogenic exposures, genetic disorders, or family histories of birth defects.

  20. Zika virus infection and microcephaly: Evidence regarding geospatial associations.

    PubMed

    Vissoci, João Ricardo Nickenig; Rocha, Thiago Augusto Hernandes; Silva, Núbia Cristina da; de Sousa Queiroz, Rejane Christine; Thomaz, Erika Bárbara Abreu Fonseca; Amaral, Pedro Vasconcelos Maia; Lein, Adriana; Branco, Maria Dos Remédios Freitas Carvalho; Aquino, José; Rodrigues, Zulimar Márita Ribeiro; da Silva, Antônio Augusto Moura; Staton, Catherine

    2018-04-01

    Although the Zika virus (ZIKV) epidemic ceased to be a public health emergency by the end of 2016, studies to improve knowledge about this emerging disease are still needed, especially those investigating a causal relationship between ZIKV in pregnant women and microcephaly in neonates. However, there are still many challenges in describing the relationship between ZIKV and microcephaly. The few studies focusing on the epidemiological profile of ZIKV and its changes over time are largely limited to systematic reviews of case reports and dispersal mapping of ZIKV spread over time without quantitative methods to analyze patterns and their covariates. Since Brazil has been at the epicenter of the ZIKV epidemic, this study examines the geospatial association between ZIKV and microcephaly in Brazil. Our study is categorized as a retrospective, ecological study based on secondary databases. Data were obtained from January to December 2016, from the following data sources: Brazilian System for Epidemiological Surveillance, Disease Notification System, System for Specialized Management Support, and Brazilian Institute of Geography and Statistics. Data were aggregated by municipality. Incidence rates were estimated per 100,000 inhabitants. Analyses consisted of mapping the aggregated incidence rates of ZIKV and microcephaly, followed by a Getis-Ord-Gi spatial cluster analysis and a Bivariate Local Moran's I analysis. The incidence of ZIKV cases is changing the virus's spatial pattern, shifting from Brazil's Northeast region to the Midwest and North regions. The number of municipalities in clusters of microcephaly incidence is also shifting from the Northeast region to the Midwest and North, after a time lag is considered. Our findings suggest an increase in microcephaly incidence in the Midwest and North regions, associated with high levels of ZIKV infection months before. The greatest burden of microcephaly shifted from the Northeast to other Brazilian regions at the

  1. A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?: Brain tumors and microcephaly arise from opposing derangements regulating progenitor growth. Drivers of microcephaly could be attractive brain tumor targets.

    PubMed

    Lang, Patrick Y; Gershon, Timothy R

    2018-05-01

    New targets for brain tumor therapies may be identified by mutations that cause hereditary microcephaly. Brain growth depends on the repeated proliferation of stem and progenitor cells. Microcephaly syndromes result from mutations that specifically impair the ability of brain progenitor or stem cells to proliferate, by inducing either premature differentiation or apoptosis. Brain tumors that derive from brain progenitor or stem cells may share many of the specific requirements of their cells of origin. These tumors may therefore be susceptible to disruptions of the protein products of genes that are mutated in microcephaly. The potential for the products of microcephaly genes to be therapeutic targets in brain tumors are highlighted hereby reviewing research on EG5, KIF14, ASPM, CDK6, and ATR. Treatments that disrupt these proteins may open new avenues for brain tumor therapy that have increased efficacy and decreased toxicity. © 2018 WILEY Periodicals, Inc.

  2. Primary microcephaly caused by novel compound heterozygous mutations in ASPM

    PubMed Central

    Okamoto, Nobuhiko; Kohmoto, Tomohiro; Naruto, Takuya; Masuda, Kiyoshi; Imoto, Issei

    2018-01-01

    Autosomal recessive primary microcephaly (microcephaly primary hereditary, MCPH) is a genetically heterogeneous rare developmental disorder that is characterized by prenatal onset of abnormal brain growth, which leads to intellectual disability of variable severity. We report a 5-year-old male who presented with a severe form of primary microcephaly. Targeted panel sequencing revealed compound heterozygous truncating mutations of the abnormal spindle-like microcephaly-associated (ASPM) gene, which confirmed the MCPH5 diagnosis. A novel NM_018136.4: c.9742_9745del (p.Lys3248Serfs*13) deletion mutation was identified. PMID:29644084

  3. Primary microcephaly caused by novel compound heterozygous mutations in ASPM.

    PubMed

    Okamoto, Nobuhiko; Kohmoto, Tomohiro; Naruto, Takuya; Masuda, Kiyoshi; Imoto, Issei

    2018-01-01

    Autosomal recessive primary microcephaly (microcephaly primary hereditary, MCPH) is a genetically heterogeneous rare developmental disorder that is characterized by prenatal onset of abnormal brain growth, which leads to intellectual disability of variable severity. We report a 5-year-old male who presented with a severe form of primary microcephaly. Targeted panel sequencing revealed compound heterozygous truncating mutations of the abnormal spindle-like microcephaly-associated ( ASPM ) gene, which confirmed the MCPH5 diagnosis. A novel NM_018136.4: c.9742_9745del (p.Lys3248Serfs*13) deletion mutation was identified.

  4. Microcephaly: computational and organotypic modeling of a ...

    EPA Pesticide Factsheets

    lecture discusses computational and organotypic models of microcephaly in an AOP Framework and ToxCast assays. Lecture slide presentation at UNC Chapel Hill for Advanced Toxicology course lecture on Computational Approaches to Developmental and Reproductive Toxicology with presentation on computational and organotypic modeling of a complex human birth defect microcephaly with is associated with the recent Zika virus outbreak.

  5. Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.

    PubMed

    Stephen, Joshi; Nampoothiri, Sheela; Banerjee, Aditi; Tolman, Nathanial J; Penninger, Josef Martin; Elling, Ullrich; Agu, Chukwuma A; Burke, John D; Devadathan, Kalpana; Kannan, Rajesh; Huang, Yan; Steinbach, Peter J; Martinis, Susan A; Gahl, William A; Malicdan, May Christine V

    2018-04-01

    Progressive microcephaly and neurodegeneration are genetically heterogenous conditions, largely associated with genes that are essential for the survival of neurons. In this study, we interrogate the genetic etiology of two siblings from a non-consanguineous family with severe early onset of neurological manifestations. Whole exome sequencing identified novel compound heterozygous mutations in VARS that segregated with the proband: a missense (c.3192G>A; p.Met1064Ile) and a splice site mutation (c.1577-2A>G). The VARS gene encodes cytoplasmic valyl-tRNA synthetase (ValRS), an enzyme that is essential during eukaryotic translation. cDNA analysis on patient derived fibroblasts revealed that the splice site acceptor variant allele led to nonsense mediated decay, thus resulting in a null allele. Three-dimensional modeling of ValRS predicts that the missense mutation lies in a highly conserved region and could alter side chain packing, thus affecting tRNA binding or destabilizing the interface between the catalytic and tRNA binding domains. Further quantitation of the expression of VARS showed remarkably reduced levels of mRNA and protein in skin derived fibroblasts. Aminoacylation experiments on patient derived cells showed markedly reduced enzyme activity of ValRS suggesting the mutations to be loss of function. Bi-allelic mutations in cytoplasmic amino acyl tRNA synthetases are well-known for their role in neurodegenerative disorders, yet human disorders associated with VARS mutations have not yet been clinically well characterized. Our study describes the phenotype associated with recessive VARS mutations and further functional delineation of the pathogenicity of novel variants identified, which widens the clinical and genetic spectrum of patients with progressive microcephaly.

  6. Asparagine synthetase deficiency detected by whole exome sequencing causes congenital microcephaly, epileptic encephalopathy and psychomotor delay.

    PubMed

    Ben-Salem, Salma; Gleeson, Joseph G; Al-Shamsi, Aisha M; Islam, Barira; Hertecant, Jozef; Ali, Bassam R; Al-Gazali, Lihadh

    2015-06-01

    Deficiency of Asparagine Synthetase (ASNSD, MIM 615574) is a very rare autosomal recessive disorder presenting with some brain abnormalities. Affected individuals have congenital microcephaly and progressive encephalopathy associated with severe intellectual disability and intractable seizures. The loss of function of the asparagine synthetase (ASNS, EC 6.3.5.4), particularly in the brain, is the major cause of this particular congenital microcephaly. In this study, we clinically evaluated an affected child from a consanguineous Emirati family presenting with congenital microcephaly and epileptic encephalopathy. In addition, whole-exome sequencing revealed a novel homozygous substitution mutation (c.1193A > C) in the ASNS gene. This mutation resulted in the substitution of highly conserved tyrosine residue by cysteine (p.Y398C). Molecular modeling analysis predicts hypomorphic and damaging effects of this mutation on the protein structure and altering its enzymatic activity. Therefore, we conclude that the loss of ASNS function is most likely the cause of this condition in the studied family. This report brings the number of reported families with this very rare disorder to five and the number of pathogenic mutations in the ASNS gene to four. This finding extends the ASNS pathogenic mutations spectrum and highlights the utility of whole-exome sequencing in elucidation the causes of rare recessive disorders that are heterogeneous and/or overlap with other conditions.

  7. Available Evidence of Association between Zika Virus and Microcephaly

    PubMed Central

    Wu, Jing; Huang, Da-Yong; Ma, Jun-Tao; Ma, Ying-Hua; Hu, Yi-Fei

    2016-01-01

    Objective: To clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly. Data Sources: We did a comprehensive literature review with the keywords “zika” and/or “microcephaly” from inception to May 27, 2016, with PubMed. Study Selection: Studies were included and analyzed if they met all of the following criteria: “probable or confirmed infant microcephaly” and “probable or confirmed ZIKV infection among mothers or infants”. Results: We emphasize the diagnosis of ZIKV infection, including maternal clinical manifestations, maternal and fetal laboratory confirmation, and possible autopsy if need. Other confounders that may lead to microcephaly should be excluded from the study. We presented the results from clinical manifestations of ZIKV infection, testing methods evolving but the mechanism of microcephaly uncertain, flexible definition challenging the diagnosis of microcephaly, and limited causal reference on pregnant women. We made analog comparison of severe acute respiratory syndrome and chikungunya virus in terms of DNA mutation and global movement to provide further research recommendation. The chance of catch-up growth may decrease the number of pervious “diagnosed” microcephaly. Conclusions: There are some evidence available through mice models and direct isolation of ZIKV in affected pregnancies on kindly causal relationship but not convincible enough. We analyzed and presented the weakness or limitation of published reports with the desire to shed light to further study directions. PMID:27647195

  8. Zika Virus Infection and Microcephaly: Evidence for a Causal Link.

    PubMed

    Wang, Jin-Na; Ling, Feng

    2016-10-20

    Zika virus (ZIKV) is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden increase in the number of microcephaly cases has been observed in infants of women who were pregnant when they contracted the virus. The severity of this condition raises grave concerns, and extensive studies on the possible link between ZIKV infection and microcephaly have been conducted. There is substantial evidence suggesting that there is a causal link between ZIKV and microcephaly, however, future studies are warranted to solidify this association. To summarize the most recent evidence on this issue and provide perspectives for future studies, we reviewed the literature to identify existing evidence of the causal link between ZIKV infection and microcephaly within research related to the epidemics, laboratory diagnosis, and possible mechanisms.

  9. A syndrome of microcephaly, short stature, polysyndactyly, and dental anomalies caused by a homozygous KATNB1 mutation.

    PubMed

    Yigit, Gökhan; Wieczorek, Dagmar; Bögershausen, Nina; Beleggia, Filippo; Möller-Hartmann, Claudia; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Wollnik, Bernd

    2016-03-01

    Using whole-exome sequencing, we identified a homozygous acceptor splice-site mutation in intron 6 of the KATNB1 gene in a patient from a consanguineous Turkish family who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. cDNA analysis revealed complete loss of the natural acceptor splice-site resulting either in the usage of an alternative, exonic acceptor splice-site inducing a frame-shift and premature protein truncation or, to a minor extent, in complete skipping of exon 7. Both effects most likely lead to complete loss of KATNB1 function. Homozygous and compound heterozygous mutations in KATNB1 have very recently been described as a cause of microcephaly with brain malformations and seizures. We extend the KATNB1 associated phenotype by describing a syndrome characterized by primordial dwarfism, lissencephaly, polysyndactyly, and dental anomalies, which is caused by a homozygous truncating KATNB1 mutation. © 2015 Wiley Periodicals, Inc.

  10. Molecular genetics of human primary microcephaly: an overview

    PubMed Central

    2015-01-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

  11. Microcephaly epidemic related to the Zika virus and living conditions in Recife, Northeast Brazil.

    PubMed

    Souza, Wayner Vieira de; Albuquerque, Maria de Fátima Pessoa Militão de; Vazquez, Enrique; Bezerra, Luciana Caroline Albuquerque; Mendes, Antonio da Cruz Gouveia; Lyra, Tereza Maciel; Araujo, Thalia Velho Barreto de; Oliveira, André Luiz Sá de; Braga, Maria Cynthia; Ximenes, Ricardo Arraes de Alencar; Miranda-Filho, Demócrito de Barros; Cabral Silva, Amanda Priscila de Santana; Rodrigues, Laura; Martelli, Celina Maria Turchi

    2018-01-12

    Starting in August 2015, there was an increase in the number of cases of neonatal microcephaly in Northeast Brazil. These findings were identified as being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The present study aims to analyse the spatial distribution of microcephaly cases in Recife (2015-2016), which is in Northeast Brazil, and its association with the living conditions in this city. This was an ecological study that used data from reported cases of microcephaly from the State Health Department of Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the 94 districts of Recife. The case definition of microcephaly was: neonates with a head circumference of less than the cut-off point of -2 standard deviations below the mean value from the established Fenton growth curve. As an indicator of the living conditions of the 94 districts, the percentage of heads of households with an income of less than twice the minimum wage was calculated. The districts were classified into four homogeneous strata using the K-means clustering algorithm. We plotted the locations of each microcephaly case over a layer of living conditions. During the study period, 347 microcephaly cases were reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case. Stratification of the 94 districts resulted in the identification of four strata. The highest stratum in relation to the living conditions presented the lowest prevalence rate of microcephaly, and the overall difference between this rate and the rates of the other strata was statistically significant. The results of the Kruskal-Wallis test demonstrated that there was a strong association between a higher prevalence of microcephaly and poor living conditions. After the first 6 months of the study period, there were no microcephaly cases recorded within the population living in the richest socio-economic strata. This study showed that those residing in areas with

  12. RBBP8 syndrome with microcephaly, intellectual disability, short stature and brachydactyly.

    PubMed

    Mumtaz, Sara; Yıldız, Esra; Jabeen, Saliha; Khan, Amjad; Tolun, Aslıhan; Malik, Sajid

    2015-12-01

    Primary microcephaly is clinically variable and genetically heterogeneous. Four phenotypically distinct types of autosomal recessive microcephaly syndromes are due to different RBBP8 mutations. We report on a consanguineous Pakistani family with homozygous RBBP8 mutation c.1808_1809delTA (p.Ile603Lysfs*7) manifesting microcephaly and a distinct combination of skeletal, limb and ectodermal defects, mild intellectual disability, minor facial anomalies, anonychia, disproportionate short stature and brachydactyly, and additionally talipes in one patient. © 2015 Wiley Periodicals, Inc.

  13. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015.

    PubMed

    Schuler-Faccini, Lavinia; Ribeiro, Erlane M; Feitosa, Ian M L; Horovitz, Dafne D G; Cavalcanti, Denise P; Pessoa, André; Doriqui, Maria Juliana R; Neri, Joao Ivanildo; Neto, Joao Monteiro de Pina; Wanderley, Hector Y C; Cernach, Mirlene; El-Husny, Antonette S; Pone, Marcos V S; Serao, Cassio L C; Sanseverino, Maria Teresa V

    2016-01-29

    In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear

  14. Perception of Musical Emotion in the Students with Cognitive and Acquired Hearing Loss.

    PubMed

    Mazaheryazdi, Malihe; Aghasoleimani, Mina; Karimi, Maryam; Arjmand, Pirooz

    2018-01-01

    Hearing loss can affect the perception of emotional reaction to the music. The present study investigated whether the students with congenital hearing loss exposed to the deaf culture, percept the same emotion from the music as students with acquired hearing loss. Participants were divided into two groups; 30 students with bilaterally congenital moderate to severe hearing loss that were selected from deaf schools located in Tehran, Iran and 30 students with an acquired hearing loss with the same degree of hearing loss selected from Amiralam Hospital, Tehran, Iran and compared with the group of 30 age and gender-matched normal hearing subjects served our control in 2012. The musical stimuli consisted of three different sequences of music, (sadness, happiness, and fear) each with the duration of 60 sec. The students were asked to point to the lists of words that best matched with their emotions. Emotional perception of sadness, happiness, and fear in congenital hearing loss children was significantly poorly than acquired hearing loss and normal hearing group ( P <0.001). There was no significant difference in the emotional perception of sadness, happiness, and fear among the group of acquired hearing loss and normal hearing group ( P =0.75), ( P =1) and ( P =0.16) respectively. Neural plasticity induced by hearing assistant devises may be affected by the time when a hearing aid was first fitted and how the auditory system responds to the reintroduction of certain sounds via amplification. Therefore, children who experienced auditory input of different sound patterns in their early childhood will show more perceptual flexibility in different situations than the children with congenital hearing loss and Deaf culture.

  15. Chornobyl, radiation, neural tube defects, and microcephaly.

    PubMed

    Wertelecki, Wladimir; Yevtushok, Lyubov; Kuznietsov, Illia; Komov, Oleksandr; Lapchenko, Serhii; Akhmedzanova, Diana; Ostapchuk, Lyubov

    2018-06-13

    Pregnant women residing in areas impacted by the Chornobyl ionizing radiation of the Rivne Province in Ukraine have persistent higher levels of incorporated cesium-137. In these areas the neural tube defects and microcephaly rates are significantly higher than in areas with lower maternal cesium-137 incorporated levels. In two Rivne counties with populations proximal to nuclear power plants the rates of neural tube defects and microcephaly are the highest in the province. The neural tube defects rates in Rivne are persistently among the highest in Europe. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Mutations in STAMBP, encoding a deubiquitinating enzyme, cause Microcephaly-Capillary Malformation syndrome

    PubMed Central

    McDonell, Laura M.; Mirzaa, Ghayda M.; Alcantara, Diana; Schwartzentruber, Jeremy; Carter, Melissa T.; Lee, Leo J.; Clericuzio, Carol L.; Graham, John M.; Morris-Rosendahl, Deborah J.; Polster, Tilman; Acsadi, Gyula; Townshend, Sharron; Williams, Simon; Halbert, Anne; Isidor, Bertrand; Smyser, Christopher D.; Paciorkowski, Alex R.; Willing, Marcia; Woulfe, John; Das, Soma; Beaulieu, Chandree L.; Marcadier, Janet; Geraghty, Michael T.; Frey, Brendan J.; Majewski, Jacek; Bulman, Dennis E.; Dobyns, William B.; O’Driscoll, Mark; Boycott, Kym M.

    2014-01-01

    Microcephaly-capillary malformation (MIC-CAP) syndrome exhibits severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay and multiple small capillary malformations on the skin. We employed whole-exome sequencing of five patients with MIC-CAP syndrome and identified novel recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB) isopeptidase STAMBP (STAM-binding protein)/AMSH (Associated Molecule with the SH3 domain of STAM), that plays a key role in cell surface receptor-mediated endocytosis and sorting. Patient cell lines showed reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and PI3K-AKT-mTOR pathways. The latter cellular phenotype is significant considering the established connection between these pathways and their association with vascular and capillary malformations. Furthermore, our findings of a congenital human disorder caused by a defective DUB protein that functions in endocytosis, implicates ubiquitin-conjugate aggregation and elevated apoptosis as factors potentially influencing the progressive neuronal loss underlying MIC-CAP. PMID:23542699

  17. Social identity management strategies used by workers with acquired hearing loss.

    PubMed

    Jennings, Mary Beth; Southall, Kenneth; Gagné, Jean-Pierre

    2013-01-01

    There is a paucity of knowledge about social identity-management by persons with hearing loss. The objective of the study was to gain an understanding from the perspective of the participants, the ways in which workers with acquired hearing loss manage their identity in the workplace. Twelve persons with acquired hearing loss, who were gainfully employed in a variety of settings and occupations in three Canadian cities, participated in audio-recorded semi-structured interviews. A secondary qualitative analysis was conducted on transcripts of interviews collected in a previous study on factors that influence disclosure of hearing loss in the workplace. A qualitative descriptive research paradigm was adopted and content analyses were used to extract pertinent information from verbatim transcripts. Participants described a range of identity-management strategies enacted in the workplace. Five recurrent themes emerged as important considerations in the Art of Identity Management in the workplace: 1. Managing the situation, 2. Having a buddy system, 3. Feeling comfortable, 4. Using personal resources, 5. It gets easier with time. Social identity-management is a complex process. Although persons with acquired hearing loss experience different challenges from other persons with invisible stigmas, similarities in the range of social identity-management strategies employed were evident in our findings. In addition, the social cognitive learning model of disclosure appears to be relevant to the experiences of our participants. The implications of the findings emphasize the importance of all stakeholders working collaboratively to address the issues of the growing population of workers with hearing loss.

  18. The Challenge of Assessing Microcephaly in the Context of the Zika Virus Epidemic.

    PubMed

    Quintó, Llorenç; García-Basteiro, Alberto L; Bardají, Azucena; González, Raquel; Padilla, Norma; Martinez-Espinosa, Flor E; Arévalo-Herrera, Myriam; Macete, Eusébio; Menéndez, Clara

    2017-03-10

    The present article examines the impact of the current limitations of the microcephaly definition in the context of the Zika virus outbreak. It highlights its dependence on the method used for determining gestational age and other anthropometric parameters, and includes original results of prevalence of microcephaly in four countries from two different continents (Mozambique, Brazil, Guatemala and Colombia). Alternative definitions of microcephaly are proposed to allow the identification of true cases of microcephaly in a more accurate manner. © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Mutations in the murine homologue of TUBB5 cause microcephaly by perturbing cell cycle progression and inducing p53-associated apoptosis.

    PubMed

    Breuss, Martin; Fritz, Tanja; Gstrein, Thomas; Chan, Kelvin; Ushakova, Lyubov; Yu, Nuo; Vonberg, Frederick W; Werner, Barbara; Elling, Ulrich; Keays, David A

    2016-04-01

    Microtubules play a crucial role in the generation, migration and differentiation of nascent neurons in the developing vertebrate brain. Mutations in the constituents of microtubules, the tubulins, are known to cause an array of neurological disorders, including lissencephaly, polymicrogyria and microcephaly. In this study we explore the genetic and cellular mechanisms that cause TUBB5-associated microcephaly by exploiting two new mouse models: a conditional E401K knock-in, and a conditional knockout animal. These mice present with profound microcephaly due to a loss of upper-layer neurons that correlates with massive apoptosis and upregulation of p53. This phenotype is associated with a delay in cell cycle progression and ectopic DNA elements in progenitors, which is dependent on the dosage of functional Tubb5. Strikingly, we report ectopic Sox2-positive progenitors and defects in spindle orientation in our knock-in mouse line, which are absent in knockout animals. This work sheds light on the functional repertoire of Tubb5, reveals that the E401K mutation acts by a complex mechanism, and demonstrates that the cellular pathology driving TUBB5-associated microcephaly is cell death. © 2016. Published by The Company of Biologists Ltd.

  20. A Possible Link Between Pyriproxyfen and Microcephaly

    PubMed Central

    Parens, Raphael; Nijhout, H. Frederik; Morales, Alfredo; Xavier Costa, Felipe; Bar-Yam, Yaneer

    2017-01-01

    The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. While evidence for Zika being the cause of some of the cases is strong, its role as the primary cause of the large number of cases in Brazil has not been confirmed. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus's role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has metabolites that bind to the mammalian retinoid X receptor, and has been shown to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly—incomplete formation of the anterior cerebral hemispheres—in exposed rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented—it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, and have not been adequately confirmed. Given this combination of information about

  1. Does Zika Virus Cause Microcephaly - Applying the Bradford Hill Viewpoints

    PubMed Central

    Awadh, Asma; Chughtai, Abrar Ahmad; Dyda, Amalie; Sheikh, Mohamud; Heslop, David J.; MacIntyre, Chandini Raina

    2017-01-01

    Introduction: Zika virus has been documented since 1952, but been associated with mild, self-limiting disease. Zika virus is classified as an arbovirus from a family of Flaviviridae and primarily spread by Aedes Aegypti mosquitos. However, in a large outbreak in Brazil in 2015, Zika virus has been associated with microcephaly. Methods: In this review we applied the Bradford-Hill viewpoints  to investigate the association between Zika virus and microcephaly. We examined historical studies, available data and also compared historical rates of microcephaly prior to the Zika virus outbreak. The available evidence was reviewed against the Bradford Hill viewpoints. Results: All  the nine criteria were met to varying degrees: strength of association, consistency of the association, specificity, temporality, plausibility, coherence, experimental evidence, biological gradient and analogy. Conclusion: Using the Bradford Hill Viewpoints as an evaluation framework for causation is highly suggestive that the association between Zika virus and microcephaly is causal. Further studies using animal models on the viewpoints which were not as strongly fulfilled would be helpful. PMID:28357156

  2. Neural Alterations in Acquired Age-Related Hearing Loss

    PubMed Central

    Mudar, Raksha A.; Husain, Fatima T.

    2016-01-01

    Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although, we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches. PMID:27313556

  3. Case report: microcephaly associated with Zika virus infection, Colombia.

    PubMed

    Mattar, Salim; Ojeda, Carolina; Arboleda, Janna; Arrieta, German; Bosch, Irene; Botia, Ingrid; Alvis-Guzman, Nelson; Perez-Yepes, Carlos; Gerhke, Lee; Montero, German

    2017-06-13

    Recently there has been a large outbreak of Zika virus infections in Colombia, South America. The epidemic began in September 2015 and continued to April 2017, for the total number of Zika cases reported of 107,870. For those confirmed Zika cases, there were nearly 20,000 (18.5%) suspected to be pregnant women, resulting in 157 confirmed cases of microcephaly in newborns reported by their health government agency. There is a clear under-estimation of the total number of cases and in addition no prior publications have been published to demonstrate the clinical aspects of the Zika infection in Colombia. We characterized one Zika presentation to be able to compare and contrast with other cases of Zika infection already reported in the literature. In this case report, we demonstrate congenital microcephaly at week 19 of gestation in a 34-year-old mother who showed symptoms compatible with Zika virus infection from Sincelejo, State of Sucre, in the Colombian Caribbean. Zika virus RNA was detected in the placenta using real-time reverse transcriptase polymerase chain reaction (RT-PCR). At week 25, the fetus weigh estimate was 770 g, had a cephalic perimeter of 20.2 cm (5th percentile), ventriculomegaly on the right side and dilatation of the fourth ventricle. At week 32, the microcephaly was confirmed with a cephalic perimeter of 22 cm, dilatation of the posterior atrium to 13 mm, an abnormally small cerebellum (29 mm), and an augmented cisterna magna. At birth (39 weeks by cesarean section), the head circumference was 27.5 cm, and computerized axial tomography (Siemens Corp, 32-slides) confirmed microcephaly with calcifications. We report a first case of maternal Zika virus infection associated with fetal microcephaly in Colombia and confirmed similar presentation to those observed previous in Brazil, 2015-2016.

  4. Congenital Zika Virus Infection: Beyond Neonatal Microcephaly.

    PubMed

    Melo, Adriana Suely de Oliveira; Aguiar, Renato Santana; Amorim, Melania Maria Ramos; Arruda, Monica B; Melo, Fabiana de Oliveira; Ribeiro, Suelem Taís Clementino; Batista, Alba Gean Medeiros; Ferreira, Thales; Dos Santos, Mayra Pereira; Sampaio, Virgínia Vilar; Moura, Sarah Rogéria Martins; Rabello, Luciana Portela; Gonzaga, Clarissa Emanuelle; Malinger, Gustavo; Ximenes, Renato; de Oliveira-Szejnfeld, Patricia Soares; Tovar-Moll, Fernanda; Chimelli, Leila; Silveira, Paola Paz; Delvechio, Rodrigo; Higa, Luiza; Campanati, Loraine; Nogueira, Rita M R; Filippis, Ana Maria Bispo; Szejnfeld, Jacob; Voloch, Carolina Moreira; Ferreira, Orlando C; Brindeiro, Rodrigo M; Tanuri, Amilcar

    2016-12-01

    Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. Description of the major lesions caused by ZIKV congenital infection. Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and

  5. Microcephaly/lymphedema and terminal deletion of the long arm of chromosome 13

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

    Fryns, J.P.

    1995-07-03

    Recently, we examined a 2-year-old boy with the association of microcephaly and significant pedal edema that extended to the distal parts of the legs. Prometaphase chromosome studies showed a small terminal deletion in the long arm of chromosome 13 of band 13q34, karyotype 46,XY,del(13)(q34{yields}qter). The present finding of a small terminal 13q34 deletion in this young boy with microcephaly/lymphedema is a first indication that the lymphedema/microcephaly association can be due to a small terminal 13q deletion. 2 refs.

  6. Zika Virus Associated with Microcephaly.

    PubMed

    Mlakar, Jernej; Korva, Misa; Tul, Nataša; Popović, Mara; Poljšak-Prijatelj, Mateja; Mraz, Jerica; Kolenc, Marko; Resman Rus, Katarina; Vesnaver Vipotnik, Tina; Fabjan Vodušek, Vesna; Vizjak, Alenka; Pižem, Jože; Petrovec, Miroslav; Avšič Županc, Tatjana

    2016-03-10

    A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.

  7. Genetics Home Reference: autosomal recessive primary microcephaly

    MedlinePlus

    ... microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Am J Hum Genet. 2005 May;76( ... genome editing and CRISPR-Cas9? What is precision medicine? What is newborn screening? New Pages Alopecia areata ...

  8. Loss-of-function mutation in RUSC2 causes intellectual disability and secondary microcephaly.

    PubMed

    Alwadei, Ali H; Benini, Ruba; Mahmoud, Adel; Alasmari, Ali; Kamsteeg, Erik-Jan; Alfadhel, Majid

    2016-12-01

    Inherited aberrancies in intracellular vesicular transport are associated with a variety of neurological and non-neurological diseases. RUSC2 is a gene found on chromosome 9p13.3 that codes for iporin, a ubiquitous protein with high expression in the brain that interacts with Rab proteins (GTPases implicated in intracellular protein trafficking). Although mutations in Rab proteins have been described as causing brain abnormalities and intellectual disability, until now no disease-causing mutations in RUSC2 have ever been reported in humans. We describe, to our knowledge for the first time, three patients with inherited homozygous nonsense mutations identified in RUSC2 on whole-exome sequencing. All three patients had central hypotonia, microcephaly, and moderate to severe intellectual disability. Two patients had additional features of early-onset epilepsy and absence of the splenium. This report adds to the ever-expanding landscape of genetic causes of intellectual disability and increases our understanding of the cellular processes underlying this important neurological entity. © 2016 Mac Keith Press.

  9. Genetics Home Reference: Amish lethal microcephaly

    MedlinePlus

    ... occurs in approximately 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population. Related Information What information about a genetic condition can statistics provide? Why ... in the SLC25A19 gene cause Amish lethal microcephaly . The SLC25A19 ...

  10. Zika virus infection, associated microcephaly, and low yellow fever vaccination coverage in Brazil: is there any causal link?

    PubMed

    De Góes Cavalcanti, Luciano Pamplona; Tauil, Pedro Luiz; Alencar, Carlos Henrique; Oliveira, Wanderson; Teixeira, Mauro Martins; Heukelbach, Jorg

    2016-06-30

    Since the end of 2014, Zika virus (ZIKV) infection has been rapidly spreading in Brazil. To analyze the possible association of yellow fever vaccine with a protective effect against ZIKV-related microcephaly, the following spatial analyses were performed, using Brazilian municipalities as units: i) yellow fever vaccination coverage in Brazilian municipalities in individuals aged 15-49; ii) reported cases of microcephaly by municipality; and iii) confirmed cases of microcephaly related to ZIKV, by municipality. SaTScan software was used to identify clusters of municipalities for high risk of microcephaly. There were seven significant high risk clusters of confirmed microcephaly cases, with four of them located in the Northeast where yellow fever vaccination rates were the lowest. The clusters harbored only 2.9% of the total population of Brazil, but 15.2% of confirmed cases of microcephaly. We hypothesize that pregnant women in regions with high yellow fever vaccination coverage may pose their offspring to lower risk for development of microcephaly. There is an urgent need for systematic studies to confirm the possible link between low yellow fever vaccination coverage, Zika virus infection and microcephaly.

  11. Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles.

    PubMed

    Chen, Hsin-Yi; Wu, Chien-Ting; Tang, Chieh-Ju C; Lin, Yi-Nan; Wang, Won-Jing; Tang, Tang K

    2017-08-15

    Mutations in many centriolar protein-encoding genes cause primary microcephaly. Using super-resolution and electron microscopy, we find that the human microcephaly protein, RTTN, is recruited to the proximal end of the procentriole at early S phase, and is located at the inner luminal walls of centrioles. Further studies demonstrate that RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly. CRISPR/Cas9-mediated RTTN gene knockout in p53-deficient cells induce amplification of primitive procentriole bodies that lack the distal-half centriolar proteins, POC5 and POC1B. Additional analyses show that RTTN serves as an upstream effector of CEP295, which mediates the loading of POC1B and POC5 to the distal-half centrioles. Interestingly, the naturally occurring microcephaly-associated mutant, RTTN (A578P), shows a low affinity for STIL binding and blocks centriole assembly. These findings reveal that RTTN contributes to building full-length centrioles and illuminate the molecular mechanism through which the RTTN (A578P) mutation causes primary microcephaly.Mutations in many centriolar protein-encoding genes cause primary microcephaly. Here the authors show that human microcephaly protein RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly, contributing to building full-length centrioles.

  12. CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination.

    PubMed

    Marjanović, Marko; Sánchez-Huertas, Carlos; Terré, Berta; Gómez, Rocío; Scheel, Jan Frederik; Pacheco, Sarai; Knobel, Philip A; Martínez-Marchal, Ana; Aivio, Suvi; Palenzuela, Lluís; Wolfrum, Uwe; McKinnon, Peter J; Suja, José A; Roig, Ignasi; Costanzo, Vincenzo; Lüders, Jens; Stracker, Travis H

    2015-07-09

    CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63-deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death, and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63-deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination.

  13. Computational and Organotypic Modeling of Microcephaly (Teratology Society)

    EPA Science Inventory

    Microcephaly is associated with reduced cortical surface area and ventricular dilations. Many genetic and environmental factors precipitate this malformation, including prenatal alcohol exposure and maternal Zika infection. This complexity motivates the engineering of computation...

  14. Radiological Characterization of Cerebral Phenotype in Newborn Microcephaly Cases from 2015 Outbreak in Brazil

    PubMed Central

    Ramalho Rocha, Yuri Raoni; Cavalcanti Costa, José Ricardo; Almeida Costa, Pericles; Maia, Gessica; Vasconcelos, Rafael de Medeiros; Ramos Tejo, Cynthia; Martins Batista, Rafaella; Lima Neto, Manoel; Martins de Lima, Gustavo Graco; Negromonte, Francisco; Borba, Marcelle; Bezerra Jeronimo, Selma Maria; Sequerra, Eduardo Bouth; Moreira Neto, Manuel

    2016-01-01

    Introduction: Brazil is facing, since October of 2015, an outbreak of microcephalic fetuses. This outbreak is correlated with the beginning of circulation of Zika virus (ZIKV) in the country. Although it is clear that the size of the head is diminished in these fetuses, the brain phenotype associated with these malformations is unknown. Methods: We collected computed tomography images of the microcephaly cases from the region of Natal, Rio Grande do Norte, from September 2015 to February 2016. Findings: The microcephalies derived from the current outbreak are associated with intracerebral calcifications, malformation of the ventricular system, migratory disorders in the telencephalon and, in a lower frequency, malformation of the cerebellum and brainstem. Discussion: The characteristics described herein are not usually found in other types of microcephaly. We suggest that this work can be used as a guideline to identify microcephaly cases associated to the current outbreak. PMID:27617166

  15. Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals

    PubMed Central

    2014-01-01

    Background Genes associated with the neurodevelopmental disorder microcephaly display a strong signature of adaptive evolution in primates. Comparative data suggest a link between selection on some of these loci and the evolution of primate brain size. Whether or not either positive selection or this phenotypic association are unique to primates is unclear, but recent studies in cetaceans suggest at least two microcephaly genes evolved adaptively in other large brained mammalian clades. Results Here we analyse the evolution of seven microcephaly loci, including three recently identified loci, across 33 eutherian mammals. We find extensive evidence for positive selection having acted on the majority of these loci not just in primates but also across non-primate mammals. Furthermore, the patterns of selection in major mammalian clades are not significantly different. Using phylogenetically corrected comparative analyses, we find that the evolution of two microcephaly loci, ASPM and CDK5RAP2, are correlated with neonatal brain size in Glires and Euungulata, the two most densely sampled non-primate clades. Conclusions Together with previous results, this suggests that ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size in mammals. Nevertheless, several limitations of currently available data and gene-phenotype tests are discussed, including sparse sampling across large evolutionary distances, averaging gene-wide rates of evolution, potential phenotypic variation and evolutionary reversals. We discuss the implications of our results for studies of the genetic basis of brain evolution, and explicit tests of gene-phenotype hypotheses. PMID:24898820

  16. CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination

    PubMed Central

    Marjanović, Marko; Sánchez-Huertas, Carlos; Terré, Berta; Gómez, Rocío; Scheel, Jan Frederik; Pacheco, Sarai; Knobel, Philip A.; Martínez-Marchal, Ana; Aivio, Suvi; Palenzuela, Lluís; Wolfrum, Uwe; McKinnon, Peter J.; Suja, José A.; Roig, Ignasi; Costanzo, Vincenzo; Lüders, Jens; Stracker, Travis H.

    2015-01-01

    CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63 deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63 deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination. PMID:26158450

  17. Zika virus infection during pregnancy and microcephaly occurrence: a review of literature and Brazilian data.

    PubMed

    De Carvalho, Newton Sérgio; De Carvalho, Beatriz Freitas; Fugaça, Cyllian Arias; Dóris, Bruna; Biscaia, Evellyn Silverio

    2016-01-01

    In November of 2015, the Ministry of Health of Brazil published an announcement confirming the relationship between Zika virus and the microcephaly outbreak in the Northeast, suggesting that infected pregnant women might have transmitted the virus to their fetuses. The objectives of this study were to conduct a literature review about Zika virus infection and microcephaly, evaluate national and international epidemiological data, as well as the current recommendations for the health teams. Zika virus is an arbovirus, whose main vector is the Aedes sp. The main symptoms of the infection are maculopapular rash, fever, non-purulent conjunctivitis, and arthralgia. Transmission of this pathogen occurs mainly by mosquito bite, but there are also reports via the placenta. Microcephaly is defined as a measure of occipto-frontal circumference being more than two standard deviations below the mean for age and gender. The presence of microcephaly demands evaluation of the patient, in order to diagnose the etiology. Health authorities issued protocols, reports and notes concerning the management of microcephaly caused by Zika virus, but there is still controversy about managing the cases. The Ministry of Health advises notifying any suspected or confirmed cases of children with microcephaly related to the pathogen, which is confirmed by a positive specific laboratory test for the virus. The first choice for imaging exam in children with this malformation is transfontanellar ultrasound. The most effective way to control this outbreak of microcephaly probably caused by this virus is to combat the vector. Since there is still uncertainty about the period of vulnerability of transmission via placenta, the use of repellents is crucial throughout pregnancy. More investigations studying the consequences of this viral infection on the body of newborns and in their development are required. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  18. Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial Dysostosis with Microcephaly

    PubMed Central

    Lines, Matthew A.; Huang, Lijia; Schwartzentruber, Jeremy; Douglas, Stuart L.; Lynch, Danielle C.; Beaulieu, Chandree; Guion-Almeida, Maria Leine; Zechi-Ceide, Roseli Maria; Gener, Blanca; Gillessen-Kaesbach, Gabriele; Nava, Caroline; Baujat, Geneviève; Horn, Denise; Kini, Usha; Caliebe, Almuth; Alanay, Yasemin; Utine, Gulen Eda; Lev, Dorit; Kohlhase, Jürgen; Grix, Arthur W.; Lohmann, Dietmar R.; Hehr, Ute; Böhm, Detlef; Majewski, Jacek; Bulman, Dennis E.; Wieczorek, Dagmar; Boycott, Kym M.

    2012-01-01

    Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. PMID:22305528

  19. Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth.

    PubMed

    Lim, Nicholas R; Shohayeb, Belal; Zaytseva, Olga; Mitchell, Naomi; Millard, S Sean; Ng, Dominic C H; Quinn, Leonie M

    2017-07-11

    The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume. Moreover, loss of function in glia not only decreased the glial population but also non-autonomously caused neuroblast loss. We further demonstrated that WDR62 controls brain growth through lineage-specific interactions with master mitotic signaling kinase, AURKA. Depletion of AURKA in neuroblasts drives brain overgrowth, which was suppressed by WDR62 co-depletion. In contrast, glial-specific depletion of AURKA significantly decreased brain volume, which was further decreased by WDR62 co-depletion. Thus, dissecting relative contributions of MCPH factors to individual neural lineages will be critical for understanding complex diseases such as microcephaly. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  20. Dominantly inherited syndrome of microcephaly and cleft palate.

    PubMed

    Halal, F

    1983-05-01

    Two sisters and their mother had a syndrome of microcephaly, cleft palate, and variable anomalies such as unusual facial appearance, hypotelorism, abnormal retinal pigmentation, maxillary hypoplasia, goiter, camptodactyly, mild mental retardation, and abnormal dermatoglyphics. This is an evidently dominantly inherited trait, either autosomal or X-linked.

  1. Profound microcephaly, primordial dwarfism with developmental brain malformations: a new syndrome.

    PubMed

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Saleem, Sahar N; Ahmed, Mahmoud K H; Issa, Mahmoud; Effat, Laila K; Kayed, Hisham F; Zaki, Maha S; Gaber, Khaled R

    2012-08-01

    We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. Copyright © 2012 Wiley Periodicals, Inc.

  2. Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly.

    PubMed

    Lines, Matthew A; Huang, Lijia; Schwartzentruber, Jeremy; Douglas, Stuart L; Lynch, Danielle C; Beaulieu, Chandree; Guion-Almeida, Maria Leine; Zechi-Ceide, Roseli Maria; Gener, Blanca; Gillessen-Kaesbach, Gabriele; Nava, Caroline; Baujat, Geneviève; Horn, Denise; Kini, Usha; Caliebe, Almuth; Alanay, Yasemin; Utine, Gulen Eda; Lev, Dorit; Kohlhase, Jürgen; Grix, Arthur W; Lohmann, Dietmar R; Hehr, Ute; Böhm, Detlef; Majewski, Jacek; Bulman, Dennis E; Wieczorek, Dagmar; Boycott, Kym M

    2012-02-10

    Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Prevalence of Antibodies to Zika Virus in Mothers from Hawaii Who Delivered Babies with and without Microcephaly between 2009-2012.

    PubMed

    Kumar, Mukesh; Ching, Lauren; Astern, Joshua; Lim, Eunjung; Stokes, Alexander J; Melish, Marian; Nerurkar, Vivek R

    2016-12-01

    Zika virus (ZIKV) is an emerging mosquito-borne pathogen. ZIKV infection is linked to the development of severe fetal abnormalities that include spontaneous abortion, stillbirth, hydranencephaly, and microcephaly. ZIKV outbreaks have been recorded in the United States. We recently demonstrated the first congenital ZIKV infection in the United States. In this study, we investigated archived blood samples from six mothers who gave birth to babies with microcephaly and 12 mothers who gave birth to healthy babies in Hawaii between 2009 and 2012. We tested maternal blood for the presence of ZIKV IgM and IgG antibodies using commercially available human ZIKV IgM and IgG ELISA kits. Blood from one mother who delivered babies with microcephaly tested positive for ZIKV IgM antibody (16.6%) and blood from three mothers tested positive for ZIKV IgG antibody (50%). ZIKV showed a trend toward significance with microcephaly. ZIKV IgG antibody positive mothers were more likely to deliver babies with microcephaly than mothers who were negative for ZIKV IgG antibodies (Odds ratio [OR] = 11.0, 95% confidence interval [CI] = 0.8-147.9, p = 0.083). Similarly, ZIKV IgM antibody positive mothers were also more likely to deliver babies with microcephaly than mothers who were negative for ZIKV IgM antibody (OR = 6.8, 95% CI = 0.2-195.1). These data provide further evidence of a link between ZIKV infection and microcephaly and suggests presence of ZIKV positive cases and associated microcephaly in the United States as early as 2009.

  4. Estimating the numbers of pregnant women infected with Zika virus and infants with congenital microcephaly in Colombia, 2015-2017.

    PubMed

    Adamski, Alys; Bertolli, Jeanne; Castañeda-Orjuela, Carlos; Devine, Owen J; Johansson, Michael A; Duarte, Maritza Adegnis Gonzalez; Farr, Sherry L; Tinker, Sarah C; Reyes, Marcela Maria Mercado; Tong, Van T; Garcia, Oscar Eduardo Pacheco; Valencia, Diana; Ortiz, Diego Alberto Cuellar; Honein, Margaret A; Jamieson, Denise J; Martínez, Martha Lucía Ospina; Gilboa, Suzanne M

    2018-06-01

    Colombia experienced a Zika virus (ZIKV) outbreak in 2015-2016. To assist with planning for medical and supportive services for infants affected by prenatal ZIKV infection, we used a model to estimate the number of pregnant women infected with ZIKV and the number of infants with congenital microcephaly from August 2015 to August 2017. We used nationally reported cases of symptomatic ZIKV disease among pregnant women and information from the literature on the percent of asymptomatic infections to estimate the number of pregnant women with ZIKV infection occurring August 2015-December 2016. We then estimated the number of infants with congenital microcephaly expected to occur August 2015-August 2017. To compare to the observed counts of infants with congenital microcephaly due to all causes reported through the national birth defects surveillance system, the model was time limited to produce estimates for February-November 2016. We estimated 1140-2160 (interquartile range [IQR]) infants with congenital microcephaly in Colombia, during August 2015-August 2017, whereas 340-540 infants with congenital microcephaly would be expected in the absence of ZIKV. Based on the time limited version of the model, for February-November 2016, we estimated 650-1410 infants with congenital microcephaly in Colombia. The 95% uncertainty interval for the latter estimate encompasses the 476 infants with congenital microcephaly reported during that approximate time frame based on national birth defects surveillance. Based on modeled estimates, ZIKV infection during pregnancy in Colombia could lead to 3-4 times as many infants with congenital microcephaly in 2015-2017 as would have been expected in the absence of the ZIKV outbreak. This publication was made possible through support provided by the Bureau for Global Health, U.S. Agency for International Development under the terms of an Interagency Agreement with Centers for Disease Control and Prevention. Published by Elsevier Ltd.

  5. Microcephaly and Zika virus: Neuroradiological aspects, clinical findings and a proposed framework for early evaluation of child development.

    PubMed

    Cicuto Ferreira Rocha, Nelci Adriana; de Campos, Ana Carolina; Cicuto Ferreira Rocha, Fellipe; Pereira Dos Santos Silva, Fernanda

    2017-11-01

    As the recent outbreak of microcephaly cases caused by Zika virus has been declared a global health emergency, providing assessment guidelines for multidisciplinary teams providing early developmental screening and stimulation to infants with microcephaly is much needed. Thus, the aim of this manuscript is to provide an overview on what is known about neuroradiological aspects and clinical findings in infants with microcephaly caused by Zika virus and to propose a framework for early evaluation of child development. The keywords "Zika virus" and "microcephaly" were searched in PubMed database for articles published from incept to May 2017. These texts were reviewed, and the ones addressing neuroradiological and clinical findings in infants were selected. Recommendations for early assessment were made based on the International Classification of Functionality Disability and Health (ICF) model. The database search yielded 599 publications and 36 were selected. The studies detected microcephaly with diffuse brain malformations and calcifications, ventriculomegaly, optic nerve hypoplasia, macular atrophy, cataracts, impaired visual and hearing function, arthrogryposis, spasticity, hyperreflexia, irritability, tremors, and seizures, but very little is known about early development. Early assessments were described based on the ICF domains (Body Function and Structures, Activities and Participation and Contextual factors). Studies published showed abnormal brain, optic, neurologic and orthopedic findings, but very little is known about other aspects of functioning in infants with microcephaly caused by Zika virus. The biopsychosocial model based on the ICF paradigm provides an adequate framework to describe the condition of the infant with microcephaly receiving rehabilitative efforts to minimize disability. Efforts towards early identification of developmental delays should be taken within the first six months of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Population-Based Microcephaly Surveillance in the United States, 2009 to 2013: An Analysis of Potential Sources of Variation

    PubMed Central

    Cragan, Janet D.; Isenburg, Jennifer L.; Parker, Samantha E.; Alverson, C.J.; Meyer, Robert E.; Stallings, Erin B.; Kirby, Russell S.; Lupo, Philip J.; Liu, Jennifer S.; Seagroves, Amanda; Ethen, Mary K.; Cho, Sook Ja; Evans, MaryAnn; Liberman, Rebecca F.; Fornoff, Jane; Browne, Marilyn L.; Rutkowski, Rachel E.; Nance, Amy E.; Anderka, Marlene; Fox, Deborah J.; Steele, Amy; Copeland, Glenn; Romitti, Paul A.; Mai, Cara T.

    2017-01-01

    Background Congenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging. Methods Thirty birth defects surveillance programs provided data on infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of microcephaly per 10,000 live births was estimated overall and by maternal/infant characteristics. Variation in prevalence was examined across case finding methods. Nine programs provided data on head circumference and conditions potentially contributing to microcephaly. Results The pooled prevalence of microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live births) was similar among programs using active (6.7) and passive (6.6) methods; the interdecile range of prevalence estimates was wider among programs using passive methods for all race/ethnicity categories except Hispanic. Prevalence (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates followed a U-shaped distribution by maternal age with the highest prevalence among mothers <20 years (11.5) and ≥40 years (13.2). For gestational age and birth weight, the highest prevalence was among infants <32 weeks gestation and infants <1500 gm. Case definitions varied; 41.8% of cases had an HC ≥ the 10th percentile for sex and gestational age. Conclusion Differences in methods, population distribution of maternal/infant characteristics, and case definitions for microcephaly can contribute to the wide range of observed prevalence estimates across individual birth defects surveillance programs. Addressing these factors in the setting of Zika virus infection can improve the quality of prevalence estimates. PMID:27891783

  7. Inherited and acquired thrombophilia in Indian women experiencing unexplained recurrent pregnancy loss.

    PubMed

    Patil, Rucha; Ghosh, Kanjaksha; Vora, Sonal; Shetty, Shrimati

    2015-10-01

    The most frequently hypothesized cause of unexplained recurrent pregnancy loss (RPL) refers to a defective maternal haemostatic response leading to uteroplacental thrombosis. Approximately 20% women suffering from pregnancy loss (PL) are associated with autoimmune disorders and more than 50% remain idiopathic after common traditional investigations. The present study aims to investigate the prevalence of different genetic and acquired thrombophilia markers in a large series of Indian women with RPL. Such studies will help analyze the markers which pose maximum risk and help in the appropriate treatment in subsequent pregnancies. The study comprised of 587 women with no apparent etiological causes of RPL and 115 healthy women controls. p values were calculated with two tailed Fisher's exact test; statistical significance was assumed at p<0.05, 95% confidence interval. Relative risks were also calculated. Among genetic thrombophilia, the risk of PL was highest with protein S deficiency (16%, p=0.006) followed by plasminogen activator inhibitor-1 4G/4G (23%, p=0.007) polymorphism. Among acquired markers, the risk of PL was the highest in women with anti-cardiolipin antibodies (24%, p=0.0001), followed by anti-annexin V antibodies (23%, p=0.0009) and lupus anticoagulants (8%, p=0.02). Thrombophilia, inherited and acquired, is an important contributing factor in unexplained RPL and should be screened in the order of its prevalence. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: a surveillance-based analysis.

    PubMed

    de Oliveira, Wanderson Kleber; de França, Giovanny Vinícius Araújo; Carmo, Eduardo Hage; Duncan, Bruce Bartholow; de Souza Kuchenbecker, Ricardo; Schmidt, Maria Inês

    2017-08-26

    On Nov 11, 2015, the Brazilian Ministry of Health declared a Public Health Emergency of National Concern in response to an increased number of microcephaly cases, possibly related to previous Zika virus outbreaks. We describe the course of the dual epidemics of the Zika virus infection during pregnancy and microcephaly in Brazil up to Nov 12, 2016, the first anniversary of this declaration. We used secondary data for Zika virus and microcephaly cases obtained through the Brazilian Ministry of Health's surveillance systems from Jan 1, 2015, to Nov 12, 2016. We deemed possible Zika virus infections during pregnancy as all suspected cases of Zika virus disease and all initially suspected, but later discarded, cases of dengue and chikungunya fever. We defined confirmed infection-related microcephaly in liveborn infants as the presence of a head circumference of at least 2 SDs below the mean for their age and sex, accompanied by diagnostic imaging consistent with an infectious cause, or laboratory, clinical, or epidemiological results positive for Zika virus or STORCH (infectious agents known to cause congenital infection, mainly syphilis, toxoplasmosis, cytomegalovirus, and herpes simplex virus). We excluded cases of congenital anomalies or death without microcephaly. We analyse the spatial clustering of these diseases in Brazil to obtain the kernel density estimation. Two distinct waves of possible Zika virus infection extended across all Brazilian regions in 2015 and 2016. 1 673 272 notified cases were reported, of which 41 473 (2·5%) were in pregnant women. During this period, 1950 cases of infection-related microcephaly were confirmed. Most cases (1373 [70·4%]) occurred in the northeast region after the first wave of Zika virus infection, with peak monthly occurrence estimated at 49·9 cases per 10 000 livebirths. After a major, well documented second wave of Zika virus infection in all regions of Brazil from September, 2015, to September, 2016

  9. Microcephaly in north-east Brazil: a retrospective study on neonates born between 2012 and 2015.

    PubMed

    Soares de Araújo, Juliana Sousa; Regis, Cláudio Teixeira; Gomes, Renata Grigório Silva; Tavares, Thiago Ribeiro; Rocha Dos Santos, Cícera; Assunção, Patrícia Melo; Nóbrega, Renata Valéria; Pinto, Diana de Fátima Alves; Bezerra, Bruno Vinícius Dantas; Mattos, Sandra da Silva

    2016-11-01

    To assess the number of children born with microcephaly in the State of Paraíba, north-east Brazil. We contacted 21 maternity centres belonging to a paediatric cardiology network, with access to information regarding more than 100 000 neonates born between 1 January 2012 and 31 December 2015. For 10% of these neonates, nurses were requested to retrieve head circumference measurements data from delivery-room books. We used three separate criteria to classify whether a neonate had microcephaly: (i) the Brazilian Ministry of Health proposed criterion: term neonates (gestational age ≥ 37 weeks) with a head circumference of less than 32 cm; (ii) Fenton curves: neonates with a head circumference of less than -3 standard deviation for age and gender; or (iii) the proportionality criterion: neonates with a head circumference of less than ((height/2))+10) ± 2. Between 1 and 31 December 2015, nurses obtained data for 16 208 neonates. Depending on which criterion we used, the number of neonates with microcephaly varied from 678 to 1272 (4.2-8.2%). Two per cent (316) of the neonates fulfilled all three criteria. We observed temporal fluctuations of microcephaly prevalence from late 2012. The numbers of microcephaly reported here are much higher than the 6.4 per 10 000 live births reported by the Brazilian live birth information system. The results raise questions about the notification system, the appropriateness of the diagnostic criteria and future implications for the affected children and their families. More studies are needed to understand the epidemiology and the implications for the Brazilian health system.

  10. Hospital-acquired pressure ulcer prevalence--evaluating low-air-loss beds.

    PubMed

    Johnson, Jane; Peterson, Darcie; Campbell, Betty; Richardson, Regina; Rutledge, Dana

    2011-01-01

    Higher-category pressure redistribution mattresses are considered a critical component of a pressure ulcer prevention program, but few studies have quantified the impact of specific preventive measures on the incidence or prevalence of hospital-acquired pressure ulcers (HAPUs). Therefore, this study was undertaken to determine the impact of low-air-loss beds on HAPU prevalence. This prospective, comparative cohort study monitored the prevalence of HAPU at our hospital and compared rates of matched medical-surgical units with and without low-air-loss beds. Units without low-air-loss beds used a variety of alternative pressure redistribution devices for patients deemed at risk for pressure ulceration. The prevalence of HAPU was operationally defined as the number of patients with HAPUs divided by numbers of patients observed. The prevalence of HAPU over 3 quarters in 2008 ranged from 1.0% to 3.3% (overall rate 2.4%). Eighty-three percent of patients with HAPUs were cared for on low-air-loss beds. Of 12 patients with 16 HAPUs during this time, 75% were aged 70 years or older and 25% were managed in critical care units. Over half of patients who developed HAPUs had been hospitalized for 20 days or more. Half of the patients with HAPUs were scored as no-low risk on the Braden Scale.On the paired medical-surgical units, no statistically significant differences were found when patients with low-air-loss beds were compared to standard hospital mattresses supplemented by a variety of pressure redistribution devices. Seven of 11 HAPUs (63%) occurred in patients placed on low-air-loss beds. The prevalence of HAPU in patients placed on low-air-loss beds was no different from patients placed on standard hospital mattresses supplemented by a variety of pressure redistribution devices. Further research is needed to determine the impact of specific strategies on prevention of HAPU.

