Horizontal transmission of group B streptococcus in a neonatal intensive care unit.

PubMed

Morinis, Julia; Shah, Jay; Murthy, Prashanth; Fulford, Martha

2011-06-01

The incidence of early-onset group B streptococcal (GBS) sepsis in the neonatal population has decreased substantially since the introduction of maternal intrapartum antibiotic prophylaxis and routine prenatal screening. However, these strategies have not reduced the incidence of late-onset GBS infections. Additional research pertaining to the transmission of late-onset GBS infections is required to develop effective preventive methods. The present report describes probable horizontal transmission of late-onset GBS infection among three infants in a neonatal intensive care unit. GBS strain confirmation was based on the microbiological picture, antibiogram and pulsed-field gel electrophoresis. These cases highlight the morbidity associated with late-onset GBS disease and the importance of considering horizontal transmission as an etiological factor in GBS infection in the newborn period. Further studies assessing horizontal transmission in late-onset GBS disease may improve prevention and early intervention.

The Burden of Invasive Early-Onset Neonatal Sepsis in the United States, 2005–2008

PubMed Central

Weston, Emily J.; Pondo, Tracy; Lewis, Melissa M.; Martell-Cleary, Pat; Morin, Craig; Jewell, Brenda; Daily, Pam; Apostol, Mirasol; Petit, Sue; Farley, Monica; Lynfield, Ruth; Reingold, Art; Hansen, Nellie I.; Stoll, Barbara J.; Shane, Andi L.; Zell, Elizabeth; Schrag, Stephanie J.

2011-01-01

Background Sepsis in the first 3 days of life is a leading cause of morbidity and mortality among infants. Group B Streptococcus (GBS), historically the primary cause of early-onset sepsis, has declined through widespread use of intrapartum chemoprophylaxis. We estimated the national burden of invasive early-onset sepsis (EOS) cases and deaths in the era of GBS prevention. Methods Population-based surveillance for invasive EOS was conducted in 4 of CDC’s Active Bacterial Core surveillance (ABCs) sites from 2005–2008. We calculated incidence using state and national live birth files. Estimates of the national number of cases and deaths were calculated, standardizing by race and gestational age. Results ABCs identified 658 cases of EOS; 72 (10.9%) were fatal. Overall incidence remained stable during the three years (2005:0.77 cases/1,000 live births; 2008:0.76 cases/1,000 live births). GBS (~38%) was the most commonly reported pathogen followed by Escherichia coli (~24%). Black preterm infants had the highest incidence (5.14 cases/1,000 live births) and case fatality (24.4%). Non-black term infants had the lowest incidence (0.40 cases/1,000 live births) and case fatality (1.6%). The estimated national annual burden of EOS was approximately 3,320 cases (95% CI: 3,060–3,580) including 390 deaths (95% CI: 300–490). Among preterm infants, 1,570 cases (95% CI: 1,400–1,770; 47.3% of the overall) and 360 deaths (95% CI: 280–460; 92.3% of the overall) occurred annually. Conclusions The burden of invasive early-onset sepsis remains substantial in the era of GBS prevention and disproportionately affects preterm and black infants. Identification of strategies to prevent preterm births is needed to reduce the neonatal sepsis burden. PMID:21654548

Strategies for preventing group B streptococcal infections in newborns: a nation-wide survey of Italian policies.

PubMed

Tzialla, Chryssoula; Berardi, Alberto; Farina, Claudio; Clerici, Pierangelo; Borghesi, Alessandro; Viora, Elsa; Scollo, Paolo; Stronati, Mauro

2017-11-02

There are no Italian data regarding the strategies for preventing neonatal group B streptococcal (GBS) infection. We conducted a national survey in order to explore obstetrical, neonatal and microbiological practices for the GBS prevention. Three distinct questionnaires were sent to obstetricians, neonatologists and microbiologists. Questionnaires included data on prenatal GBS screening, maternal risk factors, intrapartum antibiotic prophylaxis, microbiological information concerning specimen processing and GBS antimicrobial susceptibility. All respondent obstetrical units used the culture-based screening approach to identify women who should receive intrapartum antibiotic prophylaxis, and more than half of the microbiological laboratories (58%) reported using specimen processing consistent with CDC guidelines. Most neonatal units (89 out of 107, 82%) reported using protocols for preventing GBS early-onset sepsis consistent with CDC guidelines. The screening-based strategy is largely prevalent in Italy, and most protocols for preventing GBS early-onset sepsis are consistent with CDC guidelines. However, we found discrepancies in practices among centers that may reflect the lack of Italian guidelines issued by public health organizations.

Group B Streptococcal infection in neonates and colonization in pregnant women: An epidemiological retrospective analysis.

PubMed

Cho, Ching-Yi; Tang, Yi-Hsuan; Chen, Yu-Hsuan; Wang, Szu-Yao; Yang, Yi-Hsin; Wang, Ting-Hao; Yeh, Chang-Ching; Wu, Keh-Gong; Jeng, Mei-Jy

2017-08-23

Group B Streptococcus (GBS) infection is one of the major causes of neonatal morbidity and mortality. Universal GBS screening with intrapartum antibiotic prophylaxis (IAP) in pregnant women were initiated in 2012 in Taiwan. This study aimed to analyze the most recent maternal GBS colonization rate and the changes in neonatal GBS infection rate from 2011 to 2016. All pregnant women and their live born neonates between January 2011 and June 2016 were retrospectively reviewed. Whether GBS screening was done, screening results, presence of risk factors, the use of antibiotics, and neonatal outcome were analyzed. In addition, hospitalized neonates diagnosed with GBS infections were retrieved for comparison of early onset disease (EOD) (<7 days) and late onset disease (LOD) (≥7 days). A total of 9535 women delivered babies during the study period. The maternal GBS screening rate was 71.0% and the colonization rate was 22.6%. The overall neonatal invasive GBS infection rate was 0.81 per 1000 live births and the vertical transmission rate was 1.2%. After 2012, the invasive neonatal GBS infection rate declined from 1.1-1.6‰ to 0.6-0.7‰ in 2014 and thereafter, the GBS EOD incidence rate declined from 2.8‰ to 0.0-0.6‰, but the LOD incidence rate remained approximately 0.7‰. Infants with EOD had strong association with obstetric risk factors. Taiwan's universal GBS screening with IAP program reduced the incidence rate of neonatal GBS EOD to be lower than 1‰ after 2012. Pediatricians still should pay attention to infants with GBS LOD since its incidence rate remained unchanged. Copyright © 2017. Published by Elsevier B.V.

Prevention and treatment strategy in pregnant women with group B streptococcal infection.

PubMed

Tevdorashvili, G; Tevdorashvili, D; Andghuladze, M; Tevdorashvili, M

2015-04-01

Group B streptococcus (GBS; Streptococcus agalactiae) are encapsulated gram-positive cocci belonging to Lancefield group B, that frequently colonizes the human genital and gastrointestinal tracts. It is an important cause of illness in three categories of population: infants, pregnant women, and adults with underlying medical conditions. In pregnant women and postpartum women, GBS is a frequent cause of asymptomatic bacteriuria, urinary tract infection, upper genital tract infection (i.e. intraamniotic infection or chorioamnionitis), postpartum endometritis (8%), pneumonia (2%), puerperal sepsis (2%), and bacteremia without a focal site (31%). It also can cause focal infections such as pneumonia, meningitis, and endocarditis, albeit rarely. Invasive maternal infection with GBS is associated with pregnancy loss and preterm delivery. Prior to the widespread use of maternal intrapartum chemoprophylaxis, maternal colonization with GBS conferred an increased risk of chorioamnionitis, and early postpartum infection. The serotype distribution of invasive GBS infection in pregnant women is similar to that of early-onset neonatal disease. The most common GBS serotypes causing invasive disease in adults and neonates are Ia, Ib, III, and V. Vaccination of adolescent women is considered an ideal solution. However, recent reports (April 2015) have shown that serotype IV GBS is emerging in pregnant carriers and causing infections in neonates and adults. This emergence is of concern because GBS conjugate vaccines that are being developed to prevent invasive disease may protect only against serotypes Ia, Ib, II, III, and V, or combinations thereof. Though research for the development of such a vaccine is underway, a good candidate vaccine has yet to surface.

Group B streptococcal infections in the newborn infant and the potential value of maternal vaccination.

PubMed

Berardi, Alberto; Cattelani, Chiara; Creti, Roberta; Berner, Reinhard; Pietrangiolillo, Zaira; Margarit, Immaculada; Maione, Domenico; Ferrari, Fabrizio

2015-01-01

Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections in developed countries. Early-onset disease (EOD) occurs at day 0-6 and late-onset disease occurs at day 7-89. Currently, the prevention of EOD relies upon intrapartum antibiotic prophylaxis (IAP) given to women who are GBS positive at prenatal screening or women with risk factors for EOD. Although successfully implemented, IAP has not fully eradicated EOD, and incidence rates of late-onset disease remain unchanged. Furthermore, antibiotic resistance may result from widespread antibiotic use. New prophylactic strategies are therefore of critical importance. A vaccine active against GBS, administered during pregnancy and combined with targeted IAP, could overcome these problems and reduce the mortality and morbidity associated with invasive diseases.

[Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome].

PubMed

von Schnakenburg, C; Hufnagel, M; Superti-Furga, A; Rieger-Fackeldey, E; Berner, R

2009-01-01

Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

Culture-proven early-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study.

PubMed

Hammoud, Majeda S; Al-Taiar, Abdullah; Al-Abdi, Sameer Y; Bozaid, Hussain; Khan, Anwar; AlMuhairi, Laila M; Rehman, Moghis Ur

2017-02-01

To investigate the incidence and the pattern of causative organisms of culture-proven early-onset sepsis (EOS) in Arab states in the Gulf region. Five neonatal care units participated in this 2-year prospective study in Kuwait, the United Arab Emirates, and Saudi Arabia. Data were collected prospectively using a standardized data collection form. EOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants within 72h of birth, with clinical and laboratory findings consistent with infection. Out of 67 474 live births, 102 cases of EOS occurred. The overall incidence of EOS was 1.5 (95% confidence interval 1.2-1.8) per 1000 live-births, ranging from 2.64 per 1000 live-births in Kuwait to 0.40 per 1000 live-births in King Abdulaziz Hospital in Saudi Arabia. The most common causative organism of EOS was group B Streptococcus (GBS; 60.0%), followed by Escherichia coli (13%). The incidence of invasive GBS disease was 0.90 per 1000 live-births overall and ranged from 1.4 per 1000 live-births in Kuwait to 0.6 per 1000 live-births in Dubai Hospital. The incidence of EOS and the patterns of the causative organisms in the Arab states in the Gulf region are similar to those in developed countries before the era of intrapartum antibiotic prophylaxis. Efforts should be made to improve intrapartum antibiotic prophylaxis in the Arab state setting, which could avert large numbers of GBS infections. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rapidly-growing mycobacterial infection: a recognized cause of early-onset prosthetic joint infection.

PubMed

Jitmuang, Anupop; Yuenyongviwat, Varah; Charoencholvanich, Keerati; Chayakulkeeree, Methee

2017-12-28

Prosthetic joint infection (PJI) is a major complication of total hip and total knee arthroplasty (THA, TKA). Although mycobacteria are rarely the causative pathogens, it is important to recognize and treat them differently from non-mycobacterial infections. This study aimed to compare the clinical characteristics, associated factors and long-term outcomes of mycobacterial and non-mycobacterial PJI. We conducted a retrospective case-control study of patients aged ≥18 years who were diagnosed with PJI of the hip or knee at Siriraj Hospital from January 2000 to December 2012. Patient characteristics, clinical data, treatments and outcomes were evaluated. A total of 178 patients were included, among whom 162 had non-mycobacterial PJI and 16 had mycobacterial PJI. Rapidly growing mycobacteria (RGM) (11) and M. tuberculosis (MTB) (5) were the causative pathogens of mycobacterial PJI. PJI duration and time until onset were significantly different between mycobacterial and non-mycobacterial PJI. Infection within 90 days of arthroplasty was significantly associated with RGM infection (OR 21.86; 95% CI 4.25-112.30; p < .001). Implant removal was associated with improved favorable outcomes at 6 months (OR 5.96; 95% CI 1.88-18.88; p < .01) and 12 months (OR 3.96; 95% CI 1.15-13.71; p = .03) after the infection. RGM were the major pathogens of early onset PJI after THA and TKA. Both a high clinical index of suspicion and mycobacterial cultures are recommended when medically managing PJI with negative cultures or non-response to antibiotics. Removal of infected implants was associated with favorable outcomes.

HIV positive patient with GBS-like syndrome.

PubMed

Shepherd, Samantha J; Black, Heather; Thomson, Emma C; Gunson, Rory N

2017-08-01

Introduction. Guillain-Barré Syndrome (GBS) is an acute demyelinating polyneuropathy which can occur post-infection. Criteria of diagnosis of GBS include areflexia with progressive bilateral weakness in arms and legs. GBS can lead to severe respiratory and cardiac complications. The fatality rate can be up to 5 % in patients, depending on the severity of the symptoms. HIV can cause a range of neurological disorders including, on rare occasions, GBS. GBS can occur at any stage of HIV infection, highlighting the complexity of diagnosis of GBS within HIV patients. Case presentation. A 57 year old female with lumbar back pain radiating to the legs, poor mobility and tiredness, with reports of a viral-like illness four days previously, was initially diagnosed with a lower respiratory tract infection and discharged. Seventeen days later the patient was readmitted to hospital with progressive lower and upper limb weakness, areflexia and sensory loss. She was diagnosed with GBS and was unexpectedly discovered to be HIV-positive. HIV avidity was low indicating a recently acquired HIV infection. The patient was treated with intravenous immunoglobulin for five days for the GBS and commenced antriretrovirals for HIV. The patient was discharge from hospital 53 days after admission with walking aids and regular physiotherapy follow-up. . This case highlighted the need for all clinicians to be aware that patients with symptoms of GBS, regardless of clinical history should be offered an HIV test. GBS can be the first sign a patient is HIV-positive.

Gene expression profiling at birth characterizing the preterm infant with early onset infection.

PubMed

Hilgendorff, Anne; Windhorst, Anita; Klein, Manuel; Tchatalbachev, Svetlin; Windemuth-Kieselbach, Christine; Kreuder, Joachim; Heckmann, Matthias; Gkatzoflia, Anna; Ehrhardt, Harald; Mysliwietz, Josef; Maier, Michael; Izar, Benjamin; Billion, Andre; Gortner, Ludwig; Chakraborty, Trinad; Hossain, Hamid

2017-02-01

Early onset infection (EOI) in preterm infants <32 weeks gestational age (GA) is associated with a high mortality rate and the development of severe acute and long-term complications. The pathophysiology of EOI is not fully understood and clinical and laboratory signs of early onset infections in this patient cohort are often not conclusive. Thus, the aim of this study was to identify signatures characterizing preterm infants with EOI by using genome-wide gene expression (GWGE) analyses from umbilical arterial blood of preterm infants. This prospective cohort study was conducted in preterm infants <32 weeks GA. GWGE analyses using CodeLink human microarrays were performed from umbilical arterial blood of preterm infants with and without EOI. GWGE analyses revealed differential expression of 292 genes in preterm infants with EOI as compared to infants without EOI. Infants with EOI could be further differentiated into two subclasses and were distinguished by the magnitude of the expression of genes involved in both neutrophil and T cell activation. A hallmark activity for both subclasses of EOI was a common suppression of genes involved in natural killer (NK) cell function, which was independent from NK cell numbers. Significant results were recapitulated in an independent validation cohort. Gene expression profiling may enable early and more precise diagnosis of EOI in preterm infants. Gene expression (GE) profiling at birth characterizes preterm infants with EOI. GE analysis indicates dysregulation of NK cell activity. NK cell activity at birth may be a useful marker to improve early diagnosis of EOI.

Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis

PubMed Central

Chan, Grace J.; Lee, Anne CC; Baqui, Abdullah H.; Tan, Jingwen; Black, Robert E.

2013-01-01

Background Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period. Methods and Findings We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors. Conclusions Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high

Relevance of the hygiene hypothesis to early vs. late onset allergic rhinitis.

PubMed

Matheson, M C; Walters, E H; Simpson, J A; Wharton, C L; Ponsonby, A-L; Johns, D P; Jenkins, M A; Giles, G G; Hopper, J L; Abramson, M J; Dharmage, S C

2009-03-01

The hygiene hypothesis proposes that reduced exposure to infections in early life increases the risk of developing allergic conditions including allergic rhinitis. We examined the association between markers of the hygiene hypothesis and allergic rhinitis that developed before 7 years of age and allergic rhinitis that developed after 7 years of age. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort (n=8583) study of respiratory disease. Participants have been followed from 7 to 44 years of age. Information on potential risk factors, allergies and respiratory symptoms was collected longitudinally. Using multi-nomial logistic regression, exposure to siblings, infections, tonsillectomy and farm residence during childhood were examined as risk factors for allergic rhinitis that developed before or after 7 years of age. All analyses were adjusted for gender, maternal and paternal atopy, mother's age at participant's birth, paternal socio-economic status in 1968 and personal socio-economic status in 2004. Greater cumulative exposure to siblings before the age of 2 years was strongly inversely associated with early onset allergic rhinitis (<1 year sib exposure: OR=0.6, 95% CI 0.3-1.0; 1-3 years sib exposure: OR=0.6, 95% CI 0.4-0.9; >3 years sib exposure: OR=0.4, 95% CI 0.3-0.8) less so with later onset allergic rhinitis. The risk of early onset allergic rhinitis decreased with increasing viral infections (OR=0.7, 95% CI 0.5-0.9) during childhood. Having a tonsillectomy before 7 years of age increased the risk of early onset allergic rhinitis (OR=1.7, 95% CI 1.2-2.5). None of these factors was associated with later onset allergic rhinitis. Exposures relevant to the hygiene hypothesis were important predictors for the development of early onset but less so for later onset allergic rhinitis. The exact mechanisms by which siblings and infections protect against allergic rhinitis are unclear. The stronger findings for earlier onset allergic rhinitis

Exploring the Pregnant Guinea Pig as a Model for Group B Streptococcus Intrauterine Infection.

PubMed

Harrell, Maria I; Burnside, Kellie; Whidbey, Christopher; Vornhagen, Jay; Adams Waldorf, Kristina M; Rajagopal, Lakshmi

2017-09-01

Infection of the amniotic cavity remains a major cause of preterm birth, stillbirth, fetal injury and early onset, fulminant infections in newborns. Currently, there are no effective therapies to prevent in utero infection and consequent co-morbidities. This is in part due to the lack of feasible and appropriate animal models to understand mechanisms that lead to in utero infections. Use of mouse and rat models do not fully recapitulate human pregnancy, while pregnant nonhuman primate models are limited by ethical considerations, technical constraints, and cost. Given these limitations, the guinea pig is an attractive animal model for studying pregnancy infections, particularly as the placental structure is quite similar to the human placenta. Here, we describe our studies that explored the pregnant guinea pig as a model to study in utero Group B Streptococci (GBS) infections. We observed that intrauterine inoculation of wild type GBS in pregnant guinea pigs resulted in bacterial invasion and dissemination to the placenta, amniotic fluid and fetal organs. Also, hyperhemolytic GBS such as those lacking the hemolysin repressor CovR/S showed increased dissemination into the amniotic fluid and fetal organs such as the fetal lung and brain. These results are similar to those observed in mouse and non-human primate models of in utero infection, and support use of the guinea pig as a model for studying GBS infections in pregnancy.

Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib.

PubMed

Ghez, David; Calleja, Anne; Protin, Caroline; Baron, Marine; Ledoux, Marie-Pierre; Damaj, Gandhi; Dupont, Mathieu; Dreyfus, Brigitte; Ferrant, Emmanuelle; Herbaux, Charles; Laribi, Kamel; Le Calloch, Ronan; Malphettes, Marion; Paul, Franciane; Souchet, Laetitia; Truchan-Graczyk, Malgorzata; Delavigne, Karen; Dartigeas, Caroline; Ysebaert, Loïc

2018-04-26

Ibrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, the observation of a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis (IA) was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia, or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular IA with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present. © 2018 by The American Society of Hematology.

Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009–2011

PubMed Central

Greene, Sharon K.; Rett, Melisa D.; Vellozzi, Claudia; Li, Lingling; Kulldorff, Martin; Marcy, S. Michael; Daley, Matthew F.; Belongia, Edward A.; Baxter, Roger; Fireman, Bruce H.; Jackson, Michael L.; Omer, Saad B.; Nordin, James D.; Jin, Robert; Weintraub, Eric S.; Vijayadeva, Vinutha; Lee, Grace M.

2013-01-01

Background Guillain-Barré Syndrome (GBS) can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1) pandemic in the United States, monovalent inactivated influenza vaccine (MIV) availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited. Methods We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009–10 MIV, 2010–11 trivalent inactivated influenza vaccine (TIV), and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls. Results Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009–10 MIV recipients and 2.80 million 2010–11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009–10 MIV/2010–11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI), 0.59–3.99; risk difference = 0.93 per million doses, 95% CI, −0.71–5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60–16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49–26.94. These findings were consistent in sensitivity analyses using alternative infection definitions

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

PubMed Central

Adams Waldorf, Kristina M.; Gravett, Michael G.; McAdams, Ryan M.; Paolella, Louis J.; Gough, G. Michael; Carl, David J.; Bansal, Aasthaa; Liggitt, H. Denny; Kapur, Raj P.; Reitz, Frederick B.; Rubens, Craig E.

2011-01-01

Background Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. Methodology/Principal Findings Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. Conclusions/Significance A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently

[Epidemiology of nosocomial infections in neonates].

PubMed

Lachassinne, E; Letamendia-Richard, E; Gaudelus, J

2004-03-01

Epidemiology of nosocomial infections in neonates has to be described according to our definitions (early onset GBS diseases excluded) and according to levels of care. Nosocomial risk exists in maternity departments (3% in postnatal beds), incidence rates are 7.5-12.7% or 1.3-8.5 per 1000 days in neonatal care units and 14.2% or 11.7 per 1000 days in neonatal intensive care units (NICU). Gram-positive cocci bloodstream infections are the most common nosocomial infections in NICU but viral gastroenteritis are more frequent in neonatal care units. Risk factors are low birthweight, small gestational age and intravascular catheter in NICU, and for viral nosocomial infections, visits and winter outbreaks.

Reductions in neonatal listeriosis: "Collateral benefit" of Group B streptococcal prophylaxis?

PubMed

Lee, Brian; Newland, Jason G; Jhaveri, Ravi

2016-03-01

We tested the hypothesis that declines in Listeria monocytogenes in infants are related to declines in rates of early-onset Group B Streptococcus (GBS) infections associated with widespread prophylaxis using agents with Listeria activity. We performed a retrospective cohort analysis using a national administrative database Pediatric Health Information System (PHIS). We searched for ICD-9 codes for Listeriosis in infants <30 days old and for early-onset GBS infection of any kind in infants <5 days old during the study period. We identified 183 cases of Listeriosis in infants <30 days in the PHIS database from 1992 to 2013. We noted a statistically significant decline in case rates over the years studied: 4.78 cases per 10,000 admissions (1992-1995) to 2.24 (1996-2002) to 1.31 from (2003-2013) (p < 0.0001). Case rates of early-onset GBS dropped significantly over the study period: 30.10 cases per 1000 admissions (1992-1995) to 21.70 (1996-2002) to 18.57 (2003-2013) (p < 0.0001). There was a statistically significant correlation between yearly rates of Listeriosis and early-onset GBS (rho: 0.53; p = 0.01). These results support the hypothesis of a "collateral benefit" to widespread GBS prophylaxis and further support the position that empiric antibiotic regimens for febrile infants may no longer require Listeria activity. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

2010 Perinatal GBS Prevention Guideline and Resource Utilization

PubMed Central

Mukhopadhyay, Sagori; Dukhovny, Dmitry; Mao, Wenyang; Eichenwald, Eric C.

2014-01-01

OBJECTIVES: To quantify differences in early-onset sepsis (EOS) evaluations, evaluation-associated resource utilization, and EOS cases detected, when comparing time periods before and after the implementation of an EOS algorithm based on the Centers for Disease Control and Prevention (CDC) 2010 guidelines for prevention of perinatal Group B Streptococcus (GBS) disease. METHODS: Retrospective cohort study of infants born at ≥36 weeks’ gestation from 2009 to 2012 in a single tertiary care center. One 12-month period during which EOS evaluations were based on the CDC 2002 guideline was compared with a second 12-month period during which EOS evaluations were based on the CDC 2010 guideline. A cost minimization analysis was performed to determine the EOS evaluation-associated costs and resources during each time period. RESULTS: During the study periods, among well-appearing infants ≥36 weeks’ gestation, EOS evaluations for inadequate GBS prophylaxis decreased from 32/1000 to <1/1000 live births; EOS evaluation-associated costs decreased by $6994 per 1000 live births; and EOS evaluation-associated work hours decreased by 29 per 1000 live births. We found no increase in EOS evaluations for other indications, total NICU admissions, frequency of infants evaluated for symptoms before hospital discharge, or incidence of EOS during the 2 study periods. CONCLUSIONS: Implementation of an EOS algorithm based on CDC 2010 GBS guidelines resulted in a 25% decrease in EOS evaluations performed among well-appearing infants ≥36 weeks’ gestation, attributable to decreased evaluation of infants born in the setting of inadequate indicated GBS prophylaxis. This resulted in significant changes in EOS evaluation-associated resource expenditures. PMID:24446442

Clinical Features of Guillain-Barré Syndrome With vs Without Zika Virus Infection, Puerto Rico, 2016.

PubMed

Dirlikov, Emilio; Major, Chelsea G; Medina, Nicole A; Lugo-Robles, Roberta; Matos, Desiree; Muñoz-Jordan, Jorge L; Colon-Sanchez, Candimar; Garcia, Myriam; Olivero-Segarra, Marangely; Malave, Graciela; Rodríguez-Vega, Gloria M; Thomas, Dana L; Waterman, Stephen H; Sejvar, James J; Luciano, Carlos A; Sharp, Tyler M; Rivera-García, Brenda

2018-05-21

The pathophysiologic mechanisms of Guillain-Barré syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features. To identify specific clinical features of GBS associated with ZIKV infection. During the ZIKV epidemic in Puerto Rico, prospective and retrospective strategies were used to identify patients with GBS who had neurologic illness onset in 2016 and were hospitalized at all 57 nonspecialized hospitals and 2 rehabilitation centers in Puerto Rico. Guillain-Barré syndrome diagnosis was confirmed via medical record review using the Brighton Collaboration criteria. Specimens (serum, urine, cerebrospinal fluid, and saliva) from patients with GBS were tested for evidence of ZIKV infection by real-time reverse transcriptase-polymerase chain reaction; serum and cerebrospinal fluid were also tested by IgM enzyme-linked immunosorbent assay. In this analysis of public health surveillance data, a total of 123 confirmed GBS cases were identified, of which 107 had specimens submitted for testing; there were 71 patients with and 36 patients without evidence of ZIKV infection. Follow-up telephone interviews with patients were conducted 6 months after neurologic illness onset; 60 patients with and 27 patients without evidence of ZIKV infection participated. Acute and long-term clinical characteristics of GBS associated with ZIKV infection. Of 123 patients with confirmed GBS, the median age was 54 years (age range, 4-88 years), and 68 patients (55.3%) were male. The following clinical features were more frequent among patients with GBS and evidence of ZIKV infection compared with patients with GBS without evidence of ZIKV infection: facial weakness (44 [62.0%] vs 10 [27.8%]; P < .001), dysphagia (38 [53.5%] vs 9 [25.0%]; P = .005), shortness of breath (33 [46.5%] vs 9 [25.0%]; P = .03), facial paresthesia (13 [18.3%] vs 1 [2.8%]; P = .03), elevated levels of protein in cerebrospinal fluid (49 [94.2%] vs 23 [71

The link between early onset drinking and early onset alcohol-impaired driving in young males.

PubMed

Zhang, Lening; Wieczorek, William F; Welte, John W

2014-05-01

Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. The present study aimed to assess this link along with potentially confounding factors. The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population-based sample of 625 males at aged 16-19. Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving.

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

PubMed Central

Wisniewska, Monika; Cremer, Malte; Wiehe, Lennart; Becker, Niels-Peter; Rijntjes, Eddy; Martitz, Janine; Renko, Kostja; Bührer, Christoph; Schomburg, Lutz

2017-01-01

Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections. PMID:28358335

Late-onset cytomegalovirus infection complicated by Guillain-Barre syndrome in a kidney transplant recipient: case report and review of the literature.

PubMed

Shaban, E; Gohh, R; Knoll, B M

2016-04-01

Cytomegalovirus (CMV) infection remains a common infection after solid-organ transplantation. In the general population CMV disease is associated with Guillain-Barre syndrome (GBS), an autoimmune disease leading to an acute peripheral neuropathy, in 1 of 1000 cases. Interestingly, GBS is a rarely observed complication in solid-organ transplant recipients, possibly related to maintenance immunosuppression. We describe a case of CMV infection complicated by GBS in a kidney transplant recipient and review the literature.

THE LINK BETWEEN EARLY ONSET DRINKING AND EARLY ONSET ALCOHOL-IMPAIRED DRIVING IN YOUNG MALES

PubMed Central

Zhang, Lening; Wieczorek, William F.; Welte, John W.

2014-01-01

Background Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. Objectives The present study aimed to assess this link along with potentially confounding factors. Methods The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population based sample of 625 males at ages of 16–19 years old. Results Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Conclusion Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving. PMID:24766089

Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

PubMed

Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p < 0.001) were risk factors independently associated with early-onset peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p < 0.001) and worse technique survival (p < 0.001), while patient survival did not differ significantly between the 2 groups during the long-term follow-up (p > 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

Early- versus Late-Onset Dysthymia

PubMed Central

Sansone, Lori A.

2009-01-01

In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

Group B Streptococcus vaccine: state of the art

PubMed Central

Nuccitelli, Annalisa; Rinaudo, C. Daniela

2015-01-01

Group B Streptococcus (GBS) is cause of neonatal invasive diseases as well as of severe infections in the elderly and immune-compromised patients. Despite significant advances in the prevention and treatment of neonatal disease, sepsis and meningitis caused by GBS still represent a significant public health care concern globally and additional prevention and therapeutic strategies against infection are highly desirable. The introduction of national recommended guidelines in several countries to screen pregnant women for GBS carriage and the use of antibiotics during delivery significantly reduced disease occurring within the first hours of life (early-onset disease), but it has had no effect on the late-onset diseases occurring after the first week and is not feasible in most countries. Availability of an effective vaccine against GBS would provide an effective means of controlling GBS disease. This review provides an overview of the burden of invasive disease caused by GBS in infants and adults, and highlights the strategies for the development of an effective vaccine against GBS infections. PMID:26288735

Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma.

PubMed

Scott, Kate M; Von Korff, Michael; Alonso, Jordi; Angermeyer, Matthias C; Benjet, Corina; Bruffaerts, Ronny; de Girolamo, Giovanni; Haro, Josep Maria; Kessler, Ronald C; Kovess, Viviane; Ono, Yutaka; Ormel, Johan; Posada-Villa, José

2008-11-01

To investigate a) whether childhood adversity predicts adult-onset asthma; b) whether early-onset depressive/anxiety disorders predict adult-onset asthma; and c) whether childhood adversity and early-onset depressive/anxiety disorders predict adult-onset asthma independently of each other. Previous research has suggested, but not established, that childhood adversity may predict adult-onset asthma and, moreover, that the association between mental disorders and asthma may be a function of shared risk factors, such as childhood adversity. Ten cross-sectional population surveys of household-residing adults (>18 years, n = 18,303) assessed mental disorders with the Composite International Diagnostic Interview (CIDI 3.0) as part of the World Mental Health surveys. Assessment of a range of childhood family adversities was included. Asthma was ascertained by self-report of lifetime diagnosis and age of diagnosis. Survival analyses calculated hazard ratios (HRs) for risk of adult-onset (>age 20 years) asthma as a function of number and type of childhood adversities and early-onset (onset asthma with risk increasing with the number of adversities experienced (HRs = 1.49-1.71). Early-onset depressive and anxiety disorders also predicted adult-onset asthma (HRs = 1.67-2.11). Childhood adversities and early-onset depressive and anxiety disorders both predicted adult-onset asthma after mutual adjustment (HRs = 1.43-1.91). Childhood adversities and early-onset depressive/anxiety disorders independently predict adult-onset asthma, suggesting that the mental disorder-asthma relationship is not a function of a shared background of childhood adversity.

Prevention of perinatal group B streptococcal infections: a review with an Indian perspective.

PubMed

Narava, S; Rajaram, G; Ramadevi, A; Prakash, G V; Mackenzie, S

2014-01-01

Group B Streptococcus (GBS) is an important cause of maternal and neonatal morbidity and mortality in many parts of the world. Asymptomatic colonisation of the vagina and rectum with Group B streptococci is common in pregnancy. Maternal colonisation of GBS can vary depending on ethnicity and geographical distribution. Vertical transmission of this organism from mother to foetus may lead to neonatal GBS disease. Intra-partum use of antibiotics in these women has led to a decrease in the rate of early onset but not late onset GBS disease. Identification of women with GBS is the key factor in the prevention of perinatal GBS disease. There are different screening strategies available to identify women at risk of perinatal GBS disease. Clinicians continue to face the challenge of choosing between preventive strategies to reduce the impact of perinatal GBS disease. Controversy exists regarding the ideal preventive strategy. In India, the mortality and morbidity associated with the GBS disease remains largely a under-recognised problem. This comprehensive review summarises the salient features of GBS disease and discusses the epidemiology, risk factors, screening strategies, intra-partum antibiotic prophylaxis with an Indian perspective and how it compares with the Western nations.

The burden of early-onset sepsis in Emilia-Romagna (Italy): a 4-year, population-based study.

PubMed

Berardi, Alberto; Baroni, Lorenza; Bacchi Reggiani, Maria Letizia; Ambretti, Simone; Biasucci, Giacomo; Bolognesi, Serenella; Capretti, Maria Grazia; Carretto, Edoardo; Ciccia, Matilde; Fiorini, Valentina; Fortini, Cinzia; Gargano, Giancarlo; Pedna, Maria Federica; Rizzo, Vittoria; Creti, Roberta; Ferrari, Fabrizio

2016-10-01

To provide the first Italian data on pathogens causing early-onset sepsis (EOS) and their antimicrobial susceptibility, after the successfully prevention of Group B streptococcus (GBS) EOS. Retrospective area-based cohort study from Emilia-Romagna (Italy). Cases of EOS registered (from 2009 to 2012) in all gestational age neonates were reviewed. Live births (LB) numbered 146 682. Ninety neonates had EOS and 12 died (incidence rates of 0.61 and 0.08/1000 LB, respectively). EOS and mortality were the highest among neonates with a birth weight <1000 g (20.37/1000 LB and 8.49/1000 LB, respectively). The most common pathogens were GBS (n = 27, 0.18/1000 LB) and Escherichia coli (n = 19, 0.13/1000 LB). Most infants affected by E. coli EOS were born preterm (n = 13), had complications (n = 4) or died (n = 7). Among 90 isolates tested, only 3 were resistant to both first line empirical antibiotics. Multivariate logistic regression analysis showed that low gestational age, caesarean section and low platelet count at presentation were significantly associated with death or brain lesions (area under ROC curve = 0.939, H-L = 0.944, sensitivity 76.0%, specificity 90.7%). GBS slightly exceeds E. coli as a cause of EOS. However, E. coli is the prominent cause of death, complications and in most cases affects preterm neonates. Empirical antimicrobial therapy of EOS seems appropriate.

Recolonization of group B Streptococcus (GBS) in women with prior GBS genital colonization in pregnancy.

PubMed

Tam, Teresa; Bilinski, Ewa; Lombard, Emily

2012-10-01

The purpose of the study is to evaluate the incidence of women with prior GBS genital colonization who have recolonization in subsequent pregnancies. This is a retrospective, cohort study of patients with a prior GBS genital colonization in pregnancy and a subsequent pregnancy with a recorded GBS culture result, from January 2000 through June 2007. Documentation of GBS status was through GBS culture performed between 35 to 37 weeks gestation. Exclusion criteria included pregnancies with unknown GBS status, patients with GBS bacteriuria, women with a previous neonate with GBS disease and GBS finding prior to 35 weeks. Data was analyzed using SPSS 15.0. The sample proportion of subjects with GBS genital colonization and its confidence interval were computed to estimate the incidence rate. Logistic regression was performed to assess potential determinants of GBS colonization. Regression coefficients, odds ratios and associated confidence intervals, and p-values were reported, with significant results reported. There were 371 pregnancies that met the test criteria. There were 151 subsequent pregnancies with GBS genital colonization and 220 without GBS recolonization. The incidence of GBS recolonization on patients with prior GBS genital colonization was 40.7% (95% confidence interval 35.7-45.69%). The incidence rate for the sample was significantly larger than 30% (p < .001), which is the estimated incidence rate for all pregnant women who are GBS carriers regardless of prior history. These results suggest that patients with a history of GBS are at a significantly higher risk of GBS recolonization in subsequent pregnancies.

Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children

PubMed Central

Seale, Anna C; Bianchi-Jassir, Fiorella; Russell, Neal J; Kohli-Lynch, Maya; Tann, Cally J; Hall, Jenny; Madrid, Lola; Blencowe, Hannah; Cousens, Simon; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Heath, Paul T; Ip, Margaret; Le Doare, Kirsty; Madhi, Shabir A; Rubens, Craig E; Saha, Samir K; Schrag, Stephanie J; Sobanjo-ter Meulen, Ajoke; Vekemans, Johan; Lawn, Joy E

2017-01-01

Abstract Background We aimed to provide the first comprehensive estimates of the burden of group B Streptococcus (GBS), including invasive disease in pregnant and postpartum women, fetal infection/stillbirth, and infants. Intrapartum antibiotic prophylaxis is the current mainstay of prevention, reducing early-onset infant disease in high-income contexts. Maternal GBS vaccines are in development. Methods For 2015 live births, we used a compartmental model to estimate (1) exposure to maternal GBS colonization, (2) cases of infant invasive GBS disease, (3) deaths, and (4) disabilities. We applied incidence or prevalence data to estimate cases of maternal and fetal infection/stillbirth, and infants with invasive GBS disease presenting with neonatal encephalopathy. We applied risk ratios to estimate numbers of preterm births attributable to GBS. Uncertainty was also estimated. Results Worldwide in 2015, we estimated 205000 (uncertainty range [UR], 101000–327000) infants with early-onset disease and 114000 (UR, 44000–326000) with late-onset disease, of whom a minimum of 7000 (UR, 0–19000) presented with neonatal encephalopathy. There were 90000 (UR, 36000–169000) deaths in infants <3 months age, and, at least 10000 (UR, 3000–27000) children with disability each year. There were 33000 (UR, 13000–52000) cases of invasive GBS disease in pregnant or postpartum women, and 57000 (UR, 12000–104000) fetal infections/stillbirths. Up to 3.5 million preterm births may be attributable to GBS. Africa accounted for 54% of estimated cases and 65% of all fetal/infant deaths. A maternal vaccine with 80% efficacy and 90% coverage could prevent 107000 (UR, 20000–198000) stillbirths and infant deaths. Conclusions Our conservative estimates suggest that GBS is a leading contributor to adverse maternal and newborn outcomes, with at least 409000 (UR, 144000–573000) maternal/fetal/infant cases and 147000 (UR, 47000–273000) stillbirths and infant deaths annually. An effective

Early- versus Late-Onset Systemic Sclerosis

PubMed Central

Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

2014-01-01

Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

Hippocampal Morphology and Distinguishing Late-Onset From Early-Onset Elderly Depression

PubMed Central

Ballmaier, Martina; Narr, Katherine L.; Toga, Arthur W.; Elderkin-Thompson, Virginia; Thompson, Paul M.; Hamilton, Liberty; Haroon, Ebrahim; Pham, Daniel; Heinz, Andreas; Kumar, Anand

2010-01-01

Objective Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whether these changes are regionally specific. This study used three-dimensional mapping techniques to identify regional hippocampal abnormalities in early- and late-onset depression. Neuropsychological correlates of hippocampal morphology were also investigated. Method With high-resolution magnetic resonance imaging, hippocampal morphology was compared among elderly patients with early- (N=24) and late-onset (N=22) depression and comparison subjects (N=34). Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual’s hippocampal surface model, between groups. Results Hippocampal volumes differed between depressed patients and comparison subjects but not between patients with early- and late-onset depression. However, statistical mapping results showed that regional surface contractions were significantly pronounced in late-compared to early-onset depression in the anterior of the subiculum and lateral posterior of the CA1 subfield in the left hemisphere. Significant shape differences were observed bilaterally in anterior CA1–CA3 subfields and the subiculum in patients in relation to comparison subjects. These results were similar when each disease group was separately compared to comparison subjects. Hippocampal surface contractions significantly correlated with memory measures among late- but not early-onset depressed patients or comparison subjects. Conclusions More pronounced regional volume deficits and their associations with memory in late-onset depression may suggest that these patients are more likely to develop cognitive impairment over time than individuals with early-onset depression. Mapping regional hippocampal abnormalities and their cognitive correlates may help guide research in defining risk profiles and treatment strategies. PMID:17986679

Adverse Housing Conditions and Early-Onset Delinquency.

PubMed

Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

2017-09-01

Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

Can 100Gb/s wavelengths be deployed using 10Gb/s engineering rules?

NASA Astrophysics Data System (ADS)

Saunders, Ross; Nicholl, Gary; Wollenweber, Kevin; Schmidt, Ted

2007-09-01

A key challenge set by carriers for 40Gb/s deployments was that the 40Gb/s wavelengths should be deployable over existing 10Gb/s DWDM systems, using 10Gb/s link engineering design rules. Typical 10Gb/s link engineering rules are: 1. Polarization Mode Dispersion (PMD) tolerance of 10ps (mean); 2. Chromatic Dispersion (CD) tolerance of +/-700ps/nm 3. Operation at 50GHz channel spacing, including transit through multiple cascaded [R]OADMs; 4. Optical reach up to 2,000km. By using a combination of advanced modulation formats and adaptive dispersion compensation (technologies rarely seen at 10Gb/s outside of the submarine systems space), vendors did respond to the challenge and broadly met this requirement. As we now start to explore feasible technologies for 100Gb/s optical transport, driven by 100GE port availability on core IP routers, the carrier challenge remains the same. 100Gb/s links should be deployable over existing 10Gb/s DWDM systems using 10Gb/s link engineering rules (as listed above). To meet this challenge, optical transport technology must evolve to yet another level of complexity/maturity in both modulation formats and adaptive compensation techniques. Many clues as to how this might be achieved can be gained by first studying sister telecommunications industries, e.g. satellite (QPSK, QAM, LDCP FEC codes), wireless (advanced DSP, MSK), HDTV (TCM), etc. The optical industry is not a pioneer of new ideas in modulation schemes and coding theory, we will always be followers. However, we do have the responsibility of developing the highest capacity "modems" on the planet to carry the core backbone traffic of the Internet. As such, the key to our success will be to analyze the pros and cons of advanced modulation/coding techniques and balance this with the practical limitations of high speed electronics processing speed and the challenges of real world optical layer impairments. This invited paper will present a view on what advanced technologies are likely

Group B Streptococcal Prosthetic Knee Joint Infection Linked to the Consumption of Raw Fish.

PubMed

Law, Gin Way; Wijaya, Limin; Tan, Andrew Hwee Chye

2017-01-01

Group B Streptococcal (GBS) prosthetic joint infections (PJI) are rare, accounting for only 4.6-6% of primary and revision total knee replacements (TKRs). In 2015, there was an outbreak of GBS infections in Singapore with an association confirmed between consumption of Chinese-style raw fish dishes (snakehead fish, Asian bighead carp) and GBS infection, Type III GBS ST283 strain, affecting more than 200 patients in Singapore. This outbreak is the largest of its kind in the world and also the first time that foodborne transmission of GBS has been proven. We present the first reported case in the literature of a confirmed PJI in a TKR related to foodborne transmission of GBS through consumption of raw fish (Snakehead fish). Our patient is a 66-year-old Chinese female admitted with a 24-h history of acute right knee pain and swelling with associated fever in the context of consuming raw fish porridge 3 days before the onset of her symptoms. She had a TKR performed in the same knee 7 years before this presentation. Her GBS PJI was confirmed on both blood and intraoperative tissue/fluid cultures during the outbreak of GBS infections in Singapore. This was managed with debridement, polyethylene liner change, retention of metal prosthesis, and culture-directed antibiotics with good outcomes. Snakehead fish is a popular dish in the Asian community as a traditional remedy to promote wound healing after surgery. Our paper highlights the link between raw fish consumption and invasive GBS causing PJIs. This can occur in healthy adults, even in the absence of gastrointestinal symptoms, despite being a foodborne transmission. Our paper also highlights that GBS PJIs can be managed with debridement, antibiotic therapy, and implant retention with good outcomes in the setting of acute hematogenous infection. We recommend the inclusion of raw fish consumption on history taking in the workup of suspected PJIs and counseling patients preoperatively on the risk of GBS PJIs with the

Guillain-Barré syndrome risk among individuals infected with Zika virus: a multi-country assessment.

PubMed

Mier-Y-Teran-Romero, Luis; Delorey, Mark J; Sejvar, James J; Johansson, Michael A

2018-05-15

Countries with ongoing outbreaks of Zika virus have observed a notable rise in reported cases of Guillain-Barré syndrome (GBS), with mounting evidence of a causal link between Zika virus infection and the neurological syndrome. However, the risk of GBS following a Zika virus infection is not well characterized. In this work, we used data from 11 locations with publicly available data to estimate the risk of GBS following an infection with Zika virus, as well as the location-specific incidence of infection and the number of suspect GBS cases reported per infection. We built a mathematical inference framework utilizing data from 11 locations that had reported suspect Zika and GBS cases, two with completed outbreaks prior to 2015 (French Polynesia and Yap) and nine others in the Americas covering partial outbreaks and where transmission was ongoing as of early 2017. We estimated that 2.0 (95% credible interval 0.5-4.5) reported GBS cases may occur per 10,000 Zika virus infections. The frequency of reported suspect Zika cases varied substantially and was highly uncertain, with a mean of 0.11 (95% credible interval 0.01-0.24) suspect cases reported per infection. These estimates can help efforts to prepare for the GBS cases that may occur during Zika epidemics and highlight the need to better understand the relationship between infection and the reported incidence of clinical disease.

Phrenic Nerve Conduction Study in the Early Stage of Guillain-Barre Syndrome as a Predictor of Respiratory Failure.

PubMed

Sen, Barun Kumar; Pandit, Alak

2018-01-01

Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure.

Maternal group B streptococcal (GBS) genital tract colonization at term in women who have asymptomatic GBS bacteriuria.

PubMed

McKenna, David S; Matson, Scott; Northern, Ike

2003-01-01

To determine the rate of positive group B streptococcus (GBS) cultures at 35-37 weeks gestation in women who have first trimester asymptomatic GBS bacteriuria. Pregnant women with asymptomatic first trimester GBS bacteriuria had genital cultures for GBS performed at 35-37 weeks gestational age. Serotyping was performed by the standard Lancefield capillary precipitin method. Fifty-three women with positive urine cultures had genital cultures performed at 35-37 weeks. Sixteen of the 53 (30.2%; 95% confidence interval: 18.4-44.3%) third trimester vaginal cultures were positive for GBS. Five of eight (63%) of the women with typable urine serotypes had the same typable serotype in the third trimester genital culture. Genital tract cultures at 35-37 weeks for GBS correlate poorly with first trimester asymptomatic GBS bacteriuria. Recommendations for GBS prophylaxis in labor in women who have first trimester asymptomatic GBS bacteriuria should be investigated further and reconsidered.

Mutagenesis of a bacteriophage lytic enzyme PlyGBS significantly increases its antibacterial activity against group B streptococci.

PubMed

Cheng, Qi; Fischetti, Vincent A

2007-04-01

Group B streptococci (GBS) are the leading cause of neonatal meningitis and sepsis worldwide. Intrapartum antibiotic prophylaxis (IAP) is the current prevention strategy given to pregnant women with confirmed vaginal GBS colonization. Due to antibiotic resistance identified in GBS, we previously developed another strategy using a bacteriophage lytic enzyme, PlyGBS, to reduce vaginal GBS colonization. In this study, various DNA mutagenesis methods were explored to produce PlyGBS mutants with increased lytic activity against GBS. Several hyperactive mutants were identified that contain only the endopeptidase domain found in the N-terminal region of PlyGBS and represent only about one-third of the wild-type PlyGBS in length. Significantly, these mutants not only have 18-28-fold increases in specific activities compared to PlyGBS, but they also have a similar activity spectrum against several streptococcal species. One of the hyperactive mutants, PlyGBS90-1, reduced the GBS colonization from >5 logs of growth per mouse to <50 colony-forming units (cfu) 4 h post treatment ( approximately 4-log reduction) using a single dose in a mouse vaginal model. A reduction in GBS colonization before delivery should significantly reduce neonatal GBS infection providing a safe alternative to IAP.

Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection: A case report.

PubMed

Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

2016-12-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. We report a case of acute-onset CIDP that was initially diagnosed as GBS. A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered.

Group B Streptococcal Prosthetic Knee Joint Infection Linked to the Consumption of Raw Fish

PubMed Central

Law, Gin Way; Wijaya, Limin; Tan, Andrew Hwee Chye

2017-01-01

Introduction: Group B Streptococcal (GBS) prosthetic joint infections (PJI) are rare, accounting for only 4.6-6% of primary and revision total knee replacements (TKRs). In 2015, there was an outbreak of GBS infections in Singapore with an association confirmed between consumption of Chinese-style raw fish dishes (snakehead fish, Asian bighead carp) and GBS infection, Type III GBS ST283 strain, affecting more than 200 patients in Singapore. This outbreak is the largest of its kind in the world and also the first time that foodborne transmission of GBS has been proven. We present the first reported case in the literature of a confirmed PJI in a TKR related to foodborne transmission of GBS through consumption of raw fish (Snakehead fish). Case Report: Our patient is a 66-year-old Chinese female admitted with a 24-h history of acute right knee pain and swelling with associated fever in the context of consuming raw fish porridge 3 days before the onset of her symptoms. She had a TKR performed in the same knee 7 years before this presentation. Her GBS PJI was confirmed on both blood and intraoperative tissue/fluid cultures during the outbreak of GBS infections in Singapore. This was managed with debridement, polyethylene liner change, retention of metal prosthesis, and culture-directed antibiotics with good outcomes. Conclusion: Snakehead fish is a popular dish in the Asian community as a traditional remedy to promote wound healing after surgery. Our paper highlights the link between raw fish consumption and invasive GBS causing PJIs. This can occur in healthy adults, even in the absence of gastrointestinal symptoms, despite being a foodborne transmission. Our paper also highlights that GBS PJIs can be managed with debridement, antibiotic therapy, and implant retention with good outcomes in the setting of acute hematogenous infection. We recommend the inclusion of raw fish consumption on history taking in the workup of suspected PJIs and counseling patients

Binational outbreak of Guillain-Barré syndrome associated with Campylobacter jejuni infection, Mexico and USA, 2011.

PubMed

Jackson, B R; Zegarra, J Alomía; López-Gatell, H; Sejvar, J; Arzate, F; Waterman, S; Núñez, A Sánchez; López, B; Weiss, J; Cruz, R Quintero; Murrieta, D Y López; Luna-Gierke, R; Heiman, K; Vieira, A R; Fitzgerald, C; Kwan, P; Zárate-Bermúdez, M; Talkington, D; Hill, V R; Mahon, B

2014-05-01

In June 2011, a cluster of suspected cases of Guillain-Barré syndrome (GBS), which can follow Campylobacter jejuni infection, was identified in San Luis Río Colorado (SLRC), Sonora, Mexico and Yuma County, Arizona, USA. An outbreak investigation identified 26 patients (18 from Sonora, eight from Arizona) with onset of GBS 4 May-21 July 2011, exceeding the expected number of cases (n = 1-2). Twenty-one (81%) patients reported antecedent diarrhoea, and 61% of 18 patients tested were seropositive for C. jejuni IgM antibodies. In a case-control study matched on age group, sex, ethnicity, and neighbourhood of residence, all Arizona GBS patients travelled to SLRC during the exposure period vs. 45% of matched controls (matched odds ratio 8·1, 95% confidence interval 1·5-∞). Exposure information and an environmental assessment suggested that GBS cases resulted from a large outbreak of C. jejuni infection from inadequately disinfected tap water in SLRC. Binational collaboration was essential in investigating this cross-border GBS outbreak, the first in mainland North America since 1976.

Lost human capital from early-onset chronic depression.

PubMed

Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

2000-06-01

Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

Disease evolution in late-onset and early-onset systemic lupus erythematosus.

PubMed

Aljohani, R; Gladman, D D; Su, J; Urowitz, M B

2017-10-01

Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

Phrenic Nerve Conduction Study in the Early Stage of Guillain–Barre Syndrome as a Predictor of Respiratory Failure

PubMed Central

Sen, Barun Kumar; Pandit, Alak

2018-01-01

Background: Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. Objective: To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. Methods: 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Results: Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Conclusion: Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure. PMID:29720799

Clinical Features of Post-Vaccination Guillain-Barré Syndrome (GBS) in Korea

PubMed Central

2017-01-01

Guillain-Barré syndrome (GBS) is the most common immune-mediated polyradiculoneuropathy and it is also the most commonly reported severe adverse event following immunization in adults. To evaluate the results of clinical and laboratory features of GBS after vaccination in Korea, we analyzed the claims-based data from 2002 to 2014 using materials collected for the Advisory Committee Vaccination Injury Compensation (ACVIC) meeting including, clinical features, nerve conduction studies (NCSs), cerebrospinal fluid (CSF) profiles, treatment, and outcomes. Forty-eight compensated GBS cases (median age, 15 years; interquartile range [IQR], 13–51; male:female ratio, 1:1) of 68 suspected GBS were found following immunization and all of them with influenza immunizations with either monovalent (n = 35) or trivalent (n = 13). Among them, 30 cases fulfilled the Brighton criteria level 1–3 (62.5%). The median duration between the onset of symptoms to nadir, duration of the nadir, and total admission period were 3 (IQR, 2–7 days), 2 (IQR, 1–5 days), and 14 (IQR, 6–33 days) days, respectively. The most frequently reported symptom was quadriparesis which was present in 36 cases (75%) at nadir. CSF examination revealed albuminocytologic dissociation in 25.0% and NCS was abnormal in 61.8%. After treatment, most of them showed improvement. Clinical features were similar to typical post-infectious GBS and there were both demyelinating and axonal forms suggesting heterogeneous pathogenic mechanism. In order to improve the diagnostic certainty of post-vaccination GBS, careful documentation of clinical features and timely diagnostic work-up with follow-up studies are needed. PMID:28581273

Genetics Home Reference: early-onset primary dystonia

MedlinePlus

... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder

PubMed Central

Croarkin, Paul E.; Luby, Joan L.; Cercy, Kelly; Geske, Jennifer R.; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T.; Wagner, Karen Dineen; Walkup, John T.; Nassan, Malik M.; Cuellar-Barboza, Alfredo B.; Casuto, Leah; McElroy, Susan L.; Jensen, Peter S.; Frye, Mark A.; Biernacka, Joanna M.

2018-01-01

Objective In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder. Method Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003–2008. Mayo Clinic Bipolar Biobank samples were collected from 2009–2013. Genotyping and analyses for the present study took place from 2013–2014. The diagnosis of bipolar disorder was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with bipolar disorder, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly “odz, odd Oz/ten-m homolog 4 {Drosophila}, ODZ4”]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n=69), adult patients with bipolar disorder (n=732) including a subset with early-onset illness [n=192]), and healthy controls (n=776). GRS analyses were performed comparing early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. Results GRS analysis revealed associations of the risk score with early-onset bipolar disorder (P=.01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset bipolar disorder with a CACNA1C haplotype (global test, P=.01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset bipolar disorder (P=.017), which did not remain significant after correction for multiple comparisons. Conclusion These preliminary analyses suggest that previously identified bipolar disorder risk loci

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

PubMed

Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD. �

Evidence for a genetic etiology of early-onset delinquency.

PubMed

Taylor, J; Iacono, W G; McGue, M

2000-11-01

Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

Delayed-onset and recurrent limb weakness associated with West Nile virus infection.