  11. Microcephaly Prevalence in Infants Born to Zika Virus-Infected Women: A Systematic Review and Meta-Analysis

    PubMed Central

    2017-01-01

    Zika virus is an emergent flavivirus transmitted by Aedes genus mosquitoes that recently reached the Americas and was soon implicated in an increase of microcephaly incidence. The objective of the present study is to systematically review the published data and perform a meta-analysis to estimate the prevalence of microcephaly in babies born to Zika virus-infected women during pregnancy. We searched PubMed and Cochrane databases, included cohort studies, and excluded case reports and case series publications. We extracted sample sizes and the number of microcephaly cases from eight studies, which permitted a calculation of prevalence rates that are pooled in a random-effects model meta-analysis. We estimated the prevalence of microcephaly of 2.3% (95% CI = 1.0–5.3%) among all pregnancies. Limitations include mixed samples of women infected at different pregnancy times, since it is known that infection at the first trimester is associated with higher risk to congenital anomalies. The estimates are deceptively low, given the devastating impact the infection causes over children and their families. We hope our study contributes to public health knowledge to fight Zika virus epidemics to protect mothers and their newborns. PMID:28783051

  12. Occupationally-acquired noise-induced hearing loss: a senseless workplace hazard.

    PubMed

    Kurmis, Andrew P; Apps, Stacey A

    2007-01-01

    Occupational noise-induced hearing loss (ONIHL) describes an acquired hearing deficiency directly attributable to excessive workplace noise exposure. Data suggest that excessive noise attributes to approximately 37% of all adult causes of hearing loss and remains a significant contributor to employment-related morbidity internationally. Typically insidiously-acquired, often without frank progressive symptomatology, regional medical agencies continue to struggle with this potentially debilitating condition. The aim of the study was to provide a synopsis of the current understanding of ONIHL, its impact on individual workers and the wider international community, and to identify barriers to more uniform adoption of personal hearing protection. A review of the contemporary literature was performed using defined keyword searches and OVID, PubMed, and Google Scholar as primary electronic search engines. A number of published works were identified, describing aspects of the relationship between workplace-related noise exposure and subsequent development of employee hearing impairment, which demonstrate an overwhelming gender imbalance, with up to 97% of affected individuals being male. Industry-specific associations (e.g., mining, manufacturing and heavy construction) were well documented, as were links to toxin-specific exposures, in the recognized development of hearing loss. However, evidence of integration of appraisal of the topically-current area of genetic susceptibility was often lacking. Much discordance still exists among international agencies in the prescriptive regulation and enforcement of "safe" exposure limits. Despite a high level of public awareness regarding the importance of hearing preservation and increasingly stringent international occupational health, safety and welfare requirements mandating provision of safer work environments, ONIHL continues to be a significant occupational hazard. ONIHL is permanent and may cause significant disability, for

  13. Microcephaly in north-east Brazil: a retrospective study on neonates born between 2012 and 2015

    PubMed Central

    Soares de Araújo, Juliana Sousa; Regis, Cláudio Teixeira; Gomes, Renata Grigório Silva; Tavares, Thiago Ribeiro; Rocha dos Santos, Cícera; Assunção, Patrícia Melo; Nóbrega, Renata Valéria; Pinto, Diana de Fátima Alves; Bezerra, Bruno Vinícius Dantas

    2016-01-01

    Abstract Objective To assess the number of children born with microcephaly in the State of Paraíba, north-east Brazil. Methods We contacted 21 maternity centres belonging to a paediatric cardiology network, with access to information regarding more than 100 000 neonates born between 1 January 2012 and 31 December 2015. For 10% of these neonates, nurses were requested to retrieve head circumference measurements data from delivery-room books. We used three separate criteria to classify whether a neonate had microcephaly: (i) the Brazilian Ministry of Health proposed criterion: term neonates (gestational age ≥ 37 weeks) with a head circumference of less than 32 cm; (ii) Fenton curves: neonates with a head circumference of less than −3 standard deviation for age and gender; or (iii) the proportionality criterion: neonates with a head circumference of less than ((height/2))+10) ± 2. Findings Between 1 and 31 December 2015, nurses obtained data for 16 208 neonates. Depending on which criterion we used, the number of neonates with microcephaly varied from 678 to 1272 (4.2–8.2%). Two per cent (316) of the neonates fulfilled all three criteria. We observed temporal fluctuations of microcephaly prevalence from late 2012. Conclusion The numbers of microcephaly reported here are much higher than the 6.4 per 10 000 live births reported by the Brazilian live birth information system. The results raise questions about the notification system, the appropriateness of the diagnostic criteria and future implications for the affected children and their families. More studies are needed to understand the epidemiology and the implications for the Brazilian health system. PMID:27821886

  14. Nonimmune hydrops fetalis, hydramnios, microcephaly, and intracranial meningeal hemangioendothelioma.

    PubMed

    Drut, R; Sapia, S; Gril, D; Velasco, J C; Drut, R M

    1993-01-01

    Necropsy findings in a male stillborn at 31 weeks gestational age included nonimmune hydrops, hydramnios, and microcephaly secondary to a hemangioendotheliomatous malformation at the tentorium. The vascular lesion was composed by large and small tortuous endothelium-lined vessels and leiomuscular septa. The lesion is thought to be related to the more frequent arteriovenous malformation of the vein of Galen.

  15. Reducing Unintended Pregnancies as a Strategy to Avert Zika-Related Microcephaly Births in the United States: A Simulation Study.

    PubMed

    Ahrens, Katherine A; Hutcheon, Jennifer A; Gavin, Loretta; Moskosky, Susan

    2017-05-01

    Introduction There is increasing evidence that infection with the Zika virus (ZIKV) during pregnancy can lead to severe brain abnormalities in infants exposed in utero. The objective of our analysis was to estimate the contribution of enhanced contraception access to averting ZIKV-related microcephaly births in the United States, alone and in combination with another possible strategy, anti-ZIKV vaccination. Methods We used Monte Carlo sampling techniques (n = 100,000 simulations) to estimate the number of microcephaly births expected under strategies of enhanced contraception only, vaccination only, both enhanced contraception and vaccination, and status quo (no intervention). Enhanced contraceptive access was assumed to reduce unintended pregnancy rates by 46% and anti-ZIKV vaccination was assumed to be 90% effective. Plausible values for effectiveness of enhanced contraceptive access, ZIKV cumulative incidence, ZIKV-related microcephaly risk, and anti-ZIKV vaccination parameters were derived from the literature or best available knowledge. Results Enhanced contraceptive access alone reduced the median number of ZIKV-related microcephaly births by 16% (95% simulation interval: 5, 23), while the anti-ZIKV vaccine alone reduced these births by 9% (95% SI: 0, 18), 45% (95% SI: 36, 54), and 81% (95% SI: 71, 91), under conservative (10% vaccine uptake), moderate (50% vaccine uptake), and optimistic (90% vaccine uptake) scenarios, respectively. The reduction in ZIKV-related microcephaly births was always greater if both interventions were employed. Discussion Enhanced contraceptive access alone has the ability to produce a meaningful reduction in microcephaly births, and could provide an important adjuvant prevention strategy even following the development of a highly-effective anti-ZIKV vaccine.

  16. Clinical-epidemiological description of live births with microcephaly in the state of Sergipe, Brazil, 2015.

    PubMed

    Cabral, Cibelle Mendes; Nóbrega, Martha Elizabeth Brasil da; Leite, Priscila Leal E; Souza, Mércia Simone Feitosa de; Teixeira, Daniela Cabral Pizzi; Cavalcante, Taíse Ferreira; Lima, Raulinna Gomes de Souza; Tavares, Lúcia Maria Sayde de Azevedo; Souza, Priscila Bochi de; Saad, Eduardo

    2017-01-01

    to describe the clinical and epidemiological characteristics of microcephaly cases in live births in Sergipe, Brazil, and to calculate the prevalence in its municipalities. this is a descriptive study on live births from September 1st to November 30th, 2015, with data from medical records and interviews with mothers. 83 cases of microcephaly were confirmed, with three deaths; prevalence in the 26 municipalities with confirmed cases ranged from 18 to 185/10,000 live births; the median of head circumference was 31 cm (range: 22.5-33.0); agenesis of corpus callosum (26/43), lissencephaly (12/43), absence of midline (10/43) and ventriculomegaly (8/43) were observed in the transfontanellar ultrasound; 40 mothers reported rash in pregnancy, 23 in the first trimester, with pruritus, arthralgia and headache; seven were positive for infections potentially causing malformations. there was a high occurrence of cases of microcephaly, and reports of signs and symptoms compatible with Zika virus infection during pregnancy.

  17. Microcephaly-capillary malformation syndrome: Brothers with a homozygous STAMBP mutation, uncovered by exome sequencing.

    PubMed

    Naseer, Muhammad Imran; Sogaty, Sameera; Rasool, Mahmood; Chaudhary, Adeel G; Abutalib, Yousif Ahmed; Walker, Susan; Marshall, Christian R; Merico, Daniele; Carter, Melissa T; Scherer, Stephen W; Al-Qahtani, Mohammad H; Zarrei, Mehdi

    2016-11-01

    We describe two brothers from a consanguineous family of Egyptian ancestry, presenting with microcephaly, apparent global developmental delay, seizures, spasticity, congenital blindness, and multiple cutaneous capillary malformations. Through exome sequencing, we uncovered a homozygous missense variant in STAMBP (p.K303R) in the two siblings, inherited from heterozygous carrier parents. Mutations in STAMBP are known to cause microcephaly-capillary malformation syndrome (MIC-CAP) and the phenotype in this family is consistent with this diagnosis. We compared the findings in the present brothers with those of earlier reported patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Sleep EEG of Microcephaly in Zika Outbreak.

    PubMed

    Kanda, Paulo Afonso Medeiros; Aguiar, Aline de Almeida Xavier; Miranda, Jose Lucivan; Falcao, Alexandre Loverde; Andrade, Claudia Suenia; Reis, Luigi Neves Dos Santos; Almeida, Ellen White R Bacelar; Bello, Yanes Brum; Monfredinho, Arthur; Kanda, Rafael Guimaraes

    2018-01-01

    Microcephaly (MC), previously considered rare, is now a health emergency of international concern because of the devastating Zika virus pandemic outbreak of 2015. The authors describe the electroencephalogram (EEG) findings in sleep EEG of epileptic children who were born with microcephaly in areas of Brazil with active Zika virus transmission between 2014 and 2017. The authors reviewed EEGs from 23 children. Nine were females (39.2%), and the age distribution varied from 4 to 48 months. MC was associated with mother positive serology to toxoplasmosis (toxo), rubella (rub), herpes, and dengue (1 case); toxo (1 case); chikungunya virus (CHIKV) (1 case); syphilis (1 case); and Zika virus (ZIKV) (10 cases). In addition, 1 case was associated with perinatal hypoxia and causes of 9 cases remain unknown. The main background EEG abnormality was diffuse slowing (10 cases), followed by classic (3 cases) and modified (5 cases) hypsarrhythmia. A distinct EEG pattern was seen in ZIKV (5 cases), toxo (2 cases), and undetermined cause (1 case). It was characterized by runs of frontocentrotemporal 4.5-13 Hz activity (7 cases) or diffuse and bilateral runs of 18-24 Hz (1 case). In ZIKV, this rhythmic activity was associated with hypsarrhythmia or slow background. Further studies are necessary to determine if this association is suggestive of ZIKV infection. The authors believe that EEG should be included in the investigation of all newly diagnosed congenital MC, especially those occurring in areas of autochthonous transmission of ZIKV.

  19. Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study

    PubMed Central

    Dolk, Helen; Lopez-Camelo, Jorge S; Mattos, Daniel; Poletta, Fernando A; Dutra, Maria G; Carvalho, Flavia M; Castilla, Eduardo E

    2017-01-01

    Objective To describe the prevalence and clinical spectrum of microcephaly in South America for the period 2005-14, before the start of the Zika epidemic in 2015, as a baseline for future surveillance as the Zika epidemic spreads and as other infectious causes may emerge in future. Design Prevalence and case-control study. Data sources ECLAMC (Latin American Collaborative Study of Congenital Malformations) database derived from 107 hospitals in 10 South American countries, 2005 to 2014. Data on microcephaly cases, four non-malformed controls per case, and all hospital births (all births for hospital based prevalence, resident within municipality for population based prevalence). For 2010-14, head circumference data were available and compared with Intergrowth charts. Results 552 microcephaly cases were registered, giving a hospital based prevalence of 4.4 (95% confidence interval 4.1 to 4.9) per 10 000 births and a population based prevalence of 3.0 (2.7 to 3.4) per 10 000. Prevalence varied significantly between countries and between regions and hospitals within countries. Thirty two per cent (n=175) of cases were prenatally diagnosed; 29% (n=159) were perinatal deaths. Twenty three per cent (n=128) were associated with a diagnosed genetic syndrome, 34% (n=189) polymalformed without a syndrome diagnosis, 12% (n=65) with associated neural malformations, and 26% (n=145) microcephaly only. In addition, 3.8% (n=21) had a STORCH (syphilis, toxoplasmosis, other including HIV, rubella, cytomegalovirus, and herpes simplex) infection diagnosis and 2.0% (n=11) had consanguineous parents. Head circumference measurements available for 184/235 cases in 2010-14 showed 45% (n=82) more than 3 SD below the mean, 24% (n=44) between 3 SD and 2 SD below the mean, and 32% (n=58) larger than −2 SD. Conclusion Extrapolated to the nearly 7 million annual births in South America, an estimated 2000-2500 microcephaly cases were diagnosed among births each year before the Zika

  20. Loss of the arginine methyltranserase PRMT7 causes syndromic intellectual disability with microcephaly and brachydactyly.

    PubMed

    Kernohan, K D; McBride, A; Xi, Y; Martin, N; Schwartzentruber, J; Dyment, D A; Majewski, J; Blaser, S; Boycott, K M; Chitayat, D

    2017-05-01

    Post-translational protein modifications exponentially expand the functional complement of proteins encoded by the human genome. One such modification is the covalent addition of a methyl group to arginine or lysine residues, which is used to regulate a substantial proportion of the proteome. Arginine and lysine methylation are catalyzed by protein arginine methyltransferase (PRMTs) and protein lysine methyltransferase proteins (PKMTs), respectively; each methyltransferase has a specific set of target substrates. Here, we report a male with severe intellectual disability, facial dysmorphism, microcephaly, short stature, brachydactyly, cryptorchidism and seizures who was found to have a homozygous 15,309 bp deletion encompassing the transcription start site of PRMT7, which we confirmed is functionally a null allele. We show that the patient's cells have decreased levels of protein arginine methylation, and that affected proteins include the essential histones, H2B and H4. Finally, we demonstrate that patient cells have altered Wnt signaling, which may have contributed to the skeletal abnormalities. Our findings confirm the recent disease association of PRMT7, expand the phenotypic manifestations of this disorder and provide insight into the molecular pathogenesis of this new condition. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Blastopathies and microcephaly in a Chornobyl impacted region of Ukraine

    PubMed Central

    Wertelecki, Wladimir; Yevtushok, Lyubov; Zymak-Zakutnia, Natalia; Wang, Bin; Sosyniuk, Zoriana; Lapchenko, Serhiy; Hobart, Holly H

    2014-01-01

    This population-based descriptive epidemiology study demonstrates that rates of conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia in the Rivne province of Ukraine are among the highest in Europe. The province is 200 km distant from the Chornobyl site and its northern half, a region known as Polissia, is significantly polluted by ionizing radiation. The rates of neural tube defects, microcephaly and microphthalmia in Polissia are statistically significantly higher than in the rest of the province. A survey of at-birth head size showed that values were statistically smaller in males and females born in one Polissia county than among neonates born in the capital city. These observations provide clues for confirmatory and cause-effect prospective investigations. The strength of this study stems from a reliance on international standards prevalent in Europe and a decade-long population-based surveillance of congenital malformations in two distinct large populations. The limitations of this study, as those of other descriptive epidemiology investigations, is that identified cause-effect associations require further assessment by specific prospective investigations designed to address specific teratogenic factors. PMID:24666273

  2. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

    PubMed

    Braun, Daniela A; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A; Schanze, Denny; Ashraf, Shazia; Ullmann, Jeremy F P; Hoogstraten, Charlotte A; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I Chiara; Sanchez-Ferras, Oraly; Hu, Jennifer F; Boschat, Anne-Claire; Sanquer, Sylvia; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E; Pabst, Werner L; Warejko, Jillian K; Daga, Ankana; Basta, Tamara; Matejas, Verena; Scharmann, Karin; Kienast, Sandra D; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T; Gaffney, Patrick M; Gipson, Patrick E; Hsu, Chyong-Hsin; Kari, Jameela A; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-Ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okashah; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Ozaltin, Fatih; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth R; Rump, Patrick; Schnur, Rhonda E; Shiihara, Takashi; Sinha, Manish D; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A; Tsai, Wen-Hui; Tsai, Jeng-Daw; Topaloglu, Rezan; Vester, Udo; Viskochil, David H; Vatanavicharn, Nithiwat; Waxler, Jessica L; Wierenga, Klaas J; Wolf, Matthias T F; Wong, Sik-Nin; Leidel, Sebastian A; Truglio, Gessica; Dedon, Peter C; Poduri, Annapurna; Mane, Shrikant; Lifton, Richard P; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Callewaert, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

    2017-10-01

    Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.

  3. Newly recognized recessive syndrome characterized by dysmorphic features, hypogonadotropic hypogonadism, severe microcephaly, and sensorineural hearing loss maps to 3p21.3.

    PubMed

    Jenkinson, Emma M; Kingston, Helen; Urquhart, Jill; Khan, Naz; Melville, Athalie; Swinton, Martin; Crow, Yanick J; Davis, Julian R E; Trump, Dorothy; Newman, William G

    2011-12-01

    We present a newly recognized, likely autosomal recessive, pleiotropic disorder seen in four individuals (three siblings and their nephew) from a consanguineous family of Pakistani origin. The condition is characterized by hypogonadotropic hypogonadism, severe microcephaly, sensorineural deafness, moderate learning disability, and distinctive facial dysmorphic features. Autozygosity mapping using SNP array genotyping defined a single, large autozygous region of 13.1 Mb on chromosome 3p21 common to the affected individuals. The critical region contains 227 genes and initial sequence analysis of a functional candidate gene has not identified causative mutations. Copyright © 2011 Wiley Periodicals, Inc.

  4. Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study.

    PubMed

    Orioli, Iêda M; Dolk, Helen; Lopez-Camelo, Jorge S; Mattos, Daniel; Poletta, Fernando A; Dutra, Maria G; Carvalho, Flavia M; Castilla, Eduardo E

    2017-11-21

    Objective  To describe the prevalence and clinical spectrum of microcephaly in South America for the period 2005-14, before the start of the Zika epidemic in 2015, as a baseline for future surveillance as the Zika epidemic spreads and as other infectious causes may emerge in future. Design  Prevalence and case-control study. Data sources  ECLAMC (Latin American Collaborative Study of Congenital Malformations) database derived from 107 hospitals in 10 South American countries, 2005 to 2014. Data on microcephaly cases, four non-malformed controls per case, and all hospital births (all births for hospital based prevalence, resident within municipality for population based prevalence). For 2010-14, head circumference data were available and compared with Intergrowth charts. Results  552 microcephaly cases were registered, giving a hospital based prevalence of 4.4 (95% confidence interval 4.1 to 4.9) per 10 000 births and a population based prevalence of 3.0 (2.7 to 3.4) per 10 000. Prevalence varied significantly between countries and between regions and hospitals within countries. Thirty two per cent (n=175) of cases were prenatally diagnosed; 29% (n=159) were perinatal deaths. Twenty three per cent (n=128) were associated with a diagnosed genetic syndrome, 34% (n=189) polymalformed without a syndrome diagnosis, 12% (n=65) with associated neural malformations, and 26% (n=145) microcephaly only. In addition, 3.8% (n=21) had a STORCH (syphilis, toxoplasmosis, other including HIV, rubella, cytomegalovirus, and herpes simplex) infection diagnosis and 2.0% (n=11) had consanguineous parents. Head circumference measurements available for 184/235 cases in 2010-14 showed 45% (n=82) more than 3 SD below the mean, 24% (n=44) between 3 SD and 2 SD below the mean, and 32% (n=58) larger than -2 SD. Conclusion  Extrapolated to the nearly 7 million annual births in South America, an estimated 2000-2500 microcephaly cases were diagnosed among births each year before the Zika

  5. Zika Virus IgG in Infants with Microcephaly, Guinea-Bissau, 2016.

    PubMed

    Rosenstierne, Maiken Worsøe; Schaltz-Buchholzer, Frederik; Bruzadelli, Fernanda; Có, Asson; Cardoso, Placido; Jørgensen, Charlotte Sværke; Michiels, Johan; Heyndrickx, Leo; Ariën, Kevin K; Fischer, Thea Kølsen; Fomsgaard, Anders

    2018-05-01

    We analyzed blood samples from infants born with microcephaly and their mothers in Guinea-Bissau in 2016 for pathogens associated with birth defects. No Zika virus RNA was detected, but Zika virus IgG was highly prevalent. We recommend implementing pathogen screening of infants with congenital defects in Guinea-Bissau.

  6. Time Lags between Exanthematous Illness Attributed to Zika Virus, Guillain-Barré Syndrome, and Microcephaly, Salvador, Brazil

    PubMed Central

    Paploski, Igor A.D.; Prates, Ana Paula P.B.; Cardoso, Cristiane W.; Kikuti, Mariana; Silva, Monaise M. O.; Waller, Lance A.; Reis, Mitermayer G.; Kitron, Uriel

    2016-01-01

    Zika virus infection emerged as a public health emergency after increasing evidence for its association with neurologic disorders and congenital malformations. In Salvador, Brazil, outbreaks of acute exanthematous illness (AEI) attributed to Zika virus, Guillain-Barré syndrome (GBS), and microcephaly occurred in 2015. We investigated temporal correlations and time lags between these outbreaks to identify a common link between them by using epidemic curves and time series cross-correlations. Number of GBS cases peaked after a lag of 5–9 weeks from the AEI peak. Number of suspected cases of microcephaly peaked after a lag of 30–33 weeks from the AEI peak, which corresponded to time of potential infections of pregnant mothers during the first trimester. These findings support the association of GBS and microcephaly with Zika virus infection and provide evidence for a temporal relationship between timing of arboviral infection of pregnant women during the first trimester and birth outcome. PMID:27144515

  7. Somatically Acquired Isodicentric Y and Mosaic Loss of Chromosome Y in a Boy with Hypospadias.

    PubMed

    Miyado, Mami; Muroya, Koji; Katsumi, Momori; Saito, Kazuki; Kon, Masafumi; Fukami, Maki

    2018-04-07

    Isodicentric Y chromosome [idic(Y)] represents a relatively common subtype of Y chromosomal rearrangements in the germline; however, limited evidence supports the postzygotic occurrence of idic(Y). Here, we report a boy with hypospadias and somatically acquired idic(Y). The 3.5-year-old boy has been identified in our previous study for patients with hypospadias. In the present study, cytogenetic analysis including FISH revealed a 45,X[5]/46,X,idic(Y)[7]/46,XY[8] karyotype. MLPA showed a mosaic deletion involving PPP1R12BP1 and RBMY2DP. The idic(Y) was likely to have been formed through aberrant recombination between P1 palindromes and subsequently underwent mosaic loss. The patient's phenotype was attributable to deletion of some Y chromosomal genes and/or mosaic loss of chromosome Y (mLOY). The results suggest that idic(Y) can originate in postzygotic cells via palindrome-mediated crossovers. Moreover, our data indicate that somatically acquired idic(Y) can trigger mLOY, which usually appears as an aging-related phenomenon in elderly men. © 2018 S. Karger AG, Basel.

  8. Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly

    PubMed Central

    Cottee, Matthew A; Muschalik, Nadine; Wong, Yao Liang; Johnson, Christopher M; Johnson, Steven; Andreeva, Antonina; Oegema, Karen; Lea, Susan M; Raff, Jordan W; van Breugel, Mark

    2013-01-01

    Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel proline recognition domain that forms a 1:1 complex with a short, highly conserved target motif in STIL. Crystal structures of this complex reveal an unusual, all-β structure adopted by the TCP domain and explain how a microcephaly mutation in CPAP compromises complex formation. Through point mutations, we demonstrate that complex formation is essential for centriole duplication in vivo. Our studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAP–STIL interaction constitutes a conserved key step in centriole biogenesis. DOI: http://dx.doi.org/10.7554/eLife.01071.001 PMID:24052813

  9. Description of 13 Infants Born During October 2015-January 2016 With Congenital Zika Virus Infection Without Microcephaly at Birth - Brazil.

    PubMed

    van der Linden, Vanessa; Pessoa, André; Dobyns, William; Barkovich, A James; Júnior, Hélio van der Linden; Filho, Epitacio Leite Rolim; Ribeiro, Erlane Marques; Leal, Mariana de Carvalho; Coimbra, Pablo Picasso de Araújo; Aragão, Maria de Fátima Viana Vasco; Verçosa, Islane; Ventura, Camila; Ramos, Regina Coeli; Cruz, Danielle Di Cavalcanti Sousa; Cordeiro, Marli Tenório; Mota, Vivian Maria Ribeiro; Dott, Mary; Hillard, Christina; Moore, Cynthia A

    2016-12-02

    Congenital Zika virus infection can cause microcephaly and severe brain abnormalities (1). Congenital Zika syndrome comprises a spectrum of clinical features (2); however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly (3). To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceará with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference (4).

  10. Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection using human induced neural stem cells

    PubMed Central

    Boorgu, Devi Sai Sri Kavya; Levin, Michael; Kaplan, David L.

    2018-01-01

    ABSTRACT Zika virus (ZIKV) is a mosquito-transmitted flavivirus with a causative link to microcephaly, a condition resulting in reduced cranial size and brain abnormalities. Despite recent progress, there is a current lack of in vivo models that permit the study of systemic virus on human neurons in a developing organism that replicates the pathophysiology of human disease. Furthermore, no treatment to date has been reported to reduce ZIKV-induced microcephaly. We tested the effects of ZIKV on human induced neural stem cells (hiNSCs) in vitro and found that infected hiNSCs secrete inflammatory cytokines, display altered differentiation, and become apoptotic. We also utilized this in vitro system to assess the therapeutic effects of niclosamide, an FDA-approved anthelminthic, and found that it decreases ZIKV production, partially restores differentiation, and prevents apoptosis in hiNSCs. We intracranially injected hiNSCs into developing chicks, subjected them to systemic ZIKV infection via the chorioallantoic membrane (CAM), a tissue similar in structure and function to the mammalian placenta, and found that humanized ZIKV-infected embryos developed severe microcephaly including smaller crania, decreased forebrain volume and enlarged ventricles. Lastly, we utilized this humanized model to show that CAM-delivery of niclosamide can partially rescue ZIKV-induced microcephaly and attenuate infection of hiNSCs in vivo. This article has an associated First Person interview with the first author of the paper. PMID:29378701

  11. In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

    PubMed

    Azevedo, Raimunda S S; de Sousa, Jorge R; Araujo, Marialva T F; Martins Filho, Arnaldo J; de Alcantara, Bianca N; Araujo, Fernanda M C; Queiroz, Maria G L; Cruz, Ana C R; Vasconcelos, Beatriz H Baldez; Chiang, Jannifer O; Martins, Lívia C; Casseb, Livia M N; da Silva, Eliana V; Carvalho, Valéria L; Vasconcelos, Barbara C Baldez; Rodrigues, Sueli G; Oliveira, Consuelo S; Quaresma, Juarez A S; Vasconcelos, Pedro F C

    2018-01-08

    Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

  12. Characteristics of Dysphagia in Infants with Microcephaly Caused by Congenital Zika Virus Infection, Brazil, 2015.

    PubMed

    Leal, Mariana C; van der Linden, Vanessa; Bezerra, Thiago P; de Valois, Luciana; Borges, Adriana C G; Antunes, Margarida M C; Brandt, Kátia G; Moura, Catharina X; Rodrigues, Laura C; Ximenes, Coeli R

    2017-08-01

    We summarize the characteristics of dysphagia in 9 infants in Brazil with microcephaly caused by congenital Zika virus infection. The Schedule for Oral Motor Assessment, fiberoptic endoscopic evaluation of swallowing, and the videofluoroscopic swallowing study were used as noninstrumental and instrumental assessments. All infants had a degree of neurologic damage and showed abnormalities in the oral phase. Of the 9 infants, 8 lacked oral and upper respiratory tract sensitivity, leading to delays in initiation of the pharyngeal phase of swallowing. Those delays, combined with marked oral dysfunction, increased the risk for aspiration of food, particularly liquid foods. Dysphagia resulting from congenital Zika virus syndrome microcephaly can develop in infants >3 months of age and is severe.

  13. Characteristics of Dysphagia in Infants with Microcephaly Caused by Congenital Zika Virus Infection, Brazil, 2015

    PubMed Central

    van der Linden, Vanessa; Bezerra, Thiago P.; de Valois, Luciana; Borges, Adriana C.G.; Antunes, Margarida M.C.; Brandt, Kátia G.; Moura, Catharina X.; Rodrigues, Laura C.; Ximenes, Coeli R.

    2017-01-01

    We summarize the characteristics of dysphagia in 9 infants in Brazil with microcephaly caused by congenital Zika virus infection. The Schedule for Oral Motor Assessment, fiberoptic endoscopic evaluation of swallowing, and the videofluoroscopic swallowing study were used as noninstrumental and instrumental assessments. All infants had a degree of neurologic damage and showed abnormalities in the oral phase. Of the 9 infants, 8 lacked oral and upper respiratory tract sensitivity, leading to delays in initiation of the pharyngeal phase of swallowing. Those delays, combined with marked oral dysfunction, increased the risk for aspiration of food, particularly liquid foods. Dysphagia resulting from congenital Zika virus syndrome microcephaly can develop in infants >3 months of age and is severe. PMID:28604336

  14. Functioning and Disability Profile of Children with Microcephaly Associated with Congenital Zika Virus Infection.

    PubMed

    Ferreira, Haryelle Náryma Confessor; Schiariti, Veronica; Regalado, Isabelly Cristina Rodrigues; Sousa, Klayton Galante; Pereira, Silvana Alves; Fechine, Carla Patrícia Novaes Dos Santos; Longo, Egmar

    2018-05-29

    The increase in the number of cases of microcephaly in Brazil and its association with the Zika virus (ZIKV) is a global public health problem. The International Classification of Functioning Disability and Health (ICF) model is a powerful tool and extremely relevant in managing disability. Describe the functioning profile of children with microcephaly associated with ZIKV in two states of northeastern Brazil. This is a descriptive cross-sectional study. The sociodemographic characteristics, head circumference, and other clinical data were collected from medical charts, physical examinations, measuring instruments, and interviews with the children and their parents. The Brazilian Portuguese version of the Brief Common ICF Core Set for cerebral palsy (CP) was used. Each ICF category was assigned a qualifier, which ranged from 0 to 4 (no problem, mild problem, moderate problem, severe problem, complete problem). For environmental factors, 0 represents no barrier and 4 represents complete barrier; +0, no facilitator and +4, complete facilitator. A total of 34 children with microcephaly caused by ZIKV were recruited (18 girls and 16 boys) at four rehabilitation facilities in Rio Grande do Norte and Paraíba states, Brazil. The average age of the participants was 21 months, monthly income was ≈USD 300.00, and head circumference z-scores ranged between 0.92 and -5.51. The functioning profile revealed complete disability in most of the body function categories (b). The activity and participation areas (d) were highly impacted, particularly in mobility-related categories. With respect to environmental factors (e), most of the sample reported a complete facilitator for the immediate family, friends, and health services, systems, and policies, as well as a complete barrier to societal attitudes. This is the first study that describes the functioning profile of children with microcephaly associated with ZIKV, using a tool based on the ICF in Brazil. Our findings reinforce

  15. Estimating the Number of Pregnant Women Infected With Zika Virus and Expected Infants With Microcephaly Following the Zika Virus Outbreak in Puerto Rico, 2016.

    PubMed

    Ellington, Sascha R; Devine, Owen; Bertolli, Jeanne; Martinez Quiñones, Alma; Shapiro-Mendoza, Carrie K; Perez-Padilla, Janice; Rivera-Garcia, Brenda; Simeone, Regina M; Jamieson, Denise J; Valencia-Prado, Miguel; Gilboa, Suzanne M; Honein, Margaret A; Johansson, Michael A

    2016-10-01

    Zika virus (ZIKV) infection during pregnancy is a cause of congenital microcephaly and severe fetal brain defects, and it has been associated with other adverse pregnancy and birth outcomes. To estimate the number of pregnant women infected with ZIKV in Puerto Rico and the number of associated congenital microcephaly cases. We conducted a modeling study from April to July 2016. Using parameters derived from published reports, outcomes were modeled probabilistically using Monte Carlo simulation. We used uncertainty distributions to reflect the limited information available for parameter values. Given the high level of uncertainty in model parameters, interquartile ranges (IQRs) are presented as primary results. Outcomes were modeled for pregnant women in Puerto Rico, which currently has more confirmed ZIKV cases than any other US location. Zika virus infection in pregnant women. Number of pregnant women infected with ZIKV and number of congenital microcephaly cases. We estimated an IQR of 5900 to 10 300 pregnant women (median, 7800) might be infected during the initial ZIKV outbreak in Puerto Rico. Of these, an IQR of 100 to 270 infants (median, 180) may be born with microcephaly due to congenital ZIKV infection from mid-2016 to mid-2017. In the absence of a ZIKV outbreak, an IQR of 9 to 16 cases (median, 12) of congenital microcephaly are expected in Puerto Rico per year. The estimate of 5900 to 10 300 pregnant women that might be infected with ZIKV provides an estimate for the number of infants that could potentially have ZIKV-associated adverse outcomes. Including baseline cases of microcephaly, we estimated that an IQR of 110 to 290 total cases of congenital microcephaly, mostly attributable to ZIKV infection, could occur from mid-2016 to mid-2017 in the absence of effective interventions. The primary limitation in this analysis is uncertainty in model parameters. Multivariate sensitivity analyses indicated that the cumulative incidence of ZIKV infection and

  16. False homozygous HLA genotyping results due to copy number neutral loss of heterozygosity in acquired aplastic anaemia.

    PubMed

    Heyrman, Bert; De Becker, Ann; Verheyden, Sonja; Demanet, Christian

    2017-03-02

    The aim of this case report is to draw attention on possible false human leucocyte antigen (HLA) genotyping in acquired aplastic anaemia prior to allogeneic haematopoietic stem cell transplantation. In acquired aplastic anaemia loss of heterozygosity (LOH) of chromosome 6p is known to occur in around 12%. We report false HLA genotyping results due to LOH and a coinciding steep rise in neutrophils following filgrastim stimulation in a patient with very severe aplastic anaemia. At diagnosis we obtained heterozygous results on peripheral blood. Failing to reach a partial response at 6 months with immune-suppressive therapy we repeated HLA genotyping, obtaining homozygous results. Repeated testing confirmed loss of HLA genotype heterozygosity. HLA genotyping on cells obtained by a buccal swab confirmed the previous HLA heterozygosity. A second course of filgrastim at the time of homozygous HLA genotyping resulted in a steep rise in neutrophils. Stopping filgrastim resulted in an equally steep drop. 2017 BMJ Publishing Group Ltd.

  17. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

    PubMed Central

    Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

    2016-01-01

    Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

  18. Surveillance of microcephaly and selected brain anomalies in Argentina: Relationship with Zika virus and other congenital infections.

    PubMed

    Tellechea, Ana Laura; Luppo, Victoria; Morales, María Alejandra; Groisman, Boris; Baricalla, Agustin; Fabbri, Cintia; Sinchi, Anabel; Alonso, Alicia; Gonzalez, Cecilia; Ledesma, Bibiana; Masi, Patricia; Silva, María; Israilev, Adriana; Rocha, Marcela; Quaglia, Marcela; Bidondo, María Paz; Liascovich, Rosa; Barbero, Pablo

    2018-06-19

    Zika virus (ZIKV) vertical transmission may lead to microcephaly and other congenital anomalies. In March and April 2016, the first outbreak of ZIKV occurred in Argentina. The objective was to describe the surveillance of newborns with microcephaly and other selected brain anomalies in Argentina, and evaluation different etiologies. Participants were enrolled between April 2016 and March 2017. newborns from the National Network of Congenital Abnormalities of Argentina (RENAC) with head circumference lower than the 3rd percentile according to gestational age and sex, or selected brain anomalies. Blood and urine samples from cases and their mothers were tested for ZIKV by real-time polymerase chain reaction (RT-PCR), antigen-specific Immunoglobulin M (MAC-ELISA) and plaque-reduction neutralization test (PRNT 90 ). Toxoplasmosis, rubella, herpes simplex, syphilis, and cytomegalovirus (CMV) infection were also tested. A total of 104 cases were reported, with a prevalence of 6.9 per 10,000 [95% confidence interval (CI): 5.7-8.4], a significant increase when compared with the data prior to 2016, Prevalence Rate Ratio 1.7 (95% CI 1.2-2.3). In five cases positive serology for ZIKV (IgM and IgG by PRNT) was detected. The five cases presented microcephaly with craniofacial disproportion. We detected four cases of CMV infection, three cases of congenital toxoplasmosis, two cases of herpes simplex infection, and one case of congenital syphilis. The prevalence of microcephaly was significantly higher when compared with the previous period. The system had the capacity to detect five cases with congenital ZIKV syndrome in a country with limited viral circulation. © 2018 Wiley Periodicals, Inc.

  19. Lack of Diaph3 relaxes the spindle checkpoint causing the loss of neural progenitors

    PubMed Central

    Damiani, Devid; Goffinet, André M.; Alberts, Arthur; Tissir, Fadel

    2016-01-01

    The diaphanous homologue Diaph3 (aka mDia2) is a major regulator of actin cytoskeleton. Loss of Diaph3 has been constantly associated with cytokinesis failure ascribed to impaired accumulation of actin in the cleavage furrow. Here we report that Diaph3 is required before cell fission, to ensure the accurate segregation of chromosomes. Inactivation of the Diaph3 gene causes a massive loss of cortical progenitor cells, with subsequent depletion of intermediate progenitors and neurons, and results in microcephaly. In embryonic brain extracts, Diaph3 co-immunoprecipitates with BubR1, a key regulator of the spindle assembly checkpoint (SAC). Diaph3-deficient cortical progenitors have decreased levels of BubR1 and fail to properly activate the SAC. Hence, they bypass mitotic arrest and embark on anaphase in spite of incorrect chromosome segregation, generating aneuploidy. Our data identify Diaph3 as a major guard of cortical progenitors, unravel novel functions of Diaphanous formins and add insights into the pathobiology of microcephaly. PMID:27848932

  20. Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

    PubMed Central

    Martin, Carol-Anne; Murray, Jennie E.; Carroll, Paula; Leitch, Andrea; Mackenzie, Karen J.; Halachev, Mihail; Fetit, Ahmed E.; Keith, Charlotte; Bicknell, Louise S.; Fluteau, Adeline; Gautier, Philippe; Hall, Emma A.; Joss, Shelagh; Soares, Gabriela; Silva, João; Bober, Michael B.; Duker, Angela; Wise, Carol A.; Quigley, Alan J.; Phadke, Shubha R.; Wood, Andrew J.; Vagnarelli, Paola; Jackson, Andrew P.

    2016-01-01

    Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size. PMID:27737959

  1. Elucidating an Adverse Outcome Pathway of Microcephaly for use in Computational Toxicology (SOT Annual Meeting)

    EPA Science Inventory

    While evidence now supports a causal link between maternal Zika viral infection and microcephaly, genetic errors and chemical stressors may also precipitate this malformation through disruption of neuroprogenitor cell (NPC) proliferation, migration and differentiation in the earl...

  2. A newly recognized syndrome of severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features.

    PubMed

    Vinkler, Chana; Leshinsky-Silver, Esther; Michelson, Marina; Haas, Dorothea; Lerman-Sagie, Tally; Lev, Dorit

    2014-01-01

    Genetic syndromes with proportionate severe short stature are rare. We describe two sisters born to nonconsanguineous parents with severe linear growth retardation, poor weight gain, microcephaly, characteristic facial features, cutaneous syndactyly of the toes, high myopia, and severe intellectual disability. During infancy and early childhood, the girls had transient hepatosplenomegaly and low blood cholesterol levels that normalized later. A thorough evaluation including metabolic studies, radiological, and genetic investigations were all normal. Cholesterol metabolism and transport were studied and no definitive abnormality was found. No clinical deterioration was observed and no metabolic crises were reported. After due consideration of other known hereditary causes of post-natal severe linear growth retardation, microcephaly, and intellectual disability, we propose that this condition represents a newly recognized autosomal recessive multiple congenital anomaly-intellectual disability syndrome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis.

    PubMed

    Martin, Carol-Anne; Murray, Jennie E; Carroll, Paula; Leitch, Andrea; Mackenzie, Karen J; Halachev, Mihail; Fetit, Ahmed E; Keith, Charlotte; Bicknell, Louise S; Fluteau, Adeline; Gautier, Philippe; Hall, Emma A; Joss, Shelagh; Soares, Gabriela; Silva, João; Bober, Michael B; Duker, Angela; Wise, Carol A; Quigley, Alan J; Phadke, Shubha R; Wood, Andrew J; Vagnarelli, Paola; Jackson, Andrew P

    2016-10-01

    Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size. © 2016 Martin et al.; Published by Cold Spring Harbor Laboratory Press.

  4. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans

    PubMed Central

    Shamseldin, Hanan; Alazami, Anas M.; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A. Micheil; Parboosingh, Jillian S.; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P.; Alkuraya, Fowzan S.

    2015-01-01

    Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963∗] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. PMID:26608784

  5. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study.

    PubMed

    Calvet, Guilherme; Aguiar, Renato S; Melo, Adriana S O; Sampaio, Simone A; de Filippis, Ivano; Fabri, Allison; Araujo, Eliane S M; de Sequeira, Patricia C; de Mendonça, Marcos C L; de Oliveira, Louisi; Tschoeke, Diogo A; Schrago, Carlos G; Thompson, Fabiano L; Brasil, Patricia; Dos Santos, Flavia B; Nogueira, Rita M R; Tanuri, Amilcar; de Filippis, Ana M B

    2016-06-01

    The incidence of microcephaly in Brazil in 2015 was 20 times higher than in previous years. Congenital microcephaly is associated with genetic factors and several causative agents. Epidemiological data suggest that microcephaly cases in Brazil might be associated with the introduction of Zika virus. We aimed to detect and sequence the Zika virus genome in amniotic fluid samples of two pregnant women in Brazil whose fetuses were diagnosed with microcephaly. In this case study, amniotic fluid samples from two pregnant women from the state of Paraíba in Brazil whose fetuses had been diagnosed with microcephaly were obtained, on the recommendation of the Brazilian health authorities, by ultrasound-guided transabdominal amniocentesis at 28 weeks' gestation. The women had presented at 18 weeks' and 10 weeks' gestation, respectively, with clinical manifestations that could have been symptoms of Zika virus infection, including fever, myalgia, and rash. After the amniotic fluid samples were centrifuged, DNA and RNA were extracted from the purified virus particles before the viral genome was identified by quantitative reverse transcription PCR and viral metagenomic next-generation sequencing. Phylogenetic reconstruction and investigation of recombination events were done by comparing the Brazilian Zika virus genome with sequences from other Zika strains and from flaviviruses that occur in similar regions in Brazil. We detected the Zika virus genome in the amniotic fluid of both pregnant women. The virus was not detected in their urine or serum. Tests for dengue virus, chikungunya virus, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, HIV, Treponema pallidum, and parvovirus B19 were all negative. After sequencing of the complete genome of the Brazilian Zika virus isolated from patient 1, phylogenetic analyses showed that the virus shares 97-100% of its genomic identity with lineages isolated during an outbreak in French Polynesia in 2013, and that in

  6. Application of a novel prenatal vertical cranial biometric measurement can improve accuracy of microcephaly diagnosis in utero.

    PubMed

    Leibovitz, Z; Shiran, C; Haratz, K; Tamarkin, M; Gindes, L; Schreiber, L; Malinger, G; Ben-Sira, L; Lev, D; Shapiro, I; Bakry, H; Weizman, B; Zreik, A; Kidron, D; Egenburg, S; Arad, A; Lerman-Sagie, T

    2016-05-01

    To construct a reference range for a new vertical measurement of the fetal head and to assess whether its combination with fetal head circumference (HC) can prevent the misdiagnosis of microcephaly in fetuses with an acrocephalic-like head deformation. A new vertical cranial biometric measurement was defined: the foramen magnum-to-cranium distance (FCD), measured between the foramen magnum and the upper inner cranial border along the posterior wall of the brainstem. The measurement was performed in a precise mid-sagittal plane using a three-dimensional multiplanar display of a sagittally acquired sonographic volume of the fetal head. The normal reference range was developed by measuring 396 healthy fetuses of low-risk singleton pregnancies between 15 and 40 gestational weeks. This reference was applied to 25 fetuses with microcephaly diagnosed prenatally (Fmic) based on HC ≥ 3 SD below the mean for gestational age. We determined an optimal FCD cut-off for combination with HC to detect all cases found with microcephaly at birth (micB), while excluding the fetuses with normal head circumference at birth (NHCB), who were described postnatally as having an acrocephalic-like cranial deformation. In the healthy singleton fetuses, FCD increased with gestational age, with a quadratic equation providing an optimal fit to the data (adjusted R(2) = 0.934). The measurement could be assessed in 95.2% of cases. Of the 25 cases diagnosed with Fmic prenatally, on the basis of HC alone, 14 were micB and 11 were NHCB. We observed FCD below the mean - 2SD for gestational age in all 14 micB cases, but in only four of the 11 NHCB cases (P < 0.003). An acrocephalic-like cranial deformation was described at birth in five of the seven NHCB cases with normal FCD. The mean ± SD FCD Z-score of the micB cases was significantly lower (P < 0.001) than that of the false-positive ones: -3.85 ± 0.96 SD and -1.59 ± 1.45 SD, respectively. Based on HC measurement alone, the positive predictive

  7. 5p14 deletion associated with microcephaly and seizures

    PubMed Central

    Johnson, E.; Marinescu, R; Punnett, H.; Tenenholz, B.; Overhauser, J.

    2000-01-01

    We report on a father and son who have an interstitial deletion of 5p14. The father is clinically and mentally normal while the son has significant clinical involvement including microcephaly, seizures, and global developmental delay. The extent of the 5p14 deletion was determined using fluorescence in situ hybridisation (FISH). The deletion in this present family is smaller than a deletion previously described in a multigenerational family that lacks any clinical phenotype. This report shows that a 5p14 deletion does not always lead to a normal phenotype.


Keywords: interstitial deletion; chromosome 5; fluorescence in situ hybridisation; cri du chat syndrome PMID:10662813

  8. Sex-dependent association of common variants of microcephaly genes with brain structure.

    PubMed

    Rimol, Lars M; Agartz, Ingrid; Djurovic, Srdjan; Brown, Andrew A; Roddey, J Cooper; Kähler, Anna K; Mattingsdal, Morten; Athanasiu, Lavinia; Joyner, Alexander H; Schork, Nicholas J; Halgren, Eric; Sundet, Kjetil; Melle, Ingrid; Dale, Anders M; Andreassen, Ole A

    2010-01-05

    Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717-728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637-644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2, MCPH1, and ASPM, with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample (n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample (n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.

  9. Acro-spondylo-pubic dysostosis associated with cataracts, microcephaly, and normal intelligence.

    PubMed

    Chacon-Camacho, Oscar F; Villegas-Ruiz, Vanessa; Buentello-Volante, Beatriz; Piña-Aguilar, Raul E; Peláez-González, Hugo; Ramírez, Magdalena; González-Rodríguez, Johanna; Zenteno, Juan Carlos

    2015-02-01

    We report on an adult male with normal intelligence who exhibited an unusual combination of microcephaly, dysostoses of limbs, vertebrae, patellae, and pubic bone, camptodactyly of all fingers, and syndactyly of toes, absent nails on thumbs and some fingers, bilateral cataract, cryptorchidism, polythelia, and nipple-like skin pigmentations of shoulders and upper back. We have been unable to find a description of a similar combination of manifestations in literature. The cause of the anomalies remains unknown. © 2014 Wiley Periodicals, Inc.

  10. [Concordance between a head circumference growth function and intellectual disability in relation with the cause of microcephaly].

    PubMed

    Coronado, R; Macaya Ruíz, A; Giraldo Arjonilla, J; Roig-Quilis, M

    2015-08-01

    Our aim was to investigate the correlations between patterns of head growth and intellectual disability among distinct aetiological presentations of microcephaly. 3,269 head circumference (HC) charts of patients from a tertiary neuropediatric unit were reviewed and 136 microcephalic participants selected. Using the Z-scores of registered HC measurements we defined the variables: HC Minimum, HC Drop and HC Catch-up. We classified patients according to the presence or absence of intellectual disability (IQ below 71) and according to the cause of microcephaly (idiopathic, familial, syndromic, symptomatic and mixed). Using Discriminant Analysis a C-function was defined as C=HC Minimum + HC Drop with a cut-off level of C=-4.32 Z-score. In our sample 95% of patients scoring below this level, severe microcephaly, were classified in the disabled group while the overall concordance was 66%. In the symptomatic-mixed group the concordance between HC function and outcome reached 82% in contrast to only 54% in the idiopathic-syndromic group (P-value=0.0002). We defined a HC growth function which discriminates intellectual disability of microcephalic patients better than isolated HC measurements, especially for those with secondary and mixed aetiologies. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  11. Scalp defects, polythelia, microcephaly, and developmental delay: a new syndrome with apparent autosomal dominant inheritance.

    PubMed

    Marble, Michael; Pridjian, Gabriella

    2002-04-01

    We report a family with apparent autosomal dominant inheritance of scalp defects, polythelia, microcephaly, and developmental delay. A review of the literature revealed no previous report of this combination of anomalies. We conclude that these patients have a new autosomal dominant syndrome. Copyright 2002 Wiley-Liss, Inc.

  12. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans.

    PubMed

    Shamseldin, Hanan; Alazami, Anas M; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A Micheil; Parboosingh, Jillian S; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P; Alkuraya, Fowzan S

    2015-12-03

    Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963(∗)] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  13. Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis?

    PubMed

    Leibovitz, Z; Daniel-Spiegel, E; Malinger, G; Haratz, K; Tamarkin, M; Gindes, L; Schreiber, L; Ben-Sira, L; Lev, D; Shapiro, I; Bakry, H; Weizman, B; Zreik, A; Egenburg, S; Arad, A; Tepper, R; Kidron, D; Lerman-Sagie, T

    2016-05-01

    To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction. Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history. Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references

  14. Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015-2017.

    PubMed

    Méndez, Nelson; Oviedo-Pastrana, Misael; Mattar, Salim; Caicedo-Castro, Isaac; Arrieta, German

    2017-01-01

    The Zika virus disease (ZVD) has had a huge impact on public health in Colombia for the numbers of people affected and the presentation of Guillain-Barre syndrome (GBS) and microcephaly cases associated to ZVD. A retrospective descriptive study was carried out, we analyze the epidemiological situation of ZVD and its association with microcephaly and GBS during a 21-month period, from October 2015 to June 2017. The variables studied were: (i) ZVD cases, (ii) ZVD cases in pregnant women, (iii) laboratory-confirmed ZVD in pregnant women, (iv) ZVD cases associated with microcephaly, (v) laboratory-confirmed ZVD associated with microcephaly, and (vi) ZVD associated to GBS cases. Average number of cases, attack rates (AR) and proportions were also calculated. The studied variables were plotted by epidemiological weeks and months. The distribution of ZVD cases in Colombia was mapped across the time using Kernel density estimator and QGIS software; we adopted Kernel Ridge Regression (KRR) and the Gaussian Kernel to estimate the number of Guillain Barre cases given the number of ZVD cases. One hundred eight thousand eighty-seven ZVD cases had been reported in Colombia, including 19,963 (18.5%) in pregnant women, 710 (0.66%) associated with microcephaly (AR, 4.87 cases per 10,000 live births) and 453 (0.42%) ZVD associated to GBS cases (AR, 41.9 GBS cases per 10,000 ZVD cases). It appears the cases of GBS increased in parallel with the cases of ZVD, cases of microcephaly appeared 5 months after recognition of the outbreak. The kernel density map shows that throughout the study period, the states most affected by the Zika outbreak in Colombia were mainly San Andrés and Providencia islands, Casanare, Norte de Santander, Arauca and Huila. The KRR shows that there is no proportional relationship between the number of GBS and ZVD cases. During the cross validation, the RMSE achieved for the second order polynomial kernel, the linear kernel, the sigmoid kernel, and the Gaussian

  15. Dosage changes of a segment at 17p13.1 lead to intellectual disability and microcephaly as a result of complex genetic interaction of multiple genes.

    PubMed

    Carvalho, Claudia M B; Vasanth, Shivakumar; Shinawi, Marwan; Russell, Chad; Ramocki, Melissa B; Brown, Chester W; Graakjaer, Jesper; Skytte, Anne-Bine; Vianna-Morgante, Angela M; Krepischi, Ana C V; Patel, Gayle S; Immken, LaDonna; Aleck, Kyrieckos; Lim, Cynthia; Cheung, Sau Wai; Rosenberg, Carla; Katsanis, Nicholas; Lupski, James R

    2014-11-06

    The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Adjustment to acquired vision loss in adults presenting for visual disability certification.

    PubMed

    Nakade, Aditya; Rohatgi, Jolly; Bhatia, Manjeet S; Dhaliwal, Upreet

    2017-03-01

    Rehabilitation of the visually disabled depends on how they adjust to loss; understanding contributing factors may help in effective rehabilitation. The aim of this study is to assess adjustment to acquired vision loss in adults. This observational study, conducted in the Department of Ophthalmology at a tertiary-level teaching hospital, included thirty persons (25-65 years) with <6/60 in the better eye, and vision loss since ≥6-months. Age, gender, rural/urban residence, education, current occupation, binocular distance vision, adjustment (Acceptance and Self-Worth Adjustment Scale), depression (Center for Epidemiologic Studies-Depression Scale), social support (Duke Social Support and Stress Scale), and personality (10-item Personality Inventory scale) was recorded. To determine their effect on adjustment, Student's t-test was used for categorical variables, Pearson's correlation for age, and Spearman's correlation for depression, personality trait and social support and stress. Of 30 persons recruited, 24 were men (80%); 24 lived in urban areas (80%); 9 were employed (30%); and 14 (46.6%) had studied < Class 3. Adjustment was low (range: 33%-60%; mean: 43.6 ± 5.73). Reported support was low (median: 27.2; interquartile range [IQR]: 18.1-36.3); reported stress was low (median: 0.09; IQR: 0-18.1). Predominant personality traits (max score 14) were "Agreeableness" (average 12.0 ± 1.68) and "Conscientiousness" (average 11.3 ± 2.12). Emotional stability (average 9.2 ± 2.53) was less prominent. Depression score ranged from 17 to 50 (average 31.6 ± 6.01). The factors studied did not influence adjustment. Although adjustment did not vary with factors studied, all patients were depressed. Since perceived support and emotional stability was low, attention could be directed to support networks. Training patients in handling emotions, and training family members to respond to emotional needs of persons with visual disability, might contribute to reducing stress and

  17. Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication

    PubMed Central

    Kodani, Andrew; Yu, Timothy W; Johnson, Jeffrey R; Jayaraman, Divya; Johnson, Tasha L; Al-Gazali, Lihadh; Sztriha, Lāszló; Partlow, Jennifer N; Kim, Hanjun; Krup, Alexis L; Dammermann, Alexander; Krogan, Nevan J; Walsh, Christopher A; Reiter, Jeremy F

    2015-01-01

    Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication. DOI: http://dx.doi.org/10.7554/eLife.07519.001 PMID:26297806

  18. Microcephaly Case Fatality Rate Associated with Zika Virus Infection in Brazil: Current Estimates.

    PubMed

    Cunha, Antonio José Ledo Alves da; de Magalhães-Barbosa, Maria Clara; Lima-Setta, Fernanda; Medronho, Roberto de Andrade; Prata-Barbosa, Arnaldo

    2017-05-01

    Considering the currently confirmed cases of microcephaly and related deaths associated with Zika virus in Brazil, the estimated case fatality rate is 8.3% (95% confidence interval: 7.2-9.6). However, a third of the reported cases remain under investigation. If the confirmation rates of cases and deaths are the same in the future, the estimated case fatality rate will be as high as 10.5% (95% confidence interval: 9.5-11.7).

  19. Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know.

    PubMed

    Alvarado, Maria Gabriela; Schwartz, David A

    2017-01-01

    -The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants. -To review the causal association between ZIKV infection during pregnancy and intrauterine fetal infection, microcephaly, brain damage, congenital malformation syndrome, and experimental laboratory models of fetal infection. Many questions remain regarding the risk factors, pathophysiology, epidemiology, and timing of maternal-fetal transmission and disease. These include mechanisms of fetal brain damage and microcephaly; the role of covariables, such as viral burden, duration of viremia, and host genetics, on vertical transmission; and the clinical and pathologic spectrum of congenital Zika syndrome. Additional questions include defining the potential long-term physical and neurobehavioral outcomes for infected infants, whether maternal or fetal host genetics influence the clinical outcome, and whether ZIKV infection can cause maternal morbidity. Finally, are experimental laboratory and animal models of ZIKV infection helpful in addressing maternal-fetal viral transmission and the development of congenital microcephaly? This communication provides current information and attempts to address some of these important questions. -Comprehensive review of published scientific literature. -Recent advances in epidemiology, clinical medicine, pathology, and experimental studies have provided a great amount of new information regarding vertical ZIKV transmission and the mechanisms of congenital microcephaly, brain damage, and congenital Zika syndrome in a relatively short time. However, much work still needs to be performed to more completely understand the maternal and fetal aspects of this new and emerging viral disease.

  20. An update on acquired nystagmus.

    PubMed

    Rucker, Janet C

    2008-01-01

    Proper evaluation and treatment of acquired nystagmus requires accurate characterization of nystagmus type and visual effects. This review addresses important historical and examination features of nystagmus and current concepts of pathogenesis and treatment of gaze-evoked nystagmus, nystagmus due to vision loss, acquired pendular nystagmus, peripheral and central vestibular nystagmus, and periodic alternating nystagmus.

  1. Health and Development at Age 19-24 Months of 19 Children Who Were Born with Microcephaly and Laboratory Evidence of Congenital Zika Virus Infection During the 2015 Zika Virus Outbreak - Brazil, 2017.

    PubMed

    Satterfield-Nash, Ashley; Kotzky, Kim; Allen, Jacob; Bertolli, Jeanne; Moore, Cynthia A; Pereira, Isabela Ornelas; Pessoa, André; Melo, Flavio; Santelli, Ana Carolina Faria E Silva; Boyle, Coleen A; Peacock, Georgina

    2017-12-15

    In November 2015, the Brazilian Ministry of Health (MOH) declared the Zika virus outbreak a public health emergency after an increase in microcephaly cases was reported in the northeast region of the country (1). During 2015-2016, 15 states in Brazil with laboratory-confirmed Zika virus transmission reported an increase in birth prevalence of microcephaly (2.8 cases per 10,000 live births), significantly exceeding prevalence in four states without confirmed transmission (0.6 per 10,000) (2). Although children with microcephaly and laboratory evidence of Zika virus infection have been described in early infancy (3), their subsequent health and development have not been well characterized, constraining planning for the care and support of these children and their families. The Brazilian MOH, the State Health Secretariat of Paraíba, and CDC collaborated on a follow-up investigation of the health and development of children in northeastern Brazil who were reported to national surveillance with microcephaly at birth. Nineteen children with microcephaly at birth and laboratory evidence of Zika virus infection were assessed through clinical evaluations, caregiver interviews, and review of medical records. At follow-up (ages 19-24 months), most of these children had severe motor impairment, seizure disorders, hearing and vision abnormalities, and sleep difficulties. Children with microcephaly and laboratory evidence of Zika virus infection have severe functional limitations and will require specialized care from clinicians and caregivers as they age.

  2. Persistence of weight loss and acquired behaviors 2 y after stopping a 2-y calorie restriction intervention.

    PubMed

    Marlatt, Kara L; Redman, Leanne M; Burton, Jeff H; Martin, Corby K; Ravussin, Eric

    2017-04-01

    Background: Calorie restriction (CR) influences aging processes and extends average and maximal life spans. The CALERIE 2 (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy Phase 2) study was the first randomized clinical trial to examine the metabolic and psychological effects of CR in nonobese humans. Objective: We conducted a 2-y follow-up study of adults who underwent 2 y of CR or ad libitum (control) consumption and determined whether weight loss and acquired behaviors persisted after the study ended when participants determined their own lifestyle behaviors. Design: In this prospective, longitudinal study, we assessed differences in weight, body composition, psychological function, and energy expenditure in 39 nonobese [body mass index (in kg/m 2 ): 22-28] men and women (25% CR: n = 24; control: n = 15) 12 and 24 mo after they completed the CALERIE 2 study at Pennington Biomedical. Results: Of 39 participants who were in the follow-up study, 29 subjects (CR: n = 18; control: n = 11) completed all visits at follow-up months 12 and 24. After the CR intervention, a mean ± SEM weight loss of 9.0 ± 0.6 kg was observed in the CR group, in which only 54% of the weight was regained 2 y later. Despite such a regain, weight, the percentage of body fat, and fat mass remained significantly reduced from baseline throughout follow-up and remained significantly less than in the control group ( P < 0.05). At follow-up, the CR group retained higher degrees of dietary restraint and avoidance of certain foods. Conclusion: After a 2-y intensive CR intervention, ∼50% of CR-induced weight loss was maintained 2 y later, which was probably the result of lasting effects on acquired behaviors and dietary restraint. This trial was registered at clinicaltrials.gov as NCT00943215. © 2017 American Society for Nutrition.