PubMed

Sejvar, James J; Davis, Larry E; Szabados, Erica; Jackson, Alan C

2010-02-01

Human neurologic illness following infection with West Nile virus (WNV) may include meningitis, encephalitis, and acute flaccid paralysis (AFP). Most WNV-associated AFP is due to involvement of the spinal motor neurons producing an anterior (polio)myelitis. WNV poliomyelitis is typically characterized by acute and rapidly progressing limb weakness occurring early in the course of illness, which is followed by death or clinical plateauing with subsequent improvement to varying degrees. We describe four cases of WNV poliomyelitis in which the limb weakness was characterized by an atypical temporal pattern, including one case with onset several weeks after illness onset, and three cases developing relapsing or recurrent limb weakness following a period of clinical plateauing or improvement. Delayed onset or recurrent features may be due to persistence of viral infection or delayed neuroinvasion with delayed injury by excitotoxic or other mechanisms, by immune-mediated mechanisms, or a combination thereof. Further clinical and pathogenesis studies are needed to better understand the mechanisms for these phenomena. Clinicians should be aware of these clinical patterns in patients with WNV poliomyelitis.

Structure of Streptococcus agalactiae tip pilin GBS104: a model for GBS pili assembly and host interactions

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

Krishnan, Vengadesan; Dwivedi, Prabhat; Kim, Brandon J.

The crystal structure of a 75 kDa central fragment of GBS104, a tip pilin from the 2063V/R strain of Streptococcus agalactiae (group B streptococcus; GBS), is reported. The crystal structure of a 75 kDa central fragment of GBS104, a tip pilin from the 2063V/R strain of Streptococcus agalactiae (group B streptococcus; GBS), is reported. In addition, a homology model of the remaining two domains of GBS104 was built and a model of full-length GBS104 was generated by combining the homology model (the N1 and N4 domains) and the crystal structure of the 75 kDa fragment (the N2 and N3 domains).more » This rod-shaped GBS104 model is constructed of three IgG-like domains (the N1, N2 and N4 domains) and one vWFA-like domain (the N3 domain). The N1 and N2 domains of GBS104 are assembled with distinct and remote segments contributed by the N- and C-termini. The metal-binding site in the N3 domain of GBS104 is in the closed/low-affinity conformation. Interestingly, this domain hosts two long arms that project away from the metal-binding site. Using site-directed mutagenesis, two cysteine residues that lock the N3 domain of GBS104 into the open/high-affinity conformation were introduced. Both wild-type and disulfide-locked recombinant proteins were tested for binding to extracellular matrix proteins such as collagen, fibronectin, fibrinogen and laminin, and an increase in fibronectin binding affinity was identified for the disulfide-locked N3 domain, suggesting that induced conformational changes may play a possible role in receptor binding.« less

[Risk-adjusted assessment: late-onset infection in neonates].

PubMed

Gmyrek, Dieter; Koch, Rainer; Vogtmann, Christoph; Kaiser, Annette; Friedrich, Annette

2011-01-01

The weak point of the countrywide perinatal/neonatal quality surveillance is the ignorance of interhospital differences in the case mix of patients. As a result, this approach does not produce reliable benchmarking. The objective of this study was to adjust the result of the late-onset infection incidence of different hospitals according to their risk profile of patients by multivariate analysis. The perinatal/neonatal database of 41,055 newborns of the Saxonian quality surveillance from 1998 to 2004 was analysed. Based on 18 possible risk factors, a logistic regression model was used to develop a specific risk predictor for the quality indicator "late-onset infection". The developed risk predictor for the incidence of late-onset infection could be described by 4 of the 18 analysed risk factors, namely gestational age, admission from home, hypoxic ischemic encephalopathy and B-streptococcal infection. The AUC(ROC) value of this quality indicator was 83.3%, which demonstrates its reliability. The hospital ranking based on the adjusted risk assessment was very different from hospital rankings before this adjustment. The average correction of ranking position was 4.96 for 35 clinics. The application of the risk adjustment method proposed here allows for a more objective comparison of the incidence of the quality indicator "late onset infection" among different hospitals. Copyright © 2011. Published by Elsevier GmbH.

Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

PubMed

Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

2008-03-15

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

A definition for chronic sequelae applied to campylobacter and guillian-barre syndrome (Gbs).

PubMed

Parkin; Davies-Cole; Balbus

2000-10-01

PURPOSE: Chronic sequelae (CS) are increasingly important to drinking water risk assessment and management processes, but there has been relatively little scientific rigor in defining CS or reviewing the literature on water-related CS. Our purposes were to develop a scientific definition for CS and to evaluate the definition's practical merit.METHODS: We examined scientific publications for definitions of "chronic sequela." We developed a definition that is based on scientific concepts and that can be systematically applied to literature to assess whether pathogen-related health outcomes qualify as CS. As a case study, we conducted an extensive Medline search and tested our definition on the epidemiological and clinical literature linking Campylobacter and GBS.RESULTS: We defined "chronic sequela" as the secondary adverse health outcome that 1) occurs as a result of a previous infection by a microbial pathogen, and 2) is clearly distinguishable from the health events that initially result from the causative infection, and 3) lasts 3 months or more after recognition. The 12 Campylobacter and GBS studies (five epidemiological and seven clinical) revealed that current data reporting practices limit the evaluation of all three elements in our definition. Laboratory methods and criteria to characterize infection were not always adequately reported. Primary and secondary health events were always reported, but eight of the studies required obtaining additional articles to determine the GBS criteria used. Ten of the 12 articles contained duration data for the GBS symptoms.CONCLUSIONS: Much of the evidence needed to apply our definition was found in the studies reviewed, but changes in reporting practices would facilitate the scientific evaluation of pathogen-CS relationships and estimation of their public health magnitude.

The association between maternal cervicovaginal proinflammatory cytokines concentrations during pregnancy and subsequent early-onset neonatal infection.

PubMed

Kalinka, Jarosław; Krajewski, Paweł; Sobala, Wojciech; Wasiela, Małgorzata; Brzezińska-Błaszczyk, Ewa

2006-01-01

The aim of this study was to investigate the relationship between the concentration of selected proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) in cervicovaginal fluid, as measured in midgestation, and the risk of early-onset neonatal infection (EONI). Cervicovaginal fluids were obtained from a cohort of 114 pregnant women at 22 to 34 weeks' gestation. The samples were analyzed for the concentrations of selected proinflammatory cytokines using standard enzyme-linked immunosorbent assay technique (ELISA). Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria and by culture. Mean gestational age at the time of sampling was 29.0 weeks. Mean time between sampling and delivery was 9.3 (SD 4.7) weeks. Bacterial vaginosis (BV) was diagnosed in 27.2% of subjects and M. hominis and U. urealyticum in 22.8% and 26.3%, respectively. Out of 114 women examined, 20 (17.5%) delivered newborns with EONI. Median cervicovaginal concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 did not differ between women who delivered newborns with EONI as compared to women who delivered newborns without EONI. Women with pathological lower genital tract microflora and low IL-8 concentration (below 25(th) percentile) during pregnancy presented a significant risk of delivering newborns with EONI (OR=4.9; 95% CI, 1.1-22.8). Subjects with pathological lower genital tract microflora and a low concentration of more than one cytokine had the highest risk of delivering a newborn with EONI, OR=16.2, 95% CI, 1.1-234.0. Cytokine measurement in cervicovaginal fluid in early gestation could be useful for predicting subsequent EONI only among pregnant women with lower genital tract infection. Maternal genital tract immune hyporesponsiveness as represented by low concentrations of proinflammatory cytokines may create a permissive environment for ascending infection and may lead to subsequent EONI.

Genome-Wide Mapping of Cystitis Due to Streptococcus agalactiae and Escherichia coli in Mice Identifies a Unique Bladder Transcriptome That Signifies Pathogen-Specific Antimicrobial Defense against Urinary Tract Infection

PubMed Central

Tan, Chee K.; Carey, Alison J.; Cui, Xiangqin; Webb, Richard I.; Ipe, Deepak; Crowley, Michael; Cripps, Allan W.; Benjamin, William H.; Ulett, Kimberly B.; Schembri, Mark A.

2012-01-01

The most common causes of urinary tract infections (UTIs) are Gram-negative pathogens such as Escherichia coli; however, Gram-positive organisms, including Streptococcus agalactiae, or group B streptococcus (GBS), also cause UTI. In GBS infection, UTI progresses to cystitis once the bacteria colonize the bladder, but the host responses triggered in the bladder immediately following infection are largely unknown. Here, we used genome-wide expression profiling to map the bladder transcriptome of GBS UTI in mice infected transurethrally with uropathogenic GBS that was cultured from a 35-year-old women with cystitis. RNA from bladders was applied to Affymetrix Gene-1.0ST microarrays; quantitative reverse transcriptase PCR (qRT-PCR) was used to analyze selected gene responses identified in array data sets. A surprisingly small significant-gene list of 172 genes was identified at 24 h; this compared to 2,507 genes identified in a side-by-side comparison with uropathogenic E. coli (UPEC). No genes exhibited significantly altered expression at 2 h in GBS-infected mice according to arrays despite high bladder bacterial loads at this early time point. The absence of a marked early host response to GBS juxtaposed with broad-based bladder responses activated by UPEC at 2 h. Bioinformatics analyses, including integrative system-level network mapping, revealed multiple activated biological pathways in the GBS bladder transcriptome that regulate leukocyte activation, inflammation, apoptosis, and cytokine-chemokine biosynthesis. These findings define a novel, minimalistic type of bladder host response triggered by GBS UTI, which comprises collective antimicrobial pathways that differ dramatically from those activated by UPEC. Overall, this study emphasizes the unique nature of bladder immune activation mechanisms triggered by distinct uropathogens. PMID:22733575

Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

PubMed

Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

2017-10-26

To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

Obstetrical outcomes in patients with early onset gestational diabetes.

PubMed

Gupta, Simi; Dolin, Cara; Jadhav, Ashwin; Chervenak, Judith; Timor-Tritsch, Ilan; Monteagudo, Ana

2016-01-01

The objective of this study was to characterize patients with early onset gestational diabetes and compare outcomes to patients diagnosed with standard gestational diabetes and pregestational diabetes. This is a retrospective cohort study of patients diagnosed with gestational or pregestational diabetes. All patients received a glucose challenge test at their first prenatal visit to diagnose early onset gestational diabetes and were recommended to have postpartum glucose tolerance tests to detect undiagnosed type 2 diabetes. Outcomes were compared between patients with early onset gestational diabetes and both standard gestational diabetes and pregestational diabetes with p < 0.05 was used for significance. Four hundred and twenty-four patients met the inclusion criteria. Nine percent of the patients with early onset gestational diabetes were found to have undiagnosed type 2 diabetes based on postpartum testing and 91% to have resolution in the postpartum period. No patient with early onset gestational diabetes and resolution in the postpartum period had abnormal screening for renal or ophthalmologic disease, but 5% had abnormal fetal echocardiograms. These patients were more likely to require pharmacotherapy for glycemic control than patients with standard gestational diabetes and less likely than patients with pregestational diabetes (55% versus 39% versus 81%). Most patients diagnosed with early onset gestational diabetes do not have undiagnosed type 2 diabetes but do have unique characteristics and obstetrical outcomes.

Cognitive function in early HIV infection.

PubMed

Prakash, Aanchal; Hou, Jue; Liu, Lei; Gao, Yi; Kettering, Casey; Ragin, Ann B

2017-04-01

This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman's correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.

Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae*

PubMed Central

Rego, Sara; Heal, Timothy J.; Pidwill, Grace R.; Till, Marisa; Robson, Alice; Lamont, Richard J.; Sessions, Richard B.; Jenkinson, Howard F.; Race, Paul R.; Nobbs, Angela H.

2016-01-01

Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans. Complementary crystallographic and biophysical characterization of BspA reveal a novel β-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections. PMID:27311712

Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

PubMed

Black, Donald W; Shaw, Martha; Coryell, William; Crowe, Raymond; McCormick, Brett; Allen, Jeff

2015-07-01

Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Pregnancy-related group a streptococcal infections: temporal relationships between bacterial acquisition, infection onset, clinical findings, and outcome.

PubMed

Hamilton, Stephanie M; Stevens, Dennis L; Bryant, Amy E

2013-09-01

Puerperal sepsis caused by group A Streptococcus (GAS) remains an important cause of maternal and infant mortality worldwide, including countries with modern antibiotic regimens, intensive care measures and infection control practices. To provide insights into the genesis of modern GAS puerperal sepsis, we reviewed the published cases and case series from 1974 to 2009, specifically seeking relationships between the likely source of pathogen acquisition, clinical signs, and symptoms at infection onset and patient outcomes that could provide clues for early diagnosis. Results suggest that the pathogenesis of pregnancy-related GAS infections in modern times is complex and not simply the result of exposure to GAS in the hospital setting. Additional research is needed to further explore the source of GAS, the specific M types involved, and the pathogenesis of these pregnancy-related infections to generate novel preventative and therapeutic strategies.

Pregnancy-Related Group A Streptococcal Infections: Temporal Relationships Between Bacterial Acquisition, Infection Onset, Clinical Findings, and Outcome

PubMed Central

Hamilton, Stephanie M.; Stevens, Dennis L.; Bryant, Amy E.

2013-01-01

Puerperal sepsis caused by group A Streptococcus (GAS) remains an important cause of maternal and infant mortality worldwide, including countries with modern antibiotic regimens, intensive care measures and infection control practices. To provide insights into the genesis of modern GAS puerperal sepsis, we reviewed the published cases and case series from 1974 to 2009, specifically seeking relationships between the likely source of pathogen acquisition, clinical signs, and symptoms at infection onset and patient outcomes that could provide clues for early diagnosis. Results suggest that the pathogenesis of pregnancy-related GAS infections in modern times is complex and not simply the result of exposure to GAS in the hospital setting. Additional research is needed to further explore the source of GAS, the specific M types involved, and the pathogenesis of these pregnancy-related infections to generate novel preventative and therapeutic strategies. PMID:23645851

Unusual early-onset Huntingtons disease.

PubMed

Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

2003-06-01

Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

Group B streptococci causing neonatal infections in barcelona are a stable clonal population: 18-year surveillance.

PubMed

Martins, E R; Andreu, A; Correia, P; Juncosa, T; Bosch, J; Ramirez, M; Melo-Cristino, J

2011-08-01

We analyzed 212 group B streptococci (GBS) from newborns with invasive infections in the area of Barcelona, Spain, between 1992 and 2009, with the aim of documenting changes in the prevalences of serotypes, antimicrobial resistance, and genetic lineages and evaluating their associations with either early-onset disease (EOD) or late-onset disease (LOD). Serotypes III (n = 118) and Ia (n = 47) together accounted for nearly 78% of the isolates. All isolates carried an alpha or alpha-like protein gene, and specific associations between genes and serotypes, such as serotype Ib and bca, serotype II and bca, serotype III and rib, and serotype V and alp3, reflected the presence of particular genetic lineages. Macrolide resistance (14.2%) was significantly associated with serotype V. Pulsed-field gel electrophoresis (PFGE) clustering was an excellent predictor of serotype and antibiotic resistance. The combination of PFGE and multilocus sequence typing revealed a large number of genetically distinct lineages. Still, specific lineages were dominant in our collection, particularly the serotype III/ST17/rib lineage, which had enhanced potential to cause LOD. Serotype Ia was concentrated in a single PFGE cluster composed of two genetic lineages: ST23/eps and ST24/bca. The ST24/bca sublineage of serotype Ia, which is found infrequently elsewhere, may be emerging as an important cause of neonatal invasive infections in the Mediterranean region. In spite of the introduction of prophylaxis, resulting in a pronounced decline in the frequency of EOD, the study revealed a remarkably stable clonal structure of GBS causing neonatal infections in Barcelona over a period of 18 years.

Group B Streptococci Causing Neonatal Infections in Barcelona Are a Stable Clonal Population: 18-Year Surveillance▿

PubMed Central

Martins, E. R.; Andreu, A.; Correia, P.; Juncosa, T.; Bosch, J.; Ramirez, M.; Melo-Cristino, J.

2011-01-01

We analyzed 212 group B streptococci (GBS) from newborns with invasive infections in the area of Barcelona, Spain, between 1992 and 2009, with the aim of documenting changes in the prevalences of serotypes, antimicrobial resistance, and genetic lineages and evaluating their associations with either early-onset disease (EOD) or late-onset disease (LOD). Serotypes III (n = 118) and Ia (n = 47) together accounted for nearly 78% of the isolates. All isolates carried an alpha or alpha-like protein gene, and specific associations between genes and serotypes, such as serotype Ib and bca, serotype II and bca, serotype III and rib, and serotype V and alp3, reflected the presence of particular genetic lineages. Macrolide resistance (14.2%) was significantly associated with serotype V. Pulsed-field gel electrophoresis (PFGE) clustering was an excellent predictor of serotype and antibiotic resistance. The combination of PFGE and multilocus sequence typing revealed a large number of genetically distinct lineages. Still, specific lineages were dominant in our collection, particularly the serotype III/ST17/rib lineage, which had enhanced potential to cause LOD. Serotype Ia was concentrated in a single PFGE cluster composed of two genetic lineages: ST23/eps and ST24/bca. The ST24/bca sublineage of serotype Ia, which is found infrequently elsewhere, may be emerging as an important cause of neonatal invasive infections in the Mediterranean region. In spite of the introduction of prophylaxis, resulting in a pronounced decline in the frequency of EOD, the study revealed a remarkably stable clonal structure of GBS causing neonatal infections in Barcelona over a period of 18 years. PMID:21697333

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

PubMed

von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

2011-04-01

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

PubMed

Smeets-Janssen, M M J; Meesters, P D; Comijs, H C; Eikelenboom, P; Smit, J H; de Haan, L; Beekman, A T F; Stek, M L

2013-11-01

Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2)  = 0.2). These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted. Copyright © 2013 John Wiley & Sons, Ltd.

Genetic control of osmoadaptive glycine betaine synthesis in Bacillus subtilis through the choline-sensing and glycine betaine-responsive GbsR repressor.

PubMed

Nau-Wagner, Gabriele; Opper, Daniela; Rolbetzki, Anne; Boch, Jens; Kempf, Bettina; Hoffmann, Tamara; Bremer, Erhard

2012-05-01

Synthesis of the compatible solute glycine betaine confers a considerable degree of osmotic stress tolerance to Bacillus subtilis. This osmoprotectant is produced through the uptake of the precursor choline via the osmotically inducible OpuB and OpuC ABC transporters and a subsequent two-step oxidation process by the GbsB and GbsA enzymes. We characterized a regulatory protein, GbsR, controlling the transcription of both the structural genes for the glycine betaine biosynthetic enzymes (gbsAB) and those for the choline-specific OpuB transporter (opuB) but not of that for the promiscuous OpuC transporter. GbsR acts genetically as a repressor and functions as an intracellular choline sensor. Spectroscopic analysis of the purified GbsR protein showed that it binds the inducer choline with an apparent K(D) (equilibrium dissociation constant) of approximately 165 μM. Based on the X-ray structure of a protein (Mj223) from Methanococcus jannaschii, a homology model for GbsR was derived. Inspection of this GbsR in silico model revealed a possible ligand-binding pocket for choline resembling those of known choline-binding sites present in solute receptors of microbial ABC transporters, e.g., that of the OpuBC ligand-binding protein of the OpuB ABC transporter. GbsR was not only needed to control gbsAB and opuB expression in response to choline availability but also required to genetically tune down glycine betaine production once cellular adjustment to high osmolarity has been achieved. The GbsR regulatory protein from B. subtilis thus records and integrates cellular and environmental signals for both the onset and the repression of the synthesis of the osmoprotectant glycine betaine.