  3. Increased risk of depression in patients with acquired sensory hearing loss: A 12-year follow-up study.

    PubMed

    Hsu, Wei-Ting; Hsu, Chih-Chao; Wen, Ming-Hsun; Lin, Hong-Ching; Tsai, Hsun-Tien; Su, Peijen; Sun, Chi-Te; Lin, Cheng-Li; Hsu, Chung-Yi; Chang, Kuang-Hsi; Hsu, Yi-Chao

    2016-11-01

    Acquired sensory hearing loss (SHL) is suggested to be associated with depression. However, some studies have reported conflicting results. Our study investigated the relationship between the prevalence of SHL and the incidence of depression over 12 years of follow-up by using data from the Taiwan National Health Insurance Research Database (NHIRD). We sought to determine the association between SHL and subsequent development of depression and discuss the pathophysiological mechanism underlying the association.Patients with SHL were identified from the NHIRD (SHL cohort). A non-SHL cohort, comprising patients without SHL frequency-matched with the SHL patients according to age group, sex, and the year of diagnosis of SHL at the ratio of 1:4, was constructed, and the incidence of depression was evaluated in both cohorts. A multivariable model was adjusted for age, sex, and comorbidity.The SHL cohort and non-SHL cohort comprised 5043 patients with SHL and 20,172 patients without SHL, respectively. The incidences density rates were 9.50 and 4.78 per 1000 person-years in the SHL cohort and non-SHL cohort, respectively. After adjustment for age, sex, and comorbidities, the risk of depression was higher in the SHL cohort than in the non-SHL cohort (hazard ratio = 1.73, 95% confidence interval = 1.49-2.00).Acquired SHL may increase the risk of subsequent depression. The results demonstrated that SHL was an independent risk factor regardless of sex, age, and comorbidities. Moreover, a strong association between hearing loss and subsequent depression among Taiwanese adults of all ages, particularly those aged ≤49 and >65 years and without using steroids for the treatment of SHL was observed. Prospective clinical and biomedical studies on the relationship between hearing loss and depression are warranted for determining the etiopathology.

  4. Perinatal findings of Seckel syndrome: a case report of a fetus showing primordial dwarfism and severe microcephaly.

    PubMed

    Takikawa, Keiko Miyachi; Kikuchi, Akihiko; Yokoyama, Akiko; Ono, Kyoko; Iwasawa, Yuki; Sunagawa, Sorahiro; Takagi, Kimiyo; Kawame, Hiroshi; Nakamura, Tomohiko

    2008-01-01

    Seckel syndrome is a rare form of primordial dwarfism and most of the previous reports have been limited to postnatal findings. We report on a fetus showing severe microcephaly, intrauterine growth restriction and a few gyri with shallow sulci on the fetal brain suggesting cortical dysplasia, followed by ultrasound and magnetic resonance imaging in the prenatal period. Cardiotocograph revealed a reassuring fetal status throughout the whole pregnancy period. A male infant weighing 1,556 g was delivered at 39 weeks' gestation, and a diagnosis of Seckel syndrome was made based on postnatal typical findings. Although previous reports on prenatal findings of Seckel syndrome are quite limited, we think that our case presents typical features of a fetus affected by this syndrome. When prenatal ultrasound shows severe microcephaly and intrauterine growth restriction, this rare syndrome should be included in the differential diagnosis. Moreover, magnetic resonance imaging of the affected fetal brain provides further diagnostic clues. Copyright 2008 S. Karger AG, Basel.

  5. Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model

    PubMed Central

    Schneider, Ronen; Hoogstraten, Charlotte A.; Schapiro, David; Majmundar, Amar J.; Kolb, Amy; Eddy, Kaitlyn; Shril, Shirlee; Braun, Daniela A.; Poduri, Annapurna

    2018-01-01

    Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb) to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest. PMID:29346415

  6. Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model.

    PubMed

    Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Schneider, Ronen; Hoogstraten, Charlotte A; Ullmann, Jeremy F P; Schapiro, David; Majmundar, Amar J; Kolb, Amy; Eddy, Kaitlyn; Shril, Shirlee; Braun, Daniela A; Poduri, Annapurna; Hildebrandt, Friedhelm

    2018-01-01

    Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb) to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest.

  7. Homozygous loss of function BRCA1 variant causing a Fanconi-anemia-like phenotype, a clinical report and review of previous patients.

    PubMed

    Freire, Bruna L; Homma, Thais K; Funari, Mariana F A; Lerario, Antônio M; Leal, Aline M; Velloso, Elvira D R P; Malaquias, Alexsandra C; Jorge, Alexander A L

    2018-03-01

    Fanconi Anemia (FA) is a rare and heterogeneous genetic syndrome. It is associated with short stature, bone marrow failure, high predisposition to cancer, microcephaly and congenital malformation. Many genes have been associated with FA. Previously, two adult patients with biallelic pathogenic variant in Breast Cancer 1 gene (BRCA1) had been identified in Fanconi Anemia-like condition. The proband was a 2.5 year-old girl with severe short stature, microcephaly, neurodevelopmental delay, congenital heart disease and dysmorphic features. Her parents were third degree cousins. Routine screening tests for short stature was normal. We conducted whole exome sequencing (WES) of the proband and used an analysis pipeline to identify rare nonsynonymous genetic variants that cause short stature. We identified a homozygous loss-of-function BRCA1 mutation (c.2709T > A; p. Cys903*), which promotes the loss of critical domains of the protein. Cytogenetic study with DEB showed an increased chromosomal breakage. We screened heterozygous parents of the index case for cancer and we detected, in her mother, a metastatic adenocarcinoma in an axillar lymph node with probable primary site in the breast. It is possible to consolidate the FA-like phenotype associated with biallelic loss-of-function BRCA1, characterized by microcephaly, short stature, developmental delay, dysmorphic face features and cancer predisposition. In our case, the WES allowed to establish the genetic cause of short stature in the context of a chromosome instability syndrome. An identification of BRCA1 mutations in our patient allowed precise genetic counseling and also triggered cancer screening for the patient and her family members. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice.

    PubMed

    Li, Chunfeng; Zhu, Xingliang; Ji, Xue; Quanquin, Natalie; Deng, Yong-Qiang; Tian, Min; Aliyari, Roghiyh; Zuo, Xiangyang; Yuan, Ling; Afridi, Shabbir Khan; Li, Xiao-Feng; Jung, Jae U; Nielsen-Saines, Karin; Qin, Frank Xiao-Feng; Qin, Cheng-Feng; Xu, Zhiheng; Cheng, Genhong

    2017-10-01

    Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public. Copyright © 2017. Published by Elsevier B.V.

  9. Mutations in the evolutionarily highly conserved KEOPS complex genes cause nephrotic syndrome with microcephaly

    PubMed Central

    Braun, Daniela A.; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A.; Schanze, Denny; Ashraf, Shazia; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I. Chiara; Sanchez-Ferras, Oraly; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E.; Pabst, Werner L.; Warejko, Jillian; Daga, Ankana; LeBerre, Tamara Basta; Matejas, Verena; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T.; Gipson, Patrick E.; Hsu, Chyong-Hsin; Kari, Jameela A.; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okasha; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth; Rump, Patrick; Schnur, Rhonda E.; Shiihara, Takashi; Sinha, Manish; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A.; Tsai, Wen-Hui; Tsai, Jeng-Daw; Vester, Udo; Viskochil, David H.; Vatanavicharn, Nithiwat; Waxler, Jessica L.; Wolf, Matthias T.F.; Wong, Sik-Nin; Poduri, Annapurna; Truglio, Gessica; Mane, Shrikant; Lifton, Richard P.; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Calleweart, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

    2018-01-01

    Galloway-Mowat syndrome (GAMOS) is a severe autosomal-recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies. To date, mutations of WDR73 are the only known monogenic cause of GAMOS and in most affected individuals the molecular diagnosis remains elusive. We here identify recessive mutations of OSGEP, TP53RK, TPRKB, or LAGE3, encoding the 4 subunits of the KEOPS complex in 33 individuals of 30 families with GAMOS. CRISPR/Cas9 knockout in zebrafish and mice recapitulates the human phenotype of microcephaly and results in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibits cell proliferation, which human mutations fail to rescue, and knockdown of either gene activates DNA damage response signaling and induces apoptosis. OSGEP and TP53RK molecularly interact and co-localize with the actin-regulating ARP2/3 complex. Furthermore, knockdown of OSGEP and TP53RK induces defects of the actin cytoskeleton and reduces migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identify 4 novel monogenic causes of GAMOS, describe the first link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. PMID:28805828

  10. Loss of Activating EGFR Mutant Gene Contributes to Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer Cells

    PubMed Central

    Kubo, Takuya; Murakami, Yuichi; Kawahara, Akihiko; Azuma, Koichi; Abe, Hideyuki; Kage, Masayoshi; Yoshinaga, Aki; Tahira, Tomoko; Hayashi, Kenshi; Arao, Tokuzo; Nishio, Kazuto; Rosell, Rafael; Kuwano, Michihiko; Ono, Mayumi

    2012-01-01

    Non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations attains a meaningful response to EGFR-tyrosine kinase inhibitors (TKIs). However, acquired resistance to EGFR-TKIs could affect long-term outcome in almost all patients. To identify the potential mechanisms of resistance, we established cell lines resistant to EGFR-TKIs from the human lung cancer cell lines PC9 and11–18, which harbored activating EGFR mutations. One erlotinib-resistant cell line from PC9 and two erlotinib-resistant cell lines and two gefitinib-resistant cell lines from 11–18 were independently established. Almost complete loss of mutant delE746-A750 EGFR gene was observed in the erlotinib-resistant cells isolated from PC9, and partial loss of the mutant L858R EGFR gene copy was specifically observed in the erlotinib- and gefitinib-resistant cells from 11–18. However, constitutive activation of EGFR downstream signaling, PI3K/Akt, was observed even after loss of the mutated EGFR gene in all resistant cell lines even in the presence of the drug. In the erlotinib-resistant cells from PC9, constitutive PI3K/Akt activation was effectively inhibited by lapatinib (a dual TKI of EGFR and HER2) or BIBW2992 (pan-TKI of EGFR family proteins). Furthermore, erlotinib with either HER2 or HER3 knockdown by their cognate siRNAs also inhibited PI3K/Akt activation. Transfection of activating mutant EGFR complementary DNA restored drug sensitivity in the erlotinib-resistant cell line. Our study indicates that loss of addiction to mutant EGFR resulted in gain of addiction to both HER2/HER3 and PI3K/Akt signaling to acquire EGFR-TKI resistance. PMID:22815900

  11. Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study.

    PubMed

    de Araújo, Thalia Velho Barreto; Rodrigues, Laura Cunha; de Alencar Ximenes, Ricardo Arraes; de Barros Miranda-Filho, Demócrito; Montarroyos, Ulisses Ramos; de Melo, Ana Paula Lopes; Valongueiro, Sandra; de Albuquerque, Maria de Fátima Pessoa Militão; Souza, Wayner Vieira; Braga, Cynthia; Filho, Sinval Pinto Brandão; Cordeiro, Marli Tenório; Vazquez, Enrique; Di Cavalcanti Souza Cruz, Danielle; Henriques, Cláudio Maierovitch Pessanha; Bezerra, Luciana Caroline Albuquerque; da Silva Castanha, Priscila Mayrelle; Dhalia, Rafael; Marques-Júnior, Ernesto Torres Azevedo; Martelli, Celina Maria Turchi

    2016-12-01

    The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy. We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities. Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0·12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55·5 (95% CI 8·6-∞); OR 113·3 (95% CI 14·5-∞) for seven cases with brain abnormalities; and OR 24·7 (95% CI 2·9-∞) for four cases without brain abnormalities. Our data suggest that the microcephaly epidemic is a result of congenital Zika virus infection. We await further data from this ongoing study to assess other potential risk factors and to confirm the strength of association in a larger sample size. Brazilian Ministry of Health, Pan American Health Organization

  12. The evidence base for the application of contralateral bone anchored hearing aids in acquired unilateral sensorineural hearing loss in adults.

    PubMed

    Baguley, D M; Bird, J; Humphriss, R L; Prevost, A T

    2006-02-01

    . Acquired unilateral sensorineural hearing loss reduces the ability to localize sounds and to discriminate in background noise. . Four controlled trials attempt to determine the benefit of contralateral bone anchored hearing aids over contralateral routing of signal (CROS) hearing aids and over the unaided condition. All found no significant improvement in auditory localization with either aid. Speech discrimination in noise and subjective questionnaire measures of auditory abilities showed an advantage for bone anchored hearing aid (BAHA) > CROS > unaided conditions. . All four studies have material shortfalls: (i) the BAHA was always trialled after the CROS aid; (ii) CROS aids were only trialled for 4 weeks; (iii) none used any measure of hearing handicap when selecting subjects; (iv) two studies have a bias in terms of patient selection; (v) all studies were underpowered (vi) double reporting of patients occurred. . There is a paucity of evidence to support the efficacy of BAHA in the treatment of acquired unilateral sensorineural hearing loss. Clinicians should proceed with caution and perhaps await a larger randomized trial. . It is perhaps only appropriate to insert a BAHA peg at the time of vestibular schwanoma tumour excision in patients with good preoperative hearing, as their hearing handicap increases most.

  13. Bilateral neuroblastoma in situ associated with microcephaly.

    PubMed Central

    Park, W. S.; Chi, J. G.

    1993-01-01

    We present an autopsy case of a two-day-old female infant with a very unusual combination of neuroblastoma in situ in both adrenals and microcephaly. This baby was born to a 28-year-old mother after 38 weeks of gestation, and died of respiratory difficulty 2 days later. At autopsy, the baby weighted 1,840gm, and the brain was extraordinarily small with a weight of 125gm. The gyral pattern was simplified and irregular. Microscopically massive migration defects, pachygyria, micropolygyria, leptomeningeal glioneuronal islands, small corticospinal tract and heterotopic Purkinje cells in the cerebellum were found. In addition, there were medullary nodules in both adrenals. They measured 0.7 x 0.4cm and 0.7 x 0.3cm, respectively. These nodules showed the typical histological features of undifferentiated neuroblastoma. The tumor nodules were confined to the medullary portion and did not extend to the cortex or contiguous structures meeting the criteria of neuroblastoma in situ. Based on these unusual and seemingly unrelated sets of findings, it is suggested that the histogenesis of neuroblastoma in situ could be a part of the generalized dysontogenic process. PMID:8397936

  14. Identification of a novel homozygous TRAPPC9 gene mutation causing non-syndromic intellectual disability, speech disorder, and secondary microcephaly.

    PubMed

    Abbasi, Ansar A; Blaesius, Kathrin; Hu, Hao; Latif, Zahid; Picker-Minh, Sylvie; Khan, Muhammad N; Farooq, Sundas; Khan, Muzammil A; Kaindl, Angela M

    2017-12-01

    TRAPPC9 gene mutations have been linked recently to autosomal recessive mental retardation 13 (MRT13; MIM#613192) with only eight families reported world-wide. We assessed patients from two consanguineous pedigrees of Pakistani descent with non-syndromic intellectual disability and postnatal microcephaly through whole exome sequencing (WES) and cosegregation analysis. Here we report six further patients from two pedigrees with homozygous TRAPPC9 gene mutations, the novel nonsense mutation c.2065G>T (p.E689*) and the previously identified nonsense mutation c.1423C>T (p.R475*). We provide an overview of previously reported clinical features and highlight common symptoms and variability of MRT13. Common findings are intellectual disability and absent speech, and frequently microcephaly, motor delay and pathological findings on MRI including diminished cerebral white matter volume are present. Mutations in TRAPPC9 should be considered in non-syndromic autosomal recessive intellectual disability with severe speech disorder. © 2017 Wiley Periodicals, Inc.

  15. Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly.

    PubMed

    DiStasio, Andrew; Driver, Ashley; Sund, Kristen; Donlin, Milene; Muraleedharan, Ranjith M; Pooya, Shabnam; Kline-Fath, Beth; Kaufman, Kenneth M; Prows, Cynthia A; Schorry, Elizabeth; Dasgupta, Biplab; Stottmann, Rolf W

    2017-12-15

    Primary microcephaly is a congenital brain malformation characterized by a head circumference less than three standard deviations below the mean for age and sex and results in moderate to severe mental deficiencies and decreased lifespan. We recently studied two children with primary microcephaly in an otherwise unaffected family. Exome sequencing identified an autosomal recessive mutation leading to an amino acid substitution in a WD40 domain of the highly conserved Coatomer Protein Complex, Subunit Beta 2 (COPB2). To study the role of Copb2 in neural development, we utilized genome-editing technology to generate an allelic series in the mouse. Two independent null alleles revealed that Copb2 is essential for early stages of embryogenesis. Mice homozygous for the patient variant (Copb2R254C/R254C) appear to have a grossly normal phenotype, likely due to differences in corticogenesis between the two species. Strikingly, mice heterozygous for the patient mutation and a null allele (Copb2R254C/Zfn) show a severe perinatal phenotype including low neonatal weight, significantly increased apoptosis in the brain, and death within the first week of life. Immunostaining of the Copb2R254C/Zfnbrain revealed a reduction in layer V (CTIP2+) neurons, while the overall cell density of the cortex is unchanged. Moreover, neurospheres derived from animals with Copb2 variants grew less than control. These results identify a general requirement for COPB2 in embryogenesis and a specific role in corticogenesis. We further demonstrate the utility of CRISPR-Cas9 generated mouse models in the study of potential pathogenicity of variants of potential clinical interest. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Autopsy and Postmortem Studies Are Concordant: Pathology of Zika Virus Infection Is Neurotropic in Fetuses and Infants With Microcephaly Following Transplacental Transmission.

    PubMed

    Schwartz, David A

    2017-01-01

    -Pathology studies have been important in concluding that Zika virus infection occurring in pregnant women can result in vertical transmission of the agent from mother to fetus. Fetal and infant autopsies have provided crucial direct evidence that Zika virus can infect an unborn child, resulting in microcephaly, other malformations, and, in some cases, death. -To better understand the etiologic role and mechanism(s) of Zika virus in causing birth defects such as microcephaly, this communication analyzes the spectrum of clinical and autopsy studies reported from fetuses and infants who developed intrauterine Zika virus infection, and compares these findings with experimental data related to Zika virus infection. -Retrospective analysis of reported clinical, autopsy, pathology, and related postmortem studies from 9 fetuses and infants with intrauterine Zika virus infection and microcephaly. -All fetuses and infants examined demonstrated an overlapping spectrum of gross and microscopic neuropathologic abnormalities. Direct cytopathic effects of infection by the Zika virus were confined to the brain; in cases where other organs were evaluated, no direct viral effects were identified. -There is concordance of the spectrum of brain damage, reinforcing previous data indicating that the Zika virus has a strong predilection for cells of the fetal central nervous system following vertical transmission. The occurrence of additional congenital abnormalities suggests that intrauterine brain damage from Zika virus interferes with normal fetal development, resulting in fetal akinesia. Experimental in vitro and in vivo studies of Zika virus infection corroborate the human autopsy findings of neural specificity.

  17. Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.

    PubMed

    Guemez-Gamboa, Alicia; Nguyen, Long N; Yang, Hongbo; Zaki, Maha S; Kara, Majdi; Ben-Omran, Tawfeg; Akizu, Naiara; Rosti, Rasim Ozgur; Rosti, Basak; Scott, Eric; Schroth, Jana; Copeland, Brett; Vaux, Keith K; Cazenave-Gassiot, Amaury; Quek, Debra Q Y; Wong, Bernice H; Tan, Bryan C; Wenk, Markus R; Gunel, Murat; Gabriel, Stacey; Chi, Neil C; Silver, David L; Gleeson, Joseph G

    2015-07-01

    Docosahexanoic acid (DHA) is the most abundant omega-3 fatty acid in brain, and, although it is considered essential, deficiency has not been linked to disease. Despite the large mass of DHA in phospholipids, the brain does not synthesize it. DHA is imported across the blood-brain barrier (BBB) through the major facilitator superfamily domain-containing 2a (MFSD2A) protein. MFSD2A transports DHA as well as other fatty acids in the form of lysophosphatidylcholine (LPC). We identify two families displaying MFSD2A mutations in conserved residues. Affected individuals exhibited a lethal microcephaly syndrome linked to inadequate uptake of LPC lipids. The MFSD2A mutations impaired transport activity in a cell-based assay. Moreover, when expressed in mfsd2aa-morphant zebrafish, mutants failed to rescue microcephaly, BBB breakdown and lethality. Our results establish a link between transport of DHA and LPCs by MFSD2A and human brain growth and function, presenting the first evidence of monogenic disease related to transport of DHA in humans.

  18. Loss of EGFR confers acquired resistance to AZD9291 in an EGFR-mutant non-small cell lung cancer cell line with an epithelial-mesenchymal transition phenotype.

    PubMed

    Xu, Jing; Zhao, Xiaoting; He, Dengfeng; Wang, Jinghui; Li, Weiying; Liu, Yinghui; Ma, Li; Jiang, Mei; Teng, Yu; Wang, Ziyu; Gu, Meng; Wu, Jianbin; Wang, Yue; Yue, Wentao; Zhang, Shucai

    2018-05-24

    AZD9291 is an irreversible, small-molecule inhibitor which has potency against mutant EGFR- and T790M-resistant mutation. Despite the encouraging efficacy in clinical, the acquired resistance will finally occur. Further study will need to be done to identify the acquired resistance mechanisms and determine the next treatment. We established an AZD9291-resistant cell line (HCC827/AZDR) from parental HCC827 cell line through stepwise pulsed selection of AZD9291. The expression of EGFR and its downstream pathways were determined by western blot analysis or immunofluorescence assay. The sensitivity to indicated agents were evaluated by MTS. Compared with parental HCC827 cells, the HCC827/AZDR cells showed high resistance to AZD9291 and other EGFR-TKIs, and exhibited a mesenchymal-like phenotype. Almost complete loss of EGFR expression was observed in HCC827/AZDR cells. But the activation of downstream pathway, MAPK signaling, was found in HCC827/AZDR cells even in the presence of AZD9291. Inhibition of MAPK signaling had no effect on cell viability of HCC827/AZDR and could not reverse AZD9291 resistance because of the subsequent activation of AKT signaling. When treated with the combination of AKT and MAPK inhibitor, HCC827/AZDR showed remarkable growth inhibition. Loss of EGFR could be proposed as a potential acquired resistance mechanism of AZD9291 in EGFR-mutant NSCLC cells with an EMT phenotype. Despite the loss of EGFR, the activation of MAPK pathway which had crosstalk with AKT pathway could maintain the proliferation and survival of resistant cells. Blocking MAPK and AKT signaling may be a potential therapeutic strategy following AZD9291 resistance.

  19. Cochlear synaptopathy in acquired sensorineural hearing loss: Manifestations and mechanisms.

    PubMed

    Liberman, M Charles; Kujawa, Sharon G

    2017-06-01

    Common causes of hearing loss in humans - exposure to loud noise or ototoxic drugs and aging - often damage sensory hair cells, reflected as elevated thresholds on the clinical audiogram. Recent studies in animal models suggest, however, that well before this overt hearing loss can be seen, a more insidious, but likely more common, process is taking place that permanently interrupts synaptic communication between sensory inner hair cells and subsets of cochlear nerve fibers. The silencing of affected neurons alters auditory information processing, whether accompanied by threshold elevations or not, and is a likely contributor to a variety of perceptual abnormalities, including speech-in-noise difficulties, tinnitus and hyperacusis. Work described here will review structural and functional manifestations of this cochlear synaptopathy and will consider possible mechanisms underlying its appearance and progression in ears with and without traditional 'hearing loss' arising from several common causes in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Microcephaly caused by congenital Zika virus infection and viral detection in maternal urine during pregnancy.

    PubMed

    Regadas, Vanessa Couras; Silva, Márcio de Castro E; Abud, Lucas Giansante; Labadessa, Luiz Mario Pereira Lopes; Oliveira, Rafael Gouvêa Gomes de; Miyake, Cecília Hissae; Queiroz, Rodolfo Mendes

    2018-01-01

    Currently Latin America is undergoing a major epidemic of Zika virus, which is transmitted by Aedes mosquitoes. Concern for Zika virus infection has been increasing as it is suspected of causing brain defects in newborns such as microcephaly and, more recently, potential neurological and autoimmune complications including Guillian-Barré syndrome and acute disseminated encephalomyelitis. We describe a case of virus infection in a 25-year-old woman during the first trimester of her pregnancy, confirmed by laboratory tests only for the detection of viral particles in maternal urine, with imaging studies demonstrating the progression of cranial and encephalic changes in the fetus and later in the newborn, such as head circumference reduction, cerebral calcifications and ventriculomegaly.

  1. A primary microcephaly protein complex forms a ring around parental centrioles.

    PubMed

    Sir, Joo-Hee; Barr, Alexis R; Nicholas, Adeline K; Carvalho, Ofelia P; Khurshid, Maryam; Sossick, Alex; Reichelt, Stefanie; D'Santos, Clive; Woods, C Geoffrey; Gergely, Fanni

    2011-10-09

    Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in prenatal human brain growth without alteration of the cerebral architecture and is caused by biallelic mutations in genes coding for a subset of centrosomal proteins. Although at least three of these proteins have been implicated in centrosome duplication, the nature of the centrosome dysfunction that underlies the neurodevelopmental defect in MCPH is unclear. Here we report a homozygous MCPH-causing mutation in human CEP63. CEP63 forms a complex with another MCPH protein, CEP152, a conserved centrosome duplication factor. Together, these two proteins are essential for maintaining normal centrosome numbers in cells. Using super-resolution microscopy, we found that CEP63 and CEP152 co-localize in a discrete ring around the proximal end of the parental centriole, a pattern specifically disrupted in CEP63-deficient cells derived from patients with MCPH. This work suggests that the CEP152-CEP63 ring-like structure ensures normal neurodevelopment and that its impairment particularly affects human cerebral cortex growth.

  2. Hemorrhage and blood loss-induced anemia associated with an acquired coagulation factor VIII inhibitor in a Thoroughbred mare.

    PubMed

    Winfield, Laramie S; Brooks, Marjory B

    2014-03-15

    A 23-year-old Thoroughbred mare was evaluated because of a coagulopathy causing hemoperitoneum, hematomas, and signs of blood loss-induced anemia. The mare had tachycardia, pallor, hypoperfusion, and a large mass in the right flank. The mass was further characterized ultrasonographically as an extensive hematoma in the body wall with associated hemoabdomen. Coagulation testing revealed persistent, specific prolongation of the activated partial thromboplastin time (> 100 seconds; reference interval, 24 to 44 seconds) attributable to severe factor VIII deficiency (12%; reference interval, 50% to 200%). On the basis of the horse's age, lack of previous signs of a bleeding diathesis, and subsequent quantification of plasma factor VIII inhibitory activity (Bethesda assay titer, 2.7 Bethesda units/mL), acquired hemophilia A was diagnosed. The medical history did not reveal risk factors or underlying diseases; thus, the development of inhibitory antibodies against factor VIII was considered to be idiopathic. The mare was treated with 2 transfusions of fresh whole blood and fresh-frozen plasma. Immunosuppressive treatment consisting of dexamethasone and azathioprine was initiated. Factor VIII deficiency and signs of coagulopathy resolved, and the inhibitory antibody titer decreased. The mare remained healthy with no relapse for at least 1 year after treatment. Horses may develop inhibitory antibodies against factor VIII that cause acquired hemophilia A. A treatment strategy combining transfusions of whole blood and fresh-frozen plasma and administration of immunosuppressive agents was effective and induced sustained remission for at least 1 year in the mare described here.

  3. Acquired pit of the optic nerve: a risk factor for progression of glaucoma.

    PubMed

    Ugurlu, S; Weitzman, M; Nduaguba, C; Caprioli, J

    1998-04-01

    To examine acquired pit of the optic nerve as a risk factor for progression of glaucoma. In a retrospective longitudinal study, 25 open-angle glaucoma patients with acquired pit of the optic nerve were compared with a group of 24 open-angle glaucoma patients without acquired pit of the optic nerve. The patients were matched for age, mean intraocular pressure, baseline ratio of neuroretinal rim area to disk area, visual field damage, and duration of follow-up. Serial optic disk photographs and visual fields of both groups were evaluated by three independent observers for glaucomatous progression. Of 46 acquired pits of the optic nerve in 37 eyes of 25 patients, 36 pits were located inferiorly (76%) and 11 superiorly (24%; P < .001). Progression of optic disk damage occurred in 16 patients (64%) in the group with acquired pit and in three patients (12.5%) in the group without acquired pit (P < .001). Progression of visual field loss occurred in 14 patients (56%) in the group with acquired pit and in six (25%) in the group without pit (P=.04). Bilateral acquired pit of the optic nerve was present in 12 patients (48%). Disk hemorrhages were observed more frequently in the group with acquired pit (10 eyes, 40%) compared with the group without pit (two eyes, 8%; P=.02). Among patients with glaucoma, patients with acquired pit of the optic nerve represent a subgroup who are at increased risk for progressive optic disk damage and visual field loss.

  4. Microcephaly, microtia, preauricular tags, choanal atresia and developmental delay in three unrelated patients: a mandibulofacial dysostosis distinct from Treacher Collins syndrome.

    PubMed

    Wieczorek, Dagmar; Gener, Blanca; González, Ma Jesús Martínez; Seland, Saskia; Fischer, Sven; Hehr, Ute; Kuechler, Alma; Hoefsloot, Lies H; de Leeuw, Nicole; Gillessen-Kaesbach, Gabriele; Lohmann, Dietmar R

    2009-05-01

    Treacher Collins syndrome (TCS, OMIM 154500) is a well-defined mandibulofacial dysostosis characterized by symmetric facial anomalies consisting of malar hypoplasia, coloboma of the lower eyelid, dysplastic ears, micrognathia, cleft palate and deafness. Other mandibulofacial dysostoses (MDs) such as Toriello (OMIM 301950), Bauru (OMIM 604830), Hedera-Toriello-Petty (OMIM 608257), and Guion-Almeida (OMIM 610536) syndromes are less well characterized and much rarer. Here we describe three unrelated patients showing clinical features overlapping with TCS, but who in addition have developmental delay, microcephaly and a distinct facial gestalt. Because of the distinct ear anomalies and the hearing loss a HOXA2 mutation was taken into account. CHARGE syndrome was discussed because of ear anomalies, choanal atresia, and developmental delay in our patients. But mutational analyses including sequencing of the TCOF1, the HOXA2, and the CHD7 genes, deletion screening of the TCOF1 gene as well as genomewide array analyses revealed normal results. We suggest that these three patients have a new type of mandibulofacial dysostosis. As all three cases are sporadic and both sexes are affected the pattern of inheritance might be autosomal dominant or autosomal recessive. Identification of additional patients will allow to further delineate the phenotype, to assign the inheritance pattern and to identify the molecular basis.

  5. Age-related hearing impairment and the triad of acquired hearing loss

    PubMed Central

    Yang, Chao-Hui; Schrepfer, Thomas; Schacht, Jochen

    2015-01-01

    Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species (ROS) and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI) in human and animal models and address selected aspects of the commonality (or lack thereof) of cellular responses in ARHI to drugs and noise. PMID:26283913

  6. Homozygous STIL Mutation Causes Holoprosencephaly and Microcephaly in Two Siblings

    PubMed Central

    Mouden, Charlotte; de Tayrac, Marie; Dubourg, Christèle; Rose, Sophie; Carré, Wilfrid; Hamdi-Rozé, Houda; Babron, Marie-Claude; Akloul, Linda; Héron-Longe, Bénédicte; Odent, Sylvie; Dupé, Valérie; Giet, Régis; David, Véronique

    2015-01-01

    Holoprosencephaly (HPE) is a frequent congenital malformation of the brain characterized by impaired forebrain cleavage and midline facial anomalies. Heterozygous mutations in 14 genes have been identified in HPE patients that account for only 30% of HPE cases, suggesting the existence of other HPE genes. Data from homozygosity mapping and whole-exome sequencing in a consanguineous Turkish family were combined to identify a homozygous missense mutation (c.2150G>A; p.Gly717Glu) in STIL, common to the two affected children. STIL has a role in centriole formation and has previously been described in rare cases of microcephaly. Rescue experiments in U2OS cells showed that the STIL p.Gly717Glu mutation was not able to fully restore the centriole duplication failure following depletion of endogenous STIL protein indicating the deleterious role of the mutation. In situ hybridization experiments using chick embryos demonstrated that expression of Stil was in accordance with a function during early patterning of the forebrain. It is only the second time that a STIL homozygous mutation causing a recessive form of HPE was reported. This result also supports the genetic heterogeneity of HPE and increases the panel of genes to be tested for HPE diagnosis. PMID:25658757

  7. SLC1A4 mutations cause a novel disorder of intellectual disability, progressive microcephaly, spasticity and thin corpus callosum.

    PubMed

    Heimer, G; Marek-Yagel, D; Eyal, E; Barel, O; Oz Levi, D; Hoffmann, C; Ruzzo, E K; Ganelin-Cohen, E; Lancet, D; Pras, E; Rechavi, G; Nissenkorn, A; Anikster, Y; Goldstein, D B; Ben Zeev, B

    2015-10-01

    Two unrelated patients, presenting with significant global developmental delay, severe progressive microcephaly, seizures, spasticity and thin corpus callosum (CC) underwent trio whole-exome sequencing. No candidate variant was found in any known genes related to the phenotype. However, crossing the data of the patients illustrated that they both manifested pathogenic variants in the SLC1A4 gene which codes the ASCT1 transporter of serine and other neutral amino acids. The Ashkenazi patient is homozygous for a deleterious missense c.766G>A, p.(E256K) mutation whereas the Ashkenazi-Iraqi patient is compound heterozygous for this mutation and a nonsense c.945delTT, p.(Leu315Hisfs*42) mutation. Structural prediction demonstrates truncation of significant portion of the protein by the nonsense mutation and speculates functional disruption by the missense mutation. Both mutations are extremely rare in general population databases, however, the missense mutation was found in heterozygous mode in 1:100 Jewish Ashkenazi controls suggesting a higher carrier rate among Ashkenazi Jews. We conclude that SLC1A4 is the disease causing gene of a novel neurologic disorder manifesting with significant intellectual disability, severe postnatal microcephaly, spasticity and thin CC. The role of SLC1A4 in the serine transport from astrocytes to neurons suggests a possible pathomechanism for this disease and implies a potential therapeutic approach. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

    PubMed Central

    Rabeneck, Demi B.; Martines, Roosecelis B.; Reagan-Steiner, Sarah; Ermias, Yokabed; Estetter, Lindsey B.C.; Suzuki, Tadaki; Ritter, Jana; Keating, M. Kelly; Hale, Gillian; Gary, Joy; Muehlenbachs, Atis; Lambert, Amy; Lanciotti, Robert; Oduyebo, Titilope; Meaney-Delman, Dana; Bolaños, Fernando; Saad, Edgar Alberto Parra; Shieh, Wun-Ju; Zaki, Sherif R.

    2017-01-01

    Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. PMID:27959260

  9. Energy-loss- and thickness-dependent contrast in atomic-scale electron energy-loss spectroscopy

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

    Tan, Haiyan; Zhu, Ye; Dwyer, Christian

    2014-12-31

    Atomic-scale elemental maps of materials acquired by core-loss inelastic electron scattering often exhibit an undesirable sensitivity to the unavoidable elastic scattering, making the maps counter-intuitive to interpret. Here, we present a systematic study that scrutinizes the energy-loss and sample-thickness dependence of atomic-scale elemental maps acquired using 100 keV incident electrons in a scanning transmission electron microscope. For single-crystal silicon, the balance between elastic and inelastic scattering means that maps generated from the near-threshold Si-L signal (energy loss of 99 eV) show no discernible contrast for a thickness of 0.5λ (λ is the electron mean-free path, here approximately 110 nm). Atmore » greater thicknesses we observe a counter-intuitive “negative” contrast. Only at much higher energy losses is an intuitive “positive” contrast gradually restored. Our quantitative analysis shows that the energy-loss at which a positive contrast is restored depends linearly on the sample thickness. This behavior is in very good agreement with our double-channeling inelastic scattering calculations. We test a recently-proposed experimental method to correct the core-loss inelastic scattering and restore an intuitive “positive” chemical contrast. The method is demonstrated to be reliable over a large range of energy losses and sample thicknesses. The corrected contrast for near-threshold maps is demonstrated to be (desirably) inversely proportional to sample thickness. As a result, implications for the interpretation of atomic-scale elemental maps are discussed.« less

  10. Assessment of the cochlear nerve to facial nerve size ratio using MR multiplanar reconstruction of the internal auditory canal in patients presenting with acquired long-standing hearing loss

    PubMed Central

    Hey, Constanze; Shaaban, Mohamed S; Elabd, Amr M; Hassan, Hebatallah H M; Gruber-Rouh, Tatjana; Kaltenbach, Benjamin; Harth, Marc; Ackermann, Hanns; Stöver, Timo; Vogl, Thomas J; Nour-Eldin, Nour-Eldin A

    2017-01-01

    Objective: To test using the facial nerve as a reference for assessment of the cochlear nerve size in patients with acquired long-standing sensorineural hearing loss (SNHL) using MRI multiplanar reconstruction. Methods: The study was retrospectively performed on 86 patients. Group 1 (study group, n = 53) with bilateral long-standing SNHL. Group 2 (control group, n = 33) without hearing loss. The nerve size was measured by drawing a region of interest around the cross-sectional circumference of the nerve in multiplanar reconstruction images. Results: No significant correlation was noted between the cochlear nerve and facial nerve size, and the patient's age, gender and weight (p > 0.05). In Group 1, the mean ratio of the cochlear to facial nerve size was 0.99 ± 0.30 (range: 0.52–1.86) and 1.12 ± 0.35 (range: 0.34–2.3) for the right and left sides, respectively. In Group 2, it was 1.18 ± 0.23 (range: 0.78–1.71) and 1.25 ± 0.25 (range: 0.85–1.94) for the right and left sides, respectively. The cochlear nerve size was statistically (p = 0.0004) smaller in Group 1 than in Group 2. Conclusion: The cochlear nerve size and the cochlear to facial nerve size ratio are significantly smaller in patients with acquired long-standing SNHL. Advances in knowledge: The facial nerve can be used as a reference for assessment of the cochlear nerve in patients with acquired long-standing SNHL. PMID:28368665

  11. Clonal Evolution and Clinical Significance of Copy Number Neutral Loss of Heterozygosity of Chromosome Arm 6p in Acquired Aplastic Anemia

    PubMed Central

    Betensky, Marisol; Babushok, Daria; Roth, Jacquelyn J.; Mason, Philip J; Biegel, Jaclyn A.; Busse, Tracy M; Li, Yimei; Lind, Curt; Papazoglou, Anna; Monos, Dimitri; Podsakoff, Gregory; Bessler, Monica; Olson, Timothy S.

    2015-01-01

    Acquired aplastic anemia (aAA) results from the T cell-mediated autoimmune destruction of hematopoietic stem cells. Factors predicting response to immune suppression therapy (IST) or development of myelodysplastic syndrome (MDS) are beginning to be elucidated. Our recent data suggest most patients with aAA treated with IST develop clonal somatic genetic alterations in hematopoietic cells. One frequent acquired abnormality is copy-number neutral loss of heterozygosity on chromosome 6p (6p CN-LOH) involving the human leukocyte antigen (HLA) locus. We hypothesized that because 6p CN-LOH clones may arise from selective pressure to escape immune surveillance through deletion of HLA alleles, the development of 6p CN-LOH may affect response to IST. We used single nucleotide polymorphism array genotyping and targeted next-generation sequencing of HLA alleles to assess frequency of 6p CN-LOH, identity of HLA alleles lost through 6p CN-LOH, and impact of 6p CN-LOH on response to IST. 6p CN-LOH clones were present in 11.3% of patients, remained stable over time, and were not associated with development of MDS-defining cytogenetic abnormalities. Notably, no patient with 6p CN-LOH treated with IST achieved a complete response. In summary, clonal 6p CN-LOH in aAA defines a unique subgroup of patients that may provide insights into hematopoietic clonal evolution. PMID:26702937

  12. Nuclear PTEN deficiency causes microcephaly with decreased neuronal soma size and increased seizure susceptibility.

    PubMed

    Igarashi, Atsushi; Itoh, Kie; Yamada, Tatsuya; Adachi, Yoshihiro; Kato, Takashi; Murata, Daisuke; Sesaki, Hiromi; Iijima, Miho

    2018-06-15

    Defects in phosphatase and tensin homolog (PTEN) are associated with neurological disorders and tumors. PTEN functions at two primary intracellular locations: the plasma membrane and the nucleus. At the membrane, PTEN functions as a phosphatidylinositol (3,4,5)-trisphosphate phosphatase and suppresses PI 3-kinase signaling that drives cell growth and tumorigenesis. However, the in vivo function of nuclear PTEN is unclear. Here, using CRISPR/Cas9, we generated a mouse model in which PTEN levels in the nucleus are decreased. Nuclear PTEN-deficient mice were born with microcephaly and maintained a small brain during adulthood. The size of neuronal soma was significantly smaller in the cerebellum, cerebral cortex, and hippocampus. Also, these mice were prone to seizure. No changes in PI 3-kinase signaling were observed. By contrast, the size of other organs was unaffected. Therefore, nuclear PTEN is essential for the health of the brain by promoting the growth of neuronal soma size during development. © 2018 Igarashi et al.

  13. PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

    PubMed

    Zollo, Massimo; Ahmed, Mustafa; Ferrucci, Veronica; Salpietro, Vincenzo; Asadzadeh, Fatemeh; Carotenuto, Marianeve; Maroofian, Reza; Al-Amri, Ahmed; Singh, Royana; Scognamiglio, Iolanda; Mojarrad, Majid; Musella, Luca; Duilio, Angela; Di Somma, Angela; Karaca, Ender; Rajab, Anna; Al-Khayat, Aisha; Mohan Mohapatra, Tribhuvan; Eslahi, Atieh; Ashrafzadeh, Farah; Rawlins, Lettie E; Prasad, Rajniti; Gupta, Rashmi; Kumari, Preeti; Srivastava, Mona; Cozzolino, Flora; Kumar Rai, Sunil; Monti, Maria; Harlalka, Gaurav V; Simpson, Michael A; Rich, Philip; Al-Salmi, Fatema; Patton, Michael A; Chioza, Barry A; Efthymiou, Stephanie; Granata, Francesca; Di Rosa, Gabriella; Wiethoff, Sarah; Borgione, Eugenia; Scuderi, Carmela; Mankad, Kshitij; Hanna, Michael G; Pucci, Piero; Houlden, Henry; Lupski, James R; Crosby, Andrew H; Baple, Emma L

    2017-04-01

    PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  14. Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature.

    PubMed

    Kawame, H; Sugio, Y; Fuyama, Y; Hayashi, Y; Suzuki, H; Kurosawa, K; Maekawa, K

    1999-01-01

    We report a male infant with multiple congenital anomalies and mosaic variegated aneuploidy; a rare cytogenetic abnormality characterized by mosaicism for several different aneuploidies involving many different chromosomes. He had prenatal-onset growth retardation, microcephaly, dysmorphic face, seizures, hypotonia, feeding difficulty, and developmental delay. In addition, he developed bilateral Wilms tumors. Neuroradiological examination revealed Dandy-Walker malformation and hypoplasia of the cerebral hemisphere and pons. Cytogenetic analysis revealed various multiple numerical aneuploidies in blood lymphocytes, fibroblasts, and bone marrow cells, together with premature centromere division (PCD). Peripheral blood chromosome analysis from his parents also showed PCD, but no aneuploid cells. The clinical phenotype and multiple aneuploidies of the patient may be a consequence of the homozygous PCD trait inherited from his parents. Comparison with previously reported cases of multiple aneuploidy suggests that mosaic variegated aneuploidy with PCD may be a clinically recognizable syndrome with major phenotypes being mental retardation, microcephaly, structural brain anomalies (including Dandy-Walker malformation), and possible cancer predisposition.

  15. Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy and Other Chronic Acquired Demyelinating Polyneuropathy Variants

    PubMed Central

    Barohn, Richard J.; Katz, Jonathan

    2014-01-01

    Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge

  16. Case report: unicameral bone cysts in a young patient with acquired generalized lipodystrophy.

    PubMed

    Gregory, James M; Arkader, Alexandre; Bokhari, Aqiba; Bothari, Aqiba; Dormans, John P

    2010-05-01

    We report the case of a 13-year-old boy with bilateral distal femoral unicameral bone cysts (UBCs) associated with acquired generalized lipodystrophy. As opposed to congenital generalized lipodystrophy, cystic bone lesions in acquired generalized lipodystrophy are rare. After radiographic and histologic confirmation of the UBCs, we performed percutaneous intramedullary decompression, curettage, and grafting. UBCs can be an important manifestation of acquired generalized lipodystrophy. Cystic bone lesions appear to be less common in acquired generalized lipodystrophy than in congenital generalized lipodystrophy, and intramedullary adipose tissue loss may be a predisposing factor for the development of bone lesions in patients with acquired generalized lipodystrophy. When evaluating a patient with lipodystrophy, doctors should recognize the clinical course may include the development of UBCs.

  17. Case Report: Unicameral Bone Cysts in a Young Patient with Acquired Generalized Lipodystrophy

    PubMed Central

    Gregory, James M.; Arkader, Alexandre; Bothari, Aqiba

    2009-01-01

    We report the case of a 13-year-old boy with bilateral distal femoral unicameral bone cysts (UBCs) associated with acquired generalized lipodystrophy. As opposed to congenital generalized lipodystrophy, cystic bone lesions in acquired generalized lipodystrophy are rare. After radiographic and histologic confirmation of the UBCs, we performed percutaneous intramedullary decompression, curettage, and grafting. UBCs can be an important manifestation of acquired generalized lipodystrophy. Cystic bone lesions appear to be less common in acquired generalized lipodystrophy than in congenital generalized lipodystrophy, and intramedullary adipose tissue loss may be a predisposing factor for the development of bone lesions in patients with acquired generalized lipodystrophy. When evaluating a patient with lipodystrophy, doctors should recognize the clinical course may include the development of UBCs. PMID:19924491

  18. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies

    PubMed Central

    Ji, Jianling; Lee, Hane; Argiropoulos, Bob; Dorrani, Naghmeh; Mann, John; Martinez-Agosto, Julian A; Gomez-Ospina, Natalia; Gallant, Natalie; Bernstein, Jonathan A; Hudgins, Louanne; Slattery, Leah; Isidor, Bertrand; Le Caignec, Cédric; David, Albert; Obersztyn, Ewa; Wiśniowiecka-Kowalnik, Barbara; Fox, Michelle; Deignan, Joshua L; Vilain, Eric; Hendricks, Emily; Horton Harr, Margaret; Noon, Sarah E; Jackson, Jessi R; Wilkens, Alisha; Mirzaa, Ghayda; Salamon, Noriko; Abramson, Jeff; Zackai, Elaine H; Krantz, Ian; Innes, A Micheil; Nelson, Stanley F; Grody, Wayne W; Quintero-Rivera, Fabiola

    2015-01-01

    Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from −2 SD to −5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype–phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs. PMID:25944381

  19. PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features

    PubMed Central

    Low, Karen J; Ansari, Morad; Abou Jamra, Rami; Clarke, Angus; El Chehadeh, Salima; FitzPatrick, David R; Greenslade, Mark; Henderson, Alex; Hurst, Jane; Keller, Kory; Kuentz, Paul; Prescott, Trine; Roessler, Franziska; Selmer, Kaja K; Schneider, Michael C; Stewart, Fiona; Tatton-Brown, Katrina; Thevenon, Julien; Vigeland, Magnus D; Vogt, Julie; Willems, Marjolaine; Zonana, Jonathan; Study, D D D; Smithson, Sarah F

    2017-01-01

    PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function. PMID:28327570

  20. Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia.

    PubMed

    Betensky, Marisol; Babushok, Daria; Roth, Jacquelyn J; Mason, Philip J; Biegel, Jaclyn A; Busse, Tracy M; Li, Yimei; Lind, Curt; Papazoglou, Anna; Monos, Dimitri; Podsakoff, Gregory; Bessler, Monica; Olson, Timothy S

    2016-01-01

    Acquired aplastic anemia (aAA) results from the T cell-mediated autoimmune destruction of hematopoietic stem cells. Factors predicting response to immune suppression therapy (IST) or development of myelodysplastic syndrome (MDS) are beginning to be elucidated. Our recent data suggest most patients with aAA treated with IST develop clonal somatic genetic alterations in hematopoietic cells. One frequent acquired abnormality is copy-number neutral loss of heterozygosity on chromosome 6p (6p CN-LOH) involving the human leukocyte antigen (HLA) locus. We hypothesized that because 6p CN-LOH clones may arise from selective pressure to escape immune surveillance through deletion of HLA alleles, the development of 6p CN-LOH may affect response to IST. We used single nucleotide polymorphism array genotyping and targeted next-generation sequencing of HLA alleles to assess frequency of 6p CN-LOH, identity of HLA alleles lost through 6p CN-LOH, and impact of 6p CN-LOH on response to IST. 6p CN-LOH clones were present in 11.3% of patients, remained stable over time, and were not associated with development of MDS-defining cytogenetic abnormalities. Notably, no patient with 6p CN-LOH treated with IST achieved a complete response. In summary, clonal 6p CN-LOH in aAA defines a unique subgroup of patients that may provide insights into hematopoietic clonal evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Elderly persons with ICU-acquired weakness: the potential role for β-hydroxy-β-methylbutyrate (HMB) supplementation?

    PubMed

    Rahman, Adam; Wilund, Kenneth; Fitschen, Peter J; Jeejeebhoy, Khursheed; Agarwala, Ravi; Drover, John W; Mourtzakis, Marina

    2014-07-01

    Intensive care unit (ICU)-acquired weakness is common and characterized by muscle loss, weakness, and paralysis. It is associated with poor short-term outcomes, including increased mortality, but the consequences of reduced long-term outcomes, including decreased physical function and quality of life, can be just as devastating. ICU-acquired weakness is particularly relevant to elderly patients who are increasingly consuming ICU resources and are at increased risk for ICU-acquired weakness and complications, including mortality. Elderly patients often enter critical illness with reduced muscle mass and function and are also at increased risk for accelerated disuse atrophy with acute illness. Increasingly, intensivists and researchers are focusing on strategies and therapies aimed at improving long-term neuromuscular function. β-Hydroxy-β-methylbutyrate (HMB), an ergogenic supplement, has shown efficacy in elderly patients and certain clinical populations in counteracting muscle loss. The present review discusses ICU-acquired weakness, as well as the unique physiology of muscle loss and skeletal muscle function in elderly patients, and then summarizes the evidence for HMB in elderly patients and in clinical populations. We subsequently postulate on the potential role and strategies in studying HMB in elderly ICU patients to improve muscle mass and function. © 2013 American Society for Parenteral and Enteral Nutrition.

  2. Amphiregulin and PTEN evoke a multimodal mechanism of acquired resistance to PI3K inhibition

    PubMed Central

    Edgar, Kyle A.; Crocker, Lisa; Cheng, Eric; Wagle, Marie-Claire; Wongchenko, Matthew; Yan, Yibing; Wilson, Timothy R.; Dompe, Nicholas; Neve, Richard M.; Belvin, Marcia; Sampath, Deepak; Friedman, Lori S.; Wallin, Jeffrey J.

    2014-01-01

    Phosphoinositide-3 kinase (PI3K) signaling pathway alterations occur broadly in cancer and PI3K is a promising therapeutic target. Here, we investigated acquired resistance to GDC-0941, a PI3K inhibitor in clinical trials. Colorectal cancer (CRC) cells made to be resistant to GDC-0941 were discovered to secrete amphiregulin, which resulted in increased EGFR/MAPK signaling. Moreover, prolonged PI3K pathway inhibition in cultured cells over a period of months led to a secondary loss of PTEN in 40% of the CRC lines with acquired resistance to PI3K inhibition. In the absence of PI3K inhibitor, these PTEN-null PI3K inhibitor-resistant clones had elevated PI3K pathway signaling and decreased sensitivity to MAPK pathway inhibitors. Importantly, PTEN loss was not able to induce resistance to PI3K inhibitors in the absence of amphiregulin, indicating a multimodal mechanism of acquired resistance. The combination of PI3K and MAPK pathway inhibitors overcame acquired resistance in vitro and in vivo. PMID:25053989

  3. Amphiregulin and PTEN evoke a multimodal mechanism of acquired resistance to PI3K inhibition.

    PubMed

    Edgar, Kyle A; Crocker, Lisa; Cheng, Eric; Wagle, Marie-Claire; Wongchenko, Matthew; Yan, Yibing; Wilson, Timothy R; Dompe, Nicholas; Neve, Richard M; Belvin, Marcia; Sampath, Deepak; Friedman, Lori S; Wallin, Jeffrey J

    2014-03-01

    Phosphoinositide-3 kinase (PI3K) signaling pathway alterations occur broadly in cancer and PI3K is a promising therapeutic target. Here, we investigated acquired resistance to GDC-0941, a PI3K inhibitor in clinical trials. Colorectal cancer (CRC) cells made to be resistant to GDC-0941 were discovered to secrete amphiregulin, which resulted in increased EGFR/MAPK signaling. Moreover, prolonged PI3K pathway inhibition in cultured cells over a period of months led to a secondary loss of PTEN in 40% of the CRC lines with acquired resistance to PI3K inhibition. In the absence of PI3K inhibitor, these PTEN-null PI3K inhibitor-resistant clones had elevated PI3K pathway signaling and decreased sensitivity to MAPK pathway inhibitors. Importantly, PTEN loss was not able to induce resistance to PI3K inhibitors in the absence of amphiregulin, indicating a multimodal mechanism of acquired resistance. The combination of PI3K and MAPK pathway inhibitors overcame acquired resistance in vitro and in vivo.

  4. GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.

    PubMed

    Hengel, H; Keimer, R; Deigendesch, W; Rieß, A; Marzouqa, H; Zaidan, J; Bauer, P; Schöls, L

    2018-06-07

    Various genetic defects can cause intellectual and developmental disabilities (IDD). Often IDD is a symptom of a more complex neurodevelopmental or neurodegenerative syndrome. Identifying syndromic patterns is substantive for diagnostics and for understanding the pathomechanism of a disease. Recessive GPT2 mutations have recently been associated with IDD in four families. Here, we report a novel recessive GPT2 stop mutation p.Gln24* causing a complex IDD phenotype in a homozygous state in five patients from two consanguineous Arab families. By compiling clinical information of these individuals and previously described GPT2 patients a recognizable neurodevelopmental and potentially neurodegenerative phenotype can be assigned consisting of intellectual disability, pyramidal tract affection with spastic paraplegia, microcephaly and frequently epilepsy. Due to the consistent presence of pyramidal tract affection in GPT2 patients, we further suggest that GPT2 mutations should be considered in cases with complex hereditary spastic paraplegia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Isolated chromosome 8p23.2‑pter deletion: Novel evidence for developmental delay, intellectual disability, microcephaly and neurobehavioral disorders.

    PubMed

    Shi, Shanshan; Lin, Shaobin; Chen, Baojiang; Zhou, Yi

    2017-11-01

    The current study presents a patient carrying a de novo ~6 Mb deletion of the isolated chromosome 8p23.2‑pter that was identified with a single‑nucleotide polymorphism array. The patient was characterized by developmental delay (DD)/intellectual disability (ID), microcephaly, autism spectrum disorder, attention‑deficit/hyperactivity disorders and mildly dysmorphic features. The location, size and gene content of the deletion observed in this patient were compared with those in 7 patients with isolated 8p23.2 to 8pter deletions reported in previous studies (4 patients) or recorded in the Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources (DECIPHER) database (3 patients). The deletions reported in previous studies were assessed using a chromosomal microarray analysis. The 8p23.2‑pter deletion was a distinct microdeletion syndrome, as similar phenotypes were observed in patients with this deletion. Furthermore, following a detailed review of the potential associations between the genes located from 8p23.2 to 8pter and their clinical significance, it was hypothesized that DLG associated protein 2, ceroid‑lipofuscinosis neuronal 8, Rho guanine nucleotide exchange factor 10 and CUB and sushi multiple domains 1 may be candidate genes for DD/ID, microcephaly and neurobehavioral disorders. However, firm evidence should be accumulated from high‑resolution studies of patients with small, isolated, overlapping and interstitial deletions involving the region from 8p23.2 to 8pter. These studies will allow determination of genotype‑phenotype associations for the specific genes crucial to 8p23.2‑pter.

  6. Assessing color vision loss among solvent-exposed workers.

    PubMed

    Mergler, D; Blain, L

    1987-01-01

    Acquired color vision loss has been associated with exposure to organic solvents in the workplace. However, not all tests of chromatic discrimination loss are designed to detect acquired, as opposed to congenital, loss. The Lanthony D-15 desaturated panel (D-15-d), a simple 15 cap color arrangement test, designed to identify mild acquired dyschromatopsia, can be administered rapidly in the field, under standard conditions. The objective of the present study was to evaluate the D-15-d among 23 solvent-exposed workers of a paint manufacturing plant, by comparing the results obtained with the D-15-d to those obtained with the Farnsworth-Munsell 100 Hue (FM-100), a highly sensitive measure of color vision loss. The D-15-d revealed a significantly higher prevalence of dyschromatopsia among the ten highly exposed workers (80%) as compared to the 13 moderately exposed workers (30.8%); FM-100 results revealed one false positive. All dyschromatopic workers presented blue-yellow loss; the FM-100 detected eight complex patterns, while the D-15-d identified 5. Comparison of D-15-d and FM-100 scores were highly correlated (corr. coeff. 0.87; p less than 0.001). Multiple regression analyses showed both scores to be significantly related to age and exposure level. The findings of this study indicate that the D-15-d is an adequate instrument for field study batteries. However, the FM-100 should be used for more detailed assessment.

  7. Effects of loss aversion on neural responses to loss outcomes: An event-related potential study.

    PubMed

    Kokmotou, Katerina; Cook, Stephanie; Xie, Yuxin; Wright, Hazel; Soto, Vicente; Fallon, Nicholas; Giesbrecht, Timo; Pantelous, Athanasios; Stancak, Andrej

    2017-05-01

    Loss aversion is the tendency to prefer avoiding losses over acquiring gains of the same amount. To shed light on the spatio-temporal processes underlying loss aversion, we analysed the associations between individual loss aversion and electrophysiological responses to loss and gain outcomes in a monetary gamble task. Electroencephalographic feedback-related negativity (FRN) was computed in 29 healthy participants as the difference in electrical potentials between losses and gains. Loss aversion was evaluated using non-linear parametric fitting of choices in a separate gamble task. Loss aversion correlated positively with FRN amplitude (233-263ms) at electrodes covering the lower face. Feedback related potentials were modelled by five equivalent source dipoles. From these dipoles, stronger activity in a source located in the orbitofrontal cortex was associated with loss aversion. The results suggest that loss aversion implemented during risky decision making is related to a valuation process in the orbitofrontal cortex, which manifests during learning choice outcomes. Copyright © 2017. Published by Elsevier B.V.

  8. Multiple myeloma associated with acquired cutis laxa.

    PubMed

    Cho, S Y; Maguire, R F

    1980-08-01

    Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

  9. Acquired copy-neutral loss of heterozygosity of chromosome 1p as a molecular event associated with marrow fibrosis in MPL-mutated myeloproliferative neoplasms.

    PubMed

    Rumi, Elisa; Pietra, Daniela; Guglielmelli, Paola; Bordoni, Roberta; Casetti, Ilaria; Milanesi, Chiara; Sant'Antonio, Emanuela; Ferretti, Virginia; Pancrazzi, Alessandro; Rotunno, Giada; Severgnini, Marco; Pietrelli, Alessandro; Astori, Cesare; Fugazza, Elena; Pascutto, Cristiana; Boveri, Emanuela; Passamonti, Francesco; De Bellis, Gianluca; Vannucchi, Alessandro; Cazzola, Mario

    2013-05-23

    We studied mutations of MPL exon 10 in patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF), first investigating a cohort of 892 consecutive patients. MPL mutation scanning was performed on granulocyte genomic DNA by using a high-resolution melt assay, and the mutant allele burden was evaluated by using deep sequencing. Somatic mutations of MPL, all but one involving codon W515, were detected in 26/661 (4%) patients with ET, 10/187 (5%) with PMF, and 7/44 (16%) patients with post-ET myelofibrosis. Comparison of JAK2 (V617F)-mutated and MPL-mutated patients showed only minor phenotypic differences. In an extended group of 62 MPL-mutated patients, the granulocyte mutant allele burden ranged from 1% to 95% and was significantly higher in patients with PMF or post-ET myelofibrosis compared with those with ET. Patients with higher mutation burdens had evidence of acquired copy-neutral loss of heterozygosity (CN-LOH) of chromosome 1p in granulocytes, consistent with a transition from heterozygosity to homozygosity for the MPL mutation in clonal cells. A significant association was found between MPL-mutant allele burden greater than 50% and marrow fibrosis. These observations suggest that acquired CN-LOH of chromosome 1p involving the MPL location may represent a molecular mechanism of fibrotic transformation in MPL-mutated myeloproliferative neoplasms.