Global Broadcast Service (GBS)

DTIC Science & Technology

2013-12-01

as to be unusable by smaller and more mobile units. To this end, GBS currently uses broadcast payloads on two Ultra-High Frequency Follow-On ( UFO ...operational on UFO satellites 8, 9, 10. - Full Satellite Broadcast Manager capability. - Field 20% of JPO Receive Suites (19 units). - Personnel training...capabilities. - Augment UFO GBS with leased commercial satellite services to cover gaps over CONUS. - Demonstrate smart push and user pull capability

Comparing Characteristics of Early-Onset Injection Drug Users to Those With Late-Onset Injection in Kermanshah, Iran.

PubMed

Jorjoran Shushtari, Zahra; Noroozi, Alireza; Mirzazadeh, Ali; Ahounbar, Elahe; Hajbi, Ahmad; Najafi, Mohammad; Bazrafshan, Ali; Farhadi, Mohammad Hossin; Farhoudian, Ali; Higgs, Peter; Shahboulagh, Farahnaz Mohammadi; Waye, Katherine; Noroozi, Mehdi

2017-05-12

Characteristics and behaviors of early-onset injection drug users are under studied topics in Iran. This study aimed to identify and compare the demographic characteristics as well as the drug using behaviors of early-onset and late-onset injection drug users in Kermanshah, West Iran. In this cross-sectional study using snowball and convenience sampling, we recruited 450 people during the Fall of 2014 from two drop in centers in Kermanshah, Iran. We collected data through face-to-face interviews. Early-onset injection is defined as whether the person reported their first injection at 22 years of age or younger. Subsequently, late-onset injection is defined as 23 years of age or older. We compared the characteristics of the two groups through both univariate and multiple logistic analyses. Overall, 54% (CI 95%: 44.3%, 62.2%) were early injectors. After controlling for low socioeconomic status, initiation of drug use at a young age, multiple drug use and methamphetamine use were all significantly associated with a higher likelihood of early-onset injection. Additionally, early-onset injection was associated with recent syringe borrowing (OR = 2.6, p = 0.001), recent syringe lending (OR = 1.4, p = 0.01), recent cooker sharing (OR = 3.2, p = 0.01) and injecting two or more times a day (OR = 2.2, p = 0.04). Early-onset injectors were more likely to report a lower socioeconomic status, initiation of first drug use at a younger age, using methamphetamine alongside polydrug use, and engaging in higher risk taking behaviors like borrowing needles. With these associations, the study emphasizes the need for drug-prevention programs to focus on the transition to injection drug use at younger ages.

Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

PubMed

Devanand, D P; Adorno, Elizabeth; Cheng, Jocelyn; Burt, Tal; Pelton, G H Gregory H; Roose, S P Steven P; Sackeim, H A Harold A

2004-03-01

Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. Academic clinic sample results may not generalize to community populations. In the

Prevalence of GBS serotype III and identification of a ST 17-like genotype from neonates with invasive diseases in Guangzhou, China.

PubMed

Liu, Junyan; Xu, Ruiru; Zhong, Huamin; Zhong, Yukui; Xie, Yongqiang; Li, Lin; Li, Bing; Chen, Dingqiang; Xu, Zhenbo

2018-05-03

The aim of this study is to understand the surveillance of Streptococcus agalactiae (GBS) serotype and genotype which help developing specific vaccine for GBS infection. The GBS serotype was determined by strep-B-Latex rapid agglutination method and multiplex PCR assay based on the differences among serotypes. Alleles and multilocus sequence types (MLST) were determined using the GBS MLST Web site. Four GBS serotypes (Ia, Ib, III, and V) were identified, with serotype III which was intimately associated with purulent meningitis and sepsis, as the dominance. In EOD cases, sepsis and pneumonia showed dominance, but purulent meningitis was dominant in LOD cases. Also, a new ST-17 like type which might be a clone derive from ST-17 and emerge among neonatal disease cases was identified. The prevalence of GBS serotype and genotype and their relation with GBS diseases guide the development of capsular polysaccharide vaccine. Copyright © 2018. Published by Elsevier Ltd.

Guillain-Barre syndrome following specific viral infections--an appraisal.

PubMed

Murthy, J M

1994-01-01

Fifteen cases of Gullian-Barre syndrome (GBS) following specific infection are reported. The infections include varicella, 7 infective hepatitis, 4 measles, 2 and mumps, 2. There are no specific clinical or electrophysiological features which serve to distinguish GBS seen in association of these infections from those seen in other clinical settings. There is epidemiological evidence to suggest the association between GBS and hepatitis A, and non A non B hepatitis is more of a chance occurrence. Detailed epidemiological studies are needed to established a clear relationship between other specific viral infections and GBS.

Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

PubMed Central

Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ondoa, Pascale; Ceulemans, Ann; Vereecken, Chris; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

2015-01-01

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART. Methods Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies. Results CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028). Conclusion Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype. PMID:26208109

[Analysis of gene mutation of early onset epileptic spasm with unknown reason].

PubMed

Yang, X; Pan, G; Li, W H; Zhang, L M; Wu, B B; Wang, H J; Zhang, P; Zhou, S Z

2017-11-02

Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks

Blood-Based Biomarkers of Early-Onset Breast Cancer

DTIC Science & Technology

2015-10-01

n=51). The women with early-onset breast cancer were disease and treatment free for at least 6 months at time of blood donation . Cases and controls...were age matched to age at blood donation . 2. KEYWORDS: biomarkers, early-onset breast cancer, expression profiling, risk-assessment, breast cancer...matched controls. This prospectively collected cohort consists of blood donated to blood banks ~15 years ago and subsequently linked to the California

Genetic Control of Osmoadaptive Glycine Betaine Synthesis in Bacillus subtilis through the Choline-Sensing and Glycine Betaine-Responsive GbsR Repressor

PubMed Central

Nau-Wagner, Gabriele; Opper, Daniela; Rolbetzki, Anne; Boch, Jens; Kempf, Bettina; Hoffmann, Tamara

2012-01-01

Synthesis of the compatible solute glycine betaine confers a considerable degree of osmotic stress tolerance to Bacillus subtilis. This osmoprotectant is produced through the uptake of the precursor choline via the osmotically inducible OpuB and OpuC ABC transporters and a subsequent two-step oxidation process by the GbsB and GbsA enzymes. We characterized a regulatory protein, GbsR, controlling the transcription of both the structural genes for the glycine betaine biosynthetic enzymes (gbsAB) and those for the choline-specific OpuB transporter (opuB) but not of that for the promiscuous OpuC transporter. GbsR acts genetically as a repressor and functions as an intracellular choline sensor. Spectroscopic analysis of the purified GbsR protein showed that it binds the inducer choline with an apparent KD (equilibrium dissociation constant) of approximately 165 μM. Based on the X-ray structure of a protein (Mj223) from Methanococcus jannaschii, a homology model for GbsR was derived. Inspection of this GbsR in silico model revealed a possible ligand-binding pocket for choline resembling those of known choline-binding sites present in solute receptors of microbial ABC transporters, e.g., that of the OpuBC ligand-binding protein of the OpuB ABC transporter. GbsR was not only needed to control gbsAB and opuB expression in response to choline availability but also required to genetically tune down glycine betaine production once cellular adjustment to high osmolarity has been achieved. The GbsR regulatory protein from B. subtilis thus records and integrates cellular and environmental signals for both the onset and the repression of the synthesis of the osmoprotectant glycine betaine. PMID:22408163

Barriers to implementing the NICE guidelines for early-onset neonatal infection: cross-sectional survey of neonatal blood culture reporting by laboratories in the UK.

PubMed

Paul, S P; Caplan, E M; Morgan, H A; Turner, P C

2018-04-01

The National Institute for Health and Care Excellence published guidelines for managing early-onset neonatal infections in 2012. It recommended provision for reporting blood cultures (BCs) with growth detected or not detected at 36 h. To determine if this was followed, a telephone survey was conducted amongst lead biomedical scientists based at microbiology laboratories (N = 209) in the UK. Overall, 202/209 responded and 139/202 had on-site facilities for BCs. BC results with growth detected or not detected at 36 h were available out-of-hours in 36/139 (26.6%) and 66/139 (47.5%) neonatal units, respectively. Early discontinuation of antibiotics should lead to improved antibiotic stewardship. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

[Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

PubMed

Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

2016-07-01

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

Early childhood predictors of early onset of smoking: a birth prospective study.

PubMed

Hayatbakhsh, Reza; Mamun, Abdullah A; Williams, Gail M; O'Callaghan, Michael J; Najman, Jake M

2013-10-01

Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes. This study aimed to examine early life predictors of onset of smoking in an Australian young cohort. Data were from the Mater Hospital and University of Queensland Study of Pregnancy (MUSP), a population-based prospective birth cohort study (1981-2012). The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up. Of these, data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study. Of 3714 young adults, 49.6% (49.9% males and 49.3% females) reported having ever smoked cigarettes. For those who had ever smoked, mean and median ages at first smoke were 15.5 and 16.0years, respectively. In multivariate Cox proportional hazard analysis mother's education, change in maternal marital status, maternal cigarette smoking and alcohol consumption, maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking. The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age. Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

Saccharomyces boulardii for the prevention of hospital onset Clostridium difficile infection.

PubMed

Flatley, Elizabeth A; Wilde, Ashley M; Nailor, Michael D

2015-03-01

Probiotics, including Saccharomyces boulardii, have been advocated for the prevention of Clostridium difficile infection. The aim of this project was to evaluate the effects of the removal of S. boulardii from an automatic antibiotic order set and hospital formulary on hospital onset C. difficile infection rates. A retrospective chart review was performed on all patients with hospital onset C. difficile infection during the 13 months prior (control group) and the 13 months after (study group) removal of an automatic order set linking S. boulardii capsules to certain broad spectrum antibiotics. A large 800+ bed tertiary hospital. Among all hospitalized patients, the rate of hospital onset C. difficile infection was 0.99 per 1000 patient days while the S. boulardii protocol was active compared with 1.04 per 1000 patient days (p=0.10) after S. boulardii was removed from the formulary. No difference in the rate of hospital onset C. difficile infection was detected in patients receiving the linked broad spectrum antibiotics during and after the removal of the protocol (1.25% vs. 1.51%, respectively; p=0.70). Removal of S. boulardii administration to patients receiving broad spectrum antibiotics and the hospital formulary did not impact the rate of hospital onset C. difficile infection in either the hospital population or patients receiving broad spectrum antibiotics.

Implementation of a cost-effective strategy to prevent neonatal early-onset group B haemolytic streptococcus disease in the Netherlands.

PubMed

Kolkman, Diny G E; Rijnders, Marlies E B; Wouters, Maurice G A J; van den Akker-van Marle, M Elske; van der Ploeg, Cpb Kitty; de Groot, Christianne J M; Fleuren, Margot A H

2013-07-30

Early-onset Group B haemolytic streptococcus infection (EOGBS) is an important cause of neonatal morbidity and mortality in the first week of life. Primary prevention of EOGBS is possible with intra-partum antibiotic prophylaxis (IAP.) Different prevention strategies are used internationally based on identifying pregnant women at risk, either by screening for GBS colonisation and/or by identifying risk factors for EOGBS in pregnancy or labour. A theoretical cost-effectiveness study has shown that a strategy with IAP based on five risk factors (risk-based strategy) or based on a positive screening test in combination with one or more risk factors (combination strategy) was the most cost-effective approach in the Netherlands. IAP for all pregnant women with a positive culture in pregnancy (screening strategy) and treatment in line with the current Dutch guideline (IAP after establishing a positive culture in case of pre-labour rupture of membranes or preterm birth and immediate IAP in case of intra-partum fever, previous sibling with EOGBS or GBS bacteriuria), were not cost-effective. Cost-effectiveness was based on the assumption of 100% adherence to each strategy. However, adherence in daily practice will be lower and therefore have an effect on cost-effectiveness. The aims are to: a.) implement the current Dutch guideline, the risk-based strategy and the combination strategy in three pilot regions and b.) study the effects of these strategies in daily practice. Regions where all the care providers in maternity care implement the allocated strategy will be randomised. Before the introduction of the strategy, there will be a pre-test (use of the current guideline) involving 105 pregnant women per region. This will be followed by a post-test (use of the allocated strategy) involving 315 women per region. The outcome measures are: 1.) adherence to the specific prevention strategy and the determinants of adherence among care providers and pregnant women, 2.) outcomes

Intraspinal anomalies in early-onset idiopathic scoliosis.

PubMed

Pereira, E A C; Oxenham, M; Lam, K S

2017-06-01

In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

Genetics Home Reference: early-onset glaucoma

MedlinePlus

... called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma. Other individuals experience early onset of primary open-angle glaucoma, the most ...

The Prevention of Early-Onset Neonatal Group B Streptococcal Disease.

PubMed

Money, Deborah; Allen, Victoria M

2016-12-01

To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal disease. The key revisions in this updated guideline include changed recommendations for regimens for antibiotic prophylaxis, susceptibility testing, and management of women with pre-labour rupture of membranes. Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use. Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated. Published literature was retrieved through searches of MEDLINE, CINAHL, and The Cochrane Library from January 1980 to July 2012 using appropriate controlled vocabulary and key words (group B streptococcus, antibiotic therapy, infection, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). The recommendations in this guideline are designed to help clinicians identify and manage pregnancies at risk for neonatal group B streptococcal disease to optimize maternal and perinatal outcomes. No cost-benefit analysis is provided. There is good evidence based on randomized control trial data that in women with pre-labour rupture of membranes at term who are colonized with group B streptococcus, rates of neonatal infection are

Early onset obsessive-compulsive disorder with and without tics.

PubMed

de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

2009-07-01

Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

PubMed

Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

2010-08-01

The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Early Onset Obesity and Risk of Metabolic Syndrome Among Chilean Adolescents

PubMed Central

Pacheco, Lorena Sonia; Blanco, Estela; Burrows, Raquel; Reyes, Marcela; Lozoff, Betsy

2017-01-01

Introduction Obesity and metabolic syndrome (MetS) indicators have increased globally among the pediatric population. MetS indicators in the young elevate their risk of cardiovascular disease and metabolic disorders later in life. This study examined early onset obesity as a risk factor for MetS risk in adolescence. Methods A cohort of Chilean participants (N = 673) followed from infancy was assessed at age 5 years and in adolescence (mean age, 16.8 y). Adiposity was measured at both time points; blood pressure and fasting blood samples were assessed in adolescence only. Early onset obesity was defined as a World Health Organization z score of 2 standard deviations (SDs) or more for body mass index (BMI) at age 5 years. We used linear regression to examine the association between early onset obesity and adolescent MetS risk z score, adjusting for covariates. Results Eighteen percent of participants had early onset obesity, and 50% of these remained obese in adolescence. Mean MetS risk z score in adolescence was significantly higher among those with early onset obesity than among those without (1.0; SD, 0.8 vs 0.2; SD, 0.8 [P < .001]). In the multivariable model, early onset obesity independently contributed to a higher MetS risk score in adolescence (β = 0.27, P < .001), controlling for obesity status at adolescence and sex, and explained 39% of the variance in MetS risk. Conclusion Early onset obesity as young as age 5 years relates to higher MetS risk. PMID:29023232

Acute-onset chronic inflammatory demyelinating polyneuropathy: An electrodiagnostic study.

PubMed

Anadani, Mohammad; Katirji, Bashar

2015-11-01

Acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is an increasingly recognized CIDP subtype. Differentiating A-CIDP from Guillain-Barré syndrome (GBS) is challenging but important, because there are different treatment outcomes. We report 3 patients with A-CIDP who were initially diagnosed with severe GBS but were later confirmed to have CIDP based on their clinical course and electrodiagnostic (EDx) studies. We also report on the long-term treatment of these patients and review the literature on EDx studies in this syndrome. Three patients were initially diagnosed with GBS and responded to treatment. However, all 3 had arrest in improvement or deterioration during their rehabilitation phases. EDx studies showed prominent demyelinating changes many months after the initial presentation. All responded very well to immunotherapy. Although several features may suggest the diagnosis of A-CIDP at initial presentation, close follow-up of GBS patients during the recovery phase is also needed for accurate diagnosis. EDx studies may distinguish patients with A-CIDP from GBS patients. © 2015 Wiley Periodicals, Inc.

Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.

PubMed

Nicolini, Humberto; López, Yaumara; Genis-Mendoza, Alma D; Manrique, Viana; Lopez-Canovas, Lilia; Niubo, Esperanza; Hernández, Lázaro; Bobes, María A; Riverón, Ana M; López-Casamichana, Mavil; Flores, Julio; Lanzagorta, Nuria; De la Fuente-Sandoval, Camilo; Santana, Daniel

2015-01-01

Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

Early Onset Recurrent Subtype of Adolescent Depression: Clinical and Psychosocial Correlates

ERIC Educational Resources Information Center

Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Herr, Nathaniel R.

2008-01-01

Background: Evaluated trajectories of adolescent depression and their correlates in a longitudinal study of a community sample: early onset (by age 15) with major depression (MDE) recurrence between 15 and 20; early onset with no recurrence; later onset of major depression after age 15 with and without recurrence by 20; and never-depressed.…

Early onset marijuana use is associated with learning inefficiencies.

PubMed

Schuster, Randi Melissa; Hoeppner, Susanne S; Evins, A Eden; Gilman, Jodi M

2016-05-01

Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Forty-eight young adults, aged 18-25, who used marijuana at least once per week and 48 matched nonusing controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: early onset users (EMJ), who started using marijuana at or before age 16 (n = 27), and late onset marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

ClinicalTrials.gov

2017-05-11

Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

Early intervention for late-onset ornithine transcarbamylase deficiency.

PubMed

Fujisawa, Daisuke; Mitsubuchi, Hiroshi; Matsumoto, Shirou; Iwai, Masanori; Nakamura, Kimitoshi; Hoshide, Ryuji; Harada, Nawomi; Yoshino, Makoto; Endo, Fumio

2015-01-01

We report the case of a family with late-onset ornithine transcarbamylase deficiency (OTCD). Several family members had died from OTCD, and the c.221G>A, p.Lys221Lys mutation was detected at the 3' end of exon 6 of OTC in the X-chromosome of some members. We provided genetic counseling on pregnancy, delivery, and neonate management to a 4th-generation female carrier and decided on metabolic management of her child from birth. Two male patients were diagnosed with late-onset OTCD on the basis of blood amino acid and genetic analysis, and they received arginine supplementation from the asymptomatic, early neonatal period. These children grew and developed normally, without decompensation. Patients with late-onset OTCD can and should be diagnosed and treated in the early neonatal period, especially those from families already diagnosed with late-onset OTCD, and family members must be provided with genetic counseling. © 2015 Japan Pediatric Society.

Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

PubMed Central

Arango, Celso

2014-01-01

Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis.