  10. Acquired copy-neutral loss of heterozygosity of chromosome 1p as a molecular event associated with marrow fibrosis in MPL-mutated myeloproliferative neoplasms

    PubMed Central

    Pietra, Daniela; Guglielmelli, Paola; Bordoni, Roberta; Casetti, Ilaria; Milanesi, Chiara; Sant’Antonio, Emanuela; Ferretti, Virginia; Pancrazzi, Alessandro; Rotunno, Giada; Severgnini, Marco; Pietrelli, Alessandro; Astori, Cesare; Fugazza, Elena; Pascutto, Cristiana; Boveri, Emanuela; Passamonti, Francesco; De Bellis, Gianluca; Vannucchi, Alessandro; Cazzola, Mario

    2013-01-01

    We studied mutations of MPL exon 10 in patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF), first investigating a cohort of 892 consecutive patients. MPL mutation scanning was performed on granulocyte genomic DNA by using a high-resolution melt assay, and the mutant allele burden was evaluated by using deep sequencing. Somatic mutations of MPL, all but one involving codon W515, were detected in 26/661 (4%) patients with ET, 10/187 (5%) with PMF, and 7/44 (16%) patients with post-ET myelofibrosis. Comparison of JAK2 (V617F)–mutated and MPL-mutated patients showed only minor phenotypic differences. In an extended group of 62 MPL-mutated patients, the granulocyte mutant allele burden ranged from 1% to 95% and was significantly higher in patients with PMF or post-ET myelofibrosis compared with those with ET. Patients with higher mutation burdens had evidence of acquired copy-neutral loss of heterozygosity (CN-LOH) of chromosome 1p in granulocytes, consistent with a transition from heterozygosity to homozygosity for the MPL mutation in clonal cells. A significant association was found between MPL-mutant allele burden greater than 50% and marrow fibrosis. These observations suggest that acquired CN-LOH of chromosome 1p involving the MPL location may represent a molecular mechanism of fibrotic transformation in MPL-mutated myeloproliferative neoplasms. PMID:23575445

  11. Intestinal leishmaniasis in acquired immunodeficiency syndrome.

    PubMed

    Molaei, M; Minakari, M; Pejhan, Sh; Mashayekhi, R; Modaress Fatthi, A R; Zali, M R

    2011-05-01

    In endemic regions, visceral leishmaniasis is one of the most common opportunistic infections in HIV positive patients. Simultaneous infection with Leishmania and HIV has been reported in some countries but this is the first report of such a case in Iran. Our patient was a 27 years old man with intermittent night fever, abdominal pain, loss of appetite, vomiting, watery diarrhea and severe weight loss for 6 months. He had low socio-economic status with an imprisonment history. The patient was quite cachectic and had low grade fever. Physical exam and upper GI endoscopy revealed oropharyngeal candidiasis. Microscopic evaluation of duodenal biopsy material showed Leishmania amastigotes in macrophages of lamina propria. Leishman bodies were also observed in bone marrow aspiration specimen. Serologic tests were positive for Leishmania infantum. HIV antibody was also positive with a CD4+cell count of 80/μl. The diagnosis was acquired immunodeficiency syndrome with simultaneous visceral leishmaniasis involving intestinal mucosa.

  12. Learning and behavioural difficulties but not microcephaly in three brothers resulting from undiagnosed maternal phenylketonuria.

    PubMed

    Shaw-Smith, C; Hogg, S L; Reading, R; Calvin, J; Trump, D

    2004-09-01

    Universal screening introduced in the 1960s has reduced the incidence of learning disability resulting from phenylketonuria (PKU), which is a treatable condition. Nonetheless, PKU may still be having an impact on the paediatric-age population. We report a woman with previously undiagnosed PKU who was born before the onset of universal screening. She is of normal intelligence, and so the diagnosis was not suspected until after the birth of her three children. Her serum phenylalanine concentration was found to be in excess of 1 mmol/L, well into the toxic range. She has had three sons, all of whom have a significant degree of learning disability resulting from intrauterine exposure to toxic levels of phenylalanine. None of the sons had microcephaly, a physical sign that, if present, might have helped to point towards the correct diagnosis. We suggest that maternal PKU should be suspected where there is sibling recurrence of cognitive impairment, particularly where the mother was born before the initiation of the neonatal screening programme for PKU.

  13. 26 CFR 1.1014-5 - Gain or loss.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAXES Basis Rules of General Application § 1.1014-5 Gain or loss. (a) Sale or other disposition of a life interest, remainder interest, or other interest in property acquired from a decedent. (1) Except... October 9, 1969, of a term interest in property, gain or loss from a sale or other disposition of a life...

  14. Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies.

    PubMed

    Osborn, Daniel P S; Roccasecca, Rosa Maria; McMurray, Fiona; Hernandez-Hernandez, Victor; Mukherjee, Sriparna; Barroso, Inês; Stemple, Derek; Cox, Roger; Beales, Philip L; Christou-Savina, Sonia

    2014-01-01

    Common intronic variants in the Human fat mass and obesity-associated gene (FTO) are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish) and in vitro (Fto(-/-) MEFs and HEK293T). Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca(2+) pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function.

  15. Acquired pendular nystagmus

    PubMed Central

    Kang, Sarah; Shaikh, Aasef G.

    2017-01-01

    Acquired pendular nystagmus is comprised of quasi-sinusoidal oscillations of the eyes significantly affecting gaze holding and clarity of vision. The most common causes of acquired pendular nystagmus include demyelinating disorders such as multiple sclerosis and the syndrome of ocular palatal tremor. However, several other deficits, such as pharmacological intoxication, metabolic and genetic disorders, and granulomatous disorders can lead to syndromes mimicking acquired pendular nystagmus. Study of the kinematic features of acquired pendular nystagmus has suggested a putative pathophysiology of an otherwise mysterious neurological disorder. Here we review clinical features of neurological deficits that co-occur with acquired pendular nystagmus. Subsequent discussion of the pathophysiology of individual forms of pendular nystagmus speculates on mechanisms of the underlying disease while providing insights into pharmacotherapy of nystagmus. PMID:28320194

  16. Differences in microbiological profile between community-acquired, healthcare-associated and hospital-acquired infections.

    PubMed

    Cardoso, Teresa; Ribeiro, Orquídea; Aragão, Irene; Costa-Pereira, Altamiro; Sarmento, António

    2013-01-01

    Microbiological profiles were analysed and compared for intra-abdominal, urinary, respiratory and bloodstream infections according to place of acquisition: community-acquired, with a separate analysis of healthcare-associated, and hospital-acquired. Prospective cohort study performed at a university tertiary care hospital over 1 year. Inclusion criteria were meeting the Centers for Disease Control definition of intra-abdominal, urinary, respiratory and bloodstream infections. A total of 1035 patients were included in the study. More than 25% of intra-abdominal infections were polymicrobial; multi-drug resistant gram-negatives were 38% in community-acquired, 50% in healthcare-associated and 57% in hospital-acquired. E. coli was the most prevalent among urinary infections: 69% in community-acquired, 56% in healthcare-associated and 26% in hospital-acquired; ESBL producers' pathogens were 10% in healthcare-associated and 3% in community-acquired and hospital-acquired. In respiratory infections Streptococcus pneumoniae was the most prevalent in community-acquired (54%) and MRSA in healthcare-associated (24%) and hospital-acquired (24%). A significant association was found between MRSA respiratory infection and hospitalization in the previous year (adjusted OR = 6.3), previous instrumentation (adjusted OR = 4.3) and previous antibiotic therapy (adjusted OR = 5.7); no cases were documented among patients without risk factors. Hospital mortality rate was 10% in community-acquired, 14% in healthcare-associated and 19% in hospital-acquired infection. This study shows that healthcare-associated has a different microbiologic profile than those from community or hospital acquired for the four main focus of infection. Knowledge of this fact is important because the existing guidelines for community-acquired are not entirely applicable for this group of patients.

  17. Toward immunogenetic studies of amphibian chytridiomycosis: Linking innate and acquired immunity

    USGS Publications Warehouse

    Richmond, J.Q.; Savage, Anna E.; Zamudio, Kelly R.; Rosenblum, E.B.

    2009-01-01

    Recent declines in amphibian diversity and abundance have contributed significantly to the global loss of biodiversity. The fungal disease chytridiomycosis is widely considered to be a primary cause of these declines, yet the critical question of why amphibian species differ in susceptibility remains unanswered. Considerable evidence links environmental conditions and interspecific variability of the innate immune system to differential infection responses, but other sources of individual, population, or species-typical variation may also be important. In this article we review the preliminary evidence supporting a role for acquired immune defenses against chytridiomycosis, and advocate for targeted investigation of genes controlling acquired responses, as well as those that functionally bridge the innate and acquired immune systems. Immunogenetic data promise to answer key questions about chytridiomycosis susceptibility and host-pathogen coevolution, and will draw much needed attention to the importance of considering evolutionary processes in amphibian conservation management and practice. ?? 2009 by American Institute of Biological Sciences.

  18. Acquired pendular nystagmus.

    PubMed

    Kang, Sarah; Shaikh, Aasef G

    2017-04-15

    Acquired pendular nystagmus is comprised of quasi-sinusoidal oscillations of the eyes significantly affecting gaze holding and clarity of vision. The most common causes of acquired pendular nystagmus include demyelinating disorders such as multiple sclerosis and the syndrome of ocular palatal tremor. However, several other deficits, such as pharmacological intoxication, metabolic and genetic disorders, and granulomatous disorders can lead to syndromes mimicking acquired pendular nystagmus. Study of the kinematic features of acquired pendular nystagmus has suggested a putative pathophysiology of an otherwise mysterious neurological disorder. Here we review clinical features of neurological deficits that co-occur with acquired pendular nystagmus. Subsequent discussion of the pathophysiology of individual forms of pendular nystagmus speculates on mechanisms of the underlying disease while providing insights into pharmacotherapy of nystagmus. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants.

    PubMed

    Vollmer, Brigitte; Seibold-Weiger, Karin; Schmitz-Salue, Christine; Hamprecht, Klaus; Goelz, Rangmar; Krageloh-Mann, Ingeborg; Speer, Christian P

    2004-04-01

    In preterm infants there is a high risk of transmission of cytomegalovirus (CMV) via breast milk from seropositive mothers with reactivation of the virus during lactation. There is little information about the long term sequel of early postnatally acquired CMV infection in pre-term infants. This study aimed to investigate whether there was an increased frequency of impaired neurodevelopmental outcome and sensorineural hearing loss in preterm infants with postnatally acquired CMV infection through transmission by CMV-positive breast milk. Twenty-two preterm infants [median birth weight, 1020 g (range, 600 to 1870 g); median gestational age, 27.6 weeks (range, 23.6 to 32 weeks] with early postnatally acquired CMV infection by breast-feeding (onset of viruria between Days 23 and 190 postnatally) were compared with 22 CMV-negative preterm infants individually matched for gestational age, birth weight, gender, intracranial hemorrhage and duration of ventilation. At 2 to 4.5 years of age, follow-up assessments were conducted consisting of neurologic examination, neurodevelopmental assessment and detailed audiologic tests. None of the children had sensorineural hearing loss. There was no difference between the groups with regard to neurologic, speech and language or motor development. The results of this study suggest that early postnatally acquired CMV infection via CMV-positive breast milk does not have a negative effect on neurodevelopment and hearing in this group of patients. Because we studied a small number of infants, further follow-up studies are warranted in preterm infants with early postnatally acquired CMV infection.

  20. 26 CFR 1.1502-21T - Net operating losses (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Net operating losses (temporary). 1.1502-21T...) INCOME TAX (CONTINUED) INCOME TAXES Computation of Consolidated Items § 1.1502-21T Net operating losses...)(B). (C) Partial waiver of carryback period for 2001 and 2002 losses—(1) Application. The acquiring...

  1. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which income...

  2. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which income...

  3. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which income...

  4. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND... Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired. If...

  5. Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease.

    PubMed

    Li, Rui; Sun, Le; Fang, Ai; Li, Peng; Wu, Qian; Wang, Xiaoqun

    2017-11-01

    The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.

  6. A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos.

    PubMed

    Li, Cui; Gao, Fei; Yu, Lei; Wang, Ruoke; Jiang, Yisheng; Shi, Xuanling; Yin, Chibiao; Tang, Xiaoping; Zhang, Fuchun; Xu, Zhiheng; Zhang, Linqi

    2018-05-01

    Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is generally benign in humans. However, an emergent strain of ZIKV has become widespread, causing severe pre- and post-natal neurological defects. There is now an urgent need for prophylactic and therapeutic agents. To address this, we investigated six human monoclonal antibodies with ZIKV epitope specificity and neutralizing activity in mouse models of ZIKV infection and microcephaly. A single intraperitoneal injection of these antibodies conveyed distinct levels of adult and in utero protection from ZIKV infection, which closely mirrored their respective in vitro neutralizing activities. One antibody, ZK2B10, showed the most potent neutralization activity, completely protected uninfected mice, and markedly reduced tissue pathology in infected mice. Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and informs the rational design of ZIKV vaccine. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Magnetic resonance imaging depiction of acquired Dyke-Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis: Report of two cases.

    PubMed

    Gupta, Ranjana; Joshi, Sandeep; Mittal, Amit; Luthra, Ishita; Mittal, Puneet; Verma, Vibha

    2015-01-01

    Acquired Dyke-Davidoff-Masson syndrome, also known as hemispheric atrophy, is characterized by loss of volume of one cerebral hemisphere from an insult in early life. Crossed cerebellar diaschisis refers to dysfunction/atrophy of cerebellar hemisphere which is secondary to contralateral supratentorial insult. We describe magnetic resonance imaging findings in two cases of acquired Dyke-Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis.

  8. Coagulation disorders in pregnancy: acquired and inherited thrombophilias.

    PubMed

    Benedetto, Chiara; Marozio, Luca; Tavella, Anna Maria; Salton, Loredana; Grivon, Sara; Di Giampaolo, Francesca

    2010-09-01

    Both acquired and inherited thrombophilias are associated with an increased risk of pregnancy-related venous thromboembolism (VTE) as well as with adverse pregnancy outcome. However, the extension of attributable risk for each thrombophilia and outcome is still a question of debate. Thrombophilias have been investigated in connection with VTE and pregnancy complications such as: recurrent and nonrecurrent early pregnancy loss, late fetal death, placental abruption, fetal growth restriction, and preeclampsia. This review discusses the evidence of association between thrombophilias and pregnancy outcome together with issues as to clinical management and preventive strategies. © 2010 New York Academy of Sciences.

  9. Intrinsic Functional Connectivity Patterns Predict Consciousness Level and Recovery Outcome in Acquired Brain Injury

    PubMed Central

    Wu, Xuehai; Zou, Qihong; Hu, Jin; Tang, Weijun; Mao, Ying; Gao, Liang; Zhu, Jianhong; Jin, Yi; Wu, Xin; Lu, Lu; Zhang, Yaojun; Zhang, Yao; Dai, Zhengjia; Gao, Jia-Hong; Weng, Xuchu; Northoff, Georg; Giacino, Joseph T.; He, Yong

    2015-01-01

    For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI. SIGNIFICANCE STATEMENT Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the

  10. HIV-1 Encephalopathy among Perinatally Infected Children: Neuropathogenesis and Response to Highly Active Antiretroviral Therapy

    ERIC Educational Resources Information Center

    Mitchell, Charles D.

    2006-01-01

    HIV-1 encephalopathy among perinatally infected children in the United States was initially defined by a classic triad of findings that included: (1) developmental delay, (2) secondary or acquired microcephaly, and (3) pyramidal tract neuromotor deficits. The most severe form of this disorder typically occurred among young children who developed…

  11. A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome.

    PubMed

    Alakbarzade, Vafa; Hameed, Abdul; Quek, Debra Q Y; Chioza, Barry A; Baple, Emma L; Cazenave-Gassiot, Amaury; Nguyen, Long N; Wenk, Markus R; Ahmad, Arshia Q; Sreekantan-Nair, Ajith; Weedon, Michael N; Rich, Phil; Patton, Michael A; Warner, Thomas T; Silver, David L; Crosby, Andrew H

    2015-07-01

    The major pathway by which the brain obtains essential omega-3 fatty acids from the circulation is through a sodium-dependent lysophosphatidylcholine (LPC) transporter (MFSD2A), expressed in the endothelium of the blood-brain barrier. Here we show that a homozygous mutation affecting a highly conserved MFSD2A residue (p.Ser339Leu) is associated with a progressive microcephaly syndrome characterized by intellectual disability, spasticity and absent speech. We show that the p.Ser339Leu alteration does not affect protein or cell surface expression but rather significantly reduces, although not completely abolishes, transporter activity. Notably, affected individuals displayed significantly increased plasma concentrations of LPCs containing mono- and polyunsaturated fatty acyl chains, indicative of reduced brain uptake, confirming the specificity of MFSD2A for LPCs having mono- and polyunsaturated fatty acyl chains. Together, these findings indicate an essential role for LPCs in human brain development and function and provide the first description of disease associated with aberrant brain LPC transport in humans.

  12. Effects of a Cognitive Behavioral Self-Help Program on Emotional Problems for People with Acquired Hearing Loss: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Garnefski, Nadia; Kraaij, Vivian

    2012-01-01

    The aim of the study was to examine whether a cognitive-behavioral self-help program was effective in improving depressed mood and anxiety in people with acquired deafness. Participants were 45 persons with acquired deafness, randomly allocated to the Cognitive-Behavioral Self-help (CBS) group or the Waiting List Control (WLC) group. Depression…

  13. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 9 2014-04-01 2014-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as a...

  14. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as a resident until he...

  15. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 9 2013-04-01 2013-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as a...

  16. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 9 2011-04-01 2011-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as a...

  17. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 9 2012-04-01 2012-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as a...

  18. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Acquire. 583.1 Section 583.1 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY DEFINITIONS FOR REGULATIONS AFFECTING SAVINGS AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly...

  19. Acquired neuropathies.

    PubMed

    Lozeron, Pierre; Trocello, Jean-Marc; Kubis, Nathalie

    2013-09-01

    Acquired neuropathies represent most of the neuropathies encountered in clinical practice. Hundreds of causes have been identified even though up to 41% of patients are still classified as idiopathic (Rajabally and Shah in J Neurol 258:1431-1436, 1). Routine evaluation relies on comprehensive medical history taking, clinical examination, nerve conduction studies and laboratory tests. Other investigations such as nerve biopsy or nerve or muscle imaging are performed in specific settings. This review focuses on recent advances in acquired neuropathies.

  20. Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A.

    PubMed

    Bronicki, Lucas M; Redin, Claire; Drunat, Severine; Piton, Amélie; Lyons, Michael; Passemard, Sandrine; Baumann, Clarisse; Faivre, Laurence; Thevenon, Julien; Rivière, Jean-Baptiste; Isidor, Bertrand; Gan, Grace; Francannet, Christine; Willems, Marjolaine; Gunel, Murat; Jones, Julie R; Gleeson, Joseph G; Mandel, Jean-Louis; Stevenson, Roger E; Friez, Michael J; Aylsworth, Arthur S

    2015-11-01

    The dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene, located on chromosome 21q22.13 within the Down syndrome critical region, has been implicated in syndromic intellectual disability associated with Down syndrome and autism. DYRK1A has a critical role in brain growth and development primarily by regulating cell proliferation, neurogenesis, neuronal plasticity and survival. Several patients have been reported with chromosome 21 aberrations such as partial monosomy, involving multiple genes including DYRK1A. In addition, seven other individuals have been described with chromosomal rearrangements, intragenic deletions or truncating mutations that disrupt specifically DYRK1A. Most of these patients have microcephaly and all have significant intellectual disability. In the present study, we report 10 unrelated individuals with DYRK1A-associated intellectual disability (ID) who display a recurrent pattern of clinical manifestations including primary or acquired microcephaly, ID ranging from mild to severe, speech delay or absence, seizures, autism, motor delay, deep-set eyes, poor feeding and poor weight gain. We identified unique truncating and non-synonymous mutations (three nonsense, four frameshift and two missense) in DYRK1A in nine patients and a large chromosomal deletion that encompassed DYRK1A in one patient. On the basis of increasing identification of mutations in DYRK1A, we suggest that this gene be considered potentially causative in patients presenting with ID, primary or acquired microcephaly, feeding problems and absent or delayed speech with or without seizures.

  1. Culex quinquefasciatus from areas with the highest incidence of microcephaly associated with Zika virus infections in the Northeast Region of Brazil are refractory to the virus

    PubMed Central

    Fernandes, Rosilainy Surubi; Campos, Stéphanie Silva; Ribeiro, Paulino Siqueira; Raphael, Lidiane MS; Bonaldo, Myrna C; Lourenço-de-Oliveira, Ricardo

    2017-01-01

    Zika virus (ZIKV) is widely distributed in Brazil and the Northeast Region (NE) is the most affected zone, showing the highest incidence of microcephaly associated with ZIKV congenital infections worldwide. We report attempts to infect three populations of Culex quinquefasciatus from severely affected sites in the NE and Southeast Region (SE) of Brazil with three strains of ZIKV isolated from these localities. An Aedes aegypti population from the SE was used as a positive control. All tested Cx. quinquefasciatus populations were refractory to the ZIKV isolates. For these reasons, we believe Cx. quinquefasciatus should not be considered a potential vector of ZIKV in Brazil. PMID:28767975

  2. Spirituality, Loss and Recovery in Children with Disabilities

    ERIC Educational Resources Information Center

    Erickson, David V.

    2008-01-01

    This article focuses on loss, recovery and spiritual dimensions of trauma in spinal cord injury (SCI) during adolescence. From a clinical perspective, while there are physical characteristics in common with congenital childhood disabilities such as spina bifida, life adjustment issues associated with acquired disabilities can be quite different,…

  3. Diagnostic utility of appetite loss in addition to existing prediction models for community-acquired pneumonia in the elderly: a prospective diagnostic study in acute care hospitals in Japan

    PubMed Central

    Yamamoto, Yosuke; Terada, Kazuhiko; Ohta, Mitsuyasu; Mikami, Wakako; Yokota, Hajime; Hayashi, Michio; Miyashita, Jun; Azuma, Teruhisa; Fukuma, Shingo; Fukuhara, Shunichi

    2017-01-01

    Objective Diagnosis of community-acquired pneumonia (CAP) in the elderly is often delayed because of atypical presentation and non-specific symptoms, such as appetite loss, falls and disturbance in consciousness. The aim of this study was to investigate the external validity of existing prediction models and the added value of the non-specific symptoms for the diagnosis of CAP in elderly patients. Design Prospective cohort study. Setting General medicine departments of three teaching hospitals in Japan. Participants A total of 109 elderly patients who consulted for upper respiratory symptoms between 1 October 2014 and 30 September 2016. Main outcome measures The reference standard for CAP was chest radiograph evaluated by two certified radiologists. The existing models were externally validated for diagnostic performance by calibration plot and discrimination. To evaluate the additional value of the non-specific symptoms to the existing prediction models, we developed an extended logistic regression model. Calibration, discrimination, category-free net reclassification improvement (NRI) and decision curve analysis (DCA) were investigated in the extended model. Results Among the existing models, the model by van Vugt demonstrated the best performance, with an area under the curve of 0.75(95% CI 0.63 to 0.88); calibration plot showed good fit despite a significant Hosmer-Lemeshow test (p=0.017). Among the non-specific symptoms, appetite loss had positive likelihood ratio of 3.2 (2.0–5.3), negative likelihood ratio of 0.4 (0.2–0.7) and OR of 7.7 (3.0–19.7). Addition of appetite loss to the model by van Vugt led to improved calibration at p=0.48, NRI of 0.53 (p=0.019) and higher net benefit by DCA. Conclusions Information on appetite loss improved the performance of an existing model for the diagnosis of CAP in the elderly. PMID:29122806

  4. Polymorphous hemangioendothelioma in a child with acquired immunodeficiency syndrome (AIDS).

    PubMed

    Paul, Stephan R; Hurford, Matthew T; Miettinen, Markku M; Aronoff, Stephen C; Delvecchio, Michael; Grewal, Harsh; Tuluc, Madalina

    2008-03-01

    Polymorphous hemangioendotheliomas (PH) are rare and borderline malignant tumors that are among the wide range of vascular tumors. We report here a 13-year-old male presenting with a history of weight loss, opportunistic infections, and lymphadenopathy. He was determined to be HIV positive and to have acquired immunodeficiency syndrome (AIDS). A biopsy of a femoral node was diagnostic of PH. His systemic lymphadenopathy appeared to resolve with anti-retroviral therapy. This tumor should be considered within the differential diagnoses of pediatric and immunocompromised patients. (c) 2007 Wiley-Liss, Inc.

  5. Reduced bone density in androgen-deficient women with acquired immune deficiency syndrome wasting.

    PubMed

    Huang, J S; Wilkie, S J; Sullivan, M P; Grinspoon, S

    2001-08-01

    Women with acquired immune deficiency syndrome wasting are at an increased risk of osteopenia because of low weight, changes in body composition, and hormonal alterations. Although women comprise an increasing proportion of human immunodeficiency virus-infected patients, prior studies have not investigated bone loss in this expanding population of patients. In this study we investigated bone density, bone turnover, and hormonal parameters in 28 women with acquired immune deficiency syndrome wasting and relative androgen deficiency (defined as free testosterone < or =3.0 pg/ml, weight < or =90% ideal body weight, weight loss > or =10% from preillness maximum weight, or weight <100% ideal body weight with weight loss > or =5% from preillness maximum weight). Total body (1.04 +/- 0.08 vs. 1.10 +/- 0.07 g/cm2, human immunodeficiency virus-infected vs. control respectively; P < 0.01), anteroposterior lumbar spine (0.94 +/- 0.12 vs. 1.03 +/- 0.09 g/cm2; P = 0.005), lateral lumbar spine (0.71 +/- 0.14 vs. 0.79 +/- 0.09 g/cm2; P = 0.02), and hip (Ward's triangle; 0.68 +/- 0.14 vs. 0.76 +/- 0.12 g/cm2; P = 0.05) bone density were reduced in the human immunodeficiency virus-infected compared with control subjects. Serum N-telopeptide, a measure of bone resorption, was increased in human immunodeficiency virus-infected patients, compared with control subjects (14.6 +/- 5.8 vs. 11.3 +/- 3.8 nmol/liter bone collagen equivalents, human immunodeficiency virus-infected vs. control respectively; P = 0.03). Although body mass index was similar between the groups, muscle mass was significantly reduced in the human immunodeficiency virus-infected vs. control subjects (16 +/- 4 vs. 21 +/- 4 kg, human immunodeficiency virus-infected vs. control, respectively; P < 0.0001). In univariate regression analysis, muscle mass (r = 0.53; P = 0.004) and estrogen (r = 0.51; P = 0.008), but not free testosterone (r = -0.05, P = 0.81), were strongly associated with lumbar spine bone density in the

  6. North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2

    ClinicalTrials.gov

    2018-06-06

    Epilepsy; Seizure; Neuromuscular Diseases; Brain Malformation; Intellectual Disability; Autism Spectrum Disorder; Hypotonia; Inborn Errors of Metabolism; Movement Disorders; Genetic Disease; Development Delay; Chromosome Abnormality; Hearing Loss; Dysmorphic Features; Skeletal Dysplasia; Congenital Abnormality; Microcephaly; Macrocephaly

  7. A novel mutation in PGAP2 gene causes developmental delay, intellectual disability, epilepsy and microcephaly in consanguineous Saudi family.

    PubMed

    Naseer, Muhammad Imran; Rasool, Mahmood; Jan, Mohammed M; Chaudhary, Adeel G; Pushparaj, Peter Natesan; Abuzenadah, Adel M; Al-Qahtani, Mohammad H

    2016-12-15

    PGAP2 (Post-GPI Attachment to Proteins 2) gene is involved in lipid remodeling steps of Glycosylphosphatidylinositol (GPI)-anchor maturation. At the surface of the cell this gene is required for proper expression of GPI-anchored proteins. Hyperphosphatasia with mental retardation syndrome-3 is an autosomal recessive disorder usually characterized by severe mental retardation. Mutations in the PGAP2 gene cause hyperphosphatasia mental retardation syndrome-3. We have identified a large consanguineous family from Saudi origin segregating developmental delay, intellectual disability, epilepsy and microcephaly. Whole exome sequencing with 100× coverage was performed on two affected siblings of the family. Data analysis in the patient revealed a novel missense mutation c.191C>T in PGAP2 gene resulting in Alanine to Valine substitution (Ala64Val). The mutation was reconfirmed and validated by subsequent Sanger sequencing method. The mutation was ruled out in 100 unrelated healthy controls. We suggest that this pathogenic mutation disrupts the proper function of the gene proteins resulting in the disease state. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Acquired color vision deficiency.

    PubMed

    Simunovic, Matthew P

    2016-01-01

    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Acquired platelet function defect

    MedlinePlus

    ... Some cases cannot be prevented. Alternative Names Acquired qualitative platelet disorders; Acquired disorders of platelet function Images ... Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by VeriMed Healthcare ...

  10. Beyond restoration to transformation: positive outcomes in the rehabilitation of acquired brain injury.

    PubMed

    McGrath, Joanna

    2004-11-01

    This paper compares the situation of the person with acquired brain injury to that of the people of Israel in the sixth century BCE (before the current era) during the period of exile in Babylon. Both situations are characterized by traumatic multiple losses, and a struggle to regain a sense of identity: personal, national or spiritual. Evidence from the literature on both brain injury rehabilitation and from the Hebrew Scriptures indicates that models of restoration of function and transformation of suffering have been applied to both situations. The relative strengths and weaknesses of these models are considered, and it is argued that models of transformation of suffering have much to offer, especially in the longer term psychotherapeutic rehabilitation of people with acquired brain injury, when restoration of function has reached its limits.

  11. A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly

    PubMed Central

    Abdulkarim, Baroj; Igoillo-Esteve, Mariana; Daures, Mathilde; Romero, Sophie; Philippi, Anne; Senée, Valérie; Lopes, Miguel; Cunha, Daniel A.; Harding, Heather P.; Derbois, Céline; Bendelac, Nathalie; Hattersley, Andrew T.; Eizirik, Décio L.; Ron, David

    2015-01-01

    Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) encoding the regulatory subunit of an eIF2α-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation and results in β-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to β-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities. PMID:26159176

  12. A homozygous mutation in SLC1A4 in siblings with severe intellectual disability and microcephaly.

    PubMed

    Srour, M; Hamdan, F F; Gan-Or, Z; Labuda, D; Nassif, C; Oskoui, M; Gana-Weisz, M; Orr-Urtreger, A; Rouleau, G A; Michaud, J L

    2015-07-01

    We performed exome analysis in two affected siblings with severe intellectual disability (ID), microcephaly and spasticity from an Ashkenazi Jewish consanguineous family. We identified only one rare variant, a missense in SLC1A4 (c. 766G>A [p. E256K]), that is homozygous in both siblings but not in any of their 11 unaffected siblings or their parents (Logarithm of odds, LOD score: 2.6). This variant is predicted damaging. We genotyped 450 controls of Ashkenazi Jewish ancestry and identified only 5 individuals who are heterozygous for this variant (minor allele frequency: 0.0056). SLC1A4 (ASCT1) encodes a transporter for neutral aminoacids such as alanine, serine, cysteine and threonine. L-Serine is essential for neuronal survival and differentiation. Indeed, L-serine biosynthesis disorders affect brain development and cause severe ID. In the brain, L-serine is synthesized in astrocytes but not in neurons. It has been proposed that ASCT1 mediates the uptake of L-serine into neurons and the release of glia-borne L-serine to neighboring cells. SLC1A4 disruption may thus impair brain development and function by decreasing the levels of L-serine in neurons. The identification of additional families with mutations in SLC1A4 would be necessary to confirm its involvement in ID. © 2015 John Wiley | Clinical Exome Genome Reports.

  13. Unpleasant odors increase aversion to monetary losses.

    PubMed

    Stancak, Andrej; Xie, Yuxin; Fallon, Nicholas; Bulsing, Patricia; Giesbrecht, Timo; Thomas, Anna; Pantelous, Athanasios A

    2015-04-01

    Loss aversion is the tendency to prefer avoiding losses over acquiring gains of equal nominal values. Unpleasant odors not only influence affective state but have also been shown to activate brain regions similar to those mediating loss aversion. Therefore, we hypothesized a stronger loss aversion in a monetary gamble task if gambles were associated with an unpleasant as opposed to pleasant odor. In thirty human subjects, unpleasant (methylmercaptan), pleasant (jasmine), and neutral (clean air) odors were presented for 4 s. At the same time, uncertain gambles offering an equal chance of gain or loss of a variable amount of money, or a prospect of an assured win were displayed. One hundred different gambles were presented three times, each time paired with a different odor. Loss aversion, risk aversion, and logit sensitivity were evaluated using non-linear fitting of individual gamble decisions. Loss aversion was larger when prospects were displayed in the presence of methylmercaptan compared to jasmine or clean air. Moreover, individual differences in changes in loss aversion to the unpleasant as compared to pleasant odor correlated with odor pleasantness but not with odor intensity. Skin conductance responses to losses during the outcome period were larger when gambles were associated with methylmercaptan compared to jasmine. Increased loss aversion while perceiving an unpleasant odor suggests a dynamic adjustment of loss aversion toward greater sensitivity to losses. Given that odors are biological signals of hazards, such adjustment of loss aversion may have adaptive value in situations entailing threat or danger. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Diagnostic utility of appetite loss in addition to existing prediction models for community-acquired pneumonia in the elderly: a prospective diagnostic study in acute care hospitals in Japan.

    PubMed

    Takada, Toshihiko; Yamamoto, Yosuke; Terada, Kazuhiko; Ohta, Mitsuyasu; Mikami, Wakako; Yokota, Hajime; Hayashi, Michio; Miyashita, Jun; Azuma, Teruhisa; Fukuma, Shingo; Fukuhara, Shunichi

    2017-11-08

    Diagnosis of community-acquired pneumonia (CAP) in the elderly is often delayed because of atypical presentation and non-specific symptoms, such as appetite loss, falls and disturbance in consciousness. The aim of this study was to investigate the external validity of existing prediction models and the added value of the non-specific symptoms for the diagnosis of CAP in elderly patients. Prospective cohort study. General medicine departments of three teaching hospitals in Japan. A total of 109 elderly patients who consulted for upper respiratory symptoms between 1 October 2014 and 30 September 2016. The reference standard for CAP was chest radiograph evaluated by two certified radiologists. The existing models were externally validated for diagnostic performance by calibration plot and discrimination. To evaluate the additional value of the non-specific symptoms to the existing prediction models, we developed an extended logistic regression model. Calibration, discrimination, category-free net reclassification improvement (NRI) and decision curve analysis (DCA) were investigated in the extended model. Among the existing models, the model by van Vugt demonstrated the best performance, with an area under the curve of 0.75(95% CI 0.63 to 0.88); calibration plot showed good fit despite a significant Hosmer-Lemeshow test (p=0.017). Among the non-specific symptoms, appetite loss had positive likelihood ratio of 3.2 (2.0-5.3), negative likelihood ratio of 0.4 (0.2-0.7) and OR of 7.7 (3.0-19.7). Addition of appetite loss to the model by van Vugt led to improved calibration at p=0.48, NRI of 0.53 (p=0.019) and higher net benefit by DCA. Information on appetite loss improved the performance of an existing model for the diagnosis of CAP in the elderly. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. The impact of community-acquired pneumonia on the health-related quality-of-life in elderly.

    PubMed

    Mangen, Marie-Josée J; Huijts, Susanne M; Bonten, Marc J M; de Wit, G Ardine

    2017-03-14

    The sustained health-related quality-of-life of patients surviving community-acquired pneumonia has not been accurately quantified. The aim of the current study was to quantify differences in health-related quality-of-life of community-dwelling elderly with and without community-acquired pneumonia during a 12-month follow-up period. In a matched cohort study design, nested in a prospective randomized double-blind placebo-controlled trial on the efficacy of the 13-valent pneumococcal vaccine in community-dwelling persons of ≥65 years, health-related quality-of-life was assessed in 562 subjects hospitalized with suspected community-acquired pneumonia (i.e. diseased cohort) and 1145 unaffected persons (i.e. non-diseased cohort) matched to pneumonia cases on age, sex, and health status (EQ-5D-3L-index). Health-related quality-of-life was determined 1-2 weeks after hospital discharge/inclusion and 1, 6 and 12 months thereafter, using Euroqol EQ-5D-3L and Short Form-36 Health survey questionnaires. One-year quality-adjusted life years (QALY) were estimated for both diseased and non-diseased cohorts. Separate analyses were performed for pneumonia cases with and without radiologically confirmed community-acquired pneumonia. The one-year excess QALY loss attributed to community-acquired pneumonia was 0.13. Mortality in the post-discharge follow-up year was 8.4% in community-acquired pneumonia patients and 1.2% in non-diseased persons (p < 0.001). During follow-up health-related quality-of-life was persistently lower in community-acquired pneumonia patients, compared to non-diseased persons, but differences in health-related quality-of-life between radiologically confirmed and non-confirmed community-acquired pneumonia cases were not statistically significant. Community-acquired pneumonia was associated with a six-fold increased mortality and 16% lower quality-of-life in the post-discharge year among patients surviving hospitalization for community-acquired

  16. Analysis of National Trends in Hospital Acquired Conditions Following Major Urological Surgery Before and After Implementation of the Hospital Acquired Condition Reduction Program,,✰✰✰.

    PubMed

    Rude, Tope L; Donin, Nicholas M; Cohn, Matthew R; Meeks, William; Gulig, Scott; Patel, Samir N; Wysock, James S; Makarov, Danil V; Bjurlin, Marc A

    2018-06-07

    To define the rates of common Hospital Acquired Conditions (HACs) in patients undergoing major urological surgery over a period of time encompassing the implementation of the Hospital Acquired Condition Reduction program, and to evaluate whether implementation of the HAC reimbursement penalties in 2008 was associated with a change in the rate of HACs. Using American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data, we determined rates of HACs in patients undergoing major inpatient urological surgery from 2005 to 2012. Rates were stratified by procedure type and approach (open vs. laparoscopic/robotic). Multivariable logistic regression was used to determine the association between year of surgery and HACs. We identified 39,257 patients undergoing major urological surgery, of whom 2300 (5.9%) had at least one hospital acquired condition. Urinary tract infection (UTI, 2.6%) was the most common, followed by surgical site infection (SSI, 2.5%) and venous thrombotic events (VTE, 0.7%). Multivariable logistic regression analysis demonstrated that open surgical approach, diabetes, congestive heart failure, chronic obstructive pulmonary disease, weight loss, and ASA class were among the variables associated with higher likelihood of HAC. We observed a non-significant secular trend of decreasing rates of HAC from 7.4% to 5.8% HACs during the study period, which encompassed the implementation of the Hospital Acquired Condition Reduction Program. HACs occurred at a rate of 5.9% after major urological surgery, and are significantly affected by procedure type and patient health status. The rate of HAC appeared unaffected by national reduction program in this cohort. Better understanding of the factors associated with HACs is critical in developing effective reduction programs. Copyright © 2018. Published by Elsevier Inc.

  17. Staphylococcus aureus PBP4 Is Essential for β-Lactam Resistance in Community-Acquired Methicillin-Resistant Strains▿

    PubMed Central

    Memmi, Guido; Filipe, Sergio R.; Pinho, Mariana G.; Fu, Zhibiao; Cheung, Ambrose

    2008-01-01

    Recent cases of infections caused by community-acquired methicillin-resistant Staphylococcus aureus (MRSA) (CA-MRSA) strains in healthy individuals have raised concerns worldwide. CA-MRSA strains differ from hospital-acquired MRSAs by virtue of their genomic background and increased virulence in animal models. Here, we show that in two common CA-MRSA isolates, USA300 and MW2 (USA400), a loss of penicillin binding protein 4 (PBP4) is sufficient to cause a 16-fold reduction in oxacillin and nafcillin resistance, thus demonstrating that mecA, encoding PBP2A, is not the sole determinant of methicillin resistance in CA-MRSA. The loss of PBP4 was also found to severely affect the transcription of PBP2 in cells after challenge with oxacillin, thus leading to a significant decrease in peptidoglycan cross-linking. Autolysis, which is commonly associated with the killing mechanism of penicillin and β-lactams, does not play a role in the reduced resistance phenotype associated with the loss of PBP4. We also showed that cefoxitin, a semisynthetic β-lactam that binds irreversibly to PBP4, is synergistic with oxacillin in killing CA-MRSA strains, including clinical CA-MRSA isolates. Thus, PBP4 represents a major target for drug rediscovery against CA-MRSA, and a combination of cefoxitin and synthetic penicillins may be an effective therapy for CA-MRSA infections. PMID:18725435

  18. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study.

    PubMed

    de Fatima Vasco Aragao, Maria; van der Linden, Vanessa; Brainer-Lima, Alessandra Mertens; Coeli, Regina Ramos; Rocha, Maria Angela; Sobral da Silva, Paula; Durce Costa Gomes de Carvalho, Maria; van der Linden, Ana; Cesario de Holanda, Arthur; Valenca, Marcelo Moraes

    2016-04-13

    To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Retrospective study with a case series. Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus--the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection

  19. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

    PubMed Central

    van der Linden, Vanessa; Brainer-Lima, Alessandra Mertens; Coeli, Regina Ramos; Rocha, Maria Angela; Sobral da Silva, Paula; Durce Costa Gomes de Carvalho, Maria; van der Linden, Ana; Cesario de Holanda, Arthur; Valenca, Marcelo Moraes

    2016-01-01

    Objective To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Design Retrospective study with a case series. Setting Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. Participants 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Results Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus—the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Conclusion Severe cerebral damage was

  20. Acquired hyperpigmentations*

    PubMed Central

    Cestari, Tania Ferreira; Dantas, Lia Pinheiro; Boza, Juliana Catucci

    2014-01-01

    Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis PMID:24626644

  1. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... EXCHANGE COMMISSION FORM AND CONTENT OF AND REQUIREMENTS FOR FINANCIAL STATEMENTS, SECURITIES ACT OF 1933..., INVESTMENT ADVISERS ACT OF 1940, AND ENERGY POLICY AND CONSERVATION ACT OF 1975 Article 8 Financial Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired. If...

  2. Detection of Unilateral Hearing Loss by Stationary Wavelet Entropy.

    PubMed

    Zhang, Yudong; Nayak, Deepak Ranjan; Yang, Ming; Yuan, Ti-Fei; Liu, Bin; Lu, Huimin; Wang, Shuihua

    2017-01-01

    Sensorineural hearing loss is correlated to massive neurological or psychiatric disease. T1-weighted volumetric images were acquired from fourteen subjects with right-sided hearing loss (RHL), fifteen subjects with left-sided hearing loss (LHL), and twenty healthy controls (HC). We treated a three-class classification problem: HC, LHL, and RHL. Stationary wavelet entropy was employed to extract global features from magnetic resonance images of each subject. Those stationary wavelet entropy features were used as input to a single-hidden layer feedforward neuralnetwork classifier. The 10 repetition results of 10-fold cross validation show that the accuracies of HC, LHL, and RHL are 96.94%, 97.14%, and 97.35%, respectively. Our developed system is promising and effective in detecting hearing loss. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Prenatal diagnosis and molecular cytogenetic characterization of de novo pure partial trisomy 6p associated with microcephaly, craniosynostosis and abnormal maternal serum biochemistry.

    PubMed

    Chen, Chih-Ping; Chen, Ming; Chen, Chen-Yu; Chern, Schu-Rern; Wu, Peih-Shan; Chang, Shun-Ping; Kuo, Yu-Ling; Chen, Wen-Lin; Pan, Chen-Wen; Wang, Wayseen

    2014-02-25

    We present prenatal diagnosis and molecular cytogenetic characterization of de novo pure trisomy 6p22.3 → p25.3 encompassing BMP6 in a fetus associated with microcephaly and craniosynostosis on prenatal ultrasound, abnormal maternal serum biochemistry of a low PAPP-A level in the first-trimester combined test, and a karyotype of 46,XX,der(22)t(6;22)(p22.3;p13)dn. The present case demonstrates the usefulness of rapid prenatal identification of the origin of the extra chromosome material on the short arm of an acrocentric chromosome by spectral karyotyping, fluorescence in situ hybridization and array comparative genomic hybridization. We review the phenotypic abnormality of craniosynostosis in previously reported patients with partial trisomy 6p. We discuss the genotype-phenotype correlation of the involved gene of BMP6 in this case. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries. Effective...

  5. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries. Effective...

  6. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries. Effective...

  7. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries. Effective...

  8. Johnson-McMillin syndrome, a neuroectodermal syndrome with conductive hearing loss and microtia: report of a new case.

    PubMed

    Schweitzer, Daniela N; Yano, Shoji; Earl, Dawn L; Graham, John M

    2003-07-30

    In 1983, Johnson et al. described 16 related individuals with alopecia, anosmia or hyposmia, conductive hearing loss, microtia and/or atresia of the external auditory canal, and hypogonadotrophic hypogonadism inherited in an autosomal dominant pattern. Other less constant manifestations included facial asymmetry, mental retardation, congenital heart defect, cleft palate, and choanal stenosis. An isolated case was reported later (Johnston et al. [1987: Am J Med Genet 26: 925-927]) and thereafter an affected mother and son (Hennekam and Holtus [1993: Am J Med Genet 47: 714-716]). We describe an additional unrelated female patient with features resembling those of the previously reported cases. She presented with intrauterine growth deficiency, microcephaly, alopecia, bilateral microtia with canal atresia, conductive hearing loss, partial left facial palsy, posterior cleft palate, left choanal stenosis, tetralogy of Fallot, developmental delay, and right thumb polydactyly. Because the phenotypic abnormalities in this syndrome affect the brain, facial structures, ectoderm and its derivatives, outflow tract of the heart, and Rathke's pouch derivatives, this has suggested to previous authors etiologic involvement of the ectoderm and neuroectoderm of the first and second branchial arches, Rathke's pouch, and the diencephalon. Microtia with conductive hearing loss differentiates the condition from other ectodermal dysplasias. In the initial report, females appeared somewhat less affected than males, and there was male-to-male transmission. The mother of our patient manifests subtle features, which suggest she may be a mildly affected female. Additionally, there is a family history of early-onset alopecia in the maternal grandfather's relatives. Copyright 2003 Wiley-Liss, Inc.

  9. The role of arbuscular mycorrhizas in reducing soil nutrient loss.

    PubMed

    Cavagnaro, Timothy R; Bender, S Franz; Asghari, Hamid R; Heijden, Marcel G A van der

    2015-05-01

    Substantial amounts of nutrients are lost from soils via leaching and as gaseous emissions. These losses can be environmentally damaging and expensive in terms of lost agricultural production. Plants have evolved many traits to optimize nutrient acquisition, including the formation of arbuscular mycorrhizas (AM), associations of plant roots with fungi that acquire soil nutrients. There is emerging evidence that AM have the ability to reduce nutrient loss from soils by enlarging the nutrient interception zone and preventing nutrient loss after rain-induced leaching events. Until recently, this important ecosystem service of AM had been largely overlooked. Here we review the role of AM in reducing nutrient loss and conclude that this role cannot be ignored if we are to increase global food production in an environmentally sustainable manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries. Effective...

  11. Reduction of susceptibility-induced signal losses in multi-gradient-echo images: application to improved visualization of the subthalamic nucleus.

    PubMed

    Volz, Steffen; Hattingen, Elke; Preibisch, Christine; Gasser, Thomas; Deichmann, Ralf

    2009-05-01

    T2-weighted gradient echo (GE) images yield good contrast of iron-rich structures like the subthalamic nuclei due to microscopic susceptibility induced field gradients, providing landmarks for the exact placement of deep brain stimulation electrodes in Parkinson's disease treatment. An additional advantage is the low radio frequency (RF) exposure of GE sequences. However, T2-weighted images are also sensitive to macroscopic field inhomogeneities, resulting in signal losses, in particular in orbitofrontal and temporal brain areas, limiting anatomical information from these areas. In this work, an image correction method for multi-echo GE data based on evaluation of phase information for field gradient mapping is presented and tested in vivo on a 3 Tesla whole body MR scanner. In a first step, theoretical signal losses are calculated from the gradient maps and a pixelwise image intensity correction is performed. In a second step, intensity corrected images acquired at different echo times TE are combined using optimized weighting factors: in areas not affected by macroscopic field inhomogeneities, data acquired at long TE are weighted more strongly to achieve the contrast required. For large field gradients, data acquired at short TE are favored to avoid signal losses. When compared to the original data sets acquired at different TE and the respective intensity corrected data sets, the resulting combined data sets feature reduced signal losses in areas with major field gradients, while intensity profiles and a contrast-to-noise (CNR) analysis between subthalamic nucleus, red nucleus and the surrounding white matter demonstrate good contrast in deep brain areas.

  12. Characteristics of children with unilateral hearing loss.

    PubMed

    Fitzpatrick, Elizabeth M; Al-Essa, Rakan S; Whittingham, JoAnne; Fitzpatrick, Jessica

    2017-11-01

    The purpose of this study was to describe the clinical characteristics of children with unilateral hearing loss (UHL), examine deterioration in hearing, and explore amplification decisions. Population-based data were collected prospectively from time of diagnosis. Serial audiograms and amplification details were retrospectively extracted from clinical charts to document the trajectory and management of hearing loss. The study included all children identified with UHL in one region of Canada over a 13-year period (2003-2015) after implementation of universal newborn hearing screening. Of 537 children with permanent hearing loss, 20.1% (108) presented with UHL at diagnosis. They were identified at a median age of 13.9 months (IQR: 2.8, 49.0). Children with congenital loss were identified at 2.8 months (IQR: 2.0, 3.6) and made up 47.2% (n = 51), reflecting that a substantial portion had late-onset, acquired or late-identified loss. A total of 42.4% (n = 39) showed deterioration in hearing, including 16 (17.4%) who developed bilateral loss. By study end, 73.1% (79/108) of children had received amplification recommendations. Up to 20% of children with permanent HL are first diagnosed with UHL. About 40% are at risk for deterioration in hearing either in the impaired ear and/or in the normal hearing ear.

  13. Community-acquired pneumonia.

    PubMed

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  14. Thrombophilia and Recurrent Pregnancy Loss

    PubMed Central

    Abu-Heija, Adel

    2014-01-01

    The association between thrombophilia and recurrent pregnancy loss (RPL) has become an undisputed fact. Thorombophilia creates a hypercoaguable state which leads to arterial and/or venous thrombosis at the site of implantation or in the placental blood vessels. Anticoagulants are an effective treatment against RPL in women with acquired thrombophilia due to antiphospholipid syndrome. The results of the use of anticoagulants for treating RPL in women with inherited thrombophilia (IT) are encouraging, but recently four major multicentre studies have shown that fetal outcomes (determined by live birth rates) may not be as favourable as previously suggested. Although the reported side-effects for anticoagulants are rare and usually reversible, the current recommendation is not to use anticoagulants in women with RPL and IT, or for those with unexplained losses. This review examines the strength of the association between thrombophilia and RPL and whether the use of anticoagulants can improve fetal outcomes. PMID:24516750

  15. Hospital-acquired pneumonia

    MedlinePlus

    ... pneumonia; HCAP Patient Instructions Pneumonia in adults - discharge Images Hospital-acquired pneumonia Respiratory system References Chastre J, Luyt C-E. Ventilator-associated pneumonia. In: Broaddus ...

  16. Reconstruction of acquired sub-total ear defects with autologous costal cartilage.

    PubMed

    Harris, P A; Ladhani, K; Das-Gupta, R; Gault, D T

    1999-06-01

    Acquired sub-total ear defects are common and challenging to reconstruct. We report the use of an autologous costal cartilage framework to reconstruct sub-total defects involving all anatomical regions of the ear. Twenty-eight partially damaged ears in 27 patients were reconstructed with this technique. The defects resulted from bites (14), road traffic accidents (five), burns (four), iatrogenic causes (four) and chondritis following minor trauma (one). Computerised image analysis revealed a median of 31% (range 13-72%) ear loss. An autologous costal cartilage framework was fashioned in all cases. If adequate local skin was available, this was draped over the framework, but in nine cases preliminary tissue expansion was used and in a further three cases with significant scarring, the framework was covered with a temporoparietal fascial flap. Clinical assessment after ear reconstruction was undertaken, scoring for symmetry, the helical rim, the antihelical fold, the lobe position and a 'natural look' to produce a four-point scale; 11 were excellent, 12 were good, two were fair and three were poor. Our experience suggests that formal delayed reconstruction with autologous costal cartilage is to be recommended when managing acquired, sub-total ear deformity.

  17. Children Acquire Emotion Categories Gradually

    ERIC Educational Resources Information Center

    Widen, Sherri C.; Russell, James A.

    2008-01-01

    Some accounts imply that basic-level emotion categories are acquired early and quickly, whereas others imply that they are acquired later and more gradually. Our study examined this question for fear, happiness, sadness, and anger in the context of children's categorization of emotional facial expressions. Children (N=168, 2-5 years) first labeled…

  18. Ensuring the profitability of acquired physician practices.

    PubMed

    Ortiz, J P

    1997-01-01

    Healthcare organizations are aggressively acquiring physician group practices to create primary care networks and broaden their managed care market penetration. However, few are realizing a positive return on investment after acquisition. The odds that acquired practices will be profitable can be improved if healthcare organizations plan carefully by establishing separate acquiring entities, setting clear goals for the practices, forming skilled management teams with strong physician leadership to manage the acquired practices, and carefully structuring their physician incentive compensation plans.

  19. Cortical neurogenesis in the absence of centrioles.

    PubMed

    Insolera, Ryan; Bazzi, Hisham; Shao, Wei; Anderson, Kathryn V; Shi, Song-Hai

    2014-11-01

    Neuronal production in the mammalian cortex depends on extensive mitoses of radial glial progenitors (RGPs) residing in the ventricular zone (VZ). We examined the function of centrioles in RGPs during cortical neurogenesis in mice by conditional removal of SAS-4, a protein that is required for centriole biogenesis. SAS-4 deletion led to a progressive loss of centrioles, accompanied by RGP detachment from the VZ. Delocalized RGPs did not become outer subventricular zone RGPs (oRGs). Although they remained proliferative, ectopic RGPs, as well as those in the VZ, with a centrosomal deficit exhibited prolonged mitosis, p53 upregulation and apoptosis, resulting in neuronal loss and microcephaly. Simultaneous removal of p53 fully rescued RGP death and microcephaly, but not RGP delocalization and randomized mitotic spindle orientation. Our findings define the functions of centrioles in anchoring RGPs in the VZ and ensuring their efficient mitoses, and reveal the robust adaptability of RGPs in the developing cortex.

  20. 48 CFR 1845.502-70 - Contractor-acquired property.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contractor-acquired... Possession of Contractors 1845.502-70 Contractor-acquired property. All contractor-acquired property must be... contractor-acquired. (2) Submission of DD Form 1419, DOD Industrial Plant Requisition, or equivalent format...

  1. EPHA2 blockade overcomes acquired resistance to EGFR kinase inhibitors in lung cancer

    PubMed Central

    Amato, Katherine R.; Wang, Shan; Tan, Li; Hastings, Andrew K.; Song, Wenqiang; Lovly, Christine M.; Meador, Catherine B.; Ye, Fei; Lu, Pengcheng; Balko, Justin M.; Colvin, Daniel C.; Cates, Justin M.; Pao, William; Gray, Nathanael S.; Chen, Jin

    2015-01-01

    Despite the success of treating EGFR mutant lung cancer patients with EGFR tyrosine kinase inhibitors (TKIs), all patients eventually acquire resistance to these therapies. Although various resistance mechanisms have been described, there are currently no FDA-approved therapies that target alternative mechanisms to treat lung tumors with acquired resistance to first-line EGFR TKI agents. Here we found that EPHA2 is overexpressed in EGFR TKI resistant tumor cells. Loss of EPHA2 reduced the viability of erlotinib resistant tumor cells harboring EGFRT790M mutations in vitro and inhibited tumor growth and progression in an inducible EGFRL858R+T790M mutant lung cancer model in vivo. Targeting EPHA2 in erlotinib resistant cells decreased S6K1-mediated phosphorylation of cell death agonist BAD, resulting in reduced tumor cell proliferation and increased apoptosis. Furthermore, pharmacologic inhibition of EPHA2 by the small molecule inhibitor, ALW-II-41-27, decreased both survival and proliferation of erlotinib resistant tumor cells and inhibited tumor growth in vivo. ALW-II-41-27 was also effective in decreasing viability of cells with acquired resistance to the third generation EGFR TKI, AZD9291. Collectively, these data define a role for EPHA2 in the maintenance of cell survival of TKI resistant, EGFR mutant lung cancer and indicate that EPHA2 may serve as a useful therapeutic target in TKI resistant tumors. PMID:26744526

  2. Mass Loss of Larsen B Tributary Glaciers (Antarctic Peninsula) Unabated Since 2002

    NASA Technical Reports Server (NTRS)

    Berthier, Etienne; Scambos, Ted; Shuman, Christopher A.

    2012-01-01

    Ice mass loss continues at a high rate among the large glacier tributaries of the Larsen B Ice Shelf following its disintegration in 2002. We evaluate recent mass loss by mapping elevation changes between 2006 and 201011 using differencing of digital elevation models (DEMs). The measurement accuracy of these elevation changes is confirmed by a null test, subtracting DEMs acquired within a few weeks. The overall 2006201011 mass loss rate (9.0 2.1 Gt a-1) is similar to the 2001022006 rate (8.8 1.6 Gt a-1), derived using DEM differencing and laser altimetry. This unchanged overall loss masks a varying pattern of thinning and ice loss for individual glacier basins. On Crane Glacier, the thinning pulse, initially greatest near the calving front, is now broadening and migrating upstream. The largest losses are now observed for the HektoriaGreen glacier basin, having increased by 33 since 2006. Our method has enabled us to resolve large residual uncertainties in the Larsen B sector and confirm its state of ongoing rapid mass loss.

  3. Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

    PubMed Central

    He, Miao; Kratz, Lisa E.; Michel, Joshua J.; Vallejo, Abbe N.; Ferris, Laura; Kelley, Richard I.; Hoover, Jacqueline J.; Jukic, Drazen; Gibson, K. Michael; Wolfe, Lynne A.; Ramachandran, Dhanya; Zwick, Michael E.; Vockley, Jerry

    2011-01-01

    Defects in cholesterol synthesis result in a wide variety of symptoms, from neonatal lethality to the relatively mild dysmorphic features and developmental delay found in individuals with Smith-Lemli-Opitz syndrome. We report here the identification of mutations in sterol-C4-methyl oxidase–like gene (SC4MOL) as the cause of an autosomal recessive syndrome in a human patient with psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay. This gene encodes a sterol-C4-methyl oxidase (SMO), which catalyzes demethylation of C4-methylsterols in the cholesterol synthesis pathway. C4-Methylsterols are meiosis-activating sterols (MASs). They exist at high concentrations in the testis and ovary and play roles in meiosis activation. In this study, we found that an accumulation of MASs in the patient led to cell overproliferation in both skin and blood. SMO deficiency also substantially altered immunocyte phenotype and in vitro function. MASs serve as ligands for liver X receptors α and β (LXRα and LXRβ), which are important in regulating not only lipid transport in the epidermis, but also innate and adaptive immunity. Deficiency of SMO represents a biochemical defect in the cholesterol synthesis pathway, the clinical spectrum of which remains to be defined. PMID:21285510

  4. Clinico-radiological and molecular characterization of a child with ring chromosome 2 presenting growth failure, microcephaly, kidney and brain malformations.

    PubMed

    Severino, Mariasavina; Accogli, Andrea; Gimelli, Giorgio; Rossi, Andrea; Kotzeva, Svetlana; Di Rocco, Maja; Ronchetto, Patrizia; Cuoco, Cristina; Tassano, Elisa

    2015-01-01

    Ring chromosome 2 is a rare constitutional abnormality that generally occurs de novo. About 14 cases have been described to date, but the vast majority of papers report exclusively conventional cytogenetic investigations and only two have been characterized by array-CGH. Here we describe the clinical, neuroradiological, and molecular features of a 5-year-old boy harbouring a ring chromosome 2 presenting with severe growth failure, facial and bone dysmorphisms, microcephaly, and renal malformation. Brain MR with diffusion tensor imaging revealed simplified cortical gyration, pontine hypoplasia, and abnormally thick posterior corpus callosum, suggesting an underlying axonal guidance defect. Cytogenetic investigations showed a karyotype with a ring chromosome 2 and FISH analysis with subtelomeric probes revealed the absence of signals on both arms. These results were confirmed by array-CGH showing terminal deletions on 2p25.3 (~439 kb) and 2q37.3 (~3.4 Mb). Our report describes a new patient with a ring chromosome 2 completely characterised by array-CGH providing additional information useful not only to study genotype-phenotype correlation but also to validate the role of already reported candidate genes and to suggest novel ones which could improve our understanding of the clinical features associated with ring chromosome 2.

  5. How many entities exist for the spectrum of disorders associated with brachydactyly, syndactyly, short stature, microcephaly, and intellectual disability?

    PubMed

    Ravel, Aimé; Chouery, Eliane; Stora, Samantha; Jalkh, Nadine; Villard, Laurent; Temtamy, Samia; Mégarbané, André

    2011-04-01

    We describe a French young man with digital anomalies consisting of brachydactyly, F1-5 bilateral camptodactyly, interdigital webbing, F5 bilateral radial clinodactyly, and partial syndactyly of some fingers and toes. He had psychomotor retardation, short stature, umbilical hernia, a secundum atrial septal defect, seizures, hearing impairment, and dysmorphic features consisting of microcephaly, a prominent metopic ridge, upslanting palpebral fissures, synophrys, enophthalmia, large ears, a bulbous nose, a high palate, a smooth and short philtrum, a low hanging columella, a thin upper vermillion, an everted lower lip, prognathism, pectum excavatum, and supernumerary nipples. Osteotendinous reflexes were brisk. Mild nystagmus, myopia, and astigmatia were also noted. Total body X-rays showed short terminal phalanges of the hands, short middle phalanges of the index and little fingers, clinodactyly of the little fingers, short and fused proximal 4th and 5th metacarpals of the right hand, a short 5th metacarpal of the left hand, a fused left lunate-triquetrum, fused capitate-hamates, a prominent mandibula, and partial sacral agenesis. A thin posterior corpus callosum was apparent by MRI. Differential diagnoses for mainly the Rubinstein-Taybi syndrome, the Tsukahara syndrome, the Filippi syndrome, the Feingold syndrome, and the Tonoki syndrome are discussed, and the possibility that we might be reporting a novel entity is raised. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc.

  6. 7 CFR 760.810 - Qualifying 2005, 2006, or 2007 quantity crop losses.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... production by colonies or bees was diminished, will not include losses: (1) For the 2007 crop, for production from those bees acquired on or after February 28, 2007; (2) Where the inability to extract was due to... operation; (3) Resulting from storage of honey after harvest; (4) To honey production because of bee feeding...

  7. 7 CFR 760.810 - Qualifying 2005, 2006, or 2007 quantity crop losses.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... production by colonies or bees was diminished, will not include losses: (1) For the 2007 crop, for production from those bees acquired on or after February 28, 2007; (2) Where the inability to extract was due to... operation; (3) Resulting from storage of honey after harvest; (4) To honey production because of bee feeding...

  8. 7 CFR 760.810 - Qualifying 2005, 2006, or 2007 quantity crop losses.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... production by colonies or bees was diminished, will not include losses: (1) For the 2007 crop, for production from those bees acquired on or after February 28, 2007; (2) Where the inability to extract was due to... operation; (3) Resulting from storage of honey after harvest; (4) To honey production because of bee feeding...

  9. 7 CFR 760.810 - Qualifying 2005, 2006, or 2007 quantity crop losses.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... production by colonies or bees was diminished, will not include losses: (1) For the 2007 crop, for production from those bees acquired on or after February 28, 2007; (2) Where the inability to extract was due to... operation; (3) Resulting from storage of honey after harvest; (4) To honey production because of bee feeding...

  10. A Cost-Effectiveness Tool for Informing Policies on Zika Virus Control.

    PubMed

    Alfaro-Murillo, Jorge A; Parpia, Alyssa S; Fitzpatrick, Meagan C; Tamagnan, Jules A; Medlock, Jan; Ndeffo-Mbah, Martial L; Fish, Durland; Ávila-Agüero, María L; Marín, Rodrigo; Ko, Albert I; Galvani, Alison P

    2016-05-01

    As Zika virus continues to spread, decisions regarding resource allocations to control the outbreak underscore the need for a tool to weigh policies according to their cost and the health burden they could avert. For example, to combat the current Zika outbreak the US President requested the allocation of $1.8 billion from Congress in February 2016. Illustrated through an interactive tool, we evaluated how the number of Zika cases averted, the period during pregnancy in which Zika infection poses a risk of microcephaly, and probabilities of microcephaly and Guillain-Barré Syndrome (GBS) impact the cost at which an intervention is cost-effective. From Northeast Brazilian microcephaly incidence data, we estimated the probability of microcephaly in infants born to Zika-infected women (0.49% to 2.10%). We also estimated the probability of GBS arising from Zika infections in Brazil (0.02% to 0.06%) and Colombia (0.08%). We calculated that each microcephaly and GBS case incurs the loss of 29.95 DALYs and 1.25 DALYs per case, as well as direct medical costs for Latin America and the Caribbean of $91,102 and $28,818, respectively. We demonstrated the utility of our cost-effectiveness tool with examples evaluating funding commitments by Costa Rica and Brazil, the US presidential proposal, and the novel approach of genetically modified mosquitoes. Our analyses indicate that the commitments and the proposal are likely to be cost-effective, whereas the cost-effectiveness of genetically modified mosquitoes depends on the country of implementation. Current estimates from our tool suggest that the health burden from microcephaly and GBS warrants substantial expenditures focused on Zika virus control. Our results justify the funding committed in Costa Rica and Brazil and many aspects of the budget outlined in the US president's proposal. As data continue to be collected, new parameter estimates can be customized in real-time within our user-friendly tool to provide updated

  11. 26 CFR 1.267(d)-1 - Amount of gain where loss previously disallowed.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... previously disallowed. (a) General rule. (1) If a taxpayer acquires property by purchase or exchange from a... a transferor through a sale or exchange in which a loss sustained by the transferor was not... in any manner other than by purchase or exchange. (4) The application of the provisions of this...

  12. The effect of progressive hearing loss on the morphology of endbulbs of Held and bushy cells.

    PubMed

    Connelly, Catherine J; Ryugo, David K; Muniak, Michael A

    2017-01-01

    Studies of congenital and early-onset deafness have demonstrated that an absence of peripheral sound-evoked activity in the auditory nerve causes pathological changes in central auditory structures. The aim of this study was to establish whether progressive acquired hearing loss could lead to similar brain changes that would degrade the precision of signal transmission. We used complementary physiologic hearing tests and microscopic techniques to study the combined effect of both magnitude and duration of hearing loss on one of the first auditory synapses in the brain, the endbulb of Held (EB), along with its bushy cell (BC) target in the anteroventral cochlear nucleus. We compared two hearing mouse strains (CBA/Ca and heterozygous shaker-2 +/- ) against a model of early-onset progressive hearing loss (DBA/2) and a model of congenital deafness (homozygous shaker-2 -/- ), examining each strain at 1, 3, and 6 months of age. Furthermore, we employed a frequency model of the mouse cochlear nucleus to constrain our analyses to regions most likely to exhibit graded changes in hearing function with time. No significant differences in the gross morphology of EB or BC structure were observed in 1-month-old animals, indicating uninterrupted development. However, in animals with hearing loss, both EBs and BCs exhibited a graded reduction in size that paralleled the hearing loss, with the most severe pathology seen in deaf 6-month-old shaker-2 -/- mice. Ultrastructural pathologies associated with hearing loss were less dramatic: minor changes were observed in terminal size but mitochondrial fraction and postsynaptic densities remained relatively stable. These results indicate that acquired progressive hearing loss can have consequences on auditory brain structure, with prolonged loss leading to greater pathologies. Our findings suggest a role for early intervention with assistive devices in order to mitigate long-term pathology and loss of function. Copyright © 2016 Elsevier

  13. Infection Control and Prevention: A Review of Hospital-Acquired Infections and the Economic Implications

    PubMed Central

    Reed, Deoine; Kemmerly, Sandra A.

    2009-01-01

    The Centers for Disease Control and Prevention estimates that 2 million patients suffer from hospital-acquired infections every year and nearly 100,000 of them die. Most of these medical errors are preventable. Hospital-acquired infections result in up to $4.5 billion in additional healthcare expenses annually. The U.S. government has responded to this financial loss by focusing on healthcare quality report cards and by taking strong action to curb healthcare spending. The Medicare Program has proposed changes to the Hospital Inpatient Prospective Payment System and Fiscal Year Rates: Proposed Rule CMS 1488-P-Healthcare-associated infection. Payment will be linked to performance. Under the new rule, payment will be withheld from hospitals for care associated with treating certain catheter-associated urinary tract infections, vascular catheter-associated infections, and mediastinitis after coronary artery bypass graft surgery. Infection-prevention strategies are essential. In the healthcare setting, the infection control department is categorized as non-revenue-producing. Funds dedicated to resources such as staff, educational programs, and prevention measures are vastly limited. Hospital leaders will need to balance the upfront cost needed to prevent hospital-related infections with the non-reimbursed expense accrued secondary to potentially preventable infections. The purpose of this paper is to present case studies and cost analysis of hospital-acquired infections and present strategies that reduce infections and cost. PMID:21603406

  14. EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer.

    PubMed

    Amato, Katherine R; Wang, Shan; Tan, Li; Hastings, Andrew K; Song, Wenqiang; Lovly, Christine M; Meador, Catherine B; Ye, Fei; Lu, Pengcheng; Balko, Justin M; Colvin, Daniel C; Cates, Justin M; Pao, William; Gray, Nathanael S; Chen, Jin

    2016-01-15

    Despite the success of treating EGFR-mutant lung cancer patients with EGFR tyrosine kinase inhibitors (TKI), all patients eventually acquire resistance to these therapies. Although various resistance mechanisms have been described, there are currently no FDA-approved therapies that target alternative mechanisms to treat lung tumors with acquired resistance to first-line EGFR TKI agents. Here we found that EPHA2 is overexpressed in EGFR TKI-resistant tumor cells. Loss of EPHA2 reduced the viability of erlotinib-resistant tumor cells harboring EGFR(T790M) mutations in vitro and inhibited tumor growth and progression in an inducible EGFR(L858R+T790M)-mutant lung cancer model in vivo. Targeting EPHA2 in erlotinib-resistant cells decreased S6K1-mediated phosphorylation of cell death agonist BAD, resulting in reduced tumor cell proliferation and increased apoptosis. Furthermore, pharmacologic inhibition of EPHA2 by the small-molecule inhibitor ALW-II-41-27 decreased both survival and proliferation of erlotinib-resistant tumor cells and inhibited tumor growth in vivo. ALW-II-41-27 was also effective in decreasing viability of cells with acquired resistance to the third-generation EGFR TKI AZD9291. Collectively, these data define a role for EPHA2 in the maintenance of cell survival of TKI-resistant, EGFR-mutant lung cancer and indicate that EPHA2 may serve as a useful therapeutic target in TKI-resistant tumors. ©2016 American Association for Cancer Research.

  15. Orbital volume augmentation using expandable hydrogel implants in acquired anophthalmia and phthisis bulbi.

    PubMed

    Kim, Esther Lee; Bernardino, Carlo Rob; Levin, Flora

    2016-01-01

    The purpose of this study is to describe our experience using expandable spherical hydrogel implants and injectable hydrogel pellets for orbital volume augmentation in cases of post-enucleation socket syndrome after acquired anophthalmia or phthisis bulbi. We retrospectively reviewed the clinical records of all adult patients who received an expandable hydrogel implant for orbital volume loss following enucleation or phthisis bulbi at the Emory Eye Center between 2004 and January 2007 and the Yale Eye Center between 2009 and 2011. The study included 9 women and 5 men with a mean age of 51.2 years old (range 35-76 years old). Follow-up spanned 6 to 71 months (median of 18.5 months). Four patients received spherical hydrogel implants and 10 patients received hydrogel pellet injections. On average, nine pellets (range 5-16) were placed in each patient over an average of 1.7 injections (range 1-3). Most commonly, five pellets were injected per session, as was the case for 13 of the 17 treatment sessions. Post-operative complications included 2 cases of pellet migration, one subcutaneously and one anteriorly due to insufficiently posterior implant placement, and 1 hospital admission for pain after injection of 10 pellets in one visit. All patients experienced an overall subjective improvement in cosmesis. Self-expandable hydrogel implants appear to offer several advantages over other existing options for orbital volume augmentation, as they are easy to place, generally well-tolerated, volume-titratable, and to the extent that our follow-up shows, may be a safe and durable means of treating orbital volume loss in patients with acquired anophthalmia and phthisis bulbi.

  16. The use of a logistic regression model to develop a risk assessment of intraoperatively acquired pressure ulcer.

    PubMed

    Gao, Ling; Yang, Lina; Li, Xiaoqin; Chen, Jin; Du, Juan; Bai, Xiaoxia; Yang, Xianjun

    2018-04-20

    To screen the factors of intraoperatively acquired pressure ulcer and establish a new risk assessment model of intraoperatively acquired pressure ulcer. This is a prospective study. A total of 1,963 patients who received neurosurgery, orthopaedics, paediatric surgery and cardiac surgery therapy in Sichuan Academy of Medical Science and Provincial People's Hospital in China from October 2015-October 2016 were enrolled in the study, and their clinical parameters were collected. Multivariable logistic regression analysis and decision tree analysis were used to analyse and screen the factors of intraoperatively acquired pressure ulcer and establish the risk assessment model of intraoperatively acquired pressure ulcer. The risk factors for intraoperatively acquired pressure ulcer included the application of external force during operation (β = 1.10, OR = 3.20), lean body mass (β = 1.08, OR = 2.95), time of operation ≥6 hr (β = 2.66, OR = 14.30), prone position operation (β = 1.13, OR = 3.10), cardiopulmonary bypass during operation (β = 1.72, OR = 5.59) and intraoperative blood loss (β = 0.67, OR = 1.95). The new risk assessment model showed that the AUC of ROC curve was 0.897 (p < .001). According to the maximum principle of Youden's index, the sensitivity, specificity and Youden's index J of the model were 0.81, 0.88 and 0.69, respectively, when the cut-off point was set at π = 0.025. A new and relatively reliable assessment model for intraoperatively acquired pressure ulcer is established. Pressure ulcers remain a challenge in clinical nursing. A new risk assessment model of pressure ulcers that is applicable to surgical patients is highly recommended. © 2018 John Wiley & Sons Ltd.

  17. Acquired RhD mosaicism identifies fibrotic transformation of thrombopoietin receptor-mutated essential thrombocythemia.

    PubMed

    Montemayor-Garcia, Celina; Coward, Rebecca; Albitar, Maher; Udani, Rupa; Jain, Prachi; Koklanaris, Eleftheria; Battiwalla, Minoo; Keel, Siobán; Klein, Harvey G; Barrett, A John; Ito, Sawa

    2017-09-01

    Acquired copy-neutral loss of heterozygosity has been described in myeloid malignant progression with an otherwise normal karyotype. A 65-year-old woman with MPL-mutated essential thrombocythemia and progression to myelofibrosis was noted upon routine pretransplant testing to have mixed field reactivity with anti-D and an historic discrepancy in RhD type. The patient had never received transfusions or transplantation. Gel immunoagglutination revealed group A red blood cells and a mixed-field reaction for the D phenotype, with a predominant D-negative population and a small subset of circulating red blood cells carrying the D antigen. Subsequent genomic microarray single nucleotide polymorphism profiling revealed copy-neutral loss of heterozygosity of chromosome 1 p36.33-p34.2, a known molecular mechanism underlying fibrotic progression of MPL-mutated essential thrombocythemia. The chromosomal region affected by this copy-neutral loss of heterozygosity encompassed the RHD, RHCE, and MPL genes. We propose a model of chronological molecular events that is supported by RHD zygosity assays in peripheral lymphoid and myeloid-derived cells. Copy-neutral loss of heterozygosity events that lead to clonal selection and myeloid malignant progression may also affect the expression of adjacent unrelated genes, including those encoding for blood group antigens. Detection of mixed-field reactions and investigation of discrepant blood typing results are important for proper transfusion support of these patients and can provide useful surrogate markers of myeloproliferative disease progression. © 2017 AABB.

  18. Pancreatic tuberculosis with acquired immunodeficiency syndrome: a case report and systematic review.

    PubMed

    Meesiri, Somchai

    2012-02-21

    Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration.

  19. Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.

    PubMed

    Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Martorana, Davide; Cravedi, Paolo; Maggiore, Umberto; Alinovi, Rossella; Bovino, Achiropita; Mattei, Silvia; Orlandini, Guido; Gatti, Rita; Savi, Mario; Sado, Yoshikazu; Neri, Tauro M; Allegri, Landino

    2007-01-01

    Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all]. Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury. Copyright 2007 S. Karger AG, Basel.

  20. Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI.

    PubMed

    Lukito, P; Wong, A; Jing, J; Arthur, J F; Marasco, S F; Murphy, D A; Bergin, P J; Shaw, J A; Collecutt, M; Andrews, R K; Gardiner, E E; Davis, A K

    2016-11-01

    Essentials Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored. Patients with ventricular assist devices and on extracorporeal membrane oxygenation are investigated. Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients. Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk. Background Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding. Objectives To investigate whether loss of platelet receptors occurs in vivo, and the relationship with acquired von Willebrand syndrome (AVWS). Methods Platelet counts, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 21 continuous flow VAD (CF-VAD), 20 ECMO, 12 heart failure and seven aortic stenosis patients. Levels of platelet receptors were measured by flow cytometry or ELISA. Results The loss of high molecular weight VWF multimers was observed in 18 of 19 CF-VAD and 14 of 20 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF-VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients. Conclusions These data link AVWS and increased platelet receptor shedding in patients with CF-VADs or ECMO for the first time. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CF-VAD and ECMO patients may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions. © 2016 International Society on Thrombosis and Haemostasis.

  1. Community-acquired bacterial meningitis.

    PubMed

    van de Beek, Diederik; Brouwer, Matthijs; Hasbun, Rodrigo; Koedel, Uwe; Whitney, Cynthia G; Wijdicks, Eelco

    2016-11-03

    Meningitis is an inflammation of the meninges and subarachnoid space that can also involve the brain cortex and parenchyma. It can be acquired spontaneously in the community - community-acquired bacterial meningitis - or in the hospital as a complication of invasive procedures or head trauma (nosocomial bacterial meningitis). Despite advances in treatment and vaccinations, community-acquired bacterial meningitis remains one of the most important infectious diseases worldwide. Streptococcus pneumoniae and Neisseria meningitidis are the most common causative bacteria and are associated with high mortality and morbidity; vaccines targeting these organisms, which have designs similar to the successful vaccine that targets Haemophilus influenzae type b meningitis, are now being used in many routine vaccination programmes. Experimental and genetic association studies have increased our knowledge about the pathogenesis of bacterial meningitis. Early antibiotic treatment improves the outcome, but the growing emergence of drug resistance as well as shifts in the distribution of serotypes and groups are fuelling further development of new vaccines and treatment strategies. Corticosteroids were found to be beneficial in high-income countries depending on the bacterial species. Further improvements in the outcome are likely to come from dampening the host inflammatory response and implementing preventive measures, especially the development of new vaccines.

  2. [Fegelers syndrome, acquired port-wine stain or acquired capillary malformation: three cases and a literature review].

    PubMed

    Freysz, M; Cribier, B; Lipsker, D

    2013-05-01

    Port-wine stains or capillary malformations are generally congenital. Very few cases of acquired port-wine stains in adults have been described, and these occur particularly after trauma. We report three cases of acquired port-wine stains and we performed a review of the literature using the keywords "port-wine stain", "capillary malformation", "angioma" and "acquired" in the Medline database PubMed. All relevant articles were included. Two male patients and one female patient consulted for one or more angiomatous lesions, located respectively on the upper rear part of the right thigh (case 1), the left leg (case 2) and the right side of the face, skull and chest (case 3). Each patient's skin biopsy was consistent with port-wine stain. The three patients asserted the acquired nature of the lesions: the male patients were respectively 17 and 38 years old, and the female patient was 11 years old. No causative factors were evident preceding the lesion, and there was no family history of port-wine stain. The topography was systematic in patients 2 and 3. The lesions were light red in patient 1, dark red in patient 2 and pale pink in patient 3. The remainder of the physical examination was unremarkable, except for benign angiokeratoma of the scrotum in case 1 and pigmented leucoderma-type macules in case 3. LITERATURE RESULTS: Sixty-six cases of acquired port-wine stains were reported in the literature. The average age was 25 years (3-69) with a sex-ratio of 0.88. Generally, no causative factor was given. However, trauma (30.5%), estrogenic impregnation (16.5%), and more rarely, medication, solar damage, frostbite, cluster headache, herpes zoster and acoustic neuroma were reported as causatives factors. Acquired port-wine stain is rare. Although often idiopathic, it can result from spinal trauma, which must be explored if suggested by the history. In our series, the clinical presentation suggested a latent congenital vascular malformation of late onset, in particular in

  3. A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A.

    PubMed

    Fine, Dina; Flusser, Hagit; Markus, Barak; Shorer, Zamir; Gradstein, Libe; Khateeb, Shareef; Langer, Yshia; Narkis, Ginat; Birk, Ruth; Galil, Aharon; Shelef, Ilan; Birk, Ohad S

    2015-12-01

    A consanguineous Bedouin Israeli kindred presented with a novel autosomal recessive intellectual disability syndrome of congenital microcephaly, low anterior hairline, bitemporal narrowing, low-set protruding ears, strabismus and tented thick eyebrows with sparse hair in their medial segment. Brain imaging demonstrated various degrees of agenesis of corpus callosum and hypoplasia of the vermis and cerebellum. Genome-wide linkage analysis followed by fine mapping defined a 7.67 Mb disease-associated locus (LOD score 4.99 at θ=0 for marker D10S1653). Sequencing of the 48 genes within the locus identified a single non-synonymous homozygous duplication frameshift mutation of 13 nucleotides (c.2134_2146dup13) within the coding region of FRMD4A, that was common to all affected individuals and not found in 180 non-related Bedouin controls. Three of 50 remotely related healthy controls of the same tribe were heterozygous for the mutation. FRMD4A, member of the FERM superfamily, is involved in cell structure, transport and signaling. It regulates cell polarity by playing an important role in the activation of ARF6, mediating the interaction between Par3 and the ARF6 guanine nucleotide exchange factor. ARF6 is known to modulate cell polarity in neurons, and regulates dendritic branching in hippocampal neurons and neurite outgrowth. The FRMD4 domain that is essential for determining cell polarity through interaction with Par3 is truncated by the c.2134_2146dup13 mutation. FRMD4A polymorphisms were recently suggested to be a risk factor for Alzheimer's disease. We now show a homozygous frameshift mutation of the same gene in a severe neurologic syndrome with unique dysmorphism.

  4. Molecular Characterization of Acquired Tolerance of Tumor Cells to Picropodophyllin (PPP)

    PubMed Central

    Hashemi, Jamileh; Worrall, Claire; Vasilcanu, Daiana; Fryknäs, Mårten; Sulaiman, Luqman; Karimi, Mohsen; Weng, Wen-Hui; Lui, Weng-Onn; Rudduck, Christina; Axelson, Magnus; Jernberg-Wiklund, Helena; Girnita, Leonard; Larsson, Olle; Larsson, Catharina

    2011-01-01

    Background Picropodophyllin (PPP) is a promising novel anti-neoplastic agent that efficiently kills tumor cells in vitro and causes tumor regression and increased survival in vivo. We have previously reported that PPP treatment induced moderate tolerance in two out of 10 cell lines only, and here report the acquired genomic and expression alterations associated with PPP selection over 1.5 years of treatment. Methodology/Principal Findings Copy number alterations monitored using metaphase and array-based comparative genomic hybridization analyses revealed largely overlapping alterations in parental and maximally tolerant cells. Gain/ amplification of the MYC and PVT1 loci in 8q24.21 were verified on the chromosome level. Abnormalities observed in connection to PPP treatment included regular gains and losses, as well as homozygous losses in 10q24.1-q24.2 and 12p12.3-p13.2 in one of the lines and amplification at 5q11.2 in the other. Abnormalities observed in both tolerant derivatives include amplification/gain of 5q11.2, gain of 11q12.1-q14.3 and gain of 13q33.3-qter. Using Nexus software analysis we combined the array-CGH data with data from gene expression profilings and identified genes that were altered in both inputs. A subset of genes identified as downregulated (ALDH1A3, ANXA1, TLR4 and RAB5A) or upregulated (COX6A1, NFIX, ME1, MAPK and TAP2) were validated by siRNA in the tolerant or parental cells to alter sensitivity to PPP and confirmed to alter sensitivity to PPP in further cell lines. Conclusions Long-term PPP selection lead to altered gene expression in PPP tolerant cells with increase as well as decrease of genes involved in cell death such as PTEN and BCL2. In addition, acquired genomic copy number alterations were observed that were often reflected by altered mRNA expression levels for genes in the same regions. PMID:21423728

  5. Molecular characterization of acquired tolerance of tumor cells to picropodophyllin (PPP).

    PubMed

    Hashemi, Jamileh; Worrall, Claire; Vasilcanu, Daiana; Fryknäs, Mårten; Sulaiman, Luqman; Karimi, Mohsen; Weng, Wen-Hui; Lui, Weng-Onn; Rudduck, Christina; Axelson, Magnus; Jernberg-Wiklund, Helena; Girnita, Leonard; Larsson, Olle; Larsson, Catharina

    2011-03-14

    Picropodophyllin (PPP) is a promising novel anti-neoplastic agent that efficiently kills tumor cells in vitro and causes tumor regression and increased survival in vivo. We have previously reported that PPP treatment induced moderate tolerance in two out of 10 cell lines only, and here report the acquired genomic and expression alterations associated with PPP selection over 1.5 years of treatment. Copy number alterations monitored using metaphase and array-based comparative genomic hybridization analyses revealed largely overlapping alterations in parental and maximally tolerant cells. Gain/amplification of the MYC and PVT1 loci in 8q24.21 were verified on the chromosome level. Abnormalities observed in connection to PPP treatment included regular gains and losses, as well as homozygous losses in 10q24.1-q24.2 and 12p12.3-p13.2 in one of the lines and amplification at 5q11.2 in the other. Abnormalities observed in both tolerant derivatives include amplification/gain of 5q11.2, gain of 11q12.1-q14.3 and gain of 13q33.3-qter. Using Nexus software analysis we combined the array-CGH data with data from gene expression profilings and identified genes that were altered in both inputs. A subset of genes identified as downregulated (ALDH1A3, ANXA1, TLR4 and RAB5A) or upregulated (COX6A1, NFIX, ME1, MAPK and TAP2) were validated by siRNA in the tolerant or parental cells to alter sensitivity to PPP and confirmed to alter sensitivity to PPP in further cell lines. Long-term PPP selection lead to altered gene expression in PPP tolerant cells with increase as well as decrease of genes involved in cell death such as PTEN and BCL2. In addition, acquired genomic copy number alterations were observed that were often reflected by altered mRNA expression levels for genes in the same regions.

  6. Clinical significance of acquired somatic mutations in aplastic anaemia.

    PubMed

    Marsh, J C W; Mufti, G J

    2016-08-01

    Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients.

  7. Preschoolers Acquire General Knowledge by Sharing in Pretense

    ERIC Educational Resources Information Center

    Sutherland, Shelbie L.; Friedman, Ori

    2012-01-01

    Children acquire general knowledge about many kinds of things, but there are few known means by which this knowledge is acquired. In this article, it is proposed that children acquire generic knowledge by sharing in pretend play. In Experiment 1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a "nerp" (an unfamiliar…

  8. Desmosomes in acquired disease

    PubMed Central

    Stahley, Sara N.; Kowalczyk, Andrew P.

    2015-01-01

    Desmosomes are cell-cell junctions that mediate adhesion and couple the intermediate filament cytoskeleton to sites of cell-cell contact. This architectural arrangement functions to integrate adhesion and cytoskeletal elements of adjacent cells. The importance of this robust adhesion system is evident in numerous human diseases, both inherited and acquired, that occur when desmosome function is compromised. This review focuses on autoimmune and infectious diseases that impair desmosome function. In addition, we discuss emerging evidence that desmosomal genes are often misregulated in cancer. The emphasis of our discussion is placed on how human diseases inform our understanding of basic desmosome biology, and in turn, how fundamental advances in the cell biology of desmosomes may lead to new treatments for acquired diseases of the desmosome. PMID:25795143

  9. Corpus callosum demyelination associated with acquired stuttering.

    PubMed

    Decker, Barbara McElwee; Guitar, Barry; Solomon, Andrew

    2018-04-21

    Compared with developmental stuttering, adult onset acquired stuttering is rare. However, several case reports describe acquired stuttering and an association with callosal pathology. Interestingly, these cases share a neuroanatomical localisation also demonstrated in developmental stuttering. We present a case of adult onset acquired stuttering associated with inflammatory demyelination within the corpus callosum. This patient's disfluency improved after the initiation of immunomodulatory therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Human lipodystrophies: genetic and acquired diseases of adipose tissue

    PubMed Central

    Capeau, Jacqueline; Magré, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bénédicte; Béréziat, Véronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne

    2010-01-01

    Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARγ. Importantly, lamin A/C mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their aetiology is generally unknown, they could be associated with signs of auto-immunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardio-vascular and hepatic complications. PMID:20551664

  11. Optic nerve axons and acquired alterations in the appearance of the optic disc.

    PubMed Central

    Wirtschafter, J D

    1983-01-01

    The pathophysiologic events in optic nerve axons have recently been recognized as crucial to an understanding of clinically significant acquired alterations in the ophthalmoscopic appearance of the optic disc. Stasis and related abnormalities of axonal transport appear to explain most aspects of optic nerve head swelling, including optic disc drusen and retinal cottonwool spots. Loss of axoplasm and axonal death can be invoked to interpret optic disc pallor, thinning and narrowing of rim tissue, changes in the size and outline of the optic cup, laminar dots, atrophy of the retinal nerve fiber layer, and acquired demyelination and myelination of the retinal nerve fiber layer. It is speculated that the axons may also play a role in the mechanical support of the lamina cribrosa in resisting the pressure gradient across the pars scleralis of the optic nerve head. Axons and their associated glial cells may be involved in those cases where "reversibility" of cupping of the optic disc has been reported. The structure, physiology, and experimental pathologic findings of the optic nerve head have been reviewed. Many aspects concerning the final anatomic appearance of the optic nerve head have been explained. However, many questions remain concerning the intermediate mechanisms by which increased intracranial pressure retards the various components of axonal transport in papilledema and by which increased IOP causes axonal loss in glaucoma. Investigation of the molecular biology of axonal constituents and their responses to abnormalities in their physical and chemical milieu could extend our understanding of the events that result from mechanical compression and local ischemia. Moreover, we have identified a need to further explore the role of axons in the pathophysiology of optic disc cupping. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 11 FIGURE 12 FIGURE 13 PMID:6203209

  12. Pancreatic tuberculosis with acquired immunodeficiency syndrome: A case report and systematic review

    PubMed Central

    Meesiri, Somchai

    2012-01-01

    Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration. PMID:22363146

  13. Options for Auditory Training for Adults with Hearing Loss.

    PubMed

    Olson, Anne D

    2015-11-01

    Hearing aid devices alone do not adequately compensate for sensory losses despite significant technological advances in digital technology. Overall use rates of amplification among adults with hearing loss remain low, and overall satisfaction and performance in noise can be improved. Although improved technology may partially address some listening problems, auditory training may be another alternative to improve speech recognition in noise and satisfaction with devices. The literature underlying auditory plasticity following placement of sensory devices suggests that additional auditory training may be needed for reorganization of the brain to occur. Furthermore, training may be required to acquire optimal performance from devices. Several auditory training programs that are readily accessible for adults with hearing loss, hearing aids, or cochlear implants are described. Programs that can be accessed via Web-based formats and smartphone technology are reviewed. A summary table is provided for easy access to programs with descriptions of features that allow hearing health care providers to assist clients in selecting the most appropriate auditory training program to fit their needs.

  14. 26 CFR 1.381(c)(1)-2 - Net operating loss carryovers; two or more dates of distribution or transfer in the taxable year.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Acquiring corporation X Transferor corporation Y Transferor corporation Z 1954 xxx xxx ($30,000) 1955 xxx xxx 1,000 1956 xxx xxx 1,000 1957 ($20,000) ($25,000) 1,000 Ending 6-30-58 xxx 1,000 xxx Ending 9-30-58 xxx xxx 1,000 1958 36,500 xxx xxx The sequence in which the losses of the acquiring corporation...

  15. 26 CFR 1.381(c)(1)-2 - Net operating loss carryovers; two or more dates of distribution or transfer in the taxable year.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Acquiring corporation X Transferor corporation Y Transferor corporation Z 1954 xxx xxx ($30,000) 1955 xxx xxx 1,000 1956 xxx xxx 1,000 1957 ($20,000) ($25,000) 1,000 Ending 6-30-58 xxx 1,000 xxx Ending 9-30-58 xxx xxx 1,000 1958 36,500 xxx xxx The sequence in which the losses of the acquiring corporation...

  16. Myelofibrosis and acquired hemophilia A: a case report.

    PubMed

    Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

    2016-05-07

    Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

  17. 14 CFR 1274.402 - Contractor acquired property.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Contractor acquired property. 1274.402 Section 1274.402 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS WITH COMMERCIAL FIRMS Property § 1274.402 Contractor acquired property. As provided in § 1274.923...

  18. Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015.

    PubMed

    Martines, Roosecelis Brasil; Bhatnagar, Julu; Keating, M Kelly; Silva-Flannery, Luciana; Muehlenbachs, Atis; Gary, Joy; Goldsmith, Cynthia; Hale, Gillian; Ritter, Jana; Rollin, Dominique; Shieh, Wun-Ju; Luz, Kleber G; Ramos, Ana Maria de Oliveira; Davi, Helaine Pompeia Freire; Kleber de Oliveria, Wanderson; Lanciotti, Robert; Lambert, Amy; Zaki, Sherif

    2016-02-19

    Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3).

  19. Acquired dyslexia in a Turkish-English speaker.

    PubMed

    Raman, Ilhan; Weekes, Brendan S

    2005-06-01

    The Turkish script is characterised by completely transparent bidirectional mappings between orthography and phonology. To date, there has been no reported evidence of acquired dyslexia in Turkish speakers leading to the naïve view that reading and writing problems in Turkish are probably rare. We examined the extent to which phonological impairment and orthographic transparency influence reading disorders in a native Turkish speaker. BRB is a bilingual Turkish-English speaker with deep dysphasia accompanied by acquired dyslexia in both languages. The main findings are an effect of imageability on reading in Turkish coincident with surface dyslexia in English and preserved nonword reading. BRB's acquired dyslexia suggests that damage to phonological representations might have a consequence for learning to read in Turkish. We argue that BRB's acquired dyslexia has a common locus in chronic underactivation of phonological representations in Turkish and English. Despite a common locus, reading problems manifest themselves differently according to properties of the script and the type of task.

  20. Isolated acquired factor VII deficiency: review of the literature.

    PubMed

    Mulliez, Sylvie M N; Devreese, Katrien M J

    2016-04-01

    Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

  1. De Novo Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case

    PubMed Central

    Setoh, Yin Xiang; Prow, Natalie A.; Peng, Nias; Hugo, Leon E.; Devine, Gregor; Hazlewood, Jessamine E.

    2017-01-01

    ABSTRACT Zika virus (ZIKV) has recently emerged and is the etiological agent of congenital Zika syndrome (CZS), a spectrum of congenital abnormalities arising from neural tissue infections in utero. Herein, we describe the de novo generation of a new ZIKV isolate, ZIKVNatal, using a modified circular polymerase extension reaction protocol and sequence data obtained from a ZIKV-infected fetus with microcephaly. ZIKVNatal thus has no laboratory passage history and is unequivocally associated with CZS. ZIKVNatal could be used to establish a fetal brain infection model in IFNAR−/− mice (including intrauterine growth restriction) without causing symptomatic infections in dams. ZIKVNatal was also able to be transmitted by Aedes aegypti mosquitoes. ZIKVNatal thus retains key aspects of circulating pathogenic ZIKVs and illustrates a novel methodology for obtaining an authentic functional viral isolate by using data from deep sequencing of infected tissues. IMPORTANCE The major complications of an ongoing Zika virus outbreak in the Americas and Asia are congenital defects caused by the virus’s ability to cross the placenta and infect the fetal brain. The ability to generate molecular tools to analyze viral isolates from the current outbreak is essential for furthering our understanding of how these viruses cause congenital defects. The majority of existing viral isolates and infectious cDNA clones generated from them have undergone various numbers of passages in cell culture and/or suckling mice, which is likely to result in the accumulation of adaptive mutations that may affect viral properties. The approach described herein allows rapid generation of new, fully functional Zika virus isolates directly from deep sequencing data from virus-infected tissues without the need for prior virus passaging and for the generation and propagation of full-length cDNA clones. The approach should be applicable to other medically important flaviviruses and perhaps other positive

  2. De Novo Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case.

    PubMed

    Setoh, Yin Xiang; Prow, Natalie A; Peng, Nias; Hugo, Leon E; Devine, Gregor; Hazlewood, Jessamine E; Suhrbier, Andreas; Khromykh, Alexander A

    2017-01-01

    Zika virus (ZIKV) has recently emerged and is the etiological agent of congenital Zika syndrome (CZS), a spectrum of congenital abnormalities arising from neural tissue infections in utero . Herein, we describe the de novo generation of a new ZIKV isolate, ZIKV Natal , using a modified circular polymerase extension reaction protocol and sequence data obtained from a ZIKV-infected fetus with microcephaly. ZIKV Natal thus has no laboratory passage history and is unequivocally associated with CZS. ZIKV Natal could be used to establish a fetal brain infection model in IFNAR -/- mice (including intrauterine growth restriction) without causing symptomatic infections in dams. ZIKV Natal was also able to be transmitted by Aedes aegypti mosquitoes. ZIKV Natal thus retains key aspects of circulating pathogenic ZIKVs and illustrates a novel methodology for obtaining an authentic functional viral isolate by using data from deep sequencing of infected tissues. IMPORTANCE The major complications of an ongoing Zika virus outbreak in the Americas and Asia are congenital defects caused by the virus's ability to cross the placenta and infect the fetal brain. The ability to generate molecular tools to analyze viral isolates from the current outbreak is essential for furthering our understanding of how these viruses cause congenital defects. The majority of existing viral isolates and infectious cDNA clones generated from them have undergone various numbers of passages in cell culture and/or suckling mice, which is likely to result in the accumulation of adaptive mutations that may affect viral properties. The approach described herein allows rapid generation of new, fully functional Zika virus isolates directly from deep sequencing data from virus-infected tissues without the need for prior virus passaging and for the generation and propagation of full-length cDNA clones. The approach should be applicable to other medically important flaviviruses and perhaps other positive-strand RNA

  3. Acquired Cystic Kidney Disease

    MedlinePlus

    ... care provider about when to begin screening. Eating, Diet, and Nutrition No specific diet will prevent or delay acquired ... Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de la ...

  4. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5... a corporation by another corporation in a distribution or transfer described in section 381(a) of...

  5. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5... a corporation by another corporation in a distribution or transfer described in section 381(a) of...

  6. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5... a corporation by another corporation in a distribution or transfer described in section 381(a) of...

  7. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5... a corporation by another corporation in a distribution or transfer described in section 381(a) of...

  8. Effect of levo-thyroxine treatment on weight and body mass index in children with acquired hypothyroidism.

    PubMed

    Lomenick, Jefferson P; El-Sayyid, Maysa; Smith, W Jackson

    2008-01-01

    To determine whether normalization of thyroid-stimulating hormone (TSH) in children with acquired hypothyroidism is associated with a decrease in weight or body mass index (BMI). We retrospectively identified 68 subjects with acquired hypothyroidism who were seen at least once in our center in follow-up between 1995 and 2006. Treatment with levo-thyroxine decreased the mean TSH level from 147 microU/mL initially to 5.0 microU/mL at the second visit 4.4 months later. This was not associated with a significant change in weight or BMI. Of the 68 subjects, 31% lost weight by the second visit (mean 2.3 kg). The mean initial TSH level of this group was 349 microU/mL. Thirty of the 68 children had at least 2 years of follow-up, and 19/68 had at least 4 years of follow-up. Over those intervals, weight and BMI percentiles and z scores did not change significantly from baseline values. Most children treated for acquired hypothyroidism exhibited little short-term or long-term change in weight or BMI despite near-normalization of TSH. Those children who lost weight tended to have severe hypothyroidism and to have only a small weight loss. Consequently, practitioners should not expect significant decreases in weight after treatment in most children with hypothyroidism.

  9. [Study on the prevalence of loss to follow-up and risk factors among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in Baoshan city, Yunnan province].

    PubMed

    Huang, Dongsheng; Zheng, Weibin; Yang, Jiafang; Li, Yanping; Hu, Anyan; Xu, Zhengcui

    2014-08-01

    To determine the prevalence of loss to follow-up (PLF) and risk factors among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients from 1989 to 2012 in Baoshan city, Yunnan province. The epidemic and follow-up databases of HIV/AIDS patients by the end of 2012 were downloaded from "the history card downloading site" of HIV/AIDS database in China Information System for Disease Control and Prevention and obtained the related data of patients from 1989 to 2012 who had local residence in Baoshan city. These data included demographic characteristics (genders, age at the time of HIV testing positive, and occupation, marital status, and education levels, et al), transmission routes, and disease staging, antiretroviral therapy (ART), and sources of samples, the first CD4(+)T cell counts, and status of follow-up, et al. Descriptive epidemiological study was used to describe the general characteristics of loss to follow-up. Multivariable Cox regression was used for determining risk factors associated with loss to follow-up. A total of 3 295 eligible HIV/AIDS patients from 1989 to 2012 were included. The accumulative study person-year was 11 416.59 years, 222 HIV/AIDS patients were lost to follow-up, and the PLF was 0.019 4/ person years (py). The highest PLF was 0.052 8/py in 2008, the lowest was 0.006 2/py in 2012. The lost patients included 56.76% (126/222) males and 43.24% (96/222) females, the PLFs were 0.020 4/py, 0.018 3/py, respectively. Baoshan city, other cities in Yunnan province, and other provinces, foreign nationality as the family register reached 53.60% (119/222) , 28.83% (64/222) , and 5.86% (13/222) , 11.71% (26/222) , respectively, and their PLFs were 0.012 5/py, 0.046 3/py, and 0.053 6/py, 0.095 6/py, respectively. Receiving ART and not receiving ART occupied 6.76% (15/222) , 93.24% (207/222) , respectively, and the PLFs were 0.001 9/py, 0.0588/py. AIDS and HIV staging standed at 8.11% (18/222) , 91.89% (204

  10. Connectionist neuropsychology: uncovering ultimate causes of acquired dyslexia.

    PubMed

    Woollams, Anna M

    2014-01-01

    Acquired dyslexia offers a unique window on to the nature of the cognitive and neural architecture supporting skilled reading. This paper provides an integrative overview of recent empirical and computational work on acquired dyslexia within the context of the primary systems framework as implemented in connectionist neuropsychological models. This view proposes that damage to general visual, phonological or semantic processing abilities are the root causes of different forms of acquired dyslexia. Recent case-series behavioural evidence concerning pure alexia, phonological dyslexia and surface dyslexia that supports this perspective is presented. Lesion simulations of these findings within connectionist models of reading demonstrate the viability of this approach. The commitment of such models to learnt representations allows them to capture key aspects of performance in each type of acquired dyslexia, particularly the associated non-reading deficits, the role of relearning and the influence of individual differences in the premorbid state of the reading system. Identification of these factors not only advances our understanding of acquired dyslexia and the mechanisms of normal reading but they are also relevant to the complex interactions underpinning developmental reading disorders.

  11. Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness.

    PubMed

    Hu, Hao; Matter, Michelle L; Issa-Jahns, Lina; Jijiwa, Mayumi; Kraemer, Nadine; Musante, Luciana; de la Vega, Michelle; Ninnemann, Olaf; Schindler, Detlev; Damatova, Natalia; Eirich, Katharina; Sifringer, Marco; Schrötter, Sandra; Eickholt, Britta J; van den Heuvel, Lambert; Casamina, Chanel; Stoltenburg-Didinger, Gisela; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

    2014-12-01

    To identify the cause of a so-far unreported phenotype of infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We characterized a consanguineous family of Yazidian-Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole-exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild-type and mutant mice and in patient and control fibroblasts. In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts. We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease.

  12. Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness

    PubMed Central

    Hu, Hao; Matter, Michelle L; Issa-Jahns, Lina; Jijiwa, Mayumi; Kraemer, Nadine; Musante, Luciana; de la Vega, Michelle; Ninnemann, Olaf; Schindler, Detlev; Damatova, Natalia; Eirich, Katharina; Sifringer, Marco; Schrötter, Sandra; Eickholt, Britta J; van den Heuvel, Lambert; Casamina, Chanel; Stoltenburg-Didinger, Gisela; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

    2014-01-01

    Objective To identify the cause of a so-far unreported phenotype of infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). Methods We characterized a consanguineous family of Yazidian-Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole-exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild-type and mutant mice and in patient and control fibroblasts. Results In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts. Interpretation We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease. PMID:25574476

  13. Mutations in SLC1A4, encoding the brain serine transporter, are associated with developmental delay, microcephaly and hypomyelination.

    PubMed

    Damseh, Nadirah; Simonin, Alexandre; Jalas, Chaim; Picoraro, Joseph A; Shaag, Avraham; Cho, Megan T; Yaacov, Barak; Neidich, Julie; Al-Ashhab, Motee; Juusola, Jane; Bale, Sherri; Telegrafi, Aida; Retterer, Kyle; Pappas, John G; Moran, Ellen; Cappell, Joshua; Anyane Yeboa, Kwame; Abu-Libdeh, Bassam; Hediger, Matthias A; Chung, Wendy K; Elpeleg, Orly; Edvardson, Simon

    2015-08-01

    L-serine plays an essential role in neuronal development and function. Although a non-essential amino acid, L-serine must be synthesised within the brain because of its poor permeability by the blood-brain barrier. Within the brain, its synthesis is confined to astrocytes, and its shuttle to neuronal cells is performed by a dedicated neutral amino acid transporter, ASCT1. Using exome analysis we identified the recessive mutations, p.E256K, p.L315fs, and p.R457W, in SLC1A4, the gene encoding ASCT1, in patients with developmental delay, microcephaly and hypomyelination; seizure disorder was variably present. When expressed in a heterologous system, the mutations did not affect the protein level at the plasma membrane but abolished or markedly reduced L-serine transport for p.R457W and p.E256K mutations, respectively. Interestingly, p.E256K mutation displayed a lower L-serine and alanine affinity but the same substrate selectivity as wild-type ASCT1. The clinical phenotype of ASCT1 deficiency is reminiscent of defects in L-serine biosynthesis. The data underscore that ASCT1 is essential in brain serine transport. The SLC1A4 p.E256K mutation has a carrier frequency of 0.7% in the Ashkenazi-Jewish population and should be added to the carrier screening panel in this community. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5(d) of the... corporation by another corporation in a distribution or transfer described in section 381(a) of the Code the...

  15. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

  16. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

  17. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

  18. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

  19. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

  20. Newly Acquired Gulfstream C-131B Samaritan in the Hangar

    NASA Image and Video Library

    1976-11-21

    The National Aeronautics and Space Administration (NASA) Lewis Research Center acquired this Gulfstream C-131B Samaritan from the Air Force in July 1976. The center obtained the aircraft to support its current earth resources work. The C-131B is seen here inside the Lewis hangar being refurbished and converted into a flying laboratory. The modifications were led by Lewis Chief of Flight Operations Robert Hogan. The cockpit and cabin were modified and packed with instrumentation. The new equipment included Sideways Looking Airborne Radar (SLAR), geothermal sensors, radar antennas, and an inertial navigation system. In addition, portals were installed underneath the fuselage for cameras and remote sensing equipment. NASA’s C-131B was used to support researchers tracking ice flows on the Great Lakes and in Prudhoe Bay, Alaska. It was also used for the center’s program to determine heating losses in the Cleveland area’s residential and commercial structures. The aircraft was later donated to the University of Georgia.

  1. Studies for the Loss of Atomic and Molecular Species from Io

    NASA Technical Reports Server (NTRS)

    Smyth, William H.

    1999-01-01

    A summary discussion of research undertaken in this project is presented and is related to six published papers attached in the appendix. The discussion is divided into six sections describing a variety of studies for the loss of atomic and molecular species from Io. They include studies for: (1) atomic sodium, (2) SO2, (3) O and S, (4) spectacular high-spatial resolution ultraviolet image observations of O, S, and possibly H in Io's atmosphere and/or corona acquired by the Space Telescope Imaging Spectrometer (STIS) of the Hubble Space Telescope (HST), (5) spectacular high-spatial resolution visible Io eclipse image observations acquired by the Solid State Imager (SSI) of Galileo spacecraft, (6) ground-based observations acquired by the Solid State Imager (SSI) of Galileo spacecraft, and (7) ground-based observations of Io's neutral cloud in [OI] 6300 angstrom emission. New source rates at Io's exobase for SO2, O, and H are given and a variety of interesting implications for Io's atmosphere and for the Io plasma torus are discussed. Appendices that are comprised of articles published during the contract are also presented.

  2. Neural markers of loss aversion in resting-state brain activity.

    PubMed

    Canessa, Nicola; Crespi, Chiara; Baud-Bovy, Gabriel; Dodich, Alessandra; Falini, Andrea; Antonellis, Giulia; Cappa, Stefano F

    2017-02-01

    Neural responses in striatal, limbic and somatosensory brain regions track individual differences in loss aversion, i.e. the higher sensitivity to potential losses compared with equivalent gains in decision-making under risk. The engagement of structures involved in the processing of aversive stimuli and experiences raises a further question, i.e. whether the tendency to avoid losses rather than acquire gains represents a transient fearful overreaction elicited by choice-related information, or rather a stable component of one's own preference function, reflecting a specific pattern of neural activity. We tested the latter hypothesis by assessing in 57 healthy human subjects whether the relationship between behavioral and neural loss aversion holds at rest, i.e. when the BOLD signal is collected during 5minutes of cross-fixation in the absence of an explicit task. Within the resting-state networks highlighted by a spatial group Independent Component Analysis (gICA), we found a significant correlation between strength of activity and behavioral loss aversion in the left ventral striatum and right posterior insula/supramarginal gyrus, i.e. the very same regions displaying a pattern of neural loss aversion during explicit choices. Cross-study analyses confirmed that this correlation holds when voxels identified by gICA are used as regions of interest in task-related activity and vice versa. These results suggest that the individual degree of (neural) loss aversion represents a stable dimension of decision-making, which reflects in specific metrics of intrinsic brain activity at rest possibly modulating cortical excitability at choice. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject to...

  4. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject to...

  5. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject to...

  6. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject to...

  7. Clinical features of dog- and bat-acquired rabies in humans.

    PubMed

    Udow, Sean J; Marrie, Ruth Ann; Jackson, Alan C

    2013-09-01

    Clinical differences in rabies due to canine and bat rabies virus variants have been noted, but no detailed studies have been reported to support these observations. Using the Morbidity and Mortality Weekly Report and PubMed, we identified 142 case reports of rabies from North America, South America, Europe, Africa, and Asia. We systematically abstracted 126 selected data elements and compared clinical features and investigation results in dog- and bat-acquired cases of rabies. Survivors and cases acquired from aerosolized viral exposure or tissue/organ transplant were excluded (n = 20). Of 122 cases, 49 (40.2%) were dog-acquired and 54 (44.3%) were bat-acquired. Bat-acquired cases of rabies were more often misdiagnosed and lacked a bite history. Encephalopathy, hydrophobia, and aerophobia were more common in dog-acquired rabies. Abnormal cranial nerve, motor, and sensory examinations, tremor, myoclonus, local sensory symptoms, symptoms at the exposure site, and local symptoms in the absence of a bite or scratch were more common in patients with bat-acquired rabies, as was increased cerebrospinal fluid protein (P = .031). Patients with paralytic rabies had longer survival times than those with encephalitic rabies, and also had shorter incubation periods if they had received postexposure prophylaxis. Clinical differences in dog- and bat-acquired rabies may reflect differences in the route of viral spread of rabies virus variants in the nervous system, although certain variants could cause more severe dysfunction in neuronal subpopulations. Recognition that bat-acquired rabies may present with different clinical manifestations than dog-acquired rabies may help improve the early diagnosis of rabies.

  8. Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

    PubMed

    Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu

    2016-06-01

    Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.

  9. Connectionist neuropsychology: uncovering ultimate causes of acquired dyslexia

    PubMed Central

    Woollams, Anna M.

    2014-01-01

    Acquired dyslexia offers a unique window on to the nature of the cognitive and neural architecture supporting skilled reading. This paper provides an integrative overview of recent empirical and computational work on acquired dyslexia within the context of the primary systems framework as implemented in connectionist neuropsychological models. This view proposes that damage to general visual, phonological or semantic processing abilities are the root causes of different forms of acquired dyslexia. Recent case-series behavioural evidence concerning pure alexia, phonological dyslexia and surface dyslexia that supports this perspective is presented. Lesion simulations of these findings within connectionist models of reading demonstrate the viability of this approach. The commitment of such models to learnt representations allows them to capture key aspects of performance in each type of acquired dyslexia, particularly the associated non-reading deficits, the role of relearning and the influence of individual differences in the premorbid state of the reading system. Identification of these factors not only advances our understanding of acquired dyslexia and the mechanisms of normal reading but they are also relevant to the complex interactions underpinning developmental reading disorders. PMID:24324241

  10. Preschoolers acquire general knowledge by sharing in pretense.

    PubMed

    Sutherland, Shelbie L; Friedman, Ori

    2012-01-01

    Children acquire general knowledge about many kinds of things, but there are few known means by which this knowledge is acquired. In this article, it is proposed that children acquire generic knowledge by sharing in pretend play. In Experiment 1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a "nerp" (an unfamiliar kind of animal). For instance, in one scenario, the nerp ate and disliked a carrot. When subsequently asked generic questions about real nerps, children's responses suggested that they had learned general facts (e.g., nerps dislike carrots). In Experiment 2, thirty-two 4- to 5-year-olds learned from scenarios lacking pretend speech or sound effects. The findings reveal a long overlooked means by which children can acquire generic knowledge. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

  11. Evaluation of the suitability of root cause analysis frameworks for the investigation of community-acquired pressure ulcers: a systematic review and documentary analysis.

    PubMed

    McGraw, Caroline; Drennan, Vari M

    2015-02-01

    To evaluate the suitability of root cause analysis frameworks for the investigation of community-acquired pressure ulcers. The objective was to identify the extent to which these frameworks take account of the setting where the ulcer originated as being the person's home rather than a hospital setting. Pressure ulcers involving full-thickness skin loss are increasingly being regarded as indicators of nursing patient safety failure, requiring investigation using root cause analysis frameworks. Evidence suggests that root cause analysis frameworks developed in hospital settings ignore the unique dimensions of risk in home healthcare settings. A systematic literature review and documentary analysis of frameworks used to investigate community-acquired grade three and four pressure ulcers by home nursing services in England. No published papers were identified for inclusion in the review. Fifteen patient safety investigative frameworks were collected and analysed. Twelve of the retrieved frameworks were intended for the investigation of community-acquired pressure ulcers; seven of which took account of the setting where the ulcer originated as being the patient's home. This study provides evidence to suggest that many of the root cause analysis frameworks used to investigate community-acquired pressure ulcers in England are unsuitable for this purpose. This study provides researchers and practitioners with evidence of the need to develop appropriate home nursing root cause analysis frameworks to investigate community-acquired pressure ulcers. © 2014 John Wiley & Sons Ltd.

  12. Aquatic Toxicity Information Retrieval Data Base (ACQUIRE). Data file

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

    Not Available

    The purpose of Acquire is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for ACQUIRE. Independently compiled data files that meet ACQUIRE parameter and quality assurance criteria are also included. Selected toxicity test results and related testing information for any individual chemical from laboratory and field aquatic toxicity effects are included for tests with freshwater and marine organisms. The total number of data records in ACQUIRE is now over 105,300.more » This includes data from 6000 references, for 5200 chemicals and 2400 test species. A major data file, Acute Toxicity of Organic Chemicals (ATOC), has been incorporated into ACQUIRE. The ATOC file contains laboratory acute test data on 525 organic chemicals using juvenile fathead minnows.« less

  13. Emerging therapeutic interventions against noise-induced hearing loss

    PubMed Central

    Sha, Su-Hua; Schacht, Jochen

    2017-01-01

    Introduction Noise-induced hearing loss (NIHL) due to industrial, military, and recreational noise exposure is a major, but also potentially preventable cause of acquired hearing loss. For the United States it is estimated that 26 million people (15% of the population) between the ages of 20 and 69 have a high-frequency NIHL at a detriment to the quality of life of the affected individuals and great economic cost to society. Areas covered This review outlines the pathology and pathophysiology of hearing loss as seen in humans and animal models. Results from molecular studies are presented that have provided the basis for therapeutic strategies successfully applied to animals. Several compounds emerging from these studies (mostly antioxidants) are now being tested in field trials. Expert opinion Although no clinically applicable intervention has been approved yet, recent trials are encouraging. In order to maximize protective therapies, future work needs to apply stringent criteria for noise exposure and outcome parameters. Attention needs to be paid not only to permanent NIHL due to death of sensory cells but also to temporary effects that may show delayed consequences. Existing results combined with the search for efficacious new therapies should establish a viable treatment within a decade. PMID:27918210

  14. Epidemiology of acquired aplastic anaemia in Pakistan.

    PubMed

    Ehsan, Ayesha; Shah, Shahida Amjad Riaz; Ibrahim, Tayyaba

    2011-01-01

    Acquired aplastic anaemia is a rare disease which results in morbidity and mortality at a young age. This study was carried out to determine the clinical presentation, haematological parameters and association factors of acquired aplastic anaemia in a cohort of Pakistani patients. This was a cross-sectional study conducted at Haematology Department, Shaikh Zayed Hospital, Lahore over 7 years from June 2000 to July 2007. Eighty-two patients of acquired aplastic anaemia were enrolled in the study by non-probability purposive sampling. Their diagnosis was confirmed by complete blood count, bone marrow aspirate and trephine biopsy. The cohort was classified on the basis of severity and the epidemiological, clinical and haematological parameters were analysed. Of the 82 enrolled patients of acquired aplastic anaemia, 49 (59.8%) were males and 33 (40.2%) were females. Mean age of the patients was 27.93 +/- 18.7 years with a range of 1-80 years. The male to female ratio was 1.48:1. Bone marrow cellularity was less than 25 % in 31 (38.0%) cases and between 25-30% in 51 (62%) of patients. Most of the cases were clinically severe aplastic anaemia (68%). In 62 (76%) of the cases no association factors predisposing to aplastic anaemia could be identified. Acquired Aplastic anaemia is a disease of all ages. In the second decade and the elderly predominantly severe clinical stages were seen. Males presented at a younger age while females presented at all ages with a somewhat similar incidence. No association factors of Aplastic Anaemia could be identified in majority of the patients.

  15. Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy.