PubMed

Shane, Andi L; Stoll, Barbara J

2013-02-01

Identifying neonates with sepsis is complicated by variability in clinical presentation. The incidence of early onset sepsis (EOS) resulting from invasive group B streptococcal (GBS) infections has been notably reduced by the widespread delivery of intrapartum antibiotic prophylaxis. Rates of EOS attributable to non-GBS etiologies have remained constant, and ampicillin-resistant Escherichia coli has become more prevalent. Late-onset sepsis (LOS) attributable to gram-positive organisms including coagulase-negative Staphylococci and Staphylococcus aureus is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of LOS, especially among infants who receive broad-spectrum antimicrobial agents. Prophylactic fluconazole administration to very low-birth-weight (VLBW) neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections. Targeted fluconazole prophylaxis may be beneficial in VLBW neonates who receive care in NICUs with lower rates of invasive fungal infections. Assessment of immune function, neutrophil markers, acute phase reactants, and utilization of sepsis screening scores may contribute to the management of sepsis. Maternal decolonization, antimicrobial stewardship, early enteral feeding, and optimal infection control practices are potential practical strategies for reducing the burden of neonatal sepsis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Staphylococcus aureus infections in Australasian neonatal nurseries.

PubMed

Isaacs, D; Fraser, S; Hogg, G; Li, H Y

2004-07-01

To study the incidence and outcome of systemic infections with methicillin sensitive (MSSA) and methicillin resistant Staphylococcus aureus (MRSA) infections in Australasian neonatal nurseries. Prospective longitudinal study of systemic infections (clinical sepsis plus positive cultures of blood and/or cerebrospinal fluid) in 17 Australasian neonatal nurseries. The incidence of early onset sepsis with S aureus, mainly MSSA, was 19 cases per 244 718 live births or 0.08 per 1000. From 1992 to 1994, MRSA infections caused only 8% of staphylococcal infections. From 1995 to 1998, there was an outbreak of MRSA infection, in two Melbourne hospitals. The outbreak resolved, after the use of topical mupirocin and improved handwashing. Babies with MRSA sepsis were significantly smaller than babies with MSSA sepsis (mean birth weight 1093 v 1617 g) and more preterm (mean gestation 27.5 v 30.3 weeks). The mortality of MRSA sepsis was 24.6% compared with 9.9% for MSSA infections. The mortality of early onset MSSA sepsis, however, was 39% (seven of 18) compared with 7.3% of late onset MSSA infection presenting more than two days after birth. S aureus is a rare but important cause of early onset sepsis. Late onset MRSA infections carried a higher mortality than late onset MSSA infections, but babies with early onset MSSA sepsis had a particularly high mortality.

Anti-Group B Streptococcus Glycan-Conjugate Vaccines Using Pilus Protein GBS80 As Carrier and Antigen: Comparing Lysine and Tyrosine-directed Conjugation.

PubMed

Nilo, Alberto; Morelli, Laura; Passalacqua, Irene; Brogioni, Barbara; Allan, Martin; Carboni, Filippo; Pezzicoli, Alfredo; Zerbini, Francesca; Maione, Domenico; Fabbrini, Monica; Romano, Maria Rosaria; Hu, Qi-Ying; Margarit, Immaculada; Berti, Francesco; Adamo, Roberto

2015-07-17

Gram-positive Streptococcus agalactiae or group B Streptococcus (GBS) is a leading cause of invasive infections in pregnant women, newborns, and elderly people. Vaccination of pregnant women represents the best strategy for prevention of neonatal disease, and GBS polysaccharide-based conjugate vaccines are currently under clinical testing. The potential of GBS pilus proteins selected by genome-based reverse vaccinology as protective antigens for anti-streptococcal vaccines has also been demonstrated. Dressing pilus proteins with surface glycan antigens could be an attractive approach to extend vaccine coverage. We have recently developed an efficient method for tyrosine-directed ligation of large glycans to proteins via copper-free azide-alkyne [3 + 2] cycloaddition. This method enables targeting of predetermined sites of the protein, ensuring that protein epitopes are preserved prior to glycan coupling and a higher consistency in glycoconjugate batches. Herein, we compared conjugates of the GBS type II polysaccharide (PSII) and the GBS80 pilus protein obtained by classic lysine random conjugation and by the recently developed tyrosine-directed ligation. PSII conjugated to CRM197, a carrier protein used for vaccines in the market, was used as a control. We found that the constructs made from PSII and GBS80 were able to elicit murine antibodies recognizing individually the glycan and protein epitopes on the bacterial surface. The generated antibodies were efficacious in mediating opsonophagocytic killing of strains expressing exclusively PSII or GBS80 proteins. The two glycoconjugates were also effective in protecting newborn mice against GBS infection following vaccination of the dams. Altogether, these results demonstrated that polysaccharide-conjugated GBS80 pilus protein functions as a carrier comparably to CRM197, while maintaining its properties of protective protein antigen. Glycoconjugation and reverse vaccinology can, therefore, be combined to design

Differentiating early-onset persistent versus childhood-limited conduct problem youth.

PubMed

Barker, Edward D; Maughan, Barbara

2009-08-01

Among young children who demonstrate high levels of conduct problems, less than 50% will continue to exhibit these problems into adolescence. Such developmental heterogeneity presents a serious challenge for intervention and diagnostic screening in early childhood. The purpose of the present study was to inform diagnostic screening and preventive intervention efforts by identifying youths whose conduct problems persist. The authors examined 1) the extent to which early-onset persistent versus childhood-limited trajectories can be identified from repeated assessments of childhood and early-adolescent conduct problems and 2) how prenatal and early postnatal risks differentiate these two groups. To identify heterogeneity in early-onset conduct problems, the authors used data from a large longitudinal population-based cohort of children followed from the prenatal period to age 13. Predictive risk factors examined were prenatal and postnatal measures of maternal distress (anxiety, depression), emotional and practical support, and family and child characteristics (from birth to 4 years of age). Findings revealed a distinction between early-onset persistent versus childhood-limited conduct problems in youths. Robust predictors of the early-onset persistent trajectory were maternal anxiety during pregnancy (32 weeks gestation), partner cruelty to the mother (from age 0 to 4 years), harsh parenting, and higher levels of child undercontrolled temperament. Sex differences in these risks were not identified. Interventions aiming to reduce childhood conduct problems should address prenatal risks in mothers and early postnatal risks in both mothers and their young children.

Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

PubMed Central

Vyas, Nora S.; Gogtay, Nitin

2012-01-01

Early onset schizophrenia (onset before adulthood) is a rare, severe, and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment-refractory cases. Based on the current literature, second-generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies. PMID:22485097

Trans-shell infection by pathogenic micro-organisms reduces the shelf life of non-incubated bird's eggs: a constraint on the onset of incubation?

PubMed

Cook, Mark I; Beissinger, Steven R; Toranzos, Gary A; Rodriguez, Roberto A; Arendt, Wayne J

2003-11-07

Many birds initiate incubation before clutch completion, which results in asynchronous hatching. The ensuing within-brood size disparity often places later-hatched nestlings at a developmental disadvantage, but the functional significance of the timing of the onset of incubation is poorly understood. Early incubation may serve to maintain the viability of early-laid eggs, which declines over time owing to the putative effects of ambient temperature. An unexplored risk to egg viability is trans-shell infection by micro-organisms. We experimentally investigated the rate and magnitude of microbial trans-shell infection of the egg, and the relative effects of ambient temperature and micro-organisms on hatching success. We show that infection of egg contents is prevalent and occurs within the time required to lay a clutch. The probability of infection depends on the climatic conditions, the exposure period and the phylogenetic composition of the eggshell microbiota. We also demonstrate that microbial infection and ambient temperature act independently to reduce egg viability considerably. Our results suggest that these two factors could affect the onset of avian incubation in a wide range of environments.

[Genital bacterial carriage during the last trimester of pregnancy and early-onset neonatal sepsis].

PubMed

Balaka, B; Agbèrè, A; Dagnra, A; Baeta, S; Kessie, K; Assimadi, K

2005-05-01

Bacterial infections remain a major cause of morbidity and mortality in newborn infants. To determine the bacterial ecology and pathological status of the genital organs during the last trimester of pregnancy and the germs of the following early-onset neonatal sepsis, in order to evaluate the risk of materno-foetal infections and to find out a drug prophylaxis. Vaginal and endocervical samples, usually taken during the first trimester of pregnancy were delayed and taken during the last trimester of pregnancy. A macroscopic examination described the aspect of the vagina, the cervix uteri, leukorrhea and of possible inflammatory lesions or ulcerations. A microscopic examination searched for parasites, epithelial cells, clue cells and leukocytes. The appropriate bacteriological cultures were performed after reading the Gram stain and scoring the vaginal flora. The clinical and cytobacteriological aspects were used to identify the bacterial ecology and the pathological genital states. An exploration was carried out in every newborn suspected of infection. Genital samples were collected from 306 pregnant women. Among them, 118 were at 29-32 weeks of gestation, 104 at 33-36, and 84 at 37-40. The most frequent germs were C. albicans (33,5%), Enterbacteriaceae (20.3%) including E. coli (10.9%), S. aureus (15.4%), Gardnerella (13.6%), and Trichomonas (10.6%), in monomicrobian (79.2%) and polymicrobian carriage (20.8%). Lower genital tract pathological states such as vaginitis (29.4%), bacterial vaginosis (21.5%) or endocervicitis (10.4%), asymptomatic bacterial carriage (23.5%) and normal genital flora (15%) were identified. These pregnancies led to 334 live births with 27 cases of early-onset neonatal sepsis to which endocervicitis (25%) and vaginosis (19,7%) were most often linked. Genital samples at the last trimester of pregnancy could evaluate the risk of maternofoetal infections and allow to adapt a drug prophylaxis of Enterobacteriaceae, the most frequent germ of

[Mutations of amyloid precursor protein in early-onset familial Alzheimer's disease].

PubMed

Naruse, S; Tsuji, S; Miyatake, T

1992-09-01

Genetic linkage studies of familial Alzheimer's disease (FAD) have suggested that some form of early-onset FAD is linked to proximal long arm of chromosome 21. It has been also suggested that some form of late-onset FAD is linked to long arm of chromosome 19. Goate et al have identified a mis-sense mutation (Val to Ile) in exon 17 of the amyloid precursor protein (APP) gene in 2 of 16 early-onset FAD families, and have shown that the FAD locus in an FAD family is tightly linked to the mis-sense mutation. To determine if the mis-sense mutation is observed in different ethnic origine, we have studied some early-onset FAD families. Two early-onset FAD families showed the existence of the mutation. As the mutation has been identified in different ethnic origine and the mutation has not been observed in normal individuals, it strengthen hypothesis that the mutation is pathogenic. Recently, Val to Phe and Val to Gly mutations have been also identified at the same codon (Codon 717) of the APP gene.

Genetic Determinism of Primary Early-Onset Osteoarthritis.

PubMed

Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

2016-01-01

Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Co-Occurring Problems of Early Onset Persistent, Childhood Limited, and Adolescent Onset Conduct Problem Youth

ERIC Educational Resources Information Center

Barker, Edward D.; Oliver, Bonamy R.; Maughan, Barbara

2010-01-01

Background: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems…

[Cord blood procalcitonin in the assessment of early-onset neonatal sepsis].

PubMed

Oria de Rueda Salguero, Olivia; Beceiro Mosquera, José; Barrionuevo González, Marta; Ripalda Crespo, María Jesús; Olivas López de Soria, Cristina

2017-08-01

Early diagnosis of early-onset neonatal sepsis (EONS) is essential to reduce morbidity and mortality. Procalcitonin (PCT) in cord blood could provide a diagnosis of infected patients from birth. To study the usefulness and safety of a procedure for the evaluation of newborns at risk of EONS, based on the determination of PCT in cord blood. Neonates with infectious risk factors, born in our hospital from October 2013 to January 2015 were included. They were processed according to an algorithm based on the values of cord blood procalcitonin (< 0.6ng/ml versus ≥0.6ng/ml). They were later classified as proved infection, probable, or no infection. Of the 2,519 infants born in the study period, 136 met inclusion criteria. None of 120 cases with PCT<0.6ng/ml in cord blood developed EONS (100% negative predictive value). On the other hand, of the 16 cases with PCT ≥0.6ng/ml, 10 were proven or probably infected (62.5% positive predictive value). The sensitivity of the PCT against infection was 100%, with a specificity of 95.2% (area under the receiver operator curve 0.969). The incidence of infection in the study group was 7.4%, and 26.1% in cases with maternal chorioamnionitis. 21 newborn (15.4%) received antibiotic therapy. The studied protocol has shown to be effective and safe to differentiate between patients with increased risk of developing an EONS, in those where the diagnostic and therapeutic approach was more interventionist, versus those with less likelihood of sepsis, who would benefit from a more conservative management. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

PubMed

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Diagnosis and prognosis of early-onset intrahepatic cholestasis of pregnancy: a prospective study.

PubMed

Lin, Jing; Gu, Wei; Hou, Yanyan

2017-11-07

To explore the gestational age of early-onset intrahepatic cholestasis (ICP) of pregnancy, and to analyze the relationship between the clinical biochemical indices and pregnancy outcomes in order to arrive at a reasonable diagnosis and administer appropriate treatment. This is a retrospective clinical study. We selected 47,260 pregnant women who received prenatal care and underwent childbirth at the International Peace Maternity and Child Health Hospital affiliated to Shanghai Jiao Tong University from January 2014 to December 2016 for participating in this study. Of these 47,260 women, 407 developed ICP. To calculate the gestational week cutoff between early- and late-onset ICP by the receiver-operating characteristic (ROC) curve and Youden's index. Two independent samples t tests and chi square test were used to compare the differences in biochemical indices and pregnancy outcomes between the two groups. We found that 34 weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. Early-onset ICP is characterized by early onset, long disease duration and a higher incidence of preterm labor, fetal distress, and fetal low birth weight compared to late-onset ICP. Thirty-four weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. And to reduce the adverse pregnancy outcomes in cases of early-onset ICP, we suggest prolonging gestation up to 37 weeks as far as possible before selecting iatrogenic birth.

Delayed-onset endophthalmitis associated with corneal suture infections.

PubMed

Henry, Christopher R; Flynn, Harry W; Miller, Darlene; Schefler, Amy C; Forster, Richard K; Alfonso, Eduardo C

2013-06-11

The purpose of the current study was to report the microbiology, risk factors, and treatment outcomes in patients with delayed-onset endophthalmitis associated with corneal suture infections. For this retrospective consecutive case series, a search of the ocular microbiology department database was performed to identify all patients with positive corneal and intraocular cultures (anterior chamber and/or vitreous) between 01 January 1995 and 01 January 2010. A subset of patients with a history of corneal suture infections and delayed-onset endophthalmitis was identified. Over the 15-year period of the study, 68 patients were identified to have both positive corneal and intraocular cultures. Among them, six patients were identified to have a culture-proven, delayed-onset endophthalmitis that developed from a culture-positive corneal suture infection. All of the patients in the current study were using topical corticosteroids at the time of diagnosis. In four of six patients, there was documented manipulation of a suture before the development of endophthalmitis. Streptoccocus was identified as the causative organism in five of six patients in the current study. All of the Streptoccocus isolates were sensitive to vancomycin. The single case of Serratia marcescens endophthalmitis was sensitive to amikacin, ceftazidime, ciprofloxacin, gentamicin, and tobramycin. Treatment modalities varied and were guided by the attending ophthalmologist depending upon clinical presentation. One patient with severe Streptococcus pyogenes keratitis and endophthalmitis underwent a primary enucleation after developing a wound dehiscence. Of the remaining five patients, all received topical and intravitreal antibiotics. Therapeutic penetrating keratoplasty was performed in three patients. Pars plana vitrectomy was performed in two patients. Visual acuity outcomes ranged from 20/150 to no light perception. In the current study, Streptococcus was isolated in nearly all patients with delayed-onset

Specific Intellectual Deficits in Children with Early Onset Diabetes Mellitus.

ERIC Educational Resources Information Center

Rovet, Joanne F.; And Others

1988-01-01

Compares 27 children with early onset diabetes (EOD) with 24 children with late onset diabetes (LOD) and 30 sibling controls in performance on tests of intellectual functioning and school achievement. Results revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. (Author/RWB)

Removal of Group B Streptococci Colonizing the Vagina and Oropharynx of Mice with a Bacteriophage Lytic Enzyme

PubMed Central

Cheng, Qi; Nelson, Daniel; Zhu, Shiwei; Fischetti, Vincent A.

2005-01-01

Group B streptococci (GBS) are the leading cause of neonatal meningitis and sepsis worldwide. The current treatment strategy is limited to intrapartum antibiotic prophylaxis in pregnant women to prevent early-onset neonatal diseases, but considering the potential for antibiotic resistance, the risk of losing control over the disease is high. To approach this problem, we have developed a bacteriophage (phage) lytic enzyme to remove colonizing GBS. Bacteriophage muralytic enzymes, termed lysins, are highly evolved molecules designed to degrade the cell wall of host bacteria to release phage particles from the bacterial cytoplasm. Several different lysins have been developed to specifically kill bacterial pathogens both on mucosal surfaces and in blood and represent a novel approach to control infection. A lysin cloned from a phage infecting GBS was found to contain two putative catalytic domains and one putative binding domain, which is similar to the domain organization of some staphylococcal phage lysins. The lysin (named PlyGBS) was recombinantly expressed in Escherichia coli, and purified PlyGBS efficiently killed all tested GBS serotypes in vitro. In a mouse model, a single dose of PlyGBS significantly reduced bacterial colonization in both the vagina and oropharynx. As an alternative strategy for intrapartum antibiotic prophylaxis, this approach may be used to reduce vaginal GBS colonization in pregnant women before delivery or to decontaminate newborns, thus reducing the incidence of GBS-associated neonatal meningitis and sepsis. PMID:15616283

A model for early onset of protection against lethal challenge with highly pathogenic H5N1 influenza virus.

PubMed

Röhrs, Susanne; Kalthoff, Donata; Beer, Martin

2014-05-07

Highly pathogenic avian influenza viruses of subtype H5N1 sporadically cause severe disease in humans and involve the risk of inducing a pandemic by gaining the ability for human-to-human transmission. In naïve poultry, primarily gallinaceous birds, the virus induces fatal disease and the used inactivated vaccines occasionally are unable to provide efficient and early onset of protection. Therefore, optimized vaccines must be developed and evaluated in model systems. In our study, we tested a novel H5 neuraminidase-deleted influenza A virus variant to analyze the induction of a very early onset of immunity. Ferrets, mice and chickens were each immunized with a single vaccine dose seven, three and one day before lethal challenge infection, respectively. Sound protection was conferred in 100% of animals immunized seven days prior to challenge infection. In these animals, no clinical signs were observed, and no challenge virus RNA was detected by real-time RT-PCR analyses of swabs, nasal washings, and organ samples. Moreover, the attenuated modified-live virus variant protected all chickens, mice, and ferrets as early as three days after vaccination against severe clinical signs. Chickens and ferrets developed hemagglutinin-specific antibodies after seven days, but no neuraminidase-specific antibodies, making this kind of neuraminidase-negative strain suitable for the DIVA ("differentiating vaccinated from infected animals") strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

PubMed

Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

2017-07-01

This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p < 0.05). The rate of secondary hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p < 0.05). Obesity, waist circumference, and SHBG were significantly associated with serum total testosterone level in all, early-onset, and late-onset T2DM. Both all and early-onset T2DM groups had positive correlations between total testosterone and fasting C-peptide, total cholesterol, triglycerides, and uric acid. Our results indicate that in a population of admission to a large urban hospital in China, the prevalence of hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

PubMed

Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

2014-08-01

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

Whole Exome Analysis of Early Onset Alzheimer’s Disease

DTIC Science & Technology

2015-04-01

autosomal recessive early-onset Parkinson’s disease and juvenile Parkinson disease , Parkin has been shown to promote intracellular Abeta1–42 clearance [15... Parkinsonism . Conclusions Mutations were found in 6/50 families. The presence of an APOE-4 allele may account for disease status in one affected non...AD_________________ Award Number: W81XWH-12-1-0013 TITLE: Whole Exome Analysis of Early Onset Alzheimer’s Disease PRINCIPAL INVESTIGATOR

Are early-onset cannabis smokers at an increased risk of depression spells?