    PubMed

    Honein, Margaret A; Dawson, April L; Petersen, Emily E; Jones, Abbey M; Lee, Ellen H; Yazdy, Mahsa M; Ahmad, Nina; Macdonald, Jennifer; Evert, Nicole; Bingham, Andrea; Ellington, Sascha R; Shapiro-Mendoza, Carrie K; Oduyebo, Titilope; Fine, Anne D; Brown, Catherine M; Sommer, Jamie N; Gupta, Jyoti; Cavicchia, Philip; Slavinski, Sally; White, Jennifer L; Owen, S Michele; Petersen, Lyle R; Boyle, Coleen; Meaney-Delman, Dana; Jamieson, Denise J

    2017-01-03

    Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10 000 live births. To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments. Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample. Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences. Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities

  16. No auditory experience, no tinnitus: Lessons from subjects with congenital- and acquired single-sided deafness.

    PubMed

    Lee, Sang-Yeon; Nam, Dong Woo; Koo, Ja-Won; De Ridder, Dirk; Vanneste, Sven; Song, Jae-Jin

    2017-10-01

    Recent studies have adopted the Bayesian brain model to explain the generation of tinnitus in subjects with auditory deafferentation. That is, as the human brain works in a Bayesian manner to reduce environmental uncertainty, missing auditory information due to hearing loss may cause auditory phantom percepts, i.e., tinnitus. This type of deafferentation-induced auditory phantom percept should be preceded by auditory experience because the fill-in phenomenon, namely tinnitus, is based upon auditory prediction and the resultant prediction error. For example, a recent animal study observed the absence of tinnitus in cats with congenital single-sided deafness (SSD; Eggermont and Kral, Hear Res 2016). However, no human studies have investigated the presence and characteristics of tinnitus in subjects with congenital SSD. Thus, the present study sought to reveal differences in the generation of tinnitus between subjects with congenital SSD and those with acquired SSD to evaluate the replicability of previous animal studies. This study enrolled 20 subjects with congenital SSD and 44 subjects with acquired SSD and examined the presence and characteristics of tinnitus in the groups. None of the 20 subjects with congenital SSD perceived tinnitus on the affected side, whereas 30 of 44 subjects with acquired SSD experienced tinnitus on the affected side. Additionally, there were significant positive correlations between tinnitus characteristics and the audiometric characteristics of the SSD. In accordance with the findings of the recent animal study, tinnitus was absent in subjects with congenital SSD, but relatively frequent in subjects with acquired SSD, which suggests that the development of tinnitus should be preceded by auditory experience. In other words, subjects with profound congenital peripheral deafferentation do not develop auditory phantom percepts because no auditory predictions are available from the Bayesian brain. Copyright © 2017 Elsevier B.V. All rights

  17. The pathophysiology of acquired premature ejaculation

    PubMed Central

    Jannini, Emmanuele A.; Serefoglu, Ege C.; Hellstrom, Wayne J. G.

    2016-01-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE. PMID:27652216

  18. The adaptation process following acute onset disability: an interactive two-dimensional approach applied to acquired brain injury.

    PubMed

    Brands, Ingrid M H; Wade, Derick T; Stapert, Sven Z; van Heugten, Caroline M

    2012-09-01

    To describe a new model of the adaptation process following acquired brain injury, based on the patient's goals, the patient's abilities and the emotional response to the changes and the possible discrepancy between goals and achievements. The process of adaptation after acquired brain injury is characterized by a continuous interaction of two processes: achieving maximal restoration of function and adjusting to the alterations and losses that occur in the various domains of functioning. Consequently, adaptation requires a balanced mix of restoration-oriented coping and loss-oriented coping. The commonly used framework to explain adaptation and coping, 'The Theory of Stress and Coping' of Lazarus and Folkman, does not capture this interactive duality. This model additionally considers theories concerned with self-regulation of behaviour, self-awareness and self-efficacy, and with the setting and achievement of goals. THE TWO-DIMENSIONAL MODEL: Our model proposes the simultaneous and continuous interaction of two pathways; goal pursuit (short term and long term) or revision as a result of success and failure in reducing distance between current state and expected future state and an affective response that is generated by the experienced goal-performance discrepancies. This affective response, in turn, influences the goals set. This two-dimensional representation covers the processes mentioned above: restoration of function and consideration of long-term limitations. We propose that adaptation centres on readjustment of long-term goals to new achievable but desired and important goals, and that this adjustment underlies re-establishing emotional stability. We discuss how the proposed model is related to actual rehabilitation practice.

  19. Detection of Frauds and Other Non-technical Losses in Power Utilities using Smart Meters: A Review

    NASA Astrophysics Data System (ADS)

    Ahmad, Tanveer; Ul Hasan, Qadeer

    2016-06-01

    Analysis of losses in power distribution system and techniques to mitigate these are two active areas of research especially in energy scarce countries like Pakistan to increase the availability of power without installing new generation. Since total energy losses account for both technical losses (TL) as well as non-technical losses (NTLs). Utility companies in developing countries are incurring of major financial losses due to non-technical losses. NTLs lead to a series of additional losses, such as damage to the network (infrastructure and the reduction of network reliability) etc. The purpose of this paper is to perform an introductory investigation of non-technical losses in power distribution systems. Additionally, analysis of NTLs using consumer energy consumption data with the help of Linear Regression Analysis has been carried out. This data focuses on the Low Voltage (LV) distribution network, which includes: residential, commercial, agricultural and industrial consumers by using the monthly kWh interval data acquired over a period (one month) of time using smart meters. In this research different prevention techniques are also discussed to prevent illegal use of electricity in the distribution of electrical power system.

  20. Flood loss model transfer: on the value of additional data

    NASA Astrophysics Data System (ADS)

    Schröter, Kai; Lüdtke, Stefan; Vogel, Kristin; Kreibich, Heidi; Thieken, Annegret; Merz, Bruno

    2017-04-01

    The transfer of models across geographical regions and flood events is a key challenge in flood loss estimation. Variations in local characteristics and continuous system changes require regional adjustments and continuous updating with current evidence. However, acquiring data on damage influencing factors is expensive and therefore assessing the value of additional data in terms of model reliability and performance improvement is of high relevance. The present study utilizes empirical flood loss data on direct damage to residential buildings available from computer aided telephone interviews that were carried out after the floods in 2002, 2005, 2006, 2010, 2011 and 2013 mainly in the Elbe and Danube catchments in Germany. Flood loss model performance is assessed for incrementally increased numbers of loss data which are differentiated according to region and flood event. Two flood loss modeling approaches are considered: (i) a multi-variable flood loss model approach using Random Forests and (ii) a uni-variable stage damage function. Both model approaches are embedded in a bootstrapping process which allows evaluating the uncertainty of model predictions. Predictive performance of both models is evaluated with regard to mean bias, mean absolute and mean squared errors, as well as hit rate and sharpness. Mean bias and mean absolute error give information about the accuracy of model predictions; mean squared error and sharpness about precision and hit rate is an indicator for model reliability. The results of incremental, regional and temporal updating demonstrate the usefulness of additional data to improve model predictive performance and increase model reliability, particularly in a spatial-temporal transfer setting.

  1. Hyperthyroidism caused by acquired immune deficiency syndrome.

    PubMed

    Wang, J-J; Zhou, J-J; Yuan, X-L; Li, C-Y; Sheng, H; Su, B; Sheng, C-J; Qu, S; Li, H

    2014-01-01

    Acquired immune deficiency syndrome (AIDS) is an immune deficiency disease. The etiology of hyperthyroidism, which can also be immune-related, is usually divided into six classical categories, including hypophyseal, hypothalamic, thyroid, neoplastic, autoimmune and inflammatory hyperthyroidism. Hyperthyroidism is a rare complication of highly active antimicrobial therapy (HAART) for human immunodeficiency virus (HIV). Hyperthyroidism caused directly by AIDS has not been previously reported. A 29-year-old man who complained of dyspnea and asthenia for 1 month, recurrent fever for more than 20 days, and breathlessness for 1 week was admitted to our hospital. The thyroid function test showed that the level of free thyroxine (FT4) was higher than normal and that the level of thyroid-stimulating hormone (TSH) was below normal. He was diagnosed with hyperthyroidism. Additional investigations revealed a low serum albumin level and chest infection, along with diffuse lung fibrosis. Within 1 month, he experienced significant weight loss, no hand tremors, intolerance of heat, and perspiration proneness. We recommended an HIV examination; subsequently, AIDS was diagnosed based on the laboratory parameters. This is the first reported case of hyperthyroidism caused by AIDS. AIDS may cause hyperthyroidism by immunization regulation with complex, atypical, and easily ignored symptoms. Although hyperthyroidism is rare in patients with AIDS, clinicians should be aware of this potential interaction and should carefully monitor thyroid function in HIV-positive patients.

  2. Acquired resistance to rechallenge injury in rats recovered from subclinical renal damage with uranyl acetate-Importance of proliferative activity of tubular cells

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

    Sun, Yuan; Fujigaki, Yoshihide, E-mail: yf0516@hama-med.ac.j; Sakakima, Masanori

    Animals recovered from acute renal failure are resistant to subsequent insult. We investigated whether rats recovered from mild proximal tubule (PT) injury without renal dysfunction (subclinical renal damage) acquire the same resistance. Rats 14 days after recovering from subclinical renal damage, which was induced by 0.2 mg/kg of uranyl acetate (UA) (sub-toxic dose), were rechallenged with 4 mg/kg of UA (nephrotoxic dose). Fate of PT cells and renal function were examined in response to nephrotoxic dose of UA. All divided cells after sub-toxic dose of UA insult were labeled with bromodeoxyuridine (BrdU) for 14 days then the number of PTmore » cells with or without BrdU-labeling was counted following nephrotoxic dose of UA insult. Rats recovered from subclinical renal damage gained resistance to nephrotoxic dose of UA with reduced renal dysfunction, less severity of peak damage (necrotic and TUNEL+ apoptotic cells) and accelerated PT cell proliferation, but with earlier peak of PT damage. The decrease in number of PT cells in the early phase of rechallenge injury with nephrotoxic UA was more in rats pretreated with sub-toxic dose of UA than vehicle pretreated rats. The exaggerated loss of PT cells was mainly caused by the exaggerated loss of BrdU+ divided cells. In contrast, accelerated cell proliferation in rats recovered from sub-toxic dose of UA was observed mainly in BrdU- non-divided cells. The findings suggest that rats recovered from subclinical renal damage showed partial acquired resistance to nephrotoxic insult. Accelerated recovery with increased proliferative activity of non-divided PT cells after subclinical renal damage may mainly contribute to acquired resistance.« less

  3. Toward 10 meV electron energy-loss spectroscopy resolution for plasmonics.

    PubMed

    Bellido, Edson P; Rossouw, David; Botton, Gianluigi A

    2014-06-01

    Energy resolution is one of the most important parameters in electron energy-loss spectroscopy. This is especially true for measurement of surface plasmon resonances, where high-energy resolution is crucial for resolving individual resonance peaks, in particular close to the zero-loss peak. In this work, we improve the energy resolution of electron energy-loss spectra of surface plasmon resonances, acquired with a monochromated beam in a scanning transmission electron microscope, by the use of the Richardson-Lucy deconvolution algorithm. We test the performance of the algorithm in a simulated spectrum and then apply it to experimental energy-loss spectra of a lithographically patterned silver nanorod. By reduction of the point spread function of the spectrum, we are able to identify low-energy surface plasmon peaks in spectra, more localized features, and higher contrast in surface plasmon energy-filtered maps. Thanks to the combination of a monochromated beam and the Richardson-Lucy algorithm, we improve the effective resolution down to 30 meV, and evidence of success up to 10 meV resolution for losses below 1 eV. We also propose, implement, and test two methods to limit the number of iterations in the algorithm. The first method is based on noise measurement and analysis, while in the second we monitor the change of slope in the deconvolved spectrum.

  4. [Diagnostics and antimicrobial therapy of severe community-acquired pneumonia].

    PubMed

    Sinopalnikov, A I; Zaitsev, A A

    2015-04-01

    In the current paper authors presented the latest information concerning etiology of severe community-acquired pneumonia. Most cases are caused by a relatively small number ofpathogenic bacterial and viral natures. The frequency of detection of various pathogens of severe community-acquired pneumonia may vary greatly depending on the region, season and clinical profile of patients, availability of relevant risk factors. Authors presented clinical characteristics of severe community-acquired pneumonia and comparative evaluation of a number of scales to assess the risk of adverse outcome of the disease. Diagnosis of severe community-acquired pneumonia includes the following: collecting of epidemiological history, identification of pneumonia, detection of sepsis and identification of multiple organ dysfunction syndrome, detection of acute respiratory failure, assessment of comorbidity. Authors gave recommendations concerning evaluation of the clinical manifestations of the disease, the use of instrumental and laboratory methods for diagnosis of severe community-acquired pneumonia. To select the mode of antimicrobial therapy is most important local monitoring antimicrobial resistance of pathogens. The main criteria for the effectiveness of treatment are to reduce body temperature, severe intoxication, respiratory and organ failure.

  5. An unusual cause of central retinal artery occlusion: acquired immunodeficiency syndrome.

    PubMed

    Erdol, H; Turk, A; Caylan, R

    2007-01-01

    In patients with acquired immunodeficiency syndrome (AIDS), disturbances in the circulation of retinal vessels are mostly encountered at the microvascular level. Rarely observed large retinal vessel occlusions frequently affect retinal veins. A 32-year-old woman was admitted to the authors' clinic with sudden loss of vision. Her clinical and ophthalmologic examinations and laboratory tests were carried out and the results were evaluated. The patient's history revealed a diagnosis of AIDS established 5 years ago. Her corrected visual acuity was limited to light perception in the right eye and 20/60 in the left eye. There was afferent pupillary defect in the right eye. Posterior segment examination demonstrated central retinal artery occlusion in the right eye and cotton-wool spots in the left eye. The clinical examination and laboratory test results did not reveal any comorbid disease state that can contribute to this presentation. As thrombi may develop in patients with human immunodeficiency virus infection, they should be closely followed up for the development of vasoocclusive disease.

  6. Loss Estimation Modeling Of Scenario Lahars From Mount Rainier, Washington State, Using HAZUS-MH

    NASA Astrophysics Data System (ADS)

    Walsh, T. J.; Cakir, R.

    2011-12-01

    We have adapted lahar hazard zones developed by Hoblitt and others (1998) and converted to digital data by Schilling and others (2008) into the appropriate format for HAZUS-MH, which is FEMA's loss estimation model. We assume that structures engulfed by cohesive lahars will suffer complete loss, and structures affected by post-lahar flooding will be appropriately modeled by the HAZUS-MH flood model. Another approach investigated is to estimate the momentum of lahars, calculate a lateral force, and apply the earthquake model, substituting the lahar lateral force for PGA. Our initial model used the HAZUS default data, which include estimates of building type and value from census data. This model estimated a loss of about 12 billion for a repeat lahar similar to the Electron Mudflow down the Puyallup River. Because HAZUS data are based on census tracts, this estimated damage includes everything in the census tract, even buildings outside of the lahar hazard zone. To correct this, we acquired assessors data from all of the affected counties and converted them into HAZUS format. We then clipped it to the boundaries of the lahar hazard zone to more precisely delineate those properties actually at risk in each scenario. This refined our initial loss estimate to about 6 billion with exclusion of building content values. We are also investigating rebuilding the lahar hazard zones applying Lahar-Z to a more accurate topographic grid derived from recent Lidar data acquired from the Puget Sound Lidar Consortium and Mount Rainier National Park. Final results of these models for the major drainages of Mount Rainier will be posted to the Washington Interactive Geologic Map (http://www.dnr.wa.gov/ResearchScience/Topics/GeosciencesData/Pages/geology_portal.aspx).

  7. Extensive Drug Resistance Acquired During Treatment of Multidrug-Resistant Tuberculosis

    PubMed Central

    Cegielski, J. Peter; Dalton, Tracy; Yagui, Martin; Wattanaamornkiet, Wanpen; Volchenkov, Grigory V.; Via, Laura E.; Van Der Walt, Martie; Tupasi, Thelma; Smith, Sarah E.; Odendaal, Ronel; Leimane, Vaira; Kvasnovsky, Charlotte; Kuznetsova, Tatiana; Kurbatova, Ekaterina; Kummik, Tiina; Kuksa, Liga; Kliiman, Kai; Kiryanova, Elena V.; Kim, HeeJin; Kim, Chang-ki; Kazennyy, Boris Y.; Jou, Ruwen; Huang, Wei-Lun; Ershova, Julia; Erokhin, Vladislav V.; Diem, Lois; Contreras, Carmen; Cho, Sang Nae; Chernousova, Larisa N.; Chen, Michael P.; Caoili, Janice Campos; Bayona, Jaime; Akksilp, Somsak; Calahuanca, Gloria Yale; Wolfgang, Melanie; Viiklepp, Piret; Vasilieva, Irina A.; Taylor, Allison; Tan, Kathrine; Suarez, Carmen; Sture, Ingrida; Somova, Tatiana; Smirnova, Tatyana G.; Sigman, Erika; Skenders, Girts; Sitti, Wanlaya; Shamputa, Isdore C.; Riekstina, Vija; Pua, Kristine Rose; Therese, M.; Perez, C.; Park, Seungkyu; Norvaisha, Inga; Nemtsova, Evgenia S.; Min, Seonyeong; Metchock, Beverly; Levina, Klavdia; Lei, Yung-Chao; Lee, Jongseok; Larionova, Elena E.; Lancaster, Joey; Jeon, Doosoo; Jave, Oswaldo; Khorosheva, Tatiana; Hwang, Soo Hee; Huang, Angela Song-En; Gler, M. Tarcela; Dravniece, Gunta; Eum, Seokyong; Demikhova, Olga V.; Degtyareva, Irina; Danilovits, Manfred; Cirula, Anda; Cho, Eunjin; Cai, Ying; Brand, Jeanette; Bonilla, Cesar; Barry, Clifton E.; Asencios, Luis; Andreevskaya, Sofia N.; Akksilp, Rattanawadee

    2014-01-01

    Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16–.47) for XDR tuberculosis, 0.28 (.17–.45) for FQ, and 0.15 (.06–.39) to 0.60 (.34–1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07–.62) for acquired XDR tuberculosis and 0.23 (.09–.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. PMID:25057101

  8. HER2 loss in HER2-positive gastric or gastroesophageal cancer after trastuzumab therapy: Implication for further clinical research.

    PubMed

    Pietrantonio, F; Caporale, M; Morano, F; Scartozzi, M; Gloghini, A; De Vita, F; Giommoni, E; Fornaro, L; Aprile, G; Melisi, D; Berenato, R; Mennitto, A; Volpi, C C; Laterza, M M; Pusceddu, V; Antonuzzo, L; Vasile, E; Ongaro, E; Simionato, F; de Braud, F; Torri, V; Di Bartolomeo, M

    2016-12-15

    Mechanisms of acquired resistance to trastuzumab-based treatment in gastric cancer are largely unknown. In this study, we analyzed 22 pairs of tumor samples taken at baseline and post-progression in patients receiving chemotherapy and trastuzumab for advanced HER2-positive [immunohistochemistry (IHC) 3+ or 2+ with in-situ hybridization (ISH) amplification] gastric or gastroesophageal cancers. Strict clinical criteria for defining acquired trastuzumab resistance were adopted. Loss of HER2 positivity and loss of HER2 over-expression were defined as post-trastuzumab IHC score <3+ and absence of ISH amplification, and IHC "downscoring" from 2+/3+ to 0/1+, respectively. HER2 IHC was always performed, while ISH was missing in 3 post-progression samples. Patients with initial HER2 IHC score 3+ and 2+ were 14 (64%) and 8 (36%), respectively. Loss of HER2 positivity and HER2 over-expression was observed in 32 and 32% samples, respectively. The chance of HER2 loss was not associated with any of the baseline clinicopathological variables. The only exception was in patients with initial IHC score 2+ versus 3+, for both endpoints of HER2 positivity (80 vs. 14%; p = 0.008) and HER2 over-expression (63 vs. 14%; p = 0.025). As already shown in breast cancer, loss of HER2 may be observed also in gastric cancers patients treated with trastuzumab-based chemotherapy in the clinical practice. This phenomenon may be one of the biological reasons explaining the failure of anti-HER2 second-line strategies in initially HER2-positive disease. © 2016 UICC.

  9. Cyclosporiasis: a point source outbreak acquired in Guatemala.

    PubMed

    Puente, Sabino; Morente, Adolfo; García-Benayas, Teresa; Subirats, Mercedes; Gascón, Joaquín; González-Lahoz, Juan M

    2006-01-01

    Cyclosporiasis is a disease due to Cyclospora cayetanensis, an emerging coccidian parasite first described in 1979. It is an orally transmitted disease that is more frequent in tropical and subtropical areas. Cyclospora cayetanensis has been mainly described as a cause of travelers' diarrhea. This pathogen has given rise to a number of epidemic outbreaks attributable to ingestion of imported foods, particularly from tropical areas. Descriptive study of clinical and epidemiological data of a small epidemic outbreak of C cayetanensis-induced gastroenteritis. Seven confirmed cases of C cayetanensis among Spanish nationals who had traveled to Antigua Guatemala are described. The incubation period was 6 days. Diarrhea, asthenia, anorexia, borborygmi, flatulence, and abdominal distension were present in all cases. Fever and heart burn in 85.7%. Weight loss in 71.4%. Abdominal pain, rectal tenesmus, and nausea in 42.8%. Vomiting and eructation in 14.2%. Heart burn was a frequent symptom, a finding not often previously described. The infection was probably acquired from raspberry juice. All cases improved with trimethoprim/sulphametoxazol. Cyclosporiasis is a cause of travelers' diarrhea. Parasitology laboratories must be advised of clinical suspicion of cyclosporiasis so that they can conduct a suitable targeted study; otherwise, false negative results may arise.

  10. 26 CFR 1.381(c)(1)-1 - Net operating loss carryovers in certain corporate acquisitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) 1956 ($35,000) ($5,000) Ending 12-16-57 (30,000) xxx 1957 xxx 36,500 (ii) The aggregate of the net... Corporation (acquirer) 1954 ($5,000) xxx 1955 (15,000) xxx 1956 (10,000) $20,000 1957 xxx 40,000 (ii) The...-56 (1,000) (9,000) xxx 1956 xxx xxx 73,200 (ii) The aggregate of the net operating loss carryovers of...

  11. 26 CFR 1.381(c)(1)-1 - Net operating loss carryovers in certain corporate acquisitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) 1956 ($35,000) ($5,000) Ending 12-16-57 (30,000) xxx 1957 xxx 36,500 (ii) The aggregate of the net... Corporation (acquirer) 1954 ($5,000) xxx 1955 (15,000) xxx 1956 (10,000) $20,000 1957 xxx 40,000 (ii) The...-56 (1,000) (9,000) xxx 1956 xxx xxx 73,200 (ii) The aggregate of the net operating loss carryovers of...

  12. 26 CFR 1.381(c)(1)-1 - Net operating loss carryovers in certain corporate acquisitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) 1956 ($35,000) ($5,000) Ending 12-16-57 (30,000) xxx 1957 xxx 36,500 (ii) The aggregate of the net... Corporation (acquirer) 1954 ($5,000) xxx 1955 (15,000) xxx 1956 (10,000) $20,000 1957 xxx 40,000 (ii) The...-56 (1,000) (9,000) xxx 1956 xxx xxx 73,200 (ii) The aggregate of the net operating loss carryovers of...

  13. 26 CFR 1.381(c)(1)-1 - Net operating loss carryovers in certain corporate acquisitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) 1956 ($35,000) ($5,000) Ending 12-16-57 (30,000) xxx 1957 xxx 36,500 (ii) The aggregate of the net... Corporation (acquirer) 1954 ($5,000) xxx 1955 (15,000) xxx 1956 (10,000) $20,000 1957 xxx 40,000 (ii) The...-56 (1,000) (9,000) xxx 1956 xxx xxx 73,200 (ii) The aggregate of the net operating loss carryovers of...

  14. Acquired factor VII deficiency associated with acute myeloid leukemia.

    PubMed

    Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

    2015-04-01

    Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

  15. 27 CFR 6.45 - Assistance in acquiring license.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Assistance in acquiring license. 6.45 Section 6.45 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Furnishing Things of Value § 6.45 Assistance in acquiring license. Any...

  16. Rethinking responsibility in offenders with acquired paedophilia: punishment or treatment?

    PubMed

    Gilbert, Frédéric; Focquaert, Farah

    2015-01-01

    This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) preserved moral knowledge despite their sexual disorder. The article then examines the option of offering mandatory treatment as an alternative to imprisonment for offenders with acquired paedophilia. Furthermore, the article addresses the ethical issues related to offering any form of quasi-coercive treatment as a condition of release. This study concludes that decisions to fully or partially excuse an individual who fulfil the diagnosis of acquired paedophilia should take all relevant information into account, both neurobiological and other environmental evidence, and should proceed on a careful case by case analysis before sentencing or offering treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Naturally acquired microchimerism

    PubMed Central

    GAMMILL, HILARY S.; NELSON, J. LEE

    2010-01-01

    Bi-directional transplacental trafficking occurs routinely during the course of normal pregnancy, from fetus to mother and from mother to fetus. In addition to a variety of cell-free substances, it is now well recognized that some cells are also exchanged. Microchimerism refers to a small number of cells (or DNA) harbored by one individual that originated in a genetically different individual. While microchimerism can be the result of iatrogenic interventions such as transplantation or transfusion, by far the most common source is naturally acquired microchimerism from maternal-fetal trafficking during pregnancy. Microchimerism is a subject of much current interest for a number of reasons. During pregnancy, fetal microchimerism can be sought from the mother’s blood for the purpose of prenatal diagnosis. Moreover, studies of fetal microchimerism during pregnancy may offer insight into complications of pregnancy, such as preeclampsia, as well as insights into the pathogenesis of autoimmune diseases such as rheumatoid arthritis which usually ameliorates during pregnancy. Furthermore, it is now known that microchimerism persists decades later, both fetal microchimerism in women who have been pregnant and maternal microchimerism in her progeny. Investigation of the long-term consequences of fetal and maternal microchimerism is another exciting frontier of active study, with initial results pointing both to adverse and beneficial effects. This review will provide an overview of microchimerism during pregnancy and of current knowledge regarding long-term effects of naturally acquired fetal and maternal microchimerism. PMID:19924635

  18. The inhibition of acquired fear.

    PubMed

    Izquierdo, Iván; Cammarota, Martín; Vianna, Mónica M R; Bevilaqua, Lía R M

    2004-01-01

    A conditioned stimulus (CS) associated with a fearsome unconditioned stimulus (US) generates learned fear. Acquired fear is at the root of a variety of mental disorders, among which phobias, generalized anxiety, the posttraumatic stress disorder (PTSD) and some forms of depression. The simplest way to inhibit learned fear is to extinguish it, which is usually done by repeatedly presenting the CS alone, so that a new association, CS-"no US", will eventually overcome the previously acquired CS-US association. Extinction was first described by Pavlov as a form of "internal inhibition" and was recommended by Freud and Ferenczi in the 1920s (who called it "habituation") as the treatment of choice for phobic disorders. It is used with success till this day, often in association with anxiolytic drugs. Extinction has since then been applied, also successfully and also often in association with anxiolytics, to the treatment of panic, generalized anxiety disorders and, more recently, PTSD. Extinction of learned fear involves gene expression, protein synthesis, N-methyl-D-aspartate (NMDA) receptors and signaling pathways in the hippocampus and the amygdala at the time of the first CS-no US association. It can be enhanced by increasing the exposure to the "no US" component at the time of behavioral testing, to the point of causing the complete uninstallment of the original fear response. Some theorists have recently proposed that reiteration of the CS alone may induce a reconsolidation of the learned behavior instead of its extinction. Reconsolidation would preserve the original memory from the labilization induced by its retrieval. If true, this would of course be disastrous for the psychotherapy of fear-motivated disorders. Here we show that neither the CS nor retrieval cause anything remotely like reconsolidation, but just extinction. In fact, our findings indicate that the reconsolidation hypothesis is essentially incorrect, at least for the form of contextual fear most

  19. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN...

  20. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN...

  1. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN...

  2. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN...

  3. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN...

  4. Investigation and identification of etiologies involved in the development of acquired hydronephrosis in aged laboratory mice with the use of high-frequency ultrasound imaging

    PubMed Central

    Springer, Danielle A.; Allen, Michele; Hoffman, Victoria; Brinster, Lauren; Starost, Matthew F.; Bryant, Mark; Eckhaus, Michael

    2014-01-01

    Laboratory mice develop naturally occurring lesions that affect biomedical research. Hydronephrosis is a recognized pathologic abnormality of the mouse kidney. Acquired hydronephrosis can affect any mouse, as it is caused by any naturally occurring disease that impairs free urine flow. Many etiologies leading to this condition are of particular significance to aging mice. Non-invasive ultrasound imaging detects renal pelvic dilation, renal enlargement, and parenchymal loss for pre-mortem identification of this condition. High-frequency ultrasound transducers produce high-resolution images of small structures, ideal for detecting organ pathology in mice. Using a 40 MHz linear array transducer, we obtained high-resolution images of a diversity of pathologic lesions occurring within the abdomen of seven geriatric mice with acquired hydronephrosis that enabled a determination of the underlying etiology. Etiologies diagnosed from the imaging results include pyelonephritis, neoplasia, urolithiasis, mouse urologic syndrome, and spontaneous hydronephrosis, and were confirmed at necropsy. A retrospective review of abdominal scans from an additional 149 aging mice shows that the most common etiologies associated with acquired hydronephrosis are mouse urologic syndrome and abdominal neoplasia. This report highlights the utility of high-frequency ultrasound for surveying research mice for age-related pathology, and is the first comprehensive report of multiple cases of acquired hydronephrosis in mice. PMID:25143818

  5. The goat (Capra hircus) mammary gland secretory tissue proteome as influenced by weight loss: A study using label free proteomics

    USDA-ARS?s Scientific Manuscript database

    Seasonal weight loss (SWL) is a significant limitation to animal production. Breeds that have evolved in harsh climates have acquired tolerance to SWL through selection. Herein, labelfree proteomics was used to characterize the effects of SWL in two goat breeds with different levels of adaptation to...

  6. [Hearing loss and idoneity--the segnalation of noise-induced hearing loss hearing Loss].

    PubMed

    Albera, Roberto; Dagna, Federico; Cassandro, Claudia; Canale, Andrea

    2011-01-01

    Work idoneity in hearing loss must be related to working ability and evolution risks. Working ability is referred to the difficulties found in speech comprehension and in signals perception. As regards hearing loss evolution it is necessary to define if the subject is affected by conductive or neurosensorial hearing loss. In conductive hearing loss it is necessary to evaluate entity and frequential distribution of the deficit. In neurosensorial hearing loss it is necessary to distinguish between noise-induced hearing loss and extraprofessional hearing loss. In noise-induced hearing loss the evolution risk is high if the noise exposure is less than 10-15 years or the actual noise exposure is louder than the former. In case of extraprofessional hearing loss the evolution risk is higher in presbycusis, endolymphatic hydrops and toxic hearing loss. The necessity to report the presence on professionale noise-induced hearing loss arises if audiometric threshold is more than 25 dB at 0.5-1-2-3-4 kHz and if it is verified the professional origine of hearing loss.

  7. High-resolution monochromated electron energy-loss spectroscopy of organic photovoltaic materials.

    PubMed

    Alexander, Jessica A; Scheltens, Frank J; Drummy, Lawrence F; Durstock, Michael F; Hage, Fredrik S; Ramasse, Quentin M; McComb, David W

    2017-09-01

    Advances in electron monochromator technology are providing opportunities for high energy resolution (10 - 200meV) electron energy-loss spectroscopy (EELS) to be performed in the scanning transmission electron microscope (STEM). The energy-loss near-edge structure in core-loss spectroscopy is often limited by core-hole lifetimes rather than the energy spread of the incident illumination. However, in the valence-loss region, the reduced width of the zero loss peak makes it possible to resolve clearly and unambiguously spectral features at very low energy-losses (<3eV). In this contribution, high-resolution EELS was used to investigate four materials commonly used in organic photovoltaics (OPVs): poly(3-hexlythiophene) (P3HT), [6,6] phenyl-C 61 butyric acid methyl ester (PCBM), copper phthalocyanine (CuPc), and fullerene (C 60 ). Data was collected on two different monochromated instruments - a Nion UltraSTEM 100 MC 'HERMES' and a FEI Titan 3 60-300 Image-Corrected S/TEM - using energy resolutions (as defined by the zero loss peak full-width at half-maximum) of 35meV and 175meV, respectively. The data was acquired to allow deconvolution of plural scattering, and Kramers-Kronig analysis was utilized to extract the complex dielectric functions. The real and imaginary parts of the complex dielectric functions obtained from the two instruments were compared to evaluate if the enhanced resolution in the Nion provides new opto-electronic information for these organic materials. The differences between the spectra are discussed, and the implications for STEM-EELS studies of advanced materials are considered. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Ultrasound of Inherited vs. Acquired Demyelinating Polyneuropathies

    PubMed Central

    Zaidman, Craig M.; Harms, Matthew B.; Pestronk, Alan

    2013-01-01

    Introduction We compared features of nerve enlargement in inherited and acquired demyelinating neuropathies using ultrasound. Methods We measured median and ulnar nerve cross-sectional areas in proximal and distal regions in 128 children and adults with inherited (Charcot-Marie Tooth-1 (CMT-1) (n=35)) and acquired (Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (n=55), Guillaine-Barre Syndrome (GBS) (n=21) and Multifocal Motor Neuropathy (MMN) (n=17)) demyelinating neuropathies. We classified nerve enlargement by degree and number of regions affected. We defined patterns of nerve enlargement as: none- no enlargement; mild-nerves enlarged but never more than twice normal; regional- nerves normal at at least one region and enlarged more than twice normal at atleast one region; diffuse- nerves enlarged at all four regions with atleast one region more than twice normal size. Results Nerve enlargement was commonly diffuse (89%) and generally more than twice normal size in CMT-1, but not (p<0.001) in acquired disorders which mostly had either no, mild or regional nerve enlargement (CIDP (64%), GBS (95%), and MMN (100%)). In CIDP, subjects treated within three months of disease onset had less nerve enlargement than those treated later. Discussion Ultrasound identified patterns of diffuse nerve enlargement can be used to screen patients suspected of having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede nerve enlargement. PMID:24101129

  9. Aggressive behaviour of inpatients with acquired brain injury.

    PubMed

    Visscher, Ada J M; van Meijel, Berno; Stolker, Joost J; Wiersma, Jan; Nijman, Henk

    2011-12-01

    To study the prevalence, nature and determinants of aggression among inpatients with acquired brain injury. Patients with acquired brain injury often have difficulty in controlling their aggressive impulses. A prospective observational study design. By means of the Staff Observation Aggression Scale-Revised, the prevalence, nature and severity of aggressive behaviour of inpatients with acquired brain injury was assessed on a neuropsychiatric treatment ward with 45 beds. Additional data on patient-related variables were gathered from the patients' files. In total, 388 aggressive incidents were recorded over 17 weeks. Of a total of 57 patients included, 24 (42%) patients had engaged in aggressive behaviour on one or more occasions. A relatively small proportion of patients (n=8; 14%) was found to be responsible for the majority of incidents (n=332; 86%). The vast majority of aggression incidents (n=270; 70%) were directly preceded by interactions between patients and nursing staff. In line with this, most incidents occurred at times of high contact intensity. Aggressive behaviour was associated with male gender, length of stay at the ward, legal status and hypoxia as the cause of brain injury. Aggression was found to be highly prevalent among inpatients with acquired brain injury. The results suggest that for the prevention of aggression on the ward, it may be highly effective to develop individually tailored interventions for the subgroup with serious aggression problems. Insight into the frequency, nature and determinants of aggressive behaviour in inpatients with acquired brain injury provides nurses with tools for the prevention and treatment of aggressive behaviour. © 2011 Blackwell Publishing Ltd.

  10. Post-acquisition data mining techniques for LC-MS/MS-acquired data in drug metabolite identification.

    PubMed

    Dhurjad, Pooja Sukhdev; Marothu, Vamsi Krishna; Rathod, Rajeshwari

    2017-08-01

    Metabolite identification is a crucial part of the drug discovery process. LC-MS/MS-based metabolite identification has gained widespread use, but the data acquired by the LC-MS/MS instrument is complex, and thus the interpretation of data becomes troublesome. Fortunately, advancements in data mining techniques have simplified the process of data interpretation with improved mass accuracy and provide a potentially selective, sensitive, accurate and comprehensive way for metabolite identification. In this review, we have discussed the targeted (extracted ion chromatogram, mass defect filter, product ion filter, neutral loss filter and isotope pattern filter) and untargeted (control sample comparison, background subtraction and metabolomic approaches) post-acquisition data mining techniques, which facilitate the drug metabolite identification. We have also discussed the importance of integrated data mining strategy.

  11. A case of acquired port wine stain: an association with repeated sunburn?

    PubMed

    Seremet, Sila; Benar, Elif B; Afsar, Fatma Sule; Calli, Aylin; Ulusarac, Ozlem

    2016-10-01

    Unlike congenital port wine stain (PWS), an acquired PWS is a rare vascular lesion that develops later in life. Although solar damage is associated with acquired PWS, there is no reported case of acquired PWS after sunburn in the literature. We report a case of a 54-year-old man diagnosed with acquired PWS possibly caused by repeated sunburn. We recommended laser treatment to our patient; however, the patient did not chose to receive any treatment. Our case demonstrates a possible rare occurrence of an acquired PWS after sunburn with larger lesions and more diffuse distribution. For this reason, our case differs from other acquired PWS cases. © 2016 The International Society of Dermatology.

  12. [Acquired amegacaryocytic thrombocytopenic purpura hiding acute myeloid leukemia].

    PubMed

    Eddou, Hicham; Zinebi, Ali; Khalloufi, Abdelaziz; Sina, Mohammed; Mahtat, Mehdi; Doghmi, Kamal; Mikdame, Mohammed; Moudden, Mohammed Karim; Baaj, Mohammed El

    2017-01-01

    Acquired amegakaryocytic thrombocytopenic purpura is a very rare condition characterized by severe thrombocytopenia linked to the reduction or disappearance of megakaryocytes in the bone marrow. It may be primary idiopathic or secondary to many pathological conditions including hematologic disorders. We report the case of a 24-year-old patient admitted for haemorrhagic syndrome caused by immunological thrombocytopenic purpura. The diagnosis was acquired amegakaryocytosis after the failure of corticotherapy and the performance of myelography. The patient was treated with ciclosporin with rapid progression to acute myeloblastic leukemia. The progression of acquired amegakaryocytosis to acute leukemia is reported but it is generally not so rapid and above all it is preceded by myelodysplastic syndrome or medullary aplasia. This study highlights the importance of a close follow-up of these pathologies with a benign-like appearance.

  13. 26 CFR 1.472-7 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.472-7 Inventories of acquiring corporations...

  14. 26 CFR 1.472-7 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.472-7 Inventories of acquiring corporations...

  15. 26 CFR 1.471-9 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.471-9 Inventories of acquiring corporations...

  16. 26 CFR 1.471-9 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.471-9 Inventories of acquiring corporations. For...

  17. 26 CFR 1.472-7 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.472-7 Inventories of acquiring corporations. For...

  18. 26 CFR 1.471-9 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.471-9 Inventories of acquiring corporations...

  19. 26 CFR 1.472-7 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.472-7 Inventories of acquiring corporations...

  20. 26 CFR 1.471-9 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.471-9 Inventories of acquiring corporations...

  1. 26 CFR 1.472-7 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.472-7 Inventories of acquiring corporations...

  2. 26 CFR 1.471-9 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.471-9 Inventories of acquiring corporations...

  3. Recurrent and acquired tracheoesophageal fistulae (TEF)-Minimally invasive management.

    PubMed

    Nazir, Zafar; Khan, Muhammad Arif Mateen; Qamar, Javaria

    2017-10-01

    Recurrent and acquired fistulae are a serious complication of congenital esophageal atresia and tracheoesophageal fistula (TEF) repair and foreign body ingestion (FBI) (e.g., button battery). We report our experience with a minimally invasive approach to recurrent and acquired TEF. Medical records of patients referred for management of recurrent and acquired TEF between 2003 and 2015 were reviewed retrospectively. Patients underwent endoscopic procedures (de-epithelization of fistulous tract and fibrin tissue adhesive-Tisseel R ) under general anesthesia. Nine children (7 male, 2 female) with age range 3months to 3years (mean 1.5year) were managed. TEF closed spontaneously in four patients, whereas in 5 patients the TEF closed after combined endoscopic procedure. Three patients required repeat endoscopic procedures. Follow-up ranged between 7months to 10years (mean 4.2years). Active observation and repeat combined endoscopic procedures are safe alternatives to open surgical repair of acquired and recurrent TEF. Level IV study. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A case report of inhalation anthrax acquired naturally.

    PubMed

    Azarkar, Zohreh; Bidaki, Majid Zare

    2016-03-03

    Anthrax is a zoonotic occupational disease caused by Bacillus anthracis, a rod-shaped immobile aerobic gram-positive bacteria with spore. Anthrax occurs in humans randomly and with low frequency. Most cases of anthrax are acquired through contact with infected animals or contaminated animal products. This old disease became particularly important since 2001 that the biological spores were exploited in America. Depending on the transmission method of the disease, clinical manifestations occur in three classes: Cutaneous, respiratory, and gastrointestinal anthrax. The respiratory form is considered as the most fatal and a rare form of anthrax intending to show complicated and unusual manifestations. In this case report a rare case of inhalation anthrax acquired naturally in southeast of Iran is presented. A blind 65-year-old man, living in a rural area, was admitted with respiratory infection, fever, dyspnea, loss of appetite, and myalgia. The patient was treated with outpatient antibiotics a week ago. After admission, the patient was again treated for pneumonia, but there was no improvement despite treatment and the patient was suffering from septicemia symptoms. Radiographic images showed wide mediastinum. Bacillus anthracis was isolated from blood and sputum culture and the results were confirmed by colony morphology, biochemical reactions and PCR. The treatment was changed to ciprofloxacin, clindamycin, and penicillin. On the second day of anthrax treatment, the patient was complicated with jaundice, elevation of liver enzymes, and a significant drop in hemoglobin, hematocrit, and platelet despite lack of obvious bleeding and was complicated with respiratory distress and sepsis and died a week after treatment. We could discover no specific exposure associated with anthrax infection for this patient. However, due to being located in an endemic and enzootic area, it is proposed that the exposure occurred through contact with infected airborne dust or an unknown

  5. 33 CFR 211.2 - Authority to acquire real estate.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

  6. 33 CFR 211.2 - Authority to acquire real estate.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

  7. 33 CFR 211.2 - Authority to acquire real estate.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

  8. 33 CFR 211.2 - Authority to acquire real estate.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

  9. 33 CFR 211.27 - Method of acquiring Federal jurisdiction.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROJECTS Federal Jurisdiction over Real Estate § 211.27 Method of acquiring Federal jurisdiction... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Method of acquiring Federal jurisdiction. 211.27 Section 211.27 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY...

  10. Factors associated with small head circumference at birth among infants born before the 28th week

    PubMed Central

    McElrath, Thomas F.; Allred, Elizabeth N.; Kuban, Karl; Hecht, Jonathan L.; Onderdonk, Andrew; O’Shea, T. Michael; Paneth, Nigel; Leviton, Alan

    2010-01-01

    OBJECTIVE We sought to identify risk factors for congenital microcephaly in extremely low gestational age newborns. STUDY DESIGN Demographic, clinical, and placental characteristics of 1445 infants born before the 28th week were gathered and evaluated for their relationship with congenital microcephaly. RESULTS Almost 10% of newborns (n = 138), rather than the expected 2.2%, had microcephaly defined as a head circumference >2 SD below the median. In multivariable models, microcephaly was associated with nonwhite race, severe intrauterine growth restriction, delivery for preeclampsia, placental infarction, and being female. The risk factors for a head circumference between <1 and >2 SD below the median were similar to those of microcephaly. CONCLUSION Characteristics associated with fetal growth restriction and preeclampsia are among the strongest correlates of microcephaly among children born at extremely low gestational ages. The elevated risk of a small head among nonwhites and females might reflect the lack of appropriate head circumference standards. PMID:20541727

  11. [Acquired angioedema – clinical characteristic of the patients diagnosed in 2012-2016 with acquired C1 inhibitor deficiency].

    PubMed

    Stobiecki, Marcin; Czarnobilska, Ewa; Obtułowicz, Krystyna

    Acquired angioedema is a rare disease caused by a deficiency of C1 esterase inhibitor with recurrent swelling symptoms. It may occur in the course of lymphoproliferative disorders or autoimmune diseases. Symptoms resemble hereditary angioedema, and the only differentiating features is negative family history, late onset of symptoms and accompanying lymphoproliferative disorder. The aim of the study was to analyze the cases of acquired angioedema. The retrospective analysis of 341 patients from the registry of patients with C1 inhibitor deficiency. Results: We identified 4 patients among 119 with HAE (3.57%) diagnosed in this same period of time 2012-2016 who fulfilled the criteria of acquired edema. In two cases the primary reason of angioedema was lymphoproliferive disease, in two monoclonal gammapathy of unknown reason. We analyzed also the results of laboratory tests C4, C1 inhibitor, C1q. In all cases the face was dominated localization. After the treatment of primary lymphoproliferive disease, in two cases, we observed total remission of angioedema. Only one patient with gammapathy require treatment with C1 inhibitor during the attacks. In these case we observed both plasma deriver, and recombinant C1 inhibitor were effective.

  12. Loss-Aversion or Loss-Attention: The Impact of Losses on Cognitive Performance

    ERIC Educational Resources Information Center

    Yechiam, Eldad; Hochman, Guy

    2013-01-01

    Losses were found to improve cognitive performance, and this has been commonly explained by increased weighting of losses compared to gains (i.e., loss aversion). We examine whether effects of losses on performance could be modulated by two alternative processes: an attentional effect leading to increased sensitivity to task incentives; and a…

  13. Asterless is required for centriole length control and sperm development

    PubMed Central

    Galletta, Brian J.; Jacobs, Katherine C.; Fagerstrom, Carey J.

    2016-01-01

    Centrioles are the foundation of two organelles, centrosomes and cilia. Centriole numbers and functions are tightly controlled, and mutations in centriole proteins are linked to a variety of diseases, including microcephaly. Loss of the centriole protein Asterless (Asl), the Drosophila melanogaster orthologue of Cep152, prevents centriole duplication, which has limited the study of its nonduplication functions. Here, we identify populations of cells with Asl-free centrioles in developing Drosophila tissues, allowing us to assess its duplication-independent function. We show a role for Asl in controlling centriole length in germline and somatic tissue, functioning via the centriole protein Cep97. We also find that Asl is not essential for pericentriolar material recruitment or centrosome function in organizing mitotic spindles. Lastly, we show that Asl is required for proper basal body function and spermatid axoneme formation. Insights into the role of Asl/Cep152 beyond centriole duplication could help shed light on how Cep152 mutations lead to the development of microcephaly. PMID:27185836

  14. Trade-offs between acquired and innate immune defenses in humans

    PubMed Central

    McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

    2016-01-01

    Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

  15. [Familial occurrence of acquired heart valve defect].

    PubMed

    Schieche, M

    1975-09-15

    A report is given on a family examination, issuing from 213 persons with an acquired valvular defect for the establishment of further cases on altogether 783 relations of the direct line. In 19 families other 21 patients with an acquired valvular defect were found; this corresponds to a share of 2.7 % of the relations examined and 8.1% of the families affected, respectively. The result repays the expenditure and, apart from this, leads to an essential furthering of the confidence between physician, patient and family as the smallest social unity for prophylaxis, diagnostics, therapy and metaphylaxis of chronic diseases.

  16. GETTING LOST: TOPOGRAPHIC SKILLS IN ACQUIRED AND DEVELOPMENTAL PROSOPAGNOSIA

    PubMed Central

    Lee, Edison; Pancaroglu, Raika; Burles, Ford; Duchaine, Brad; Iaria, Giuseppe; Barton, Jason J S

    2016-01-01

    Previous studies report that acquired prosopagnosia is frequently associated with topographic disorientation. Whether this is associated with a specific anatomic subtype of prosopagnosia, how frequently it is seen with the developmental variant, and what specific topographic function is impaired to account for this problem are not known. We studied ten subjects with acquired prosopagnosia from either occipitotemporal or anterior temporal lesions and seven with developmental prosopagnosia. Subjects were given a battery of topographic tests, including house and scene recognition, the road map test, a test of cognitive map formation, and a standardized self-report questionnaire. House and/or scene recognition were frequently impaired after either occipitotemporal or anterior temporal lesions in acquired prosopagnosia. Subjects with occipitotemporal lesions were also impaired in cognitive map formation: an overlap analysis identified right fusiform and parahippocampal gyri as a likely correlate. Only one subject with acquired prosopagnosia had mild difficulty with directional orientation on the road map test. Only one subject with developmental prosopagnosia had difficulty with cognitive map formation, and none were impaired on the other tests. Scores for house and scene recognition correlated most strongly with the results of the questionnaire. We conclude that topographic disorientation in acquired prosopagnosia reflects impaired place recognition, with a contribution from poor cognitive map formation when there is occipitotemporal damage. Topographic impairments are less frequent in developmental prosopagnosia. PMID:26874939

  17. 45 CFR 7.4 - Option to acquire foreign rights.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Option to acquire foreign rights. 7.4 Section 7.4... Option to acquire foreign rights. In any case where it is determined that all domestic rights should be...-wide regulations issued thereunder, that the Government shall reserve an option to require the...

  18. 34 CFR 7.4 - Option to acquire foreign rights.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Option to acquire foreign rights. 7.4 Section 7.4 Education Office of the Secretary, Department of Education EMPLOYEE INVENTIONS § 7.4 Option to acquire... issued thereunder, that the Government shall reserve an option to require the assignment of such rights...

  19. Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib.

    PubMed

    Acquaviva, Jaime; Smith, Donald L; Jimenez, John-Paul; Zhang, Chaohua; Sequeira, Manuel; He, Suqin; Sang, Jim; Bates, Richard C; Proia, David A

    2014-02-01

    Activating BRAF kinase mutations serve as oncogenic drivers in over half of all melanomas, a feature that has been exploited in the development of new molecularly targeted approaches to treat this disease. Selective BRAF(V600E) inhibitors, such as vemurafenib, typically induce initial, profound tumor regressions within this group of patients; however, durable responses have been hampered by the emergence of drug resistance. Here, we examined the activity of ganetespib, a small-molecule inhibitor of Hsp90, in melanoma lines harboring the BRAF(V600E) mutation. Ganetespib exposure resulted in the loss of mutant BRAF expression and depletion of mitogen-activated protein kinase and AKT signaling, resulting in greater in vitro potency and antitumor efficacy compared with targeted BRAF and MAP-ERK kinase (MEK) inhibitors. Dual targeting of Hsp90 and BRAF(V600E) provided combinatorial benefit in vemurafenib-sensitive melanoma cells in vitro and in vivo. Importantly, ganetespib overcame mechanisms of intrinsic and acquired resistance to vemurafenib, the latter of which was characterized by reactivation of extracellular signal-regulated kinase (ERK) signaling. Continued suppression of BRAF(V600E) by vemurafenib potentiated sensitivity to MEK inhibitors after acquired resistance had been established. Ganetespib treatment reduced, but not abolished, elevations in steady-state ERK activity. Profiling studies revealed that the addition of a MEK inhibitor could completely abrogate ERK reactivation in the resistant phenotype, with ganetespib displaying superior combinatorial activity over vemurafenib. Moreover, ganetespib plus the MEK inhibitor TAK-733 induced tumor regressions in vemurafenib-resistant xenografts. Overall these data highlight the potential of ganetespib as a single-agent or combination treatment in BRAF(V600E)-driven melanoma, particularly as a strategy to overcome acquired resistance to selective BRAF inhibitors.

  20. [Topical problems of empiric therapy of community-acquired pneumonia in outpatient practice].

    PubMed

    Stepanova, I I; Chorbinskaya, S A; Baryshnikonva, G A; Nikiforova, N V; Pokutniy, N F; Zverkov, I V; Maslovskyi, L V; Kotenko, K V

    2016-01-01

    Community-acquired pneumonia is one of prevalent infectious respiratory diseases. Adequate treatment of community-acquired pneumonia, with consideration of the disease severity and microbial resistence, remains extremely topical. The article covers contemporary views of community-acquired pneumonia treatment standards. The authors described results of personal research aimed to study antibacterial treatment for community-acquired pneumonia on outpatient basis over 2004-2012, evaluated correspondence of the treatment to the national clinical recommendations.

  1. Life Experiences and the Acquired Capability for Suicide in Incarcerated Men

    PubMed Central

    Smith, Phillip N.; Selwyn, Candice; D’Amato, Darcey; Granato, Stephani; Kuhlman, Shane; Mandracchia, Jon T.

    2016-01-01

    Suicide is a leading cause of death in US prisons. Prisoners may be at risk for suicide due to their greater likelihood of experiencing events that promote the acquired capability for suicide. The current study examined the associations of 10 domains of life experiences with the acquired capability for suicide in 399 male prisoners. All life experience domains were associated with acquired capability with certain domains evidencing relatively stronger relations. Results support that aggression, thrill seeking, suicidal thoughts and behaviors, and accidental injury may be particularly important to the development of the acquired capability for suicide in prisoners. PMID:27050295

  2. Acquired Acrodermatitis Enteropathica: A Case Study

    PubMed Central

    Stelzer, John W; Esplin, Nathan; Farooq, Ahsan; Karasik, Olga

    2017-01-01

    We present a case of severe acquired acrodermatitis enteropathica in a vegan adult female with multiple underlying comorbidities. Acquired acrodermatitis enteropathica or zinc-deficiency dermatitis is the most common diagnosis than many practitioners realize with up to 10% of the patients in developed nations with the risk of zinc deficiency. The condition can be difficult to diagnose due to many similarly-presenting conditions. Furthermore, comorbid conditions in the patients can serve as confounders to the diagnosis. The symptoms are often extremely distressing for the patients, though the treatment is simple and clinical improvement occurs rapidly with appropriate care. We recommend a high index of suspicion to practitioners as well as a low-threshold for initiating treatment in the patients with any clinical symptoms of the condition. PMID:29152424

  3. GLUT-1 deficiency without epilepsy--an exceptional case.

    PubMed

    Overweg-Plandsoen, W C G; Groener, J E M; Wang, D; Onkenhout, W; Brouwer, O F; Bakker, H D; De Vivo, D C

    2003-01-01

    The GLUT-1 deficiency is a metabolic disorder caused by a defect in glucose transport across the blood-brain barrier as a result of a defect in the glucose-transport protein. Patients present with epileptic seizures, delayed development, ataxia and hypotonia, and in many cases acquired microcephaly. In most patients, treatment with a ketogenic diet proved to be successful in controlling the epilepsy. We report a 9-year-old boy with retardation and ataxia, but without epilepsy, caused by GLUT-1 deficiency, proven biochemically and by DNA analysis. Treatment with a medium-chain triglyceride ketogenic diet had a beneficial effect.

  4. Combined Spring and Deltoid Ligament Repair in Adult-Acquired Flatfoot.

    PubMed

    Nery, Caio; Lemos, André Vitor Kerber C; Raduan, Fernando; Mansur, Nacime Salomão B; Baumfeld, Daniel

    2018-04-01

    Adult-acquired flatfoot deformity (AAFD) is usually due to a combination of mechanical failure of the osteoligamentous complex that maintains the medial longitudinal arch of the foot and attenuation or complete tear of the posterior tibial tendon. Magnetic resonance imaging studies in patients with flatfoot deformities have reported the posterior tibial tendon to be pathologic in up to 100% of patients, the spring ligament in up to 87%, and the deltoid ligament in 33%. Many studies in the literature describe reconstruction of the spring ligament or the deltoid ligament associated with AAFD, but there is no study in which both (spring and deltoid) ligaments are reconstructed at the same time. We describe a novel technique to reconstruct the deltoid ligament and the spring ligament at the same time. We described the technique and evaluated 10 consecutive patients with AAFD and insufficient ankle and midfoot ligaments. We found no postoperative complications, stiffness, or loss of correction. We present a novel technique to reconstruct the failed deltoid and spring ligament during flatfoot correction. It is unique in that it uses internal brace augmentation with FiberTape ® to help and protect the soft tissue healing. Level IV, retrospective case series.

  5. Mechanisms of Noise-Induced Hearing Loss Indicate Multiple Methods of Prevention

    PubMed Central

    Le Prell, Colleen G.; Yamashita, Daisuke; Minami, Shujiro B.; Yamasoba, Tatsuya; Miller, Josef M.

    2007-01-01

    Recent research has shown the essential role of reduced blood flow and free radical formation in the cochlea in noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant late formation 7–10 days following noise exposure, and one mechanism underlying noise-induced reduction in cochlear blood flow has finally been identified. These new insights have led to the formulation of new hypotheses regarding the molecular mechanisms of NIHL; and, from these, we have identified interventions that prevent NIHL, even with treatment onset delayed up to 3 days post-noise. It is essential to now assess the additive effects of agents intervening at different points in the cell death pathway to optimize treatment efficacy. Finding safe and effective interventions that attenuate NIHL will provide a compelling scientific rationale to justify human trials to eliminate this single major cause of acquired hearing loss. PMID:17141991

  6. 26 CFR 1.1092(b)-2T - Treatment of holding periods and losses with respect to straddle positions (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., A acquires gold. On January 1, 1985, A enters into an offsetting short gold forward contract. On April 1, 1985, A disposes of the short gold forward contract at no gain or loss. On April 10, 1985, A sells the gold at a gain. Since the gold had not been held for more than 6 months before the offsetting...

  7. Acquiring 4D Thoracic CT Scans Using Ciné CT Acquisition

    NASA Astrophysics Data System (ADS)

    Low, Daniel

    One method for acquiring 4D thoracic CT scans is to use ciné acquisition. Ciné acquisition is conducted by rotating the gantry and acquiring x-ray projections while keeping the couch stationary. After a complete rotation, a single set of CT slices, the number corresponding to the number of CT detector rows, is produced. The rotation period is typically sub second so each image set corresponds to a single point in time. The ciné image acquisition is repeated for at least one breathing cycle to acquire images throughout the breathing cycle. Once the images are acquired at a single couch position, the couch is moved to the abutting position and the acquisition is repeated. Post-processing of the images sets typically resorts the sets into breathing phases, stacking images from a specific phase to produce a thoracic CT scan at that phase. Benefits of the ciné acquisition protocol include, the ability to precisely identify the phase with respect to the acquired image, the ability to resort images after reconstruction, and the ability to acquire images over arbitrarily long times and for arbitrarily many images (within dose constraints).

  8. Developmental Correlates of Head Circumference at Birth and Two Years in a Cohort of Extremely Low Gestational Age Newborns

    PubMed Central

    Kuban, Karl C. K.; Allred, Elizabeth N.; O’Shea, T. Michael; Paneth, Nigel; Westra, Sjirk; Miller, Cindy; Rosman, N. Paul; Leviton, Alan

    2009-01-01

    Objectives To evaluate the developmental correlates of microcephaly evident at birth and at 2 years in a cohort born at extremely low gestational age. Methods We assessed development and motor function at 2 years of 958 children born before the 28th week of gestation, comparing those who had microcephaly at birth or 2 years with children with normal head circumference while considering the contribution of neonatal cranial ultrasound lesions. Results A total of 11% of infants in our sample had microcephaly at 2 years. Microcephaly at 2 years, but not at birth, predicts severe motor and cognitive impairments at 2 years. A total of 71% of children with congenital microcephaly had a normal head circumference at 2 years and had neurodevelopmental outcomes comparable with those with normal head circumference at birth and 2 years. Among children with microcephaly at 2 years, more than half had a Mental Developmental Index <70, and nearly a third had cerebral palsy. The risks were increased if the child also had cerebral white matter damage on a cranial ultrasound scan obtained 2 years previously. Conclusion Among extremely low gestational age newborns, microcephaly at 2 years, but not at birth, is associated with motor and cognitive impairment at age 2. PMID:19555967

  9. Intensive Care Unit–Acquired Weakness: Implications for Physical Therapist Management

    PubMed Central

    Moss, Marc; Quan, Dianna; Schenkman, Margaret

    2012-01-01

    Patients admitted to the intensive care unit (ICU) can develop a condition referred to as “ICU-acquired weakness.” This condition is characterized by profound weakness that is greater than might be expected to result from prolonged bed rest. Intensive care unit–acquired weakness often is accompanied by dysfunction of multiple organ systems. Individuals with ICU-acquired weakness typically have significant activity limitations, often requiring physical assistance for even the most basic activities associated with bed mobility. Many of these individuals have activity limitations months to years after hospitalization. The purpose of this article is to review evidence that guides physical rehabilitation of people with ICU-acquired weakness. Included are diagnostic criteria, medical management, and prognostic indicators, as well as criteria for beginning physical rehabilitation, with an emphasis on patient safety. Data are presented indicating that rehabilitation can be implemented with very few adverse effects. Evidence is provided for appropriate measurement approaches and for physical intervention strategies. Finally, some of the key issues are summarized that should be investigated to determine the best intervention guidelines for individuals with ICU-acquired weakness. PMID:22282769

  10. Mapping the plasmon response of Ag nanoislands on graphite at 100 nm resolution with scanning probe energy loss spectroscopy

    NASA Astrophysics Data System (ADS)

    Murphy, Shane; Bauer, Karl; Sloan, Peter A.; Lawton, James J.; Tang, Lin; Palmer, Richard E.

    2015-12-01

    We demonstrate plasmon mapping of Ag nanostructures on graphite using scanning probe energy loss spectroscopy (SPELS) with a spatial resolution of 100 nm. In SPELS, an STM tip is used as a localized source of field-emitted electrons to probe the sample surface. The energy loss spectrum of the backscattered electrons is measured to provide a chemical signature of the surface under the tip. We acquire three images simultaneously with SPELS: i) constant-current field-emission images, which provide topographical information; ii) backscattered electron images, which display material contrast; and iii) SPELS images, where material-dependent features such as plasmons are mapped.

  11. Amplitude loss of sonic waveform due to source coupling to the medium

    NASA Astrophysics Data System (ADS)

    Lee, Myung W.; Waite, William F.

    2007-03-01

    In contrast to hydrate-free sediments, sonic waveforms acquired in gas hydrate-bearing sediments indicate strong amplitude attenuation associated with a sonic velocity increase. The amplitude attenuation increase has been used to quantify pore-space hydrate content by attributing observed attenuation to the hydrate-bearing sediment's intrinsic attenuation. A second attenuation mechanism must be considered, however. Theoretically, energy radiation from sources inside fluid-filled boreholes strongly depends on the elastic parameters of materials surrounding the borehole. It is therefore plausible to interpret amplitude loss in terms of source coupling to the surrounding medium as well as to intrinsic attenuation. Analyses of sonic waveforms from the Mallik 5L-38 well, Northwest Territories, Canada, indicate a significant component of sonic waveform amplitude loss is due to source coupling. Accordingly, all sonic waveform amplitude analyses should include the effect of source coupling to accurately characterize a formation's intrinsic attenuation.

  12. Amplitude loss of sonic waveform due to source coupling to the medium

    USGS Publications Warehouse

    Lee, Myung W.; Waite, William F.

    2007-01-01

    In contrast to hydrate-free sediments, sonic waveforms acquired in gas hydrate-bearing sediments indicate strong amplitude attenuation associated with a sonic velocity increase. The amplitude attenuation increase has been used to quantify pore-space hydrate content by attributing observed attenuation to the hydrate-bearing sediment's intrinsic attenuation. A second attenuation mechanism must be considered, however. Theoretically, energy radiation from sources inside fluid-filled boreholes strongly depends on the elastic parameters of materials surrounding the borehole. It is therefore plausible to interpret amplitude loss in terms of source coupling to the surrounding medium as well as to intrinsic attenuation. Analyses of sonic waveforms from the Mallik 5L-38 well, Northwest Territories, Canada, indicate a significant component of sonic waveform amplitude loss is due to source coupling. Accordingly, all sonic waveform amplitude analyses should include the effect of source coupling to accurately characterize a formation's intrinsic attenuation.

  13. Prosthetic management of posttraumatic external auditory canal atresia: A rare cause of conductive hearing loss

    PubMed Central

    Adhershitha, A. R.; Anilkumar, S.; Rajesh, C.; Mohan, Deepak C.

    2016-01-01

    Acquired external auditory canal (EAC) atresia is an infrequent entity which can originate from a number of different causes including trauma, infection, neoplasia, inflammation, and radiotherapy. Posttraumatic atresias are exceptionally rare, only 10% of atresias are attributed to trauma in most of the series. The management of stenosis of the EAC is challenging as it is associated with residual hearing loss and late recurrence. Traditional stents often occlude the EAC, resulting in a temporary conductive hearing loss. This case report describes the technique of fabrication of a wide-bored acrylic stent which attained additional retention from the folds of the auricle. The customized earmold stent effectively prevented restenosis, while the large bore provided ventilation and improved hearing subjectively during the stenting period. PMID:27746605

  14. The relationship between chronic otitis media-induced hearing loss and the acquisition of social skills.

    PubMed

    Bidadi, Sanam; Nejadkazem, Mohammad; Naderpour, Masoud

    2008-11-01

    To investigate the effects of hearing loss caused by chronic otitis media (COM) on acquiring social skills. A case-control study of 90 patients, including patients with COM, age range 15-30 years, was conducted in the otorhinolaryngology ward of Tabriz University Hospital. Social skills were assessed with a social skills questionnaire. Social skill scores were found to be lower in hearing-impaired COM patients compared with the control group (P < 0.001). Social skill disabilities in patients with bilateral COM were more severe than in patients with unilateral COM and the controls (P < 0.001). Correlation between social skills score and degree of hearing loss was significantly negative (P = 0.014, rho = -0.314). These data indicate an inverse relationship between hearing loss and social skills. Social skills and educational level of COM patients are affected because of hearing impairment. This study suggests that COM has effects on social development and education.

  15. Rehabilitation of discourse impairments after acquired brain injury

    PubMed Central

    Gindri, Gigiane; Pagliarin, Karina Carlesso; Casarin, Fabíola Schwengber; Branco, Laura Damiani; Ferré, Perrine; Joanette, Yves; Fonseca, Rochele Paz

    2014-01-01

    Language impairments in patients with acquired brain injury can have a negative impact on social life as well as on other cognitive domains. Discourse impairments are among the most commonly reported communication deficits among patients with acquired brain damage. Despite advances in the development of diagnostic tools for detecting such impairments, few studies have investigated interventions to rehabilitate patients presenting with these conditions. Objective The aim of this study was to present a systematic review of the methods used in the rehabilitation of discourse following acquired brain injury. Methods The PubMed database was searched for articles using the following keywords: "rehabilitation", "neurological injury", "communication" and "discursive abilities". Results A total of 162 abstracts were found, but only seven of these met criteria for inclusion in the review. Four studies involved samples of individuals with aphasia whereas three studies recruited samples of individuals with traumatic brain injury. Conclusion All but one article found that patient performance improved following participation in a discourse rehabilitation program. PMID:29213880

  16. Community acquired Pseudomonas pneumonia in an immune competent host.

    PubMed

    Gharabaghi, Mehrnaz Asadi; Abdollahi, Seyed Mojtaba Mir; Safavi, Enayat; Abtahi, Seyed Hamid

    2012-05-26

    Pseudomonas aeruginosa is an uncommon cause of community-acquired pneumonia in immune-competent hosts. It is commonly seen in patients with structural lung abnormality such as cystic fibrosis or in immune compromised hosts. Here, the authors report a case of community-acquired Pseudomonas pneumonia in a 26-year old healthy man who presented with 8-week history of malaise and cough.

  17. Method for distributed object communications based on dynamically acquired and assembled software components

    NASA Technical Reports Server (NTRS)

    Sundermier, Amy (Inventor)

    2002-01-01

    A method for acquiring and assembling software components at execution time into a client program, where the components may be acquired from remote networked servers is disclosed. The acquired components are assembled according to knowledge represented within one or more acquired mediating components. A mediating component implements knowledge of an object model. A mediating component uses its implemented object model knowledge, acquired component class information and polymorphism to assemble components into an interacting program at execution time. The interactions or abstract relationships between components in the object model may be implemented by the mediating component as direct invocations or indirect events or software bus exchanges. The acquired components may establish communications with remote servers. The acquired components may also present a user interface representing data to be exchanged with the remote servers. The mediating components may be assembled into layers, allowing arbitrarily complex programs to be constructed at execution time.

  18. Numerical analysis of Eucalyptus grandis × E. urophylla heat-treatment: A dynamically detecting method of mass loss during the process

    NASA Astrophysics Data System (ADS)

    Zhao, Zijian; Ma, Qing; Mu, Jun; Yi, Songlin; He, Zhengbin

    Eucalyptus particles, lamellas and boards were applied to explore a simply-implemented method with neglected heat and mass transfer to inspect the mass loss during the heat-treatment course. The results revealed that the mass loss of a certain period was theoretically the definite integration of loss rate to time in this period, and a monitoring model for mass loss speed was developed with the particles and validated with the lamellas and boards. The loss rate was correlated to the temperature and temperature-evolving speed in the model which was composed of three functions during different temperature-evolving period. The sample mass loss was calculated in the MATLAB for the lamellas and boards and the model was validated and adjusted based on the difference between the computed results and the practically measured loss values. The error ranges of the new models were -16.30% to 18.35% for wood lamellas and -9.86% to 6.80% for wood boards. This method made it possible to acquire the instantaneous loss value through continuously detecting the wood temperature evolution. This idea could provide a reference for the Eucalyptus heat-treatment to detect the treating course and control the final material characteristics.

  19. Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer

    PubMed Central

    Bhattacharya, Bhaskar; Low, Sarah Hong Hui; Chong, Mei Ling; Chia, Dilys; Koh, King Xin; Sapari, Nur Sabrina; Kaye, Stanley; Hung, Huynh; Benoukraf, Touati; Soong, Richie

    2016-01-01

    Historically, understanding of acquired resistance (AQR) to combination treatment has been based on knowledge of resistance to its component agents. To test whether an altered drug interaction could be an additional factor in AQR to combination treatment, models of AQR to combination and single agent MEK and PI3K inhibitor treatment were generated. Combination indices indicated combination treatment of PI3K and MEK inhibitors remained synergistic in cells with AQR to single agent but not combination AQR cells. Differences were also observed between the models in cellular phenotypes, pathway signaling and drug cross-resistance. Genomics implicated TGFB2-EDN1 overexpression as candidate determinants in models of AQR to combination treatment. Supplementation of endothelin in parental cells converted synergism to antagonism. Silencing of TGFB2 or EDN1 in cells with AQR conferred synergy between PI3K and MEK inhibitor. These results highlight that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction. PMID:27081080

  20. Current aspects of hearing loss from occupational and leisure noise

    PubMed Central

    Plontke, S.; Zenner, H.-P.

    2004-01-01

    Hearing loss from occupational and leisure noise numbers amongst the most frequent causes of an acquired sensorineural hearing loss. Here we present a review of up-to-date findings on the pathophysiology of acoustic injury to the inner ear, with special attention being paid to its molecular-biological and genetic aspects. Epidemiological aspects shall also be dealt with, as shall the roles of lacking recovery from occupational noise due to additional exposure by leisure noise and the combined exposure of noise and chemicals. Based on the epidemiological and pathophysiological findings and against the background of published animal-experimental, pre-clinical and clinical findings, the various approaches for prevention, protection and therapeutic intervention with acoustic trauma are discussed. Pharmacological strategies involving anti-oxidative, anti-excitotoxic and anti-apoptotic substances as well as non-pharmacological strategies like "sound conditioning" are given attention. Furthermore, systemic and local substance application as well as the therapy of acute acoustic trauma and chronic hearing problems (including modern therapy forms for comorbidities such as tinnitus) shall be delved into. PMID:22073048

  1. Solithromycin for the treatment of community-acquired bacterial pneumonia.

    PubMed

    Viasus, Diego; Ramos, Oscar; Ramos, Leidy; Simonetti, Antonella F; Carratalà, Jordi

    2017-01-01

    Community-acquired pneumonia is a major public health problem worldwide. In recent years, there has been an increase in the frequency of resistance to the antimicrobials such as β-lactams or macrolides which have habitually been used against the causative pathogens. Solithromycin, a next-generation macrolide, is the first fluoroketolide with activity against most of the frequently isolated bacteria in community-acquired pneumonia, including typical and atypical bacteria as well as macrolide-resistant Streptococcus pneumoniae. Areas covered: A detailed assessment of the literature relating to the antimicrobial activity, pharmacokinetic/pharmacodynamic properties, efficacy, tolerability and safety of solithromycin for the treatment of community-acquired bacterial pneumonia Expert commentary: Recent randomized controlled phase II/III trials have demonstrated the equivalent efficacy of oral and intravenous solithromycin compared with fluoroquinolones in patients with lower mild-to-moderate respiratory infections, and have shown that systemic adverse events are comparable between solithromycin and alternative treatments. However, studies of larger populations which are able to identify infrequent adverse events are now needed to confirm these findings. On balance, current data supports solithromycin as a promising therapy for empirical treatment in adults with community-acquired bacterial pneumonia.

  2. Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome.

    PubMed

    Murray, Jeffrey C; Donahue, David J; Malik, Saleem I; Dzurik, Yvette B; Braly, Emily Z; Dougherty, Margaret J; Eaton, Katherine W; Biegel, Jaclyn A

    2011-05-01

    DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.

  3. Clinical role of Cefixime in community-acquired infections.

    PubMed

    Dreshaj, Sh; Doda-Ejupi, T; Tolaj, I Q; Mustafa, A; Kabashi, S; Shala, N; Geca, Nj; Aliu, A; Daka, A; Basha, N

    2011-01-01

    Cefixime is an oral third generation cephalosporin, frequently used in respiratory tract infections (RTI) in the pediatric population. However, in some publications cefixime has demonstrated poor efficacy against staphylococci and streptococci. of this study was to evaluate the efficacy of cefixime in the treatment of community-acquired infections in a country where parenteral third generation cephalosporins have been used for a long time. The present study was designed to assess the clinical efficacy, bacteriological eradication rates and tolerability of cefixime in children with community-acquired upper RTI (URTI), lower RTI (LRTI) and uncomplicated urinary tract infections (UTI). The study was prospective, open, and included 89 patients, from 6 months to 28 years, of both sexes, with the diagnosis of community-acquired URTI, LRTI and UTI. The treatment with cefixime was successful in 30/30 (100%) patients suffering from acute otitis media (AOM), in 10/12 (83.3%) with acute sinusitis, in 12/12 patients (100%) with pneumonia, in 31/35 (88.57) with uncomplicated UTI. The antibiotic was well tolerated. In 10 days treatment we recorded one case (1.3%) with acute gastroenteritis and two cases (2.6%) of maculopapular rash. Side-effects were transient and disappeared after finishing therapy in all three of the cases. Community-acquired infections, such as AOM, LRTI and UTI, caused by susceptible pathogens, can be treated with cefixime, as a good choice for a successful clinical response.

  4. Patients' Hand Washing and Reducing Hospital-Acquired Infection.

    PubMed

    Haverstick, Stacy; Goodrich, Cara; Freeman, Regi; James, Shandra; Kullar, Rajkiran; Ahrens, Melissa

    2017-06-01

    Hand hygiene is important to prevent hospital-acquired infections. Patients' hand hygiene is just as important as hospital workers' hand hygiene. Hospital-acquired infection rates remain a concern across health centers. To improve patients' hand hygiene through the promotion and use of hand washing with soap and water, hand sanitizer, or both and improve patients' education to reduce hospital-acquired infections. In August 2013, patients in a cardiothoracic postsurgical step-down unit were provided with individual bottles of hand sanitizer. Nurses and nursing technicians provided hand hygiene education to each patient. Patients completed a 6-question survey before the intervention, at hospital discharge and 1, 2, and 3 months after the intervention. Hospital-acquired infection data were tracked monthly by infection prevention staff. Significant correlations were found between hand hygiene and rates of infection with vancomycin-resistant enterococci ( P = .003) and methicillin-resistant Staphylococcus aureus ( P = .01) after the intervention. After the implementation of hand hygiene interventions, rates of both infections declined significantly and patients reported more staff offering opportunities for and encouraging hand hygiene. This quality improvement project demonstrates that increased hand hygiene compliance by patients can influence infection rates in an adult cardiothoracic step-down unit. The decreased infection rates and increased compliance with hand hygiene among the patients may be attributed to the implementation of patient education and the increased accessibility and use of hand sanitizer. ©2017 American Association of Critical-Care Nurses.

  5. 26 CFR 1.1092(b)-2T - Treatment of holding periods and losses with respect to straddle positions (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 1. On October 1, 1984, A acquires gold. On January 1, 1985, A enters into an offsetting short gold forward contract. On April 1, 1985, A disposes of the short gold forward contract at no gain or loss. On April 10, 1985, A sells the gold at a gain. Since the gold had not been held for more than 6 months...

  6. 26 CFR 1.1092(b)-2T - Treatment of holding periods and losses with respect to straddle positions (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 1. On October 1, 1984, A acquires gold. On January 1, 1985, A enters into an offsetting short gold forward contract. On April 1, 1985, A disposes of the short gold forward contract at no gain or loss. On April 10, 1985, A sells the gold at a gain. Since the gold had not been held for more than 6 months...

  7. 26 CFR 1.1092(b)-2T - Treatment of holding periods and losses with respect to straddle positions (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 1. On October 1, 1984, A acquires gold. On January 1, 1985, A enters into an offsetting short gold forward contract. On April 1, 1985, A disposes of the short gold forward contract at no gain or loss. On April 10, 1985, A sells the gold at a gain. Since the gold had not been held for more than 6 months...

  8. 26 CFR 1.1092(b)-2T - Treatment of holding periods and losses with respect to straddle positions (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 1. On October 1, 1984, A acquires gold. On January 1, 1985, A enters into an offsetting short gold forward contract. On April 1, 1985, A disposes of the short gold forward contract at no gain or loss. On April 10, 1985, A sells the gold at a gain. Since the gold had not been held for more than 6 months...

  9. Update: Noncongenital Zika Virus Disease Cases - 50 U.S. States and the District of Columbia, 2016.

    PubMed

    Hall, Victoria; Walker, William L; Lindsey, Nicole P; Lehman, Jennifer A; Kolsin, Jonathan; Landry, Kimberly; Rabe, Ingrid B; Hills, Susan L; Fischer, Marc; Staples, J Erin; Gould, Carolyn V; Martin, Stacey W

    2018-03-09

    Zika virus is a flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections also have been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-3). Most Zika virus infections are asymptomatic or result in mild clinical illness, characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis; Guillain-Barré syndrome, meningoencephalitis, and severe thrombocytopenia rarely have been associated with Zika virus infection (1). However, congenital Zika virus infection can result in fetal loss, microcephaly, and other birth defects (1,2). In 2016, a total of 5,168 noncongenital Zika virus disease cases were reported from U.S. states and the District of Columbia. Most cases (4,897, 95%) were in travelers returning from Zika virus-affected areas. A total of 224 (4%) cases were acquired through presumed local mosquitoborne transmission, and 47 (1%) were acquired by other routes. It is important that providers in the United States continue to test symptomatic patients who live in or recently traveled to areas with ongoing Zika virus transmission or had unprotected sex with someone who lives in or traveled to those areas. All pregnant women and their partners should take measures to prevent Zika virus infection during pregnancy. A list of affected areas and specific recommendations on how to prevent Zika virus infection during pregnancy are available at https://www.cdc.gov/pregnancy/zika/protect-yourself.html.

  10. Acquired Large Calcified Unruptured Sinus of Valsalva Aneurysm.

    PubMed

    Park, Sang-Hyun; Seol, Sang-Hoon; Seo, Guang-Won; Song, Pil-Sang; Kim, Dong-Kie; Kim, Ki-Hun; Kim, Doo-Il

    2015-11-01

    Acquired aneurysms of the sinus of Valsalva are rare. They are caused by infections such as tuberculosis, syphilis and endocarditis, as well as atherosclerosis and traumatic injury. They may be asymptomatic and incidentally discovered. We present a rare case of a large acquired calcified unruptured aneurysm of the right coronary sinus of Valsalva that was compressing the right ventricular outflow tract. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  11. Community-Acquired Acute Kidney Injury: A Nationwide Survey in China.

    PubMed

    Wang, Yafang; Wang, Jinwei; Su, Tao; Qu, Zhen; Zhao, Minghui; Yang, Li

    2017-05-01

    This study aimed to describe the burden of community-acquired acute kidney injury (AKI) in China based on a nationwide survey about AKI. Cross-sectional and retrospective study. A national sample of 2,223,230 hospitalized adult patients from 44 academic/local hospitals in Mainland China was used. AKI was defined according to the 2012 KDIGO AKI creatinine criteria or an increase or decrease in serum creatinine level of 50% during the hospital stay. Community-acquired AKI was identified when a patient had AKI that could be defined at hospital admission. The rate, cause, recognition, and treatment of community-acquired AKI were stratified according to hospital type, latitude, and economic development of the regions in which the patients were admitted. All-cause in-hospital mortality and recovery of kidney function at hospital discharge. 4,136 patients with community-acquired AKI were identified during the 2 single-month snapshots (January 2013 and July 2013). Of these, 2,020 (48.8%) had cases related to decreased kidney perfusion; 1,111 (26.9%), to intrinsic kidney disease; and 499 (12.1%), to urinary tract obstruction. In the north versus the south, more patients were exposed to nephrotoxins or had urinary tract obstructions. 536 (13.0%) patients with community-acquired AKI had indications for renal replacement therapy (RRT), but only 347 (64.7%) of them received RRT. Rates of timely diagnosis and appropriate use of RRT were higher in regions with higher per capita gross domestic product. All-cause in-hospital mortality was 7.3% (295 of 4,068). Delayed AKI recognition and being located in northern China were independent risk factors for in-hospital mortality, and referral to nephrology providers was an independent protective factor. Possible misclassification of AKI and community-acquired AKI due to nonstandard definitions and missing data for serum creatinine. The features of community-acquired AKI varied substantially in different regions of China and were closely

  12. Dynamic Energy Loss Characteristics in the Native Aortic Valve

    NASA Astrophysics Data System (ADS)

    Hwai Yap, Choon; Dasi, Laksmi P.; Yoganathan, Ajit P.

    2009-11-01

    Aortic Valve (AV) stenosis if untreated leads to heart failure. From a mechanics standpoint, heart failure implies failure to generate sufficient mechanical power to overcome energy losses in the circulation. Thus energy efficiency-based measures are direct measures of AV disease severity, which unfortunately is not used in current clinical measures of stenosis severity. We present an analysis of the dynamic rate of energy dissipation through the AV from direct high temporal resolution measurements of flow and pressure drop across the AV in a pulsatile left heart setup. Porcine AV was used and measurements at various conditions were acquired: varying stroke volumes; heart rates; and stenosis levels. Energy dissipation waveform has a distinctive pattern of being skewed towards late systole, attributed to the explosive growth of flow instabilities from adverse pressure gradient. Increasing heart rate and stroke volume increases energy dissipation, but does not alter the normalized shape of the dissipation temporal profile. Stenosis increases energy dissipation and also alters the normalized shape of dissipation waveform with significantly more losses during late acceleration phase. Since stenosis produces a departure from the signature dissipation waveform shape, dynamic energy dissipation analysis can be extended into a clinical tool for AV evaluation.

  13. Foodborne listeriosis acquired in hospitals.

    PubMed

    Silk, Benjamin J; McCoy, Morgan H; Iwamoto, Martha; Griffin, Patricia M

    2014-08-15

    Listeriosis is characterized by bacteremia or meningitis. We searched for listeriosis case series and outbreak investigations published in English by 2013, and assessed the strength of evidence for foodborne acquisition among patients who ate hospital food. We identified 30 reports from 13 countries. Among the case series, the median proportion of cases considered to be hospital-acquired was 25% (range, 9%-67%). The median number of outbreak-related illnesses considered to be hospital-acquired was 4.0 (range, 2-16). All patients were immunosuppressed in 18 of 24 (75%) reports with available data. Eight outbreak reports with strong evidence for foodborne acquisition in a hospital implicated sandwiches (3 reports), butter, precut celery, Camembert cheese, sausage, and tuna salad (1 report each). Foodborne acquisition of listeriosis among hospitalized patients is well documented internationally. The number of listeriosis cases could be reduced substantially by establishing hospital policies for safe food preparation for immunocompromised patients and by not serving them higher-risk foods. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. Neural loss aversion differences between depression patients and healthy individuals: A functional MRI investigation.

    PubMed

    Chandrasekhar Pammi, V S; Pillai Geethabhavan Rajesh, Purushothaman; Kesavadas, Chandrasekharan; Rappai Mary, Paramban; Seema, Satish; Radhakrishnan, Ashalatha; Sitaram, Ranganatha

    2015-04-01

    Neuroeconomics employs neuroscience techniques to explain decision-making behaviours. Prospect theory, a prominent model of decision-making, features a value function with parameters for risk and loss aversion. Recent work with normal participants identified activation related to loss aversion in brain regions including the amygdala, ventral striatum, and ventromedial prefrontal cortex. However, the brain network for loss aversion in pathologies such as depression has yet to be identified. The aim of the current study is to employ the value function from prospect theory to examine behavioural and neural manifestations of loss aversion in depressed and healthy individuals to identify the neurobiological markers of loss aversion in economic behaviour. We acquired behavioural data and fMRI scans while healthy controls and patients with depression performed an economic decision-making task. Behavioural loss aversion was higher in patients with depression than in healthy controls. fMRI results revealed that the two groups shared a brain network for value function including right ventral striatum, ventromedial prefrontal cortex, and right amygdala. However, the neural loss aversion results revealed greater activations in the right dorsal striatum and the right anterior insula for controls compared with patients with depression, and higher activations in the midbrain region ventral tegmental area for patients with depression compared with controls. These results suggest that while the brain network for loss aversion is shared between depressed and healthy individuals, some differences exist with respect to differential activation of additional areas. Our findings are relevant to identifying neurobiological markers for altered decision-making in the depressed. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. How Did Light Acquire a Velocity?

    ERIC Educational Resources Information Center

    Lauginie, Pierre

    2013-01-01

    We discuss how light acquired a velocity through history, from the ancient Greeks to the early modern era. Combining abstract debates, models of light, practical needs, planned research and chance, this history illustrates several key points that should be brought out in science education.

  16. A COMPACTRIO-BASED BEAM LOSS MONITOR FOR THE SNS RF TEST CAVE

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

    Blokland, Willem; Armstrong, Gary A

    2009-01-01

    An RF Test Cave has been built at the Spallation Neutron Source (SNS) to be able to test RF cavities without interfering the SNS accelerator operations. In addition to using thick concrete wall to minimize radiation exposure, a Beam Loss Monitor (BLM) must abort the operation within 100 usec when the integrated radiation within the cave exceeds a threshold. We choose the CompactRIO platform to implement the BLM based on its performance, cost-effectiveness, and rapid development. Each in/output module is connected through an FPGA to provide point-by-point processing. Every 10 usec the data is acquired analyzed and compared to themore » threshold. Data from the FPGA is transferred using DMA to the real-time controller, which communicates to a gateway PC to talk to the SNS control system. The system includes diagnostics to test the hardware and integrates the losses in real-time. In this paper we describe our design, implementation, and results« less

  17. Parental perspectives on adolescent hearing loss risk and prevention.

    PubMed

    Sekhar, Deepa L; Clark, Sarah J; Davis, Matthew M; Singer, Dianne C; Paul, Ian M

    2014-01-01

    .15-3.18) compared with parents who were very unwilling, unwilling, or neutral. Despite the rising prevalence of acquired adolescent hearing loss, few parents believe their adolescent is at risk. Those with higher education are more willing to promote hearing conservation, especially with younger adolescents. To create effective hearing conservation programs, parents need better education on this subject as well as effective and acceptable strategies to prevent adolescent noise exposure.

  18. Free Reading: A Powerful Tool for Acquiring a Second Language

    ERIC Educational Resources Information Center

    Priya, J.; Ponniah, R. Joseph

    2013-01-01

    The paper claims that free reading is a crucial ingredient in acquiring a second or foreign language. It contributes to the development of all measures of language competence which include grammar, vocabulary, spelling, syntax, fluency and style. The review supports the claim that readers acquire language subconsciously when they receive…

  19. Acquired Aplastic Anemia in Children

    PubMed Central

    Hartung, Helge D.; Olson, Timothy S.; Bessler, Monica

    2013-01-01

    SYNOPSIS This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder. PMID:24237973

  20. Intensive care unit-acquired weakness.

    PubMed

    Griffiths, Richard D; Hall, Jesse B

    2010-03-01

    Severe weakness is being recognized as a complication that impacts significantly on the pace and degree of recovery and return to former functional status of patients who survive the organ failures that mandate life-support therapies such as mechanical ventilation. Despite the apparent importance of this problem, much remains to be understood about its incidence, causes, prevention, and treatment. Review from literature and an expert round-table. The Brussels Round Table Conference in 2009 convened more than 20 experts in the fields of intensive care, neurology, and muscle physiology to review current understandings of intensive care unit-acquired weakness and to improve clinical outcome. Formal electrophysiological evaluation of patients with intensive care unit-acquired weakness can identify peripheral neuropathies, myopathies, and combinations of these disorders, although the correlation of these findings to weakness measurable at the bedside is not always precise. For routine clinical purposes, bedside assessment of neuromuscular function can be performed but is often confounded by complicating factors such as sedative and analgesic administration. Risk factors for development of intensive care unit-acquired weakness include bed rest itself, sepsis, and corticosteroid exposure. A strong association exists between weakness and long-term ventilator dependence; weakness is a major determinant of patient outcomes after surviving acute respiratory failure and may be present for months, or indefinitely, in the convalescence phase of critical illness. Although much has been learned about the physiology and cell and molecular biology of skeletal and diaphragm dysfunction under conditions of aging, exercise, disuse, and sepsis, the application of these understandings to the bedside requires more study in both bench models and patients. Although a trend toward greater immobilization and sedation of patients has characterized the past several decades of intensive care

  1. Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura

    PubMed Central

    Jiang, Yang; McIntosh, Jennifer J.; Reese, Jessica A.; Deford, Cassandra C.; Kremer Hovinga, Johanna A.; Lämmle, Bernhard; Terrell, Deirdra R.; Vesely, Sara K.; Knudtson, Eric J.

    2014-01-01

    Pregnancy may precipitate acute episodes of thrombotic thrombocytopenic purpura (TTP), but pregnancy outcomes in women who have recovered from acquired TTP are not well documented. We analyzed pregnancy outcomes following recovery from TTP associated with acquired, severe ADAMTS13 deficiency (ADAMTS13 activity <10%) in women enrolled in the Oklahoma TTP-HUS Registry from 1995 to 2012. We also systematically searched for published reports on outcomes of pregnancies following recovery from TTP associated with acquired, severe ADAMTS13 deficiency. Ten women in the Oklahoma Registry had 16 subsequent pregnancies from 1999 to 2013. Two women had recurrent TTP, which occurred 9 and 29 days postpartum. Five of 16 pregnancies (31%, 95% confidence interval, 11%-59%) in 3 women were complicated by preeclampsia, a frequency greater than US population estimates (2.1%-3.2%). Thirteen (81%) pregnancies resulted in normal children. The literature search identified 382 articles. Only 6 articles reported pregnancies in women who had recovered from TTP associated with acquired, severe ADAMTS13 deficiency, describing 10 pregnancies in 8 women. TTP recurred in 6 pregnancies. Conclusions: With prospective complete follow-up, recurrent TTP complicating subsequent pregnancies in Oklahoma patients is uncommon, but the occurrence of preeclampsia may be increased. Most pregnancies following recovery from TTP in Oklahoma patients result in normal children. PMID:24398329

  2. Forest abovegroundbiomass mapping using spaceborne stereo imagery acquired by Chinese ZY-3

    NASA Astrophysics Data System (ADS)

    Sun, G.; Ni, W.; Zhang, Z.; Xiong, C.

    2015-12-01

    Besides LiDAR data, another valuable type of data which is also directly sensitive to forest vertical structures and more suitable for regional mapping of forest biomass is the stereo imagery or photogrammetry. Photogrammetry is the traditional technique for deriving terrain elevation. The elevation of the top of a tree canopy can be directly measured from stereo imagery but winter images are required to get the elevation of ground surface because stereo images are acquired by optical sensors which cannot penetrate dense forest canopies with leaf-on condition. Several spaceborne stereoscopic systems with higher spatial resolutions have been launched in the past several years. For example the Chinese satellite Zi Yuan 3 (ZY-3) specifically designed for the collection of stereo imagery with a resolution of 3.6 m for forward and backward views and 2.1 m for the nadir view was launched on January 9, 2012. Our previous studies have demonstrated that the spaceborne stereo imagery acquired in summer has good performance on the description of forest structures. The ground surface elevation could be extracted from spaceborne stereo imagery acquired in winter. This study mainly focused on assessing the mapping of forest biomass through the combination of spaceborne stereo imagery acquired in summer and those in winter. The test sites of this study located at Daxing AnlingMountains areas as shown in Fig.1. The Daxing Anling site is on the south border of boreal forest belonging to frigid-temperate zone coniferous forest vegetation The dominant tree species is Dhurian larch (Larix gmelinii). 10 scenes of ZY-3 stereo images are used in this study. 5 scenes were acquired on March 14,2012 while the other 5 scenes were acquired on September 7, 2012. Their spatial coverage is shown in Fig.2-a. Fig.2-b is the mosaic of nadir images acquired on 09/07/2012 while Fig.2-c is thecorresponding digital surface model (DSM) derived from stereo images acquired on 09/07/2012. Fig.2-d is the

  3. Thymidine Kinase 1 Loss Confers Trifluridine Resistance without Affecting 5-Fluorouracil Metabolism and Cytotoxicity.

    PubMed

    Edahiro, Keitaro; Iimori, Makoto; Kobunai, Takashi; Morikawa-Ichinose, Tomomi; Miura, Daisuke; Kataoka, Yuki; Niimi, Shinichiro; Wakasa, Takeshi; Saeki, Hiroshi; Oki, Eiji; Kitao, Hiroyuki; Maehara, Yoshihiko

    2018-06-04

    Acquired resistance to therapeutic drugs is a serious problem for cancer patients receiving systemic treatment. Experimentally, drug resistance is established in cell lines in vitro by repeated, continuous exposure to escalating concentrations of the drug; however, the precise mechanism underlying the acquired resistance is not always known. Here, it is demonstrated that the human colorectal cancer cell line DLD1 with acquired resistance to trifluridine (FTD), a key component of the novel, orally administered nucleoside analog-type chemotherapeutic drug trifluridine/tipiracil, lacks functional thymidine kinase 1 (TK1) expression because of one nonsense mutation in the coding exon. Targeted disruption of the TK1 gene also conferred severe FTD resistance, indicating that the loss of TK1 protein expression is the primary cause of FTD resistance. Both FTD-resistant DLD1 cells and DLD1-TK1-/- cells exhibited similar 5-fluorouracil (5-FU) sensitivity to that of the parental DLD1 line. The quantity of cellular pyrimidine nucleotides in these cells and the kinetics of thymidylate synthase ternary complex formation in 5-FU-treated cells is similar to DLD1 cells, indicating that 5-FU metabolism and cytotoxicity were unaffected. The present data provide molecular-based evidence that acquired resistance to FTD does not confer 5-FU resistance, implying that 5-FU-based chemotherapy would be effective even in tumors that become refractory to FTD during trifluridine/tipiracil treatment. 5-fluorouracil-based chemotherapy would be effective even in tumors that become refractory to trifluridine during combined trifluridine/tipiracil treatment. Copyright ©2018, American Association for Cancer Research.

  4. Musicality: instinct or acquired skill?

    PubMed

    Marcus, Gary F

    2012-10-01

    Is the human tendency toward musicality better thought of as the product of a specific, evolved instinct or an acquired skill? Developmental and evolutionary arguments are considered, along with issues of domain-specificity. The article also considers the question of why humans might be consistently and intensely drawn to music if musicality is not in fact the product of a specifically evolved instinct. Copyright © 2012 Cognitive Science Society, Inc.

  5. Value-based purchasing and hospital acquired conditions: are we seeing improvement?

    PubMed

    Spaulding, Aaron; Zhao, Mei; Haley, D Rob

    2014-12-01

    To determine if the Value-Based Purchasing Performance Scoring system correlates with hospital acquired condition quality indicators. This study utilizes the following secondary data sources: the American Hospital Association (AHA) annual survey and the Centers for Medicare and Medicaid (CMS) Value-Based Purchasing and Hospital Acquired Conditions databases. Zero-inflated negative binomial regression was used to examine the effect of CMS total performance score on counts of hospital acquired conditions. Hospital structure variables including size, ownership, teaching status, payer mix, case mix, and location were utilized as control variables. The secondary data sources were merged into a single database using Stata 10. Total performance scores, which are used to determine if hospitals should receive incentive money, do not correlate well with quality outcome in the form of hospital acquired conditions. Value-based purchasing does not appear to correlate with improved quality and patient safety as indicated by Hospital Acquired Condition (HAC) scores. This leads us to believe that either the total performance score does not measure what it should, or the quality outcome measurements do not reflect the quality of the total performance scores measure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Cytomegalovirus retinitis associated with acquired immunodeficiency syndrome.

    PubMed

    Geng, Shuang; Ye, Jun-jie; Zhao, Jia-liang; Li, Tai-sheng; Han, Yang

    2011-04-01

    Cytomegalovirus (CMV) retinitis is the most severe intraocular complication that results in total retinal destruction and loss of visual acuity in patients with acquired immunodeficiency syndrome (AIDS). This study aimed to investigate the fundus characteristics, systemic manifestations and therapeutic outcomes of CMV retinitis associated with AIDS. It was a retrospective case series. CMV retinitis was present in 39 eyes (25 patients). Best corrected visual acuities, anterior segment, fundus features, fundus fluorescence angiography (FFA) and CD4(+) T-lymphocyte counts of the patients with CMV retinitis associated with AIDS were analyzed. Intravitreal injections of ganciclovir (400 µg) were performed in 4 eyes (2 patients). Retinal vasculitis, dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface were present in 28 eyes. The vitreous was clear or mildly opaque. Late stage of the retinopathy was demonstrated in 8 eyes characterized as atrophic retina, sclerotic and attenuated vessels, retinal pigment epithelium (RPE) atrophy, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The average CD4(+) T-lymphocyte count in peripheral blood of the patients with CMV retinitis was (30.6 ± 25.3) × 10(6)/L (range, (0 - 85) × 10(6)/L). After intravitreal injections of ganciclovir, visual acuity was improved and fundus lesions regressed. CMV retinitis is the most severe and the most common intraocular complication in patients with AIDS. For the patients with yellow-white retinal lesions, hemorrhage and retinal vasculitis without clear cause, human immunodeficiency virus (HIV) serology should be performed. Routine eye examination is also indicated in HIV positive patients.

  7. Endogenous Opioid Mechanisms Are Implicated in Obesity and Weight Loss in Humans.

    PubMed

    Burghardt, Paul R; Rothberg, Amy E; Dykhuis, Kate E; Burant, Charles F; Zubieta, Jon-Kar

    2015-08-01

    Successful long-term weight loss is challenging. Brain endogenous opioid systems regulate associated processes; however, their role in the maintenance of weight loss has not been adequately explored in humans. In a preliminary study, the objective was to assess central μ-opioid receptor (MOR) system involvement in eating behaviors and their relationship to long-term maintenance of weight loss. This was a case-control study with follow-up of the treatment group at 1 year after intervention. The study was conducted at a tertiary care university medical center. Lean healthy (n = 7) and chronically obese (n = 7) men matched for age and ethnicity participated in the study. MOR availability measures were acquired with positron emission tomography and [(11)C]carfentanil. Lean healthy men were scanned twice under both fasted and fed conditions. Obese men were placed on a very low-calorie diet to achieve 15% weight loss from baseline weight and underwent two positron emission tomography scans before and two after weight loss, incorporating both fasted and fed states. Brain MOR availability and activation were measured by reductions in MOR availability (nondisplaceable binding potential) from the fed compared with the fasted-state scans. Baseline MOR nondisplaceable binding potential was reduced in obese compared with the lean and partially recovered obese after weight loss in regions that regulate homeostatic, hedonic, and emotional responses to feeding. Reductions in negative affect and feeding-induced MOR system activation in the right temporal pole were highly correlated in leans but not in obese men. A trend for an association between MOR activation in the right temporal pole before weight loss and weight regain 1 year was found. Although these preliminary studies have a small sample size, these results suggest that obesity and diet-induced weight loss impact central MOR binding and endogenous opioid system function. MOR system activation in response to an acute meal

  8. A rare case of acquired lymphangioma circumscriptum of the penis.

    PubMed

    Adikari, S; Philippidou, M; Samuel, M

    2017-02-01

    Acquired lymphangioma circumscriptum is a rare occurrence on the penis. We report a case of a 47-year-old man who presented with a single lesion of acquired lymphangioma circumscriptum on the penis resembling genital warts. We report the case to increase awareness of this rare condition which may mimic sexually transmitted infections such as genital warts.

  9. Rocky Mountain spotted fever acquired in Florida, 1973-83.

    PubMed Central

    Sacks, J J; Janowski, H T

    1985-01-01

    From 1973 to 1983, 49 Florida residents were reported with confirmed Rocky Mountain spotted fever (RMSF), 25 of whom were considered to have had Florida-acquired disease. Although there was no history of tick exposure for six of these 25 persons, all had contact with dogs or outdoor activities during the incubation period. The tick vectors of RMSF are widely distributed throughout Florida. We conclude that RMSF, although rare in Florida, can be acquired in the state. PMID:4061716

  10. Acquired Elastotic Hemangioma: Case Series and Comprehensive Literature Review

    PubMed Central

    Hinds, Brian R

    2017-01-01

    Background Acquired elastotic hemangioma is a benign vascular proliferation that typically presents as an asymptomatic red plaque on a sun-exposed site of an adult. Material and Methods The PubMed database was used to search the following words: acquired, angioma, arm, basal, carcinoma, cell, elastosis, elastotic, exposed, forearm, hemangioma, solar, sun, and vascular. The relevant papers and reference cited generated by the search were reviewed. The features from a case series of 11 patients with acquired elastotic hemangioma are presented. In addition, a comprehensive review of the characteristics of this unique hemangioma—not only in our 11 patients but also in the previously reported 34 individuals with this lesion—is provided. Results Acquired elastotic hemangioma, reported in 45 patients (24 women and 21 men), typically appeared as an asymptomatic solitary red plaque in sun-exposed areas—most commonly the forearm--of adults aged 50 years or older. The pathology shows a proliferation of vascular channels—surrounded and intertwined by intense solar elastosis--in the upper dermis, located parallel to the overlying epidermis, and separated from it by a zone of normal-appearing superficial papillary dermis. There was extensive solar elastosis surrounding and between the new blood vessels; some of the endothelial cells protrude (in a hob-nail pattern) into the vessel lumen. The clinical differential diagnosis includes basal cell carcinoma and the pathologic differential diagnosis includes other benign, malignant, and reactive vascular lesions. Ultraviolet radiation may contribute to the pathogenesis of this hemangioma since it occurs on sun-exposed sites. There was no recurrence of the lesion following either excision or observation. Conclusions The possibility of acquired elastotic hemangioma should be considered by clinicians when they encounter an older individual with a new red plaque on a sun-exposed site that clinically appears to be a superficial

  11. The renal concentrating mechanism and the clinical consequences of its loss

    PubMed Central

    Agaba, Emmanuel I.; Rohrscheib, Mark; Tzamaloukas, Antonios H.

    2012-01-01

    The integrity of the renal concentrating mechanism is maintained by the anatomical and functional arrangements of the renal transport mechanisms for solute (sodium, potassium, urea, etc) and water and by the function of the regulatory hormone for renal concentration, vasopressin. The discovery of aquaporins (water channels) in the cell membranes of the renal tubular epithelial cells has elucidated the mechanisms of renal actions of vasopressin. Loss of the concentrating mechanism results in uncontrolled polyuria with low urine osmolality and, if the patient is unable to consume (appropriately) large volumes of water, hypernatremia with dire neurological consequences. Loss of concentrating mechanism can be the consequence of defective secretion of vasopressin from the posterior pituitary gland (congenital or acquired central diabetes insipidus) or poor response of the target organ to vasopressin (congenital or nephrogenic diabetes insipidus). The differentiation between the three major states producing polyuria with low urine osmolality (central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia) is done by a standardized water deprivation test. Proper diagnosis is essential for the management, which differs between these three conditions. PMID:23293407

  12. Pregnancy loss: French clinical practice guidelines.

    PubMed

    Huchon, C; Deffieux, X; Beucher, G; Capmas, P; Carcopino, X; Costedoat-Chalumeau, N; Delabaere, A; Gallot, V; Iraola, E; Lavoue, V; Legendre, G; Lejeune-Saada, V; Leveque, J; Nedellec, S; Nizard, J; Quibel, T; Subtil, D; Vialard, F; Lemery, D

    2016-06-01

    In intrauterine pregnancies of uncertain viability with a gestational sac without a yolk sac (with a mean of three orthogonal transvaginal ultrasound measurements <25mm), the suspected pregnancy loss should only be confirmed after a follow-up scan at least 14 days later shows no embryo with cardiac activity (Grade C). In intrauterine pregnancies of uncertain viability with an embryo <7mm on transvaginal ultrasound, the suspected pregnancy loss should only be confirmed after a follow-up scan at least 7 days later (Grade C). In pregnancies of unknown location after transvaginal ultrasound (i.e. not visible in the uterus), a threshold of at least 3510IU/l for the serum human chorionic gonadotrophin assay is recommended; above that level, a viable intrauterine pregnancy can be ruled out (Grade C). Postponing conception after an early miscarriage in women who want a new pregnancy is not recommended (Grade A). A work-up for women with recurrent pregnancy loss should include the following: diabetes (Grade A), antiphospholipid syndrome (Grade A), hypothyroidism with anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies (Grade A), vitamin deficiencies (B9, B12) (Grade C), hyperhomocysteinaemia (Grade C), hyperprolactinaemia (Grade B), diminished ovarian reserve (Grade C), and a uterine malformation or an acquired uterine abnormality amenable to surgical treatment (Grade C). The treatment options recommended for women with a missed early miscarriage are vacuum aspiration (Grade A) or misoprostol (Grade B); and the treatment options recommended for women with an incomplete early miscarriage are vacuum aspiration (Grade A) or expectant management (Grade A). In the absence of both chorioamnionitis and rupture of the membranes, women with a threatened late miscarriage and an open cervix, with or without protrusion of the amniotic sac into the vagina, should receive McDonald cerclage, tocolysis with indomethacin, and antibiotics (Grade C). Among women

  13. Neuroimaging findings of congenital Zika virus infection: a pictorial essay.

    PubMed

    Zare Mehrjardi, Mohammad; Poretti, Andrea; Huisman, Thierry A G M; Werner, Heron; Keshavarz, Elham; Araujo Júnior, Edward

    2017-03-01

    Zika virus (ZIKV) is a mosquito-borne arbovirus from the Flaviviridae family. It had caused several epidemics since its discovery in 1947, but there was no significant attention to this virus until the recent outbreak in Brazil in 2015. The main concern is the causal relationship between prenatal ZIKV infection and congenital microcephaly, which has been confirmed recently. Moreover, ZIKV may cause other central nervous system abnormalities such as brain parenchymal atrophy with secondary ventriculomegaly, intracranial calcification, malformations of cortical development (such as polymicrogyria, and lissencephaly-pachygyria), agenesis/hypoplasia of the corpus callosum, cerebellar and brainstem hypoplasia, sensorineural hearing-loss, and ocular abnormalities as well as arthrogryposis in the infected fetuses. Postnatal (acquired) ZIKV infection usually has an asymptomatic or mildly symptomatic course, while prenatal (congenital) ZIKV infection has a more severe course and may cause severe brain anomalies that are described as congenital Zika syndrome. In this pictorial essay, we aim to illustrate the prenatal and postnatal neuroimaging findings that may be seen in fetuses and neonates with congenital Zika syndrome, and will discuss possible radiological differential diagnoses. A detailed knowledge of these findings is paramount for an early correct diagnosis, prognosis determination, and counseling of the affected children and families.

  14. Changes in food intake and abnormal behavior using a puzzle feeder in newly acquired sub-adult rhesus monkeys (Macaca mulatta): a short term study.

    PubMed

    Lee, Jae-Il; Lee, Chi-Woo; Kwon, Hyouk-Sang; Kim, Young-Tae; Park, Chung-Gyu; Kim, Sang-Joon; Kang, Byeong-Cheol

    2008-10-01

    The majority of newly acquired nonhuman primates encounter serious problems adapting themselves to new environments or facilities. In particular, loss of appetite and abnormal behavior can occur in response to environmental stresses. These adaptation abnormalities can ultimately have an affect on the animal's growth and well-being. In this study, we evaluated the affects of a puzzle feeder on the food intake and abnormal behavior of newly acquired rhesus monkeys for a short period. The puzzle feeder was applied to 47- to 58-month-old animals that had never previously encountered one. We found that there was no difference in the change of food intake between the bucket condition and the puzzle feeder condition. In contrast, the time spent for consumption of food was three times longer in the puzzle feeder condition than in the bucket condition. Two monkeys initially exhibited stereotypic behavior. One showed a decreasing, and the other an increasing pattern of abnormal behavior after introduction of the puzzle feeder. In conclusion, this result suggests that over a short period, the puzzle feeder can only affect the time for food consumption since it failed to affect the food intake and did not consistently influence stereotypic behaviors in newly acquired rhesus monkeys.

  15. 25 CFR 243.7 - How can a non-Native acquire live reindeer?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false How can a non-Native acquire live reindeer? 243.7 Section 243.7 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE REINDEER IN ALASKA § 243.7 How can a non-Native acquire live reindeer? If you are a non-Native who wants to acquire live Alaskan reindeer, you must apply to us in...

  16. Management of Acquired Atresia of the External Auditory Canal.

    PubMed

    Bajin, Münir Demir; Yılmaz, Taner; Günaydın, Rıza Önder; Kuşçu, Oğuz; Sözen, Tevfik; Jafarov, Shamkal

    2015-08-01

    The aim was to evaluate surgical techniques and their relationship to postoperative success rate and hearing outcomes in acquired atresia of the external auditory canal. In this article, 24 patients with acquired atresia of the external auditory canal were retrospectively evaluated regarding their canal status, hearing, and postoperative success. Acquired stenosis occurs more commonly in males with a male: female ratio of 2-3:1; it seems to be a disorder affecting young adults. Previous ear surgery (13 patients, 54.2%) and external ear trauma (11 patients, 45.8%) were the main etiological factors of acquired ear canal stenosis. Mastoidectomy (12/13) and traffic accidents (8/11) comprise the majority of these etiological factors. Endaural incision is performed in 79.2% and postauricular incision for 20.8% of cases during the operation. As types of surgical approach, transcanal (70.8%), transmastoid (20.8%), and combined (8.4%) approaches are chosen. The atretic plate is generally located at the bony-cartilaginous junction (37.5%) and in the cartilaginous canal (33.3%); the bony canal is involved in a few cases only. Preserved healthy canal skin, split- or full-thickness skin grafts, or pre- or postauricular skin flaps are used to line the ear canal, but preserved healthy canal skin is preferred. The results of surgery are generally satisfactory, and complications are few if surgical principles are followed.

  17. Does the accuracy of blood pressure measurement correlate with hearing loss of the observer?

    PubMed

    Song, Soohwa; Lee, Jongshill; Chee, Youngjoon; Jang, Dong Pyo; Kim, In Young

    2014-02-01

    The auscultatory method is influenced by the hearing level of the observers. If the observer has hearing loss, it is possible to measure blood pressure inaccurately by misreading the Korotkoff sounds at systolic blood pressure (SBP) and diastolic blood pressure (DBP). Because of the potential clinical problems this discrepancy may cause, we used a hearing loss simulator to determine how hearing level affects the accuracy of blood pressure measurements. Two data sets (data set A, 32 Korotkoff sound video clips recorded by the British Hypertension Society; data set B, 28 Korotkoff sound data acquired from the Korotkoff sound recording system developed by Hanyang University) were used and all the data were attenuated to simulate a hearing loss of 5, 10, 15, 20, and 25 dB using the hearing loss simulator. Five observers with normal hearing assessed the blood pressures from these data sets and the differences between the values measured from the original recordings (no attenuation) and the attenuated versions were analyzed. Greater attenuation of the Korotkoff sounds, or greater hearing loss, resulted in larger blood pressure measurement differences when compared with the original data. When measuring blood pressure with hearing loss, the SBP tended to be underestimated and the DBP was overestimated. The mean differences between the original data and the 25 dB hearing loss data for the two data sets combined were 1.55±2.71 and -4.32±4.21 mmHg for SBP and DBP, respectively. This experiment showed that the accuracy of blood pressure measurements using the auscultatory method is affected by observer hearing level. Therefore, to reduce possible error using the auscultatory method, observers' hearing should be tested.

  18. Is amplitude loss of sonic waveforms due to intrinsic attenuation or source coupling to the medium?

    USGS Publications Warehouse

    Lee, Myung W.

    2006-01-01

    Sonic waveforms acquired in gas-hydrate-bearing sediments indicate strong amplitude loss associated with an increase in sonic velocity. Because the gas hydrate increases sonic velocities, the amplitude loss has been interpreted as due to intrinsic attenuation caused by the gas hydrate in the pore space, which apparently contradicts conventional wave propagation theory. For a sonic source in a fluid-filled borehole, the signal amplitude transmitted into the formation depends on the physical properties of the formation, including any pore contents, in the immediate vicinity of the source. A signal in acoustically fast material, such as gas-hydrate-bearing sediments, has a smaller amplitude than a signal in acoustically slower material. Therefore, it is reasonable to interpret the amplitude loss in the gas-hydrate-bearing sediments in terms of source coupling to the surrounding medium as well as intrinsic attenuation. An analysis of sonic waveforms measured at the Mallik 5L-38 well, Northwest Territories, Canada, indicates that a significant part of the sonic waveform's amplitude loss is due to a source-coupling effect. All amplitude analyses of sonic waveforms should include the effect of source coupling in order to accurately characterize the formation's intrinsic attenuation.

  19. Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis.

    PubMed

    MacKenzie-Graham, Allan; Kurth, Florian; Itoh, Yuichiro; Wang, He-Jing; Montag, Michael J; Elashoff, Robert; Voskuhl, Rhonda R

    2016-08-01

    Multiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown. To understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS. In this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014. Voxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores). Among the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations. These biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

  20. Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis.

    PubMed

    Veronese, Nicola; Facchini, Silvia; Stubbs, Brendon; Luchini, Claudio; Solmi, Marco; Manzato, Enzo; Sergi, Giuseppe; Maggi, Stefania; Cosco, Theodore; Fontana, Luigi

    2017-01-01

    Whilst obesity is associated with a higher risk of cognitive impairment, the influence of weight loss on cognitive function in obese/overweight people is equivocal. We conducted a meta-analysis of randomized controlled trials (RCTs) and longitudinal studies evaluating the influence of voluntary weight loss on cognitive function in obese/overweight individuals. Articles were acquired from a systematic search of major databases from inception till 01/2016. A random effect meta-analysis of weight loss interventions (diet, physical activity, bariatric surgery) on different cognitive domains (memory, attention, executive functions, language and motor speed) was conducted. Twenty studies (13 longitudinal studies=551 participants; 7 RCTs=328 treated vs. 140 controls) were included. Weight loss was associated with a significant improvement in attention and memory in both longitudinal studies and RCTs, whereas executive function and language improved in longitudinal and RCT studies, respectively. In conclusion, intentional weight loss in obese/overweight people is associated with improvements in performance across various cognitive domains. Future adequately powered RCTs are required to confirm/refute these findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Primary acquired cold urticaria.

    PubMed

    Lee, Chyh-Woei; Sheffer, Albert L

    2003-01-01

    Primary acquired cold urticaria (ACU) is the most common type of cold urticaria characterized by rapid onset of pruritic hives, swelling, and possible severe systemic reactions including hypotension and shock after cold exposure. Primary ACU is diagnosed by history of such symptoms, a positive immediate cold-contact stimulation test, and negative laboratory evaluation for underlying systemic disorders. Clinicians should be aware that patients with ACU may be susceptible to life-threatening systemic reactions especially during aquatic activities and that proper patient education is extremely important. This article reviews the clinical presentation, pathogenesis, diagnosis, and management of primary ACU.

  2. Acinetobacter community-acquired pneumonia in a healthy child.

    PubMed

    Moreira Silva, G; Morais, L; Marques, L; Senra, V

    2012-01-01

    Acinetobacter is involved in a variety of infectious diseases primarily associated with healthcare. Recently there has been increasing evidence of the important role these pathogens play in community acquired infections. We report on the case of a previously healthy child, aged 28 months, admitted for fever, cough and pain on the left side of the chest, which on radiographic examination corresponded to a lower lobe necrotizing pneumonia. After detailed diagnostic work-up, community acquired Acinetobacter lwoffii pneumonia was diagnosed. The child had frequently shared respiratory equipment with elderly relatives with chronic obstructive pulmonary disease. As there were no other apparent risk factors, it could be assumed that the sharing of the equipment was the source of infection. The authors wish to draw attention to this possibility, that a necrotising community-acquired pneumonia due to Acinetobacter lwoffii can occur in a previously healthy child and to the dangers of inappropriate use and poor sterilisation of nebulisers. This case is a warning of the dangers that these bacteria may pose in the future in a community setting. Copyright © 2011 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  3. [Acquired disorders of color vision].

    PubMed

    Lascu, Lidia; Balaş, Mihaela

    2002-01-01

    This article is a general view of acquired disorders of color vision. The revision of the best known methods and of the etiopathogenic classification is not very important in ophthalmology but on the other hand, the detection of the blue defect advertise and associated ocular pathology. There is a major interest in serious diseases as multiple sclerosis, AIDS, diabetes melitus, when the first ocular sign can be a defect in the color vision.

  4. Toxoplasmic Encephalitis in Patient with Acquired Immunodeficiency Syndrome.

    PubMed

    Lee, Sang-Bok; Lee, Tae-Gyu

    2017-04-01

    Toxoplasmic encephalitis (TE) is an opportunistic infection found in immunocompromised patients and TE related cerebral mass lesion is often reported in acquired immunodeficiency acquired immunodeficiency syndrome (AIDS) patients. However, incidence of TE related AIDS in Korea is still rare and is unfamiliar to neurosurgeons. Differential diagnosis is needed to rule out other brain lesions. A 39-year-old man visited the emergency room with rapid progressive left hemiparesis. Magnetic resonance imaging showed a ring-enhanced mass lesion in his right frontal lobe. Human immunodeficiency virus and Toxoplasma gondii immunoglobulin G were tested positive by a serologic test. We report here a rare case of patient with TE related AIDS.

  5. Prediction of functional loss in glaucoma from progressive optic disc damage.

    PubMed

    Medeiros, Felipe A; Alencar, Luciana M; Zangwill, Linda M; Bowd, Christopher; Sample, Pamela A; Weinreb, Robert N

    2009-10-01

    To evaluate the ability of progressive optic disc damage detected by assessment of longitudinal stereophotographs to predict future development of functional loss in those with suspected glaucoma. The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R(2) index. Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R(2) of 79%. The R(2)s for other predictive factors ranged from 6% to 26%. Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.