PubMed

Fairman, Brian J; Anthony, James C

2012-04-01

A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005-2009 (74-76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR=1.7 and 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk. Copyright © 2011

Are early-onset cannabis smokers at an increased risk of depression spells?

PubMed Central

Fairman, Brian J.; Anthony, James C.

2012-01-01

Background A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). Methods The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005–2009 (74–76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. Results About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR = 1.7 & 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Limitations Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Conclusion Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to

Key goals and indicators for successful aging of adults with early-onset disability.

PubMed

LaPlante, Mitchell P

2014-01-01

Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and independence. However, indicators suggest that elevated risk factors for aging-related chronic diseases, including smoking, obesity, and inactivity, as well as barriers to prevention and the diminished social and economic situation of adults with disabilities are continuing impediments to successful aging that must be addressed. Increased provider awareness that people with early-onset disabilities are aging and can age successfully and the integration of disability and aging services systems are transformative steps that will help adults with early-onset disability to age more successfully. Copyright © 2014 Elsevier Inc. All rights reserved.

Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.

PubMed

Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapaporn; Sriussadaporn, Sutin; Vannaseang, Sathit; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

2009-06-01

Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes. Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations. We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands. Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.

Trans-shell infection by pathogenic micro-organisms reduces the shelf life of non-incubated bird's eggs: a constraint on the onset of incubation?

PubMed Central

Cook, Mark I; Beissinger, Steven R; Toranzos, Gary A; Rodriguez, Roberto A; Arendt, Wayne J

2003-01-01

Many birds initiate incubation before clutch completion, which results in asynchronous hatching. The ensuing within-brood size disparity often places later-hatched nestlings at a developmental disadvantage, but the functional significance of the timing of the onset of incubation is poorly understood. Early incubation may serve to maintain the viability of early-laid eggs, which declines over time owing to the putative effects of ambient temperature. An unexplored risk to egg viability is trans-shell infection by micro-organisms. We experimentally investigated the rate and magnitude of microbial trans-shell infection of the egg, and the relative effects of ambient temperature and micro-organisms on hatching success. We show that infection of egg contents is prevalent and occurs within the time required to lay a clutch. The probability of infection depends on the climatic conditions, the exposure period and the phylogenetic composition of the eggshell microbiota. We also demonstrate that microbial infection and ambient temperature act independently to reduce egg viability considerably. Our results suggest that these two factors could affect the onset of avian incubation in a wide range of environments. PMID:14613609

[Clinical characteristics and renal uric acid excretion in early-onset gout patients].

PubMed

Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

2018-03-01

Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), P< 0.05], significantly higher serum UA level [(634±124)μmol/L vs.(527±169)μmol/L] and glomerular load of UA[(7.2±2.8)mg·min(-1)·1.73m(-2) vs. (4.4±2.2)mg·min(-1)·1.73m(-2)] and estimated glomerular filtration rate (GFR) [(83±21)ml·min(-1)·1.73m(-2) vs. (67±21)ml·min(-1)·1.73m(-2)] (all P< 0.05), lower fractional excretion of UA [4.4% (3.4%,6.1%) vs. 7.2% (5.2%,9.6%), P< 0.05], whereas 24h urinary UA excretion was comparable [(2 788±882)μmol/1.73m(2) vs. (2 645±1 140)μmol/1.73m(2), P= 0.274]. Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5%(3.3%,6.1%) vs. 6.7% (5.1%,8.7%), P< 0.05]. Logistic regression analysis showed that obesity ( OR= 3.25) and fractional excretion of UA less than 7% ( OR= 9.01, all P< 0.05) were risk factors of gout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection.

PubMed

Alexander, Siobhan E; Arlen, Angela M; Storm, Douglas W; Kieran, Kathleen; Cooper, Christopher S

2015-04-01

Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making. Copyright © 2015 American Urological Association Education and Research, Inc. Published by

Characterization of Early Partial Seizure Onset: Frequency, Complexity and Entropy

PubMed Central

Jouny, Christophe C.; Bergey, Gregory K.

2011-01-01

Objective A clear classification of partial seizures onset features is not yet established. Complexity and entropy have been very widely used to describe dynamical systems, but a systematic evaluation of these measures to characterize partial seizures has never been performed. Methods Eighteen different measures including power in frequency bands up to 300Hz, Gabor atom density (GAD), Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample entropy, and permutation entropy, were selected to test sensitivity to partial seizure onset. Intracranial recordings from forty-five patients with mesial temporal, neocortical temporal and neocortical extratemporal seizure foci were included (331 partial seizures). Results GAD, Lempel-Ziv complexity, HFD, high frequency activity, and sample entropy were the most reliable measures to assess early seizure onset. Conclusions Increases in complexity and occurrence of high-frequency components appear to be commonly associated with early stages of partial seizure evolution from all regions. The type of measure (frequency-based, complexity or entropy) does not predict the efficiency of the method to detect seizure onset. Significance Differences between measures such as GAD and HFD highlight the multimodal nature of partial seizure onsets. Improved methods for early seizure detection may be achieved from a better understanding of these underlying dynamics. PMID:21872526

CDKL5 and ARX mutations in males with early-onset epilepsy.

PubMed

Mirzaa, Ghayda M; Paciorkowski, Alex R; Marsh, Eric D; Berry-Kravis, Elizabeth M; Medne, Livija; Alkhateeb, Asem; Grix, Art; Wirrell, Elaine C; Powell, Berkley R; Nickels, Katherine C; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B; Das, Soma

2013-05-01

Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. Although numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only 10 males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging, and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. These 18 patients include eight new males with CDKL5 mutations and 10 with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large dataset therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy in boys. Copyright © 2013 Elsevier Inc. All rights reserved.

CDKL5 and ARX mutations in males with early-onset epilepsy

PubMed Central

Mirzaa, Ghayda M.; Paciorkowski, Alex R.; Marsh, Eric D.; Berry-Kravis, Elizabeth M.; Medne, Livija; Grix, Art; Wirrell, Elaine C.; Powell, Berkley R.; Nickels, Katherine C.; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B.; Das, Soma

2013-01-01

Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. While numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only ten males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. The 18 patients include eight new males with CDKL5 mutations and ten with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large data set therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy. PMID:23583054

Early onset dementia in New Zealand Pacific boxers: a case series.

PubMed

Payman, Vahid; Yates, Susan; Cullum, Sarah

2018-05-04

To describe the biopsychosocial characteristics of a series of Pacific men living in South Auckland with a history of boxing presenting with early onset dementia. We discuss the history of boxing in Pacific people and the possibility of increased risk of early onset dementia in New Zealand Pacific men compared to their European counterparts. We reviewed the files of Pacific men with a history of amateur or professional boxing who presented to our memory and older adult mental health services with early onset dementia over a 45-month period. We gathered relevant information to construct a biopsychosocial paradigm as possible explanation of this phenomenon. We identified a series of eight New Zealand Pacific men with early onset dementia and with a history of boxing. Alcohol was a contributing factor in seven of the eight cases, and vascular risk factors in five. Historical, cultural and socio-economic factors underpin the attraction of some Pacific men to boxing as a sport. Given that New Zealand Pacific peoples may have an earlier onset of dementia than their European counterparts, further research is required to establish whether boxing is a contributory factor. Sports physicians should advise young New Zealand Pacific boxers about the long-term risks associated with their sport.

Antiganglioside antibodies in Guillain-Barré syndrome after a recent cytomegalovirus infection

PubMed Central

Khalili-Shirazi, A.; Gregson, N.; Gray, I.; Rees, J.; Winer, J.; Hughes, R.

1999-01-01

OBJECTIVE—To study the association between anti-ganglioside antibody responses and Guillan-Barré syndrome (GBS) after a recent cytomegalovirus (CMV) infection.
METHODS—Enzyme linked immunosorbant assay (ELISA) was undertaken on serum samples from 14 patients with GBS with recent cytomegalovirus (CMV) infection (CMV+GBS) and 12 without (CMV-GBS), 17 patients with other neurological diseases (OND), 11 patients with a recent CMV infection but without neurological involvement, 11 patients with recent Epstein-Barr virus (EBV) infection but without neurological involvement, and 20 normal control (NC) subjects.
RESULTS—IgM antibodies were found at 1:100 serum dilution to gangliosides GM2 (six of 14 patients), GM1 (four of 14), GD1a (three of 14) and GD1b (two of 14) in the serum samples of the CMV+GBS patients, but not in those of any of the CMV-GBS patients. IgM antibodies were also found to gangliosides GM1, GD1a, and GD1b in one of 11 OND patients, to ganglioside GM1 in one of 11 non- neurological CMV patients, and to ganglioside GD1b in one of 20NC subjects. Some patients with EBV infection had IgM antibodies to gangliosides GM1 (five of 11), GM2 (three of 11), and GD1a (two of 11). However, the antibodies to ganglioside GM2 had a low titre, none being positive at 1:200 dilution, whereas five of the CMV+GBS serum samples remained positive at this dilution.
CONCLUSION—Antibodies to ganglioside GM2 are often associated with GBS after CMV infection, but their relevance is not known. It is unlikely that CMV infection and anti-ganglioside GM2 antibodies are solely responsible and an additional factor is required to elicit GBS.

 PMID:10084538

Antiganglioside antibodies in Guillain-Barré syndrome after a recent cytomegalovirus infection.

PubMed

Khalili-Shirazi, A; Gregson, N; Gray, I; Rees, J; Winer, J; Hughes, R

1999-03-01

To study the association between anti-ganglioside antibody responses and Guillan-Barré syndrome (GBS) after a recent cytomegalovirus (CMV) infection. Enzyme linked immunosorbant assay (ELISA) was undertaken on serum samples from 14 patients with GBS with recent cytomegalovirus (CMV) infection (CMV+GBS) and 12 without (CMV-GBS), 17 patients with other neurological diseases (OND), 11 patients with a recent CMV infection but without neurological involvement, 11 patients with recent Epstein-Barr virus (EBV) infection but without neurological involvement, and 20 normal control (NC) subjects. IgM antibodies were found at 1:100 serum dilution to gangliosides GM2 (six of 14 patients), GM1 (four of 14), GD1a (three of 14) and GD1b (two of 14) in the serum samples of the CMV+GBS patients, but not in those of any of the CMV-GBS patients. IgM antibodies were also found to gangliosides GM1, GD1a, and GD1b in one of 11 OND patients, to ganglioside GM1 in one of 11 non- neurological CMV patients, and to ganglioside GD1b in one of 20 NC subjects. Some patients with EBV infection had IgM antibodies to gangliosides GM1 (five of 11), GM2 (three of 11), and GD1a (two of 11). However, the antibodies to ganglioside GM2 had a low titre, none being positive at 1:200 dilution, whereas five of the CMV+GBS serum samples remained positive at this dilution. Antibodies to ganglioside GM2 are often associated with GBS after CMV infection, but their relevance is not known. It is unlikely that CMV infection and anti-ganglioside GM2 antibodies are solely responsible and an additional factor is required to elicit GBS.

Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

PubMed

Hartz, Sarah M; Short, Susan E; Saccone, Nancy L; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Gubjartsson, Daniel; Hansel, Nadia N; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo-Pekka; Michel, Martha; Rawal, Rajesh; Rosenberger, Albert; Scheet, Paul; Shaffer, John R; Teumer, Alexander; Thompson, John R; Vink, Jacqueline M; Vogelzangs, Nicole; Wenzlaff, Angela S; Wheeler, William; Xiao, Xiangjun; Yang, Bao-Zhu; Aggen, Steven H; Balmforth, Anthony J; Baumeister, Sebastian E; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W; Boyd, Heather A; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu-Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M; Hayward, Caroline; Heikkilä, Kauko; Hewitt, John K; Hottenga, Jouke Jan; Jensen, Majken K; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J; Konte, Bettina; Korhonen, Tellervo; Landi, Maria-Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M; Mathias, Rasika A; McNeil, Daniel W; Medland, Sarah E; Montgomery, Grant W; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J; Francks, Clyde; Gejman, Pablo V; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S; Lehtimäki, Terho; Levinson, Douglas F; Marazita, Mary L; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D; Murray, Jeffrey C; Nöthen, Markus M; Penninx, Brenda W; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J; Sanders, Alan R; Schwartz, Ann G; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H-Erich; Amos, Christopher I; Breslau, Naomi; Cannon, Dale S; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G; Stevens, Victoria L; Stitzel, Jerry A; Weiss, Robert B; Kraft, Peter; Bierut, Laura J

2012-08-01

Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

Immune activation and suppression by group B streptococcus in a murine model of urinary tract infection.

PubMed

Kline, Kimberly A; Schwartz, Drew J; Lewis, Warren G; Hultgren, Scott J; Lewis, Amanda L

2011-09-01

Group B streptococcus (GBS) is a common commensal of the gastrointestinal and vaginal mucosa and a leading cause of serious infections in newborns, the elderly, and immunocompromised populations. GBS also causes infections of the urinary tract. However, little is known about host responses to GBS urinary tract infection (UTI) or GBS virulence factors that participate in UTI. Here we describe a novel murine model of GBS UTI that may explain some features of GBS urinary tract association in the human host. We observed high titers and heightened histological signs of inflammation and leukocyte recruitment in the GBS-infected kidney. However, extensive inflammation and leukocyte recruitment were not observed in the bladder, suggesting that GBS may suppress bladder inflammation during cystitis. Acute GBS infection induced the localized expression of proinflammatory cytokines interleukin-1α (IL-1α), macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and IL-9, as well as IL-10, more commonly considered an anti-inflammatory cytokine. Using isogenic GBS strains with different capsule structures, we show that capsular sialic acid residues contribute to GBS urinary tract pathogenesis, while high levels of sialic acid O-acetylation attenuate GBS pathogenesis in the setting of UTI, particularly in direct competition experiments. In vitro studies demonstrated that GBS sialic acids participate in the suppression of murine polymorphonuclear leukocyte (PMN) bactericidal activities, in addition to reducing levels of IL-1α, tumor necrosis factor alpha, IL-1β, MIP-1α, and KC produced by PMNs. These studies define several basic molecular and cellular events characterizing GBS UTI in an animal model, showing that GBS participates simultaneously in the activation and suppression of host immune responses in the urinary tract.

Operational Thought in Alzheimer's Disease Early Onset and SDAT.

ERIC Educational Resources Information Center

Emery, Olga B.; Breslau, Lawrence D.

For more than a decade it has been convention to assume that senile dementia Alzheimer's type (SDAT) and Alzheimer's disease early onset represent a unitary disease process with only an onset difference. This assumption has been neither confirmed nor disconfirmed. To address this issue, a study was conducted which analyzed the dissolution of…

The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians.

PubMed

Yang, M Y; Kim, J M; Kim, G W; Mun, J H; Song, M; Ko, H C; Kim, B S; Kim, H S; Kim, M B

2017-01-01

Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group. © 2016 European Academy of Dermatology and Venereology.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

PubMed

Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

2015-09-01

Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Electrodiagnostic features of acute paralytic poliomyelitis associated with West Nile virus infection.

PubMed

Al-Shekhlee, Amer; Katirji, Bashar

2004-03-01

West Nile virus (WNV) infection is a potentially fatal disease, with meningoencephalitis being its most common neurological manifestation. Guillain-Barré syndrome (GBS) has also been described, but acute paralytic poliomyelitis has only recently been recognized. We report the clinical and electrodiagnostic findings of five patients with WNV infection, who presented with acute paralytic poliomyelitis. Three patients manifested focal asymmetrical weakness, and two had rapid ascending quadriplegia mimicking GBS. Electrodiagnostic studies during the acute illness showed normal sensory nerve action potentials, compound motor action potentials of normal or reduced amplitude, and no slowing of nerve conduction velocities. Depending on the timing of the examination, fibrillation potentials were widespread, including in those with focal weakness. Cervical magnetic resonance imaging in one patient showed abnormal T2-weighted signals in the spinal cord gray matter. On follow-up, signs of clinical improvement were seen in one patient, whereas two remained quadriplegic and ventilator-dependent 5 months after the onset. This report highlights the value of the electrodiagnostic studies in the diagnosis and prognosis of focal or generalized weakness due to acute paralytic poliomyelitis associated with WNV infection.

Epidemiology of invasive group B streptococcal disease in infants from urban area of South China, 2011-2014.

PubMed

Guan, Xiaoshan; Mu, Xiaoping; Ji, Wenjing; Yuan, Chunlei; He, Ping; Zhang, Lian; Huang, Yanfen; Li, Juan; Chen, Jianfeng; Zhong, Huamin; Pang, Shuyin; Tan, Nan; Deng, Qiulian; Gao, Kankan; Huang, Yu-Ping; Chang, Chien-Yi; Liu, Haiying

2018-01-08

Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants in both developed and developing countries. To our knowledge, only a few studies have been reported the clinical features, treatment and outcomes of the GBS disease in China. The severity of neonatal GBS disease in China remains unclear. Population-based surveillance in China is therefore required. We retrospectively collected data of <3 months old infants with culture-positive GBS in sterile samples from three large urban tertiary hospitals in South China from Jan 2011 to Dec 2014. The GBS isolates and their antibiotic susceptibility were routinely identified in clinical laboratories in participating hospitals. Serotyping and multi-locus sequence typing (MLST) were also conducted for further analysis of the neonatal GBS disease. Total 70 cases of culture-confirmed invasive GBS infection were identified from 127,206 live births born in studying hospitals, giving an overall incidence of 0.55 per 1000 live births (95% confidence interval [CI] 0.44-0.69). They consisted of 49 with early-onset disease (EOD, 0.39 per 1000 live births (95% CI 0.29-0.51)) and 21 with late-onset disease (LOD, 0.17 per 1000 live births (95% CI 0.11-0.25)). The incidence of EOD increased significantly over the studying period. Five infants (4 EOD and 1 LOD) died before discharge giving a mortality rate of 7.1% and five infants (7.1%, 2 EOD and 3 LOD) had neurological sequelae. Within 68 GBS isolates from GBS cases who born in the studying hospitals or elsewhere, serotype III accounted for 77.9%, followed by Ib (14.7%), V (4.4%), and Ia (2.9%). MLST analysis revealed the presence of 13 different sequence types among the 68 GBS isolates and ST-17 was the most frequent sequence type (63.2%). All isolates were susceptible to penicillin, ceftriaxone, vancomycin and linezolid, while 57.4% and 51.5% were resistant to erythromycin and clindamycin, respectively. This study gains the insight into the spectrum of GBS

Designer vaccines to prevent infections due to group B Streptococcus.