  6. Acquired Brachial Cutaneous Dyschromatosis in a Middle Aged Male

    PubMed Central

    Choi, Min Jung; Byun, Ji Yeon; Choi, Hae Young

    2018-01-01

    Acquired brachial cutaneous dyschromatosis (ABCD) is an acquired disorder of pigmentary change that presents as chronic, asymptomatic, geographic-shaped, gray-brown patches, consisting of mixed hyper and hypopigmented macules on the dorsal aspect of the forearms. We report a case of a 40-year-old male who presented with asymptomatic, multiple brown-colored macules on the outer aspects of both arms. He had no history of hypertension and had never taken angiotensin converting enzyme inhibitors. He also denied chronic sun exposure history. Histologic examination demonstrated epidermal atrophy, increased basal layer pigmentation, and several telangiectatic vessels in the upper dermis. Solar elastosis was not remarkable. The patient's clinical and histopathologic features were consistent with a diagnosis of ABCD. Poikiloderma of Civatte, melasma, acquired bilateral telangiectatic macules and other pigmentary disorders should be considered in the differential diagnosis of ABCD. Herein, we report a case of ABCD in a middle-aged male without hypertension and medication. PMID:29853750

  7. Origins and consequences of technology acquirement by independent-living seniors: towards an integrative model.

    PubMed

    Peek, S T M; Luijkx, K G; Vrijhoef, H J M; Nieboer, M E; Aarts, S; van der Voort, C S; Rijnaard, M D; Wouters, E J M

    2017-08-22

    Living independently can be challenging for seniors. Technologies are expected to help older adults age in place, yet little empirical research is available on how seniors develop a need for technologies, how they acquire these technologies, and how these subsequently affect their lives. Aging is complex, dynamic and personal. But how does this translate to seniors' adoption and acceptance of technology? To better understand origins and consequences of technology acquirement by independent-living seniors, an explorative longitudinal qualitative field study was set up. Home visits were made to 33 community-dwelling seniors living in the Netherlands, on three occasions (2012-2014). Semi-structured interviews were conducted on the timeline of acquirements, and people and factors involved in acquirements. Additionally, participants were interviewed on experiences in using technologies since acquirement. Thematic analysis was employed to analyze interview transcripts, using a realist approach to better understand the contexts, mechanisms and outcomes of technology acquirements. Findings were accumulated in a new conceptual model: The Cycle of Technology Acquirement by Independent-Living Seniors (C-TAILS), which provides an integrative perspective on why and how technologies are acquired, and why these may or may not prove to be appropriate and effective, considering an independent-living senior's needs and circumstances at a given point in time. We found that externally driven and purely desire-driven acquirements led to a higher risk of suboptimal use and low levels of need satisfaction. Technology acquirement by independent-living seniors may be best characterized as a heterogeneous process with many different origins, pathways and consequences. Furthermore, technologies that are acquired in ways that are not congruent with seniors' personal needs and circumstances run a higher risk of proving to be ineffective or inappropriate. Yet, these needs and circumstances are

  8. Mass loss

    NASA Technical Reports Server (NTRS)

    Goldberg, Leo

    1987-01-01

    Observational evidence for mass loss from cool stars is reviewed. Spectra line profiles are used for the derivation of mass-loss rates with the aid of the equation of continuity. This equation implies steady mass loss with spherical symmetry. Data from binary stars, Mira variables, and red giants in globular clusters are examined. Silicate emission is discussed as a useful indicator of mass loss in the middle infrared spectra. The use of thermal millimeter-wave radiation, Very Large Array (VLA) measurement of radio emission, and OH/IR masers are discussed as a tool for mass loss measurement. Evidence for nonsteady mass loss is also reviewed.

  9. Falls risk and hospitalization among retired workers with occupational noise-induced hearing loss.

    PubMed

    Girard, Serge André; Leroux, Tony; Verreault, René; Courteau, Marilène; Picard, Michel; Turcotte, Fernand; Baril, Julie

    2014-03-01

    This study sought to ascertain whether occupational noise-induced hearing loss (NIHL) increased the risk of falls requiring hospitalization among retired workers. The study population consisted of males (age ≥ 65) with an average occupational noise exposure of 30.6 years and whose mean bilateral hearing loss was 42.2 dB HL at 3, 4, and 6 kHz. Seventy-two retired workers admitted to hospitals after a fall were matched with 216 controls from the same industrial sectors. Conditional logistic regression models were used to estimate the risk (odds ratio; [OR]) of falls leading to hospitalization by NIHL categories. Results showed a relationship between severe NIHL (≥ 52.5 dB HL) and the occurrence of a fall (OR: 1.97, CI95%: 1.001-3.876). Reducing falls among seniors fosters the maintenance of their autonomy. There is a definite need to acquire knowledge about harmful effects of occupational noise to support the prevention of NIHL and ensure healthier workplaces.

  10. Functionality predictors in acquired brain damage.

    PubMed

    Huertas Hoyas, E; Pedrero Pérez, E J; Águila Maturana, A M; García López-Alberca, S; González Alted, C

    2015-01-01

    Most individuals who have survived an acquired brain injury present consequences affecting the sensorimotor, cognitive, affective or behavioural components. These deficits affect the proper performance of daily living activities. The aim of this study is to identify functional differences between individuals with unilateral acquired brain injury using functional independence, capacity, and performance of daily activities. Descriptive cross-sectional design with a sample of 58 people, with right-sided injury (n=14 TBI; n=15 stroke) or left-sided injury (n = 14 TBI, n = 15 stroke), right handed, and with a mean age of 47 years and time since onset of 4 ± 3.65 years. The functional assessment/functional independence measure (FIM/FAM) and the International Classification of Functioning (ICF) were used for the study. The data showed significant differences (P<.000), and a large size effect (dr=0.78) in the cross-sectional estimates, and point to fewer restrictions for patients with a lesion on their right side. The major differences were in the variables 'speaking' and 'receiving spoken messages' (ICF variables), and 'Expression', 'Writing' and 'intelligible speech' (FIM/FAM variables). In the linear regression analysis, the results showed that only 4 FIM/FAM variables, taken together, predict 44% of the ICF variance, which measures the ability of the individual, and up to 52% of the ICF, which measures the individual's performance. Gait alone predicts a 28% of the variance. It seems that individuals with acquired brain injury in the left hemisphere display important differences regarding functional and communication variables. The motor aspects are an important prognostic factor in functional rehabilitation. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Local Transmission of Zika Virus--Puerto Rico, November 23, 2015-January 28, 2016.

    PubMed

    Thomas, Dana L; Sharp, Tyler M; Torres, Jomil; Armstrong, Paige A; Munoz-Jordan, Jorge; Ryff, Kyle R; Martinez-Quiñones, Alma; Arias-Berríos, José; Mayshack, Marrielle; Garayalde, Glenn J; Saavedra, Sonia; Luciano, Carlos A; Valencia-Prado, Miguel; Waterman, Steve; Rivera-García, Brenda

    2016-02-19

    Zika virus, a mosquito-borne flavivirus, spread to the Region of the Americas (Americas) in mid-2015, and appears to be related to congenital microcephaly and Guillain-Barré syndrome (1,2). On February 1, 2016, the World Health Organization (WHO) declared the occurrence of microcephaly cases in association with Zika virus infection to be a Public Health Emergency of International Concern.* On December 31, 2015, Puerto Rico Department of Health (PRDH) reported the first locally acquired (index) case of Zika virus disease in a jurisdiction of the United States in a patient from southeastern Puerto Rico. During November 23, 2015-January 28, 2016, passive and enhanced surveillance for Zika virus disease identified 30 laboratory-confirmed cases. Most (93%) patients resided in eastern Puerto Rico or the San Juan metropolitan area. The most frequently reported signs and symptoms were rash (77%), myalgia (77%), arthralgia (73%), and fever (73%). Three (10%) patients were hospitalized. One case occurred in a patient hospitalized for Guillain-Barré syndrome, and one occurred in a pregnant woman. Because the most common mosquito vector of Zika virus, Aedes aegypti, is present throughout Puerto Rico, Zika virus is expected to continue to spread across the island. The public health response in Puerto Rico is being coordinated by PRDH with assistance from CDC. Clinicians in Puerto Rico should report all cases of microcephaly, Guillain-Barré syndrome, and suspected Zika virus disease to PRDH. Other adverse reproductive outcomes, including fetal demise associated with Zika virus infection, should be reported to PRDH. To avoid infection with Zika virus, residents of and visitors to Puerto Rico, particularly pregnant women, should strictly follow steps to avoid mosquito bites, including wearing pants and long-sleeved shirts, using permethrin-treated clothing and gear, using an Environmental Protection Agency (EPA)-registered insect repellent, and ensuring that windows and doors

  12. 26 CFR 1.1502-9T - Consolidated overall foreign losses, separate limitation losses, and overall domestic losses...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... limitation losses, and overall domestic losses (temporary). 1.1502-9T Section 1.1502-9T Internal Revenue... overall domestic losses (temporary). (a) In general. This section provides rules for applying section 904...(g) concerns rules relating to overall domestic losses (ODLs) and the consequences of such losses...

  13. Acquired pellicle as a modulator for dental erosion.

    PubMed

    Vukosavljevic, Dusa; Custodio, William; Buzalaf, Marilia A R; Hara, Anderson T; Siqueira, Walter L

    2014-06-01

    Dental erosion is a multifactorial condition that can result in the loss of tooth structure and function, potentially increasing tooth sensitivity. The exposure of enamel to acids from non-bacterial sources is responsible for the progression of erosion. These erosive challenges are counteracted by the anti-erosive properties of the acquired pellicle (AP), an integument formed in vivo as a result of selective adsorption of salivary proteins on the tooth surface, containing also lipids and glycoproteins. This review provides an in-depth discussion regarding how the physical structure of the AP, along with its composition, contributes to AP anti-erosive properties. The physical properties that contribute to AP protective nature include pellicle thickness, maturation time, and site of development. The pellicle contains salivary proteins embedded within its structure that demonstrate anti-erosive properties; however, rather than individual proteins, protein-protein interactions play a fundamental role in the protective nature of the AP. In addition, dietary and synthetic proteins can modify the pellicle, enhancing its protective efficiency against dental erosion. The salivary composition of the AP and its corresponding protein-profile may be employed as a diagnostic tool, since it likely contains salivary biomarkers for oral diseases that initiate at the enamel surface, including dental erosion. Finally, by modifying the composition and structure of the AP, this protein integument has the potential to be used as a target-specific treatment option for oral diseases related to tooth demineralization. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. [Community acquired bacterial meningitis in patients over 60].

    PubMed

    Mora Mora, Luis A; Arco Espinosa, Micke E de; Plumet, Javier; Micheli, Federico

    2015-01-01

    Acute bacterial meningitis has a global mortality rate of 135000 cases per year. In Argentina over the last 12 years, the annual incidence rate has been 5.5/100 000. About 20% of patients present neurological sequelae, which are more common in patients aged 60 or older. Our objective here is to determine the clinical characteristics, the most common causes and to measure evolution in patients over 60 years old diagnosed with meningitis and treated at the Hospital de Clinicas José de San Martín. This is a retrospective study based on a review of medical records from 2003 to 2013 that takes into account patients older than 60 who were diagnosed with acute bacterial meningitis acquired in the community by a microbiological diagnosis of CSF or those included due to a high suspicion of bacterial meningitis (pleocitosis > 2000 cells/mm3, proteins > 220 mg/dl, glycorrhachia < 34 mg/dl, glycorrhachia/glucose index < 0.23). Cases of TB meningitis, nosocomial, postoperative and other nonbacterial meningitis were excluded. Sixty nine patients were included, 45 (65%) were women with an average age of 78 ± 10.6 years. Only 40% had the triad of classical meningitis symptoms (stiff neck, fever and altered mental status). In 52% of the patients germs developed in the CSF, the most frequent being Streptococcus pneumoniae present in 47% of cases. Lethality rate was 41%, all of them by methicillin-sensitive Staphylococcus aureus. Only 24 (35%) cases were admitted into intensive care. The main sequelae present were motor disorders (12%) and hearing loss (5%).

  15. Plasma Membrane Cyclic Nucleotide Gated Calcium Channels Control Land Plant Thermal Sensing and Acquired Thermotolerance[C][W

    PubMed Central

    Finka, Andrija; Cuendet, America Farinia Henriquez; Maathuis, Frans J.M.; Saidi, Younousse; Goloubinoff, Pierre

    2012-01-01

    Typically at dawn on a hot summer day, land plants need precise molecular thermometers to sense harmless increments in the ambient temperature to induce a timely heat shock response (HSR) and accumulate protective heat shock proteins in anticipation of harmful temperatures at mid-day. Here, we found that the cyclic nucleotide gated calcium channel (CNGC) CNGCb gene from Physcomitrella patens and its Arabidopsis thaliana ortholog CNGC2, encode a component of cyclic nucleotide gated Ca2+ channels that act as the primary thermosensors of land plant cells. Disruption of CNGCb or CNGC2 produced a hyper-thermosensitive phenotype, giving rise to an HSR and acquired thermotolerance at significantly milder heat-priming treatments than in wild-type plants. In an aequorin-expressing moss, CNGCb loss-of-function caused a hyper-thermoresponsive Ca2+ influx and altered Ca2+ signaling. Patch clamp recordings on moss protoplasts showed the presence of three distinct thermoresponsive Ca2+ channels in wild-type cells. Deletion of CNGCb led to a total absence of one and increased the open probability of the remaining two thermoresponsive Ca2+ channels. Thus, CNGC2 and CNGCb are expected to form heteromeric Ca2+ channels with other related CNGCs. These channels in the plasma membrane respond to increments in the ambient temperature by triggering an optimal HSR, leading to the onset of plant acquired thermotolerance. PMID:22904147

  16. Lipopolysaccharide loss produces partial colistin dependence and collateral sensitivity to azithromycin, rifampicin and vancomycin in Acinetobacter baumannii.

    PubMed

    García-Quintanilla, Meritxell; Carretero-Ledesma, Marta; Moreno-Martínez, Patricia; Martín-Peña, Reyes; Pachón, Jerónimo; McConnell, Michael J

    2015-12-01

    Treatment options for multidrug-resistant (MDR) strains of Acinetobacter baumannii that acquire resistance to colistin are limited. Acinetobacter baumannii can become highly resistant to colistin through complete loss of lipopolysaccharide (LPS) owing to mutations in the genes encoding the first three enzymes involved in lipid A biosynthesis (lpxA, lpxC and lpxD). The objective of this study was to characterise the susceptibility to 15 clinically relevant antibiotics and 6 antimicrobial peptides (AMPs) of MDR A. baumannii clinical isolates that acquired colistin resistance due to mutations in lpxA, lpxC and lpxD as well as their colistin-susceptible counterparts. A dramatic increase in antibiotic susceptibility (≥16-fold increase) was observed upon LPS loss for azithromycin, rifampicin and vancomycin, whereas a moderate increase in susceptibility was seen for amikacin, ceftazidime, imipenem, cefepime and meropenem. Importantly, concentrations ranging from 8 mg/L to 32 mg/L of the six AMPs were able to reduce bacterial viability by ≥3 log10 in growth curve assays. We also demonstrate that colistin resistance results in partial colistin dependence for growth in LPS-deficient strains containing mutations in lpxA, lpxC and lpxD, but not when colistin resistance occurs via LPS modification due to mutations in the PmrA/B two-component system. The results of this study indicate that loss of LPS expression results in collateral sensitivity to azithromycin, rifampicin and vancomycin, and that the six AMPs tested retain activity against LPS-deficient strains, indicating that these antibiotics may be viable treatment options for infections caused by these strains. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  17. 13 CFR 107.880 - Assets acquired in liquidation of Portfolio securities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Portfolio securities. 107.880 Section 107.880 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... liquidation of Portfolio securities. You may acquire assets in full or partial liquidation of a Small Business... assets. You must dispose of assets acquired in liquidation of a Portfolio security within a reasonable...

  18. The estimated lifetime probability of acquiring human papillomavirus in the United States.

    PubMed

    Chesson, Harrell W; Dunne, Eileen F; Hariri, Susan; Markowitz, Lauri E

    2014-11-01

    Estimates of the lifetime probability of acquiring human papillomavirus (HPV) can help to quantify HPV incidence, illustrate how common HPV infection is, and highlight the importance of HPV vaccination. We developed a simple model, based primarily on the distribution of lifetime numbers of sex partners across the population and the per-partnership probability of acquiring HPV, to estimate the lifetime probability of acquiring HPV in the United States in the time frame before HPV vaccine availability. We estimated the average lifetime probability of acquiring HPV among those with at least 1 opposite sex partner to be 84.6% (range, 53.6%-95.0%) for women and 91.3% (range, 69.5%-97.7%) for men. Under base case assumptions, more than 80% of women and men acquire HPV by age 45 years. Our results are consistent with estimates in the existing literature suggesting a high lifetime probability of HPV acquisition and are supported by cohort studies showing high cumulative HPV incidence over a relatively short period, such as 3 to 5 years.

  19. Similar age-dependent levothyroxine requirements of schoolchildren with congenital or acquired hypothyroidism.

    PubMed

    Perlsteyn, Martin; Deladoëy, Johnny; Van Vliet, Guy

    2016-06-01

    A recent study in children suggested that levothyroxine requirements are higher in congenital than in acquired hypothyroidism but did not match for severity of disease. Here, we studied only children with congenital or acquired hypothyroidism who had an undetectable fT4 at diagnosis. There were eight girls with congenital hypothyroidism due to athyreosis and eight girls with acquired hypothyroidism due to autoimmune thyroid disease. The median levothyroxine dose received at the most recent visit when serum TSH was <5.0 mU/L (at a median age of 7.86 and 14.29 years, respectively) was 3.2 mcg/kg/day in the former and 2.4 mcg/kg/day in the latter (N.S.). Combining both groups, the levothyroxine requirement decreased by 0.5 mcg/kg/day for every 4-year period. When strictly matched for severity of disease, levothyroxine requirements are similar in school-age children with congenital or acquired hypothyroidism and decrease with age. Thus, in congenital hypothyroidism treated early with high-dose levothyroxine, pituitary resistance to thyroxine feedback does not appear to be present at school age. • Pediatric studies unmatched for severity have suggested that levothyroxine requirements are higher in congenital than in acquired hypothyroidism. What is new: • When strictly matched for severity, levothyroxine requirements are similar in children with congenital or acquired hypothyroidism and decrease with age.

  20. Acquired pathology of the pediatric spine and spinal cord.

    PubMed

    Palasis, Susan; Hayes, Laura L

    2015-09-01

    Pediatric spine pathology poses a diagnostic challenge for radiologists. Acquired spine pathology often yields nonspecific signs and symptoms in children, especially in the younger age groups, and diagnostic delay can carry significant morbidity. This review is focused on some of the more common diagnostic dilemmas we face when attempting to evaluate and diagnose acquired pediatric spine anomalies in daily practice. An understanding of some of the key differentiating features of these disease processes in conjunction with pertinent history, physical exam, and advanced imaging techniques can indicate the correct diagnosis.

  1. [Acquired toxoplasmosis of ocular or neurologic site: 49 cases].

    PubMed

    Couvreur, J; Thulliez, P

    1996-03-16

    Over a period of 13 years (1982-1995), 49 cases of acquired toxoplasmosis complicated with ocular and/or neurologic or meningeal involvement were observed in our toxoplasmosis laboratory. This series includes 43 cases of isolated ocular lesions, 3 cases of meningoencephalitis (associated with retinochoroiditis in 1 case), 1 case of meningitis with uveitis, 1 case of polyradiculoneuritis and 1 case of facial nerve palsy. The patients were aged 1 to 62 years. None had either spontaneous or iatrogenic immunodeficiency. There were two steps in the diagnosis. First congenital infection was eliminated on one or several of the following criteria: any possibility of maternal infection during pregnancy ruled out in 26 cases, evidence of recent acquired infection (i.e. clinical and/or serological evidence of recent acquired toxoplasmosis in 17 cases, retinochoroiditis in non-twin siblings in 3 cases). The second step was to confirm the diagnosis of toxoplasma infection. Apart from serological evidence of recent infection, confirmation included specific local antibody synthesis in the aqueous humor of the eye and/or in cerebro-spinal fluid or ocular lesions characteristic of toxoplasmosis and absence of other etiology. Ocular lesions were unilateral in 43 cases among 45. A mean follow-up of 37.9 months revealed relapses in 14 among 36 patients (39%). As routine serological examination for toxoplasmosis is compulsory in France since 1978, it was possible to document retrospectively the immune status of the mothers of many of the patients of the present series during pregnancy and to rule out congenital toxoplasmosis in a number of cases. This might explain the discrepancy between the relatively large number of cases in the present series and the fact that complicated acquired toxoplasmosis has been considered hitherto as relatively rare in immunocompetent patients. Based on the epidemiology of ocular toxoplasmosis and the data obtained here, it is suggested that the acquired

  2. Epidemiology of limb loss and congenital limb deficiency: a review of the literature.

    PubMed

    Ephraim, Patti L; Dillingham, Timothy R; Sector, Mathilde; Pezzin, Liliana E; Mackenzie, Ellen J

    2003-05-01

    To examine the state of research on population-based studies of the incidence of limb amputation and birth prevalence of limb deficiency. A total of 18 publication databases were searched, including MEDLINE, CINAHL, and the Cochrane Library. The search was performed by using a hierarchical process. Articles were reviewed for inclusion by 3 reviewers. Inclusion criteria included defined catchment area, calculation of population-based incidence rates, defined etiology of limb loss, and English language. Review articles, animal studies, case reports, cohort studies, letters, and editorials were excluded. Figures on the estimated incidence of amputation and birth prevalence of congenital limb deficiency were gleaned from selected reports and assembled into a table format by etiology. The studies varied in scope, quality, and methodology, making comparisons between studies difficult. Incidence rates of acquired amputation varied greatly between and within nations. Rates of all-cause acquired amputation ranged from 1.2 first major amputations per 10,000 women in Japan to 4.4 per 10,000 men in the Navajo Nation in the United States between 1992 and 1997. Consistent among all nations, the risk of amputation was greatest among persons with diabetes mellitus. Surveillance of congenital limb deficiency exists in much of the developed world. Existing studies of acquired amputation suffer from a host of methodologic problems. Future efforts should be directed toward the application of standardized measures and methods to enable trends to be evaluated over time and comparisons to be made within and between countries.

  3. Military Throwaways Why Acquirers Should Go Disposable

    DTIC Science & Technology

    2016-02-01

    Defense AT&L: January–February 2016 34 Military Throwaways? Why Acquirers Should Go Disposable Maj. Patrick Dugan, USAF Maj. Jon D. McComb...outdated they no longer are manufactured. Unfortunately, the military regularly deals with DMS issues. Going disposable would alleviate DMS concerns

  4. The locus of color sensation: Cortical color loss and the chromatic visual evoked potential

    PubMed Central

    Crognale, Michael A.; Duncan, Chad S.; Shoenhard, Hannah; Peterson, Dwight J.; Berryhill, Marian E.

    2013-01-01

    Color losses of central origin (cerebral achromatopsia and dyschromatopsia) can result from cortical damage and are most commonly associated with stroke. Such cases have the potential to provide useful information regarding the loci of the generation of the percept of color. One available tool to examine this issue is the chromatic visual evoked potential (cVEP). The cVEP has been used successfully to objectively quantify losses in color vision capacity in both congenital and acquired deficiencies of retinal origin but has not yet been applied to cases of color losses of cortical origin. In addition, it is not known with certainty which cortical sites are responsible for the generation of the cVEP waveform components. Here we report psychophysical and electrophysiological examination of a patient with color deficits resulting from a bilateral cerebral infarct in the ventral occipitotemporal region. Although this patient demonstrated pronounced color losses of a general nature, the waveform of the cVEP remains unaffected. Contrast response functions of the cVEP are also normal for this patient. The results suggest that the percept of color arises after the origin of the cVEP and that normal activity in those areas that give rise to the characteristic negative wave of the cVEP are not sufficient to provide for the normal sensation of color. PMID:23986535

  5. Pregnancy Loss

    MedlinePlus

    ... tool Subscribe To receive Pregnancy email updates Submit Pregnancy loss Pregnancy loss is a harsh reality faced ... have successful pregnancies. Expand all | Collapse all Why pregnancy loss happens As many as 10 to 15 ...

  6. Method to acquire regions of fruit, branch and leaf from image of red apple in orchard

    NASA Astrophysics Data System (ADS)

    Lv, Jidong; Xu, Liming

    2017-07-01

    This work proposed a method to acquire regions of fruit, branch and leaf from red apple image in orchard. To acquire fruit image, R-G image was extracted from the RGB image for corrosive working, hole filling, subregion removal, expansive working and opening operation in order. Finally, fruit image was acquired by threshold segmentation. To acquire leaf image, fruit image was subtracted from RGB image before extracting 2G-R-B image. Then, leaf image was acquired by subregion removal and threshold segmentation. To acquire branch image, dynamic threshold segmentation was conducted in the R-G image. Then, the segmented image was added to fruit image to acquire adding fruit image which was subtracted from RGB image with leaf image. Finally, branch image was acquired by opening operation, subregion removal and threshold segmentation after extracting the R-G image from the subtracting image. Compared with previous methods, more complete image of fruit, leaf and branch can be acquired from red apple image with this method.

  7. Assessing Plural Morphology in Children Acquiring /S/-Leniting Dialects of Spanish

    ERIC Educational Resources Information Center

    Miller, Karen

    2014-01-01

    Purpose: To examine the production of plural morphology in children acquiring a dialect of Spanish with syllable-final /s/ lenition with the goal of comparing how plural marker omissions in the speech of these children compare with plural marker omissions in children with language impairment acquiring other varieties of Spanish. Method: Three…

  8. White Matter Changes in Tinnitus: Is It All Age and Hearing Loss?

    PubMed

    Yoo, Hye Bin; De Ridder, Dirk; Vanneste, Sven

    2016-02-01

    Tinnitus is a condition characterized by the perception of auditory phantom sounds. It is known as the result of complex interactions between auditory and nonauditory regions. However, previous structural imaging studies on tinnitus patients showed evidence of significant white matter changes caused by hearing loss that are positively correlated with aging. Current study focused on which aspects of tinnitus pathologies affect the white matter integrity the most. We used the diffusion tensor imaging technique to acquire images that have higher contrast in brain white matter to analyze how white matter is influenced by tinnitus-related factors using voxel-based methods, region of interest analysis, and deterministic tractography. As a result, white matter integrity in chronic tinnitus patients was both directly affected by age and also mediated by the hearing loss. The most important changes in white matter regions were found bilaterally in the anterior corona radiata, anterior corpus callosum, and bilateral sagittal strata. In the tractography analysis, the white matter integrity values in tracts of right parahippocampus were correlated with the subjective tinnitus loudness.

  9. Reversible chronic acquired complete atrioventricular block.

    PubMed

    Rakovec, P; Milcinski, G; Voga, G; Korsic, L

    1982-01-01

    The return of atrioventricular conduction is reported in a case after nearly four years of complete acquired heart block. After recovery from atrioventricular block, right bundle branch block persisted, but P-R interval and H-V interval were normal. Three months later a relapse of second degree infranodal atrioventricular block was noted. A short review of similar cases from the literature is given.

  10. Ruling out Legionella in community-acquired pneumonia.

    PubMed

    Haubitz, Sebastian; Hitz, Fabienne; Graedel, Lena; Batschwaroff, Marcus; Wiemken, Timothy Lee; Peyrani, Paula; Ramirez, Julio A; Fux, Christoph Andreas; Mueller, Beat; Schuetz, Philipp

    2014-10-01

    Assessing the likelihood for Legionella sp. in community-acquired pneumonia is important because of differences in treatment regimens. Currently used antigen tests and culture have limited sensitivity with important time delays, making empirical broad-spectrum coverage necessary. Therefore, a score with 6 variables recently has been proposed. We sought to validate these parameters in an independent cohort. We analyzed adult patients with community-acquired pneumonia from a large multinational database (Community Acquired Pneumonia Organization) who were treated between 2001 and 2012 with more than 4 of the 6 prespecified clinical variables available. Association and discrimination were assessed using logistic regression analysis and area under the curve (AUC). Of 1939 included patients, the infectious cause was known in 594 (28.9%), including Streptococcus pneumoniae in 264 (13.6%) and Legionella sp. in 37 (1.9%). The proposed clinical predictors fever, cough, hyponatremia, lactate dehydrogenase, C-reactive protein, and platelet count were all associated or tended to be associated with Legionella cause. A logistic regression analysis including all these predictors showed excellent discrimination with an AUC of 0.91 (95% confidence interval, 0.87-0.94). The original dichotomized score showed good discrimination (AUC, 0.73; 95% confidence interval, 0.65-0.81) and a high negative predictive value of 99% for patients with less than 2 parameters present. With the use of a large independent patient sample from an international database, this analysis validates previously proposed clinical variables to accurately rule out Legionella sp., which may help to optimize initial empiric therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Prevalence of quinolone resistance mechanisms in Enterobacteriaceae producing acquired AmpC β-lactamases and/or carbapenemases in Spain.

    PubMed

    Machuca, Jesús; Agüero, Jesús; Miró, Elisenda; Conejo, María Del Carmen; Oteo, Jesús; Bou, Germán; González-López, Juan José; Oliver, Antonio; Navarro, Ferran; Pascual, Álvaro; Martínez-Martínez, Luis

    2017-10-01

    Quinolone resistance in Enterobacteriaceae species has increased over the past few years, and is significantly associated to beta-lactam resistance. The aim of this study was to evaluate the prevalence of chromosomal- and plasmid-mediated quinolone resistance in acquired AmpC β-lactamase and/or carbapenemase-producing Enterobacteriaceae isolates. The presence of chromosomal- and plasmid-mediated quinolone resistance mechanisms [mutations in the quinolone resistance determining region (QRDR) of gyrA and parC and qnr, aac(6')-Ib-cr and qepA genes] was evaluated in 289 isolates of acquired AmpC β-lactamase- and/or carbapenemase-producing Enterobacteriaceae collected between February and July 2009 in 35 Spanish hospitals. Plasmid mediated quinolone resistance (PMQR) genes were detected in 92 isolates (31.8%), qnr genes were detected in 83 isolates (28.7%), and the aac(6')-Ib-cr gene was detected in 20 isolates (7%). qnrB4 gene was the most prevalent qnr gene detected (20%), associated, in most cases, with DHA-1. Only 14.6% of isolates showed no mutations in gyrA or parC with a ciprofloxacin MIC of 0.5mg/L or higher, whereas PMQR genes were detected in 90% of such isolates. qnrB4 gene was the most prevalent PMQR gene detected, and was significantly associated with acquired AmpC β-lactamase DHA-1. PMQR determinants in association with other chromosomal-mediated quinolone resistance mechanisms, different to mutations in gyrA and parC (increased energy-dependent efflux, altered lipopolysaccharide or porin loss), could lead to ciprofloxacin MIC values that exceed breakpoints established by the main international committees to define clinical antimicrobial susceptibility breakpoints. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Clustering analysis strategies for electron energy loss spectroscopy (EELS).

    PubMed

    Torruella, Pau; Estrader, Marta; López-Ortega, Alberto; Baró, Maria Dolors; Varela, Maria; Peiró, Francesca; Estradé, Sònia

    2018-02-01

    In this work, the use of cluster analysis algorithms, widely applied in the field of big data, is proposed to explore and analyze electron energy loss spectroscopy (EELS) data sets. Three different data clustering approaches have been tested both with simulated and experimental data from Fe 3 O 4 /Mn 3 O 4 core/shell nanoparticles. The first method consists on applying data clustering directly to the acquired spectra. A second approach is to analyze spectral variance with principal component analysis (PCA) within a given data cluster. Lastly, data clustering on PCA score maps is discussed. The advantages and requirements of each approach are studied. Results demonstrate how clustering is able to recover compositional and oxidation state information from EELS data with minimal user input, giving great prospects for its usage in EEL spectroscopy. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Use of CD25 as an immunohistochemical marker for acquired ocular toxoplasmosis.

    PubMed

    Miyamoto, Cristina; Mattos Neto, Rubens Belfort; Cesare, Sebastian Di; Belfort Junior, Rubens; Burnier, Miguel N

    2010-01-01

    Toxoplasmosis is the most common cause of posterior infectious uveitis worldwide. It is often impossible to determine its congenital or acquired nature. Interleukin-2 (IL-2) in peripheral blood has been described as a possible marker for acquired toxoplasmosis. The purpose of this study is to evaluate the histopathological characteristics of ocular toxoplasmosis cases using CD25 as a marker for the expression of interleukin-2. Ten formalin-fixed, paraffin-embedded enucleated globes from ten immunocompetent patients with clinical diagnosis of toxoplasmosis were evaluated. Four patients had the acquired form of ocular toxoplasmosis (positive IgM) while six were IgM negative and IgG positive for toxoplasmosis. Histopathological slides were reviewed for the extension of the retinal necrosis, number of toxo cysts, the granulomatous inflammatory reaction, the presence of T and B cells within the choroid and the IL-2 expression. Immunohistochemistry using monoclonal antibodies was performed to observe the expression of CD4, CD8, CD20, CD25, and CD68. The histopathological evaluation disclosed no differences between acquired and the other ocular toxoplasmosis cases regarding the characteristics studied. However, CD25 showed a higher expression of IL-2 on the 4 acquired cases of ocular toxoplasmosis compared to the remainders. To the best of our knowledge, this is the first report showing that the use of CD25 as a marker for interleukin-2 could differentiate acquired ocular toxoplasmosis.

  14. Compensatory Expressive Behavior for Facial Paralysis: Adaptation to Congenital or Acquired Disability

    PubMed Central

    Bogart, Kathleen R.; Tickle-Degnen, Linda; Ambady, Nalini

    2015-01-01

    Purpose/Objective Although there has been little research on the adaptive behavior of people with congenital compared to acquired disability, there is reason to predict that people with congenital conditions may be better adapted because they have lived with their conditions for their entire lives (Smart, 2008). We examined whether people with congenital facial paralysis (FP), compared to people with acquired FP, compensate more for impoverished facial expression by using alternative channels of expression (i.e. voice and body). Research Method/Design Participants with congenital (n = 13) and acquired (n = 14) FP were videotaped while recalling emotional events. Main Outcome Measures Expressive verbal behavior was measured using the Linguistic Inquiry Word Count (Pennebaker, Booth & Francis, 2007). Nonverbal behavior and FP severity were rated by trained coders. Results People with congenital FP, compared to acquired FP, used more compensatory expressive verbal and nonverbal behavior in their language, voices, and bodies. The extent of FP severity had little effect on compensatory expressivity. Conclusions/Implications This study provides the first behavioral evidence that people with congenital FP use more adaptations to express themselves than people with acquired FP. These behaviors could inform social functioning interventions for people with FP. PMID:22369116

  15. Compensatory expressive behavior for facial paralysis: adaptation to congenital or acquired disability.

    PubMed

    Bogart, Kathleen R; Tickle-Degnen, Linda; Ambady, Nalini

    2012-02-01

    Although there has been little research on the adaptive behavior of people with congenital compared to acquired disability, there is reason to predict that people with congenital conditions may be better adapted because they have lived with their conditions for their entire lives (Smart, 2008). We examined whether people with congenital facial paralysis (FP), compared to people with acquired FP, compensate more for impoverished facial expression by using alternative channels of expression (i.e., voice and body). Participants with congenital (n = 13) and acquired (n = 14) FP were videotaped while recalling emotional events. Expressive verbal behavior was measured using the Linguistic Inquiry Word Count (Pennebaker, Booth, & Francis, 2007). Nonverbal behavior and FP severity were rated by trained coders. People with congenital FP, compared to acquired FP, used more compensatory expressive verbal and nonverbal behavior in their language, voices, and bodies. The extent of FP severity had little effect on compensatory expressivity. This study provides the first behavioral evidence that people with congenital FP use more adaptations to express themselves than people with acquired FP. These behaviors could inform social functioning interventions for people with FP.

  16. Radiographic sclerotic contour loss in the identification of glenoid bone loss.

    PubMed

    Bornes, Troy D; Jaremko, Jacob L; Beaupre, Lauren A; Bouliane, Martin J

    2016-07-01

    Quantification of glenoid bone loss guides surgical management in the setting of anterior shoulder instability. Glenoid defects resulting in ≥20 % articular area loss require bony reconstruction. The objective of this study was to evaluate the utility of sclerotic glenoid contour loss on true anteroposterior radiography in the detection of varying quantities of simulated glenoid bone loss using a cadaveric model. Eight cadaveric scapulae with full radiographic sclerotic contour were osteotomized to produce glenoid surface area reductions of 10-50 %. Radiography was performed initially and following each osteotomy, and assessed by an orthopedic surgeon and radiologist twice. Quantity of glenoid loss was compared using Fisher's exact test. Sensitivity, specificity, and reliability analyses were performed. On the first radiographic review, sclerotic contour loss was detected in 6 out of 8 scapulae with 50 % area loss, but only 1 out of 8 scapulae with 20 % area loss. There was a significantly higher proportion of radiographs containing sclerotic contour loss for defects with 50 % area loss compared to those with 0-25 % loss (p ≤ 0.02). In the detection of ≥20 % area loss, sclerotic contour loss had a sensitivity of 33-43 % and specificity of 88-100 %. Moderate inter-observer reliability (Cohen's kappa value of 0.42-0.53) and intra-observer reliability (kappa value of 0.46-0.58) were found. Radiographic sclerotic contour loss is commonly observed in radiographs of scapulae with 40-50 % glenoid area loss and less often with smaller lesions. However, this finding lacks utility in discerning specific quantifications of glenoid bone loss. In a clinical setting, sclerotic contour loss suggests the presence of a large glenoid defect that may require bony reconstruction. However, an intact sclerotic contour does not rule out significant bone loss.

  17. Hair Loss

    MedlinePlus

    Hair loss Overview Hair loss can affect just your scalp or your entire body. It can be the result of heredity, hormonal changes, medical conditions or medications. Anyone can experience hair loss, but it's more common in men. Baldness ...

  18. SU-E-I-20: Dead Time Count Loss Compensation in SPECT/CT: Projection Versus Global Correction

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

    Siman, W; Kappadath, S

    Purpose: To compare projection-based versus global correction that compensate for deadtime count loss in SPECT/CT images. Methods: SPECT/CT images of an IEC phantom (2.3GBq 99mTc) with ∼10% deadtime loss containing the 37mm (uptake 3), 28 and 22mm (uptake 6) spheres were acquired using a 2 detector SPECT/CT system with 64 projections/detector and 15 s/projection. The deadtime, Ti and the true count rate, Ni at each projection, i was calculated using the monitor-source method. Deadtime corrected SPECT were reconstructed twice: (1) with projections that were individually-corrected for deadtime-losses; and (2) with original projections with losses and then correcting the reconstructed SPECTmore » images using a scaling factor equal to the inverse of the average fractional loss for 5 projections/detector. For both cases, the SPECT images were reconstructed using OSEM with attenuation and scatter corrections. The two SPECT datasets were assessed by comparing line profiles in xyplane and z-axis, evaluating the count recoveries, and comparing ROI statistics. Higher deadtime losses (up to 50%) were also simulated to the individually corrected projections by multiplying each projection i by exp(-a*Ni*Ti), where a is a scalar. Additionally, deadtime corrections in phantoms with different geometries and deadtime losses were also explored. The same two correction methods were carried for all these data sets. Results: Averaging the deadtime losses in 5 projections/detector suffices to recover >99% of the loss counts in most clinical cases. The line profiles (xyplane and z-axis) and the statistics in the ROIs drawn in the SPECT images corrected using both methods showed agreement within the statistical noise. The count-loss recoveries in the two methods also agree within >99%. Conclusion: The projection-based and the global correction yield visually indistinguishable SPECT images. The global correction based on sparse sampling of projections losses allows for accurate SPECT

  19. Acquired antiprothrombin antibodies: an unusual cause of bleeding.

    PubMed

    Carvalho, Cristiana; Viveiro, Carolina; Maia, Paulo; Rezende, Teresa

    2013-01-07

    Acquired inhibitors of coagulation causing bleeding manifestations are rare in children. They emerge, normally in the context of autoimmune diseases or drug ingestion, but transient and self-limiting cases can occur after viral infection. We describe, an otherwise healthy, 7-year-old girl who had gingival bleeding after a tooth extraction. The prothrombin time (PT) and the activated partial thromboplastin time (APTT) were both prolonged with evidence of an immediate acting inhibitor (lupic anticoagulant). Further coagulation studies demonstrated prothrombin (FII) deficiency and prothrombin directed (FII) antibodies. The serological tests to detect an underlying autoimmune disease were all negative. The coagulation studies normalised alongside the disappearance of the antibody. This article presents lupus anticoagulant hypoprothrombinaemia syndrome (LAHS) as a rare case of acquired bleeding diathesis in childhood.

  20. 12 CFR 225.140 - Disposition of property acquired in satisfaction of debts previously contracted.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... satisfaction of debts previously contracted. 225.140 Section 225.140 Banks and Banking FEDERAL RESERVE SYSTEM... property acquired in satisfaction of debts previously contracted. (a) The Board recently considered the... acquiring and holding assets acquired in satisfaction of a debt previously contracted in good faith (a “dpc...

  1. Detection and Prevention of Perinatal Infection: Cytomegalovirus and Zika Virus.

    PubMed

    Wood, Amber M; Hughes, Brenna L

    2018-06-01

    Congenital cytomegalovirus is the most common viral congenital infection, and affects up to 2% of neonates. Significant sequelae may develop after congenital cytomegalovirus, including hearing loss, cognitive defects, seizures, and death. Zika virus is an emerging virus with perinatal implications; a congenital Zika virus syndrome has been identified, and includes findings such as microcephaly, fetal nervous system abnormalities, and neurologic sequelae after birth. Screening, diagnosis, prevention, and treatment of these perinatal infections are reviewed in this article. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Differential patterns of acquired virulence genes distinguish Salmonella strains

    PubMed Central

    Conner, Christopher P.; Heithoff, Douglas M.; Julio, Steven M.; Sinsheimer, Robert L.; Mahan, Michael J.

    1998-01-01

    Analysis of several Salmonella typhimurium in vivo-induced genes located in regions of atypical base composition has uncovered acquired genetic elements that cumulatively engender pathogenicity. Many of these regions are associated with mobile elements, encode predicted adhesin and invasin-like functions, and are required for full virulence. Some of these regions distinguish broad host range from host-adapted Salmonella serovars and may contribute to inherent differences in host specificity, tissue tropism, and disease manifestation. Maintenance of this archipelago of acquired sequence by selection in specific hosts reveals a fossil record of the evolution of pathogenic species. PMID:9539791

  3. Intervention and societal costs of residential community reintegration for patients with acquired brain injury: a cost-analysis of the Brain Integration Programme.

    PubMed

    van Heugten, Caroline M; Geurtsen, Gert J; Derksen, R Elze; Martina, Juan D; Geurts, Alexander C H; Evers, Silvia M A A

    2011-06-01

    The objective of this study was to examine the intervention costs of a residential community reintegration programme for patients with acquired brain injury and to compare the societal costs before and after treatment. A cost-analysis was performed identifying costs of healthcare, informal care, and productivity losses. The costs in the year before the Brain Integration Programme (BIP) were compared with the costs in the year after the BIP using the following cost categories: care consumption, caregiver support, productivity losses. Dutch guidelines were used for cost valuation. Thirty-three cases participated (72% response). Mean age was 29.8 years, 59% traumatic brain injury. The BIP costs were €68,400. The informal care and productivity losses reduced significantly after BIP (p < 0.05), while healthcare consumption increased significantly (p < 0.05). The societal costs per patient were €48,449. After BIP these costs were €39,773; a significant reduction (p < 0.05). Assuming a stable situation the break-even point is after 8 years. The reduction in societal costs after the BIP advocates the allocation of resources and, from an economic perspective, favours reimbursement of the BIP costs by healthcare insurance companies. However, this cost-analysis is limited as it does not relate costs to clinical effectiveness. :

  4. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  5. Molecular characterization of acquired phototrophs and their plastids in marine communities

    NASA Astrophysics Data System (ADS)

    Johnson, M. D.; Beaudoin, D. J.; Moeller, H.

    2016-02-01

    Acquired phototrophy is a form of mixotrophy that involves host associations with prey chloroplasts or intact algal cells as symbionts. In marine ecosystems, acquired phototrophy is widespread and alters community interactions by increasing the size class of primary production. The impact of this shift varies from enhancing growth efficiency of host cells (e.g. plastidic oligotrichs) to fueling highly productive bloom events (e.g. Mesodinium rubrum). Here we test the hypothesis that certain acquired phototrophs (e.g. M. rubrum) have species-specific prey and plastid associations, while others (e.g. plastidic oligotrichs) are generalists. Using single cell PCR and taxon-specific primers, we characterized the diversity of acquired phototrophs and their plastids in a variety of coastal marine ecosystems. In certain cases we also compare these data to community plankton diversity, using next-generation sequencing approaches. We demonstrate that Mesodinium blooms may be attributed to several clades from the M. rubrum complex, as well as M. major, and that all of these bloom events are dominated by T. amphioxeia plastids. In contrast, analysis of single M. rubrum cells from non-bloom situations can yield a more complex picture of cryptophyte associations. We also present results on host and plastid diversity of Dinophysis sp., Perispira sp., and Tontonia sp. Our results reveal that while certain species of acquired phototrophs are plastid specialists, cryptic diversity of plastid genes revealed by single cell PCR also implies some level of flexibility in prey uptake.

  6. Darwin's Difficulties and Students' Struggles with Trait Loss: Cognitive-Historical Parallelisms in Evolutionary Explanation

    NASA Astrophysics Data System (ADS)

    Ha, Minsu; Nehm, Ross H.

    2014-05-01

    Although historical changes in scientific ideas sometimes display striking similarities with students' conceptual progressions, some scholars have cautioned that such similarities lack meaningful commonalities. In the history of evolution, while Darwin and his contemporaries often used natural selection to explain evolutionary trait gain or increase, they struggled to use it to convincingly account for cases of trait loss or decrease. This study examines Darwin's evolutionary writings about trait gain and loss in the Origin of Species (On the origin of species by means of natural selection, or the preservation of favoured races in the struggle for life. D. Appleton, New York, 1859) and compares them to written evolutionary explanations for trait gain and loss in a large (n > 500), cross-cultural and cross-sectional sample (novices and experts from the USA and Korea). Findings indicate that significantly more students and experts applied natural selection to cases of trait gain, but like Darwin and his contemporaries, they more often applied `use and disuse' and `inheritance of acquired characteristics' to episodes of trait loss. Although the parallelism between Darwin's difficulties and students' struggles with trait loss are striking, significant differences also characterize explanatory model structure. Overall, however, students and scientists struggles to explain trait loss—which is a very common phenomenon in the history of life—appear to transcend time, place, and level of biological expertise. The significance of these findings for evolution education are discussed; in particular, the situated nature of biological reasoning, and the important role that the history of science can play in understanding cognitive constraints on science learning.

  7. Effect of vegetable oils applied over acquired enamel pellicle on initial erosion.

    PubMed

    Ionta, Franciny Querobim; Alencar, Catarina Ribeiro Barros de; Val, Poliana Pacifico; Boteon, Ana Paula; Jordão, Maisa Camillo; Honório, Heitor Marques; Buzalaf, Marília Afonso Rabelo; Rios, Daniela

    2017-01-01

    The prevalence of dental erosion has been recently increasing, requiring new preventive and therapeutic approaches. Vegetable oils have been studied in preventive dentistry because they come from a natural, edible, low-cost, and worldwide accessible source. This study aimed to evaluate the protective effect of different vegetable oils, applied in two concentrations, on initial enamel erosion. Initially, the acquired pellicle was formed in situ for 2 hours. Subsequently, the enamel blocks were treated in vitro according to the study group (n=12/per group): GP5 and GP100 - 5% and pure palm oil, respectively; GC5 and GC100 - 5% and pure coconut oil; GSa5 and GSa100 - 5% and pure safflower oil; GSu5 and GSu100 - 5% and pure sunflower oil; GO5 and GO100 - 5% and pure olive oil; CON- - Deionized Water (negative control) and CON+ - Commercial Mouthwash (Elmex® Erosion Protection Dental Rinse, GABA/positive control). Then, the enamel blocks were immersed in artificial saliva for 2 minutes and subjected to short-term acid exposure in 0.5% citric acid, pH 2.4, for 30 seconds, to promote enamel surface softening. The response variable was the percentage of surface hardness loss [((SHi - SHf) / SHf )×100]. Data were analyzed by one-way ANOVA and Tukey's test (p<0.05). Enamel blocks of GP100 presented similar hardness loss to GSu100 (p>0.05) and less than the other groups (p<0.05). There was no difference between GP5, GC5, GC100, GSa5, GSu100, GSa100, GSu5, GO5, GO100, CON- and CON+. Palm oil seems to be a promising alternative for preventing enamel erosion. However, further studies are necessary to evaluate a long-term erosive cycling.

  8. Effect of vegetable oils applied over acquired enamel pellicle on initial erosion

    PubMed Central

    IONTA, Franciny Querobim; de ALENCAR, Catarina Ribeiro Barros; VAL, Poliana Pacifico; BOTEON, Ana Paula; JORDÃO, Maisa Camillo; HONÓRIO, Heitor Marques; BUZALAF, Marília Afonso Rabelo; RIOS, Daniela

    2017-01-01

    Abstract Objective The prevalence of dental erosion has been recently increasing, requiring new preventive and therapeutic approaches. Vegetable oils have been studied in preventive dentistry because they come from a natural, edible, low-cost, and worldwide accessible source. This study aimed to evaluate the protective effect of different vegetable oils, applied in two concentrations, on initial enamel erosion. Material and Methods Initially, the acquired pellicle was formed in situ for 2 hours. Subsequently, the enamel blocks were treated in vitro according to the study group (n=12/per group): GP5 and GP100 – 5% and pure palm oil, respectively; GC5 and GC100 – 5% and pure coconut oil; GSa5 and GSa100 – 5% and pure safflower oil; GSu5 and GSu100 – 5% and pure sunflower oil; GO5 and GO100 – 5% and pure olive oil; CON− – Deionized Water (negative control) and CON+ – Commercial Mouthwash (Elmex® Erosion Protection Dental Rinse, GABA/positive control). Then, the enamel blocks were immersed in artificial saliva for 2 minutes and subjected to short-term acid exposure in 0.5% citric acid, pH 2.4, for 30 seconds, to promote enamel surface softening. The response variable was the percentage of surface hardness loss [((SHi - SHf) / SHf )×100]. Data were analyzed by one-way ANOVA and Tukey’s test (p<0.05). Results Enamel blocks of GP100 presented similar hardness loss to GSu100 (p>0.05) and less than the other groups (p<0.05). There was no difference between GP5, GC5, GC100, GSa5, GSu100, GSa100, GSu5, GO5, GO100, CON− and CON+. Conclusion Palm oil seems to be a promising alternative for preventing enamel erosion. However, further studies are necessary to evaluate a long-term erosive cycling. PMID:28877281

  9. Acquired prosopagnosia without word recognition deficits.

    PubMed

    Susilo, Tirta; Wright, Victoria; Tree, Jeremy J; Duchaine, Bradley

    2015-01-01

    It has long been suggested that face recognition relies on specialized mechanisms that are not involved in visual recognition of other object categories, including those that require expert, fine-grained discrimination at the exemplar level such as written words. But according to the recently proposed many-to-many theory of object recognition (MTMT), visual recognition of faces and words are carried out by common mechanisms [Behrmann, M., & Plaut, D. C. ( 2013 ). Distributed circuits, not circumscribed centers, mediate visual recognition. Trends in Cognitive Sciences, 17, 210-219]. MTMT acknowledges that face and word recognition are lateralized, but posits that the mechanisms that predominantly carry out face recognition still contribute to word recognition and vice versa. MTMT makes a key prediction, namely that acquired prosopagnosics should exhibit some measure of word recognition deficits. We tested this prediction by assessing written word recognition in five acquired prosopagnosic patients. Four patients had lesions limited to the right hemisphere while one had bilateral lesions with more pronounced lesions in the right hemisphere. The patients completed a total of seven word recognition tasks: two lexical decision tasks and five reading aloud tasks totalling more than 1200 trials. The performances of the four older patients (3 female, age range 50-64 years) were compared to those of 12 older controls (8 female, age range 56-66 years), while the performances of the younger prosopagnosic (male, 31 years) were compared to those of 14 younger controls (9 female, age range 20-33 years). We analysed all results at the single-patient level using Crawford's t-test. Across seven tasks, four prosopagnosics performed as quickly and accurately as controls. Our results demonstrate that acquired prosopagnosia can exist without word recognition deficits. These findings are inconsistent with a key prediction of MTMT. They instead support the hypothesis that face

  10. 26 CFR 301.7505-1 - Sale of personal property acquired by the United States.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Sale of personal property acquired by the... Actions by the United States § 301.7505-1 Sale of personal property acquired by the United States. (a) Sale—(1) In general. Any personal property (except bonds, notes, checks, and other securities) acquired...

  11. 26 CFR 301.7505-1 - Sale of personal property acquired by the United States.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Sale of personal property acquired by the... Actions by the United States § 301.7505-1 Sale of personal property acquired by the United States. (a) Sale—(1) In general. Any personal property (except bonds, notes, checks, and other securities) acquired...

  12. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies.

    PubMed

    Latov, Norman

    2014-08-01

    Chronic neuropathies are operationally classified as primarily demyelinating or axonal, on the basis of electrodiagnostic or pathological criteria. Demyelinating neuropathies are further classified as hereditary or acquired-this distinction is important, because the acquired neuropathies are immune-mediated and, thus, amenable to treatment. The acquired chronic demyelinating neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal IgM antibodies to myelin-associated glycoprotein (MAG; anti-MAG neuropathy), multifocal motor neuropathy (MMN), and POEMS syndrome. They have characteristic--though overlapping--clinical presentations, are mediated by distinct immune mechanisms, and respond to different therapies. CIDP is the default diagnosis if the neuropathy is demyelinating and no other cause is found. Anti-MAG neuropathy is diagnosed on the basis of the presence of anti-MAG antibodies, MMN is characterized by multifocal weakness and motor conduction blocks, and POEMS syndrome is associated with IgG or IgA λ-type monoclonal gammopathy and osteosclerotic myeloma. The correct diagnosis, however, can be difficult to make in patients with atypical or overlapping presentations, or nondefinitive laboratory studies. First-line treatments include intravenous immunoglobulin (IVIg), corticosteroids or plasmapheresis for CIDP; IVIg for MMN; rituximab for anti-MAG neuropathy; and irradiation or chemotherapy for POEMS syndrome. A correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy.

  13. The role of disability self-concept in adaptation to congenital or acquired disability.

    PubMed

    Bogart, Kathleen R

    2014-02-01

    Current theories of adaptation to disability do not address differences in adaptation to congenital or acquired disability. Although people with congenital disabilities are generally assumed to be better adapted than people with acquired disabilities, few studies have tested this, and even fewer have attempted to explain the mechanisms behind these differences. This study tested the proposition that whether a disability is congenital or acquired plays an important role in the development of the disability self-concept (consisting of disability identity and disability self-efficacy), which in turn, affects satisfaction with life. It was predicted that disability self-concept would be better developed among people with congenital, compared with acquired disabilities, predicting greater satisfaction with life in those with acquired conditions. 226 participants with congenital and acquired mobility disabilities completed a cross-sectional online questionnaire measuring satisfaction with life, self-esteem, disability identity, disability self-efficacy, and demographic information. Self-esteem, disability identity, disability self-efficacy, and income were significant predictors of satisfaction with life. Congenital onset predicted higher satisfaction with life; disability identity and disability self-efficacy, but not self-esteem, partially mediated the relationship. Findings highlight the distinction between adaptation to congenital versus acquired disability and the importance of disability self-concept, which are underresearched constructs. Results suggest that rather than attempting to "normalize" individuals with disabilities, health care professionals should foster their disability self-concept. Possible ways to improve disability self-concept are discussed, such as involvement in the disability community and disability pride. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  14. Post-osteomyelitic-acquired radial club hand deformity in children treated by centralization of ulna.

    PubMed

    Meena, Dinesh Kumar

    2017-01-01

    Radial club hand deformity acquired post haematogenous osteomyelitis of radius bone is a very rare disease. Resulting in functional and cosmetic deficit of upper limb which is similar to congenital cases. For a long-time various surgeons attempted to reconstruct the deformity by bone grafting, plating, Ilizarov, monorail external fixator, callus distraction and so on. Keeping in mind that creating single bone forearm we proposed centralization of ulna on wrist to correct the deformity. In our institute, we conducted a rare study involving small number of patients ( n = 5), between February 2013 and November 2106. The study participants comprised four male children and one female child whose average age was 1.8 months. Participant inclusion criteria were no active infection, no distal end of radius (cartilage remnant) and only haematogenous osteomyelitis. Exclusion criteria were congenital radial club hand and active infection. Decrease in the angle of radial deviation (radiologically) preoperatively from 54° to 5° and angle of volar flexion from 34° to 4° were measured. Preoperatively no ulnar angulations were observed. Length of ulna remains similar to the opposite side. No neurovascular complication noted and full range of movement regained. Our case series is unique in terms of massive bone loss, that is, distal metaphysic and epiphysis, so we followed the statement of Ono et al. and did centralization of ulna over carpus and achieved good functional and cosmetic outcome at the cost of loss of motion at the wrist, concluding that treatment is primarily considered as salvage only.

  15. Blood transfusion-acquired hemoglobin C.

    PubMed

    Suarez, A A; Polski, J M; Grossman, B J; Johnston, M F

    1999-07-01

    Unexpected and confusing laboratory test results can occur if a blood sample is inadvertently collected following a blood transfusion. A potential for transfusion-acquired hemoglobinopathy exists because heterozygous individuals show no significant abnormalities during the blood donor screening process. Such spurious results are infrequently reported in the medical literature. We report a case of hemoglobin C passively transferred during a red blood cell transfusion. The proper interpretation in our case was assisted by calculations comparing expected hemoglobin C concentration with the measured value. A review of the literature on transfusion-related preanalytic errors is provided.

  16. Constitutional and acquired autosomal aneuploidy.

    PubMed

    Jackson-Cook, Colleen

    2011-12-01

    Chromosomal imbalances can result from numerical or structural anomalies. Numerical chromosomal abnormalities are often referred to as aneuploid conditions. This article focuses on the occurrence of constitutional and acquired autosomal aneuploidy in humans. Topics covered include frequency, mosaicism, phenotypic findings, and etiology. The article concludes with a consideration of anticipated advances that might allow for the development of screening tests and/or lead to improvements in our understanding and management of the role that aneuploidy plays in the aging process and acquisition of age-related and constitutional conditions.

  17. 33 CFR 211.25 - General considerations in the acquiring of Federal jurisdiction.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... acquiring of Federal jurisdiction. 211.25 Section 211.25 Navigation and Navigable Waters CORPS OF ENGINEERS... WITH CIVIL WORKS PROJECTS Federal Jurisdiction over Real Estate § 211.25 General considerations in the acquiring of Federal jurisdiction. (a) Laws governing the acquisition of Federal jurisdiction—(1...

  18. 33 CFR 211.25 - General considerations in the acquiring of Federal jurisdiction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... acquiring of Federal jurisdiction. 211.25 Section 211.25 Navigation and Navigable Waters CORPS OF ENGINEERS... WITH CIVIL WORKS PROJECTS Federal Jurisdiction over Real Estate § 211.25 General considerations in the acquiring of Federal jurisdiction. (a) Laws governing the acquisition of Federal jurisdiction—(1...

  19. 33 CFR 211.25 - General considerations in the acquiring of Federal jurisdiction.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... acquiring of Federal jurisdiction. 211.25 Section 211.25 Navigation and Navigable Waters CORPS OF ENGINEERS... WITH CIVIL WORKS PROJECTS Federal Jurisdiction over Real Estate § 211.25 General considerations in the acquiring of Federal jurisdiction. (a) Laws governing the acquisition of Federal jurisdiction—(1...

  20. Antenatal antecedents of a small head circumference at age 24-months post-term equivalent in a sample of infants born before the 28th post-menstrual week.

    PubMed

    Leviton, Alan; Kuban, Karl; Allred, Elizabeth N; Hecht, Jonathan L; Onderdonk, Andrew; O'Shea, T Michael; McElrath, Thomas; Paneth, Nigel

    2010-08-01

    Little is known about the antecedents of microcephaly in early childhood among children born at extremely low gestational age. To identify some of the antecedents of microcephaly at age two years among children born before the 28th week of gestation. Observational cohort study. 1004 infants born before the 28th week of gestation. Head circumference Z-scores of <-2 and >or=-2, <-1. Risk of microcephaly and a less severely restricted head circumference decreased monotonically with increasing gestational age. After adjusting for gestational age and other potential confounders, the risk of microcephaly at age 2 years was increased if microcephaly was present at birth [odds ratio: 8.8 ((95% confidence interval: 3.7, 21)], alpha hemolytic Streptococci were recovered from the placenta parenchyma [2.9 (1.2, 6.9)], the child was a boy [2.8 (1.6, 4.9)], and the child's mother was not married [2.5 (1.5, 4.3)]. Antecedents associated not with microcephaly, but with a less extreme reduction in head circumference were recovery of Propionibacterium sp from the placenta parenchyma [2.9 (1.5, 5.5)], tobacco exposure [2.0 (1.4, 3.0)], and increased syncytial knots in the placenta [2.0 (1.2, 3.2)]. Although microcephaly at birth predicts a small head circumference at 2 years among children born much before term, pregnancy and maternal characteristics provide supplemental information about the risk of a small head circumference years later. Two findings appear to be novel. Tobacco exposure during pregnancy, and organisms recovered from the placenta predict reduced head circumference at age two years. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.