PubMed

Kasper, D L

1995-10-01

Group B streptococci (GBS) are the major cause of serious infections in neonates and an important cause of infection in adults, particularly peripartum women and patients with diabetes mellitus and malignancy. Immunity to GBS in neonates is associated with naturally acquired maternal antibodies to the type-specific capsular polysaccharides of these organisms. IgG class antibodies directed to these polysaccharides are passed transplacentally and protect the child from invasive GBS disease. Phase I and II clinical trials showed that the purified polysaccharides had limited immunogenicity. However, vaccine responders passed functional IgG class antibodies to their children. A glycoconjugate vaccine has been designed so that the type-specific polysaccharides are covalently linked to a carrier protein. This secondary amine linkage is between aldehyde groups created on the eighth carbon of a selected number of periodate-oxidized sialic acid residues of the polysaccharide and epsilon-amino groups on lysine residues of tetanus toxoid. Careful epitope mapping studies had demonstrated that modification by controlled periodate oxidation could be accomplished and that an important conformational epitope on the polysaccharide would be preserved. Preclinical testing of the glycoconjugate vaccines in animal models of GBS disease demonstrated the immunogenicity and protective efficacy of the vaccine-induced antibodies. Phase I clinical testing of the glycoconjugate vaccine is in progress, and the early results appear promising.

Childhood Risk Factors for Early-Onset Drinking*

PubMed Central

Donovan, John E.; Molina, Brooke S. G.

2011-01-01

Objective: There is relatively little research on the childhood antecedent predictors of early-onset alcohol use. This study examined an array of psychosocial variables assessed at age 10 and reflecting Problem Behavior Theory as potential antecedent risk factors for the initiation of alcohol use at age 14 or younger. Method: A sample of 452 children (238 girls) ages 8 or 10 and their families was drawn from Allegheny County, PA, using targeted-age directory sampling and random-digit dialing procedures. Children and parents were interviewed using computer-assisted interviews. Logistic regression analyses were used to examine the age-10 univariate and multivariate predictors of the initiation of alcohol use by age 14 or younger. Results: Twenty-five percent of the sample reported having more than a sip or a taste of alcohol in their life by age 14. Sex, race, and age cohort did not relate to early drinking status. Children with two parents were less likely to initiate drinking early. Early initiation of drinking related significantly to an array of antecedent risk factors (personality, social environment, and behavioral) assessed at age 10 that reflect psychosocial proneness for problem behavior. In the multivariate model, the variables most predictive of early-onset drinking were having a single parent, sipping or tasting alcohol by age 10, having parents who also started drinking at an early age, and parental drinking frequency. Conclusions: Initiation of alcohol use by age 14 reflects childhood psychosocial proneness to engage in problem behavior as measured by Problem Behavior Theory and having a family environment conducive to alcohol use. PMID:21906502

Early Onset Malignancies - Genomic Study of Cancer Disparities

Cancer.gov

The Early Onset Malignancies Initiative studies the genomic basis of six cancers that develop at an earlier age, occur in higher rates, and are typically more aggressive in certain minority populations.

Early onset type 2 diabetes: risk factors, clinical impact and management

PubMed Central

Idris, Iskandar

2014-01-01

Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a significant impact on the individual, healthcare service delivery and planning. The individuals are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black and minority ethnic (BME) origin and come from a less affluent socioeconomic group. They have a heightened risk of developing microvascular and macrovascular complications, often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such, early and aggressive risk factor management is warranted. Early onset T2DM is complex and impacts on service delivery with a need for multidisciplinary care of complications and comorbidities’, in addition to adequate educational and psychological support. This review on the impact of early onset T2DM provides the latest insights into this emerging epidemic. PMID:25364491

Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India

PubMed Central

Raman, Ratheesh; Kotapalli, Viswakalyan; Adduri, Raju; Gowrishankar, Swarnalata; Bashyam, Leena; Chaudhary, Ajay; Vamsy, Mohana; Patnaik, Sujith; Srinivasulu, Mukta; Sastry, Regulagadda; Rao, Subramanyeshwar; Vasala, Anjayneyulu; Kalidindi, NarasimhaRaju; Pollack, Jonathan; Murthy, Sudha; Bashyam, Murali

2012-01-01

Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for greater than 90% of late-onset colorectal cancer. Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India. PMID:23168910

CMOS plasmonics in WDM data transmission: 200 Gb/s (8 × 25Gb/s) transmission over aluminum plasmonic waveguides.

PubMed

Dabos, G; Manolis, A; Papaioannou, S; Tsiokos, D; Markey, L; Weeber, J-C; Dereux, A; Giesecke, A L; Porschatis, C; Chmielak, B; Pleros, N

2018-05-14

We demonstrate wavelength-division-multiplexed (WDM) 200 Gb/s (8 × 25 Gb/s) data transmission over 100 μm long aluminum (Al) surface-plasmon-polariton (SPP) waveguides on a Si 3 N 4 waveguide platform at telecom wavelengths. The Al SPP waveguide was evaluated in terms of signal integrity by performing bit-error-rate (BER) measurements that revealed error-free operation for all eight 25 Gb/s non-return-to-zero (NRZ) modulated data channels with power penalties not exceeding 0.2 dB at 10 -9 . To the best of our knowledge, this is the first demonstration of WDM enabled data transmission over complementary-metal-oxide-semiconductor (CMOS) SPP waveguides fueling future development of CMOS compatible plasmo-photonic devices for on-chip optical interconnections.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

ERIC Educational Resources Information Center

McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

2007-01-01

Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

Group B Streptococcus serotypes III and V induce apoptosis and necrosis of human epithelial A549 cells.

PubMed

Da Costa, Andréia Ferreira Eduardo; Pereira, Camila Serva; Santos, Gabriela Da Silva; Carvalho, Técia Maria Ulisses; Hirata, Raphael; De Mattos-Guaraldi, Ana Luiza; Rosa, Ana Cláudia De Paula; Nagao, Prescilla Emy

2011-05-01

Although group B Streptococcus (GBS) has been classically described as an exclusively extracellular pathogen, growing evidence suggests that it may be internalized by epithelial cells. However, the fates of intracellular GBS and of infected respiratory epithelial cells remain unclear. Little is known about the bacterial components involved in these processes. The present study investigated the bacterial internalization by A549 cells and the apoptosis/necrosis of the infected human epithelial cells. The morphological changes in A549 cells observed from 2 h post-infection with GBS included vacuolization and the formation of apoptotic bodies. Flow cytometry revealed that 81.2% of apoptotic A549 cells were infected with GBS serotype III 90356-liquor. Moreover, a double-staining assay using propidium iodide (PI)/Annexin V (AV) gave information about the numbers of viable (PI-/AV-) (18.27%) vs. early apoptotic (PI-/AV+) (73.83%) and late apoptotic cells (PI+/AV+) (7.37%) during infection of A549 cells with GBS III 90356-liquor. In addition, 37% necrotic cells were observed in A549 cells infected with GBS serotype V 90186-blood. In conclusion, GBS serotypes III and V induce apoptosis of epithelial cells in the early stages of GBS infection, resulting in tissue destruction, bacterial spreading and, in consequence, invasive disease or systemic infection.

Childhood exposure to infection and risk of adult onset wheeze and atopy.

PubMed

Bodner, C; Anderson, W J; Reid, T S; Godden, D J

2000-05-01

measles up to the age of three (OR 0.2, CI 0.03 to 0.8) were significantly related to a lower risk of doctor diagnosed asthma. In these well characterised subjects, exposure to infections as measured by parental reports obtained at age 10-14 years and by serological tests obtained in adulthood did not influence the development of wheezing symptoms or atopic status in adulthood. However, early exposure to measles and family size may be associated with a lower risk of adult onset doctor diagnosed asthma.

Common variants at five new loci associated with early-onset inflammatory bowel disease.

PubMed

Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

2009-12-01

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

Role of Campylobacter jejuni Infection in the Pathogenesis of Guillain-Barré Syndrome: An Update

PubMed Central

Nyati, Kishan Kumar; Nyati, Roopanshi

2013-01-01

Our current knowledge on Campylobacter jejuni infections in humans has progressively increased over the past few decades. Infection with C. jejuni is the most common cause of bacterial gastroenteritis, sometimes surpassing other infections due to Salmonella, Shigella, and Escherichia coli. Most infections are acquired due to consumption of raw or undercooked poultry, unpasteurized milk, and contaminated water. After developing the diagnostic methods to detect C. jejuni, the possibility to identify the association of its infection with new diseases has been increased. After the successful isolation of C. jejuni, reports have been published citing the occurrence of GBS following C. jejuni infection. Thus, C. jejuni is now considered as a major triggering agent of GBS. Molecular mimicry between sialylated lipooligosaccharide structures on the cell envelope of these bacteria and ganglioside epitopes on the human nerves that generates cross-reactive immune response results in autoimmune-driven nerve damage. Though C. jejuni is associated with several pathologic forms of GBS, axonal subtypes following C. jejuni infection may be more severe. Ample amount of existing data covers a large spectrum of GBS; however, the studies on C. jejuni-associated GBS are still inconclusive. Therefore, this review provides an update on the C. jejuni infections engaged in the pathogenesis of GBS. PMID:24000328

Risk of early-onset prostate cancer associated with occupation in the Nordic countries.

PubMed

Barry, Kathryn Hughes; Martinsen, Jan Ivar; Alavanja, Michael C R; Andreotti, Gabriella; Blair, Aaron; Hansen, Johnni; Kjærheim, Kristina; Koutros, Stella; Lynge, Elsebeth; Sparèn, Pär; Tryggvadottir, Laufey; Weiderpass, Elisabete; Berndt, Sonja I; Pukkala, Eero

2017-12-01

Early-onset prostate cancer is often more aggressive and may have a different aetiology than later-onset prostate cancer, but has been relatively little studied to date. We evaluated occupation in relation to early- and later-onset prostate cancer in a large pooled study. We used occupational information from census data in five Nordic countries from 1960 to 1990. We identified prostate cancer cases diagnosed from 1961 to 2005 by linkage of census information to national cancer registries and calculated standardised incidence ratios (SIRs) separately for men aged 30-49 and those aged 50 or older. We also conducted separate analyses by period of follow-up, 1961-1985 and 1986-2005, corresponding to pre- and post-prostate-specific antigen (PSA) screening. For early-onset prostate cancer (n = 1521), we observed the highest SIRs for public safety workers (e.g. firefighters) (SIR = 1.71, 95% confidence interval [CI]: 1.23-2.31) and military personnel (SIR = 1.97, 95% CI: 1.31-2.85). These SIRs were significantly higher than the SIRs for later-onset disease (for public safety workers, SIR = 1.10, 95% CI: 1.07-1.14 and for military personnel, SIR = 1.09, 95% CI: 1.05-1.13; p heterogeneity  = 0.005 and 0.002, respectively). Administrators and technical workers also demonstrated significantly increased risks for early-onset prostate cancer, but the SIRs did not differ from those of later-onset disease (p heterogeneity >0.05). While our early-onset finding for public safety workers was restricted to the post-PSA period, that for military personnel was restricted to the pre-PSA period. Our results suggest that occupational exposures, particularly for military personnel, may be associated with early-onset prostate cancer. Further evaluation is needed to explain these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of a Guillain-Barré syndrome cluster in the Republic of Fiji.

PubMed

Pastula, Daniel M; Khan, Aalisha Sahu; Sharp, Tyler M; Biaukula, Viema L; Naivalu, Taina K; Rafai, Eric; Ermias Belay; Staples, J Erin; Fischer, Marc; Kosoy, Olga I; Laven, Janeen J; Bennett, Elizabeth J; Jenney, Adam W J; Naidu, Ravi Narayan; Lanciotti, Robert S; Galloway, Renee L; Nilles, Eric J; Sejvar, James J; Kama, Mike

2017-01-15

In 2014, we investigated a cluster of Guillain-Barre syndrome (GBS) in Fiji that occurred during a dengue epidemic. We designed a case-control study to determine the etiology. Cases were patients meeting Brighton Collaboration criteria for GBS with onset from February 2014 to May 2014. Controls were persons without symptoms of GBS who were matched by age group and location. We collected information on demographics and potential exposures. Serum samples were tested for evidence of recent arboviral or Leptospira spp. infections. Nine cases of GBS were identified for an incidence of five cases per 100,000 population/year. Median age of cases was 27years (range: 0.8-52); five (56%) were male. Six (67%) reported an acute illness prior to GBS onset. Among the 9 cases and 28 controls enrolled, odds ratios for reported exposures or antibodies against various arboviruses or Leptospira spp. were not statistically significant. No clear etiologies were identified for this unusual GBS cluster. There was a temporal association between the GBS cluster and a dengue epidemic, but we were unable to substantiate an epidemiologic or laboratory association. Further study is needed to explore potential associations between arboviral infections and GBS. Copyright © 2016. Published by Elsevier B.V.

Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

ERIC Educational Resources Information Center

Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

2010-01-01

Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

ERIC Educational Resources Information Center

Danner, Stephanie; Fristad, Mary A.; Arnold, L. Eugene; Youngstrom, Eric A.; Birmaher, Boris; Horwitz, Sarah M.; Demeter, Christine; Findling, Robert L.; Kowatch, Robert A.

2009-01-01

Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current…

Early Onset Marijuana Use Is Associated with Learning Inefficiencies

PubMed Central

Schuster, Randi Melissa; Hoeppner, Susanne S.; Evins, A. Eden; Gilman, Jodi M.

2016-01-01

Objective Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early-onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Method Forty-eight young adults, aged 18–25, who used marijuana at least once per week and 48 matched non-using controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: ‘early onset’ users (EMJ), who started using marijuana at or before age 16 (n = 27), and ‘late onset’ marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Results Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Conclusions Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. PMID:26986749

Infections and Pregnancy

MedlinePlus

During pregnancy, some common infections like the common cold or a skin infection do not usually cause serious problems. ... of the infections that can be dangerous during pregnancy include Bacterial vaginosis (BV) Group B strep (GBS) ...

Demographic processes affect HIV-1 evolution in primary infection before the onset of selective processes.

PubMed

Herbeck, Joshua T; Rolland, Morgane; Liu, Yi; McLaughlin, Sherry; McNevin, John; Zhao, Hong; Wong, Kim; Stoddard, Julia N; Raugi, Dana; Sorensen, Stephanie; Genowati, Indira; Birditt, Brian; McKay, Angela; Diem, Kurt; Maust, Brandon S; Deng, Wenjie; Collier, Ann C; Stekler, Joanne D; McElrath, M Juliana; Mullins, James I

2011-08-01

HIV-1 transmission and viral evolution in the first year of infection were studied in 11 individuals representing four transmitter-recipient pairs and three independent seroconverters. Nine of these individuals were enrolled during acute infection; all were men who have sex with men (MSM) infected with HIV-1 subtype B. A total of 475 nearly full-length HIV-1 genome sequences were generated, representing on average 10 genomes per specimen at 2 to 12 visits over the first year of infection. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled during acute HIV-1 infection. Restriction to a single founder variant was not due to a lack of diversity in the transmitter as homogeneous populations were found in recipients from transmitters with chronic infection. Mutational patterns indicative of rapid viral population growth dominated during the first 5 weeks of infection and included a slight contraction of viral genetic diversity over the first 20 to 40 days. Subsequently, selection dominated, most markedly in env and nef. Mutants were detected in the first week and became consensus as early as day 21 after the onset of symptoms of primary HIV infection. We found multiple indications of cytotoxic T lymphocyte (CTL) escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with mutually exclusive mutations nearby, indicating the existence of a maturational escape process, possibly in adaptation to viral fitness constraints or to immune responses against new variants. We showed that establishment of HIV-1 infection is likely due to a biological mechanism that restricts transmission rather than to early adaptive evolution during acute infection. Furthermore, the diversity of HIV strains coupled with complex and individual-specific patterns of CTL escape did not reveal shared sequence characteristics of acute infection that could be harnessed for

Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

PubMed Central

Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

2015-01-01

Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

Genetic Profiling and Comorbidities of Zika Infection.

PubMed

Moni, Mohammad Ali; Lio', Pietro

2017-09-15

The difficulty in distinguishing infection by Zika virus (ZIKV) from other flaviviruses is a global health concern, particularly given the high risk of neurologic complications (including Guillain-Barré syndrome [GBS]) with ZIKV infection. We developed quantitative frameworks to compare and explore infectome, diseasome, and comorbidity of ZIKV infections. We analyzed gene expression microarray and RNA-Seq data from ZIKV, West Nile fever (WNF), chikungunya, dengue, yellow fever, Japanese encephalitis virus, GBS, and control datasets. Using neighborhood-based benchmarking and multilayer network topology, we constructed relationship networks based on the Online Mendelian Inheritance in Man database and our identified significant genes. ZIKV infections showed dysregulation in expression of 929 genes. Forty-seven genes were highly expressed in both ZIKV and dengue infections. However, ZIKV shared <15 significant transcripts with other flavivirus infections. Notably, dysregulation of MAFB and SELENBP1 was common to ZIKV, dengue, and GBS infection; ATF5, TNFAIP3, and BAMB1 were common to ZIKV, dengue, and WNF; and NAMPT and PMAlP1 were common to ZIKV, GBS, and WNF. Phylogenetic, ontologic, and pathway analyses showed that ZIKV infection most resembles dengue fever. We have developed methodologies to investigate disease mechanisms and predictions for infectome, diseasome, and comorbidities quantitatively, and identified particular similarities between ZIKV and dengue infections. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Early-onset facioscapulohumeral muscular dystrophy type 1 with some atypical features.

PubMed

Dorobek, Małgorzata; van der Maarel, Silvère M; Lemmers, Richard J L F; Ryniewicz, Barbara; Kabzińska, Dagmara; Frants, Rune R; Gawel, Malgorzata; Walecki, Jerzy; Hausmanowa-Petrusewicz, Irena

2015-04-01

Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes. We present early-onset cases in the Polish population that amounted to 21% of our total population with facioscapulohumeral muscular dystrophy. More than 27% of them presented with severe phenotypes (wheelchair dependency). The residual D4Z4 repeat sizes ranged from 1 to 4 units. In addition, even within early-onset facioscapulohumeral muscular dystrophy type 1 phenotypes, some cases had uncommon features (head drop, early disabling contractures, progressive ptosis, and respiratory insufficiency and cardiomyopathy). © The Author(s) 2014.

Early onset epilepsy is associated with increased mortality: a population-based study

PubMed Central

Moseley, Brian D.; Wirrell, Elaine C.; Wong-Kisiel, Lily C.; Nickels, Katherine

2013-01-01

SUMMARY We examined mortality in early onset (age <12 months) epilepsy in a population-based group of children. Children with early onset epilepsy were significantly more likely to die (case fatality, CF 8/60 versus 8/407, p<0.001; mortality rate, MR 14.5/1000 versus 2/1000 person years; standardized mortality ratio, SMR 22.25 versus 5.67). Mortality was greater in children with malignant neonatal (age <1 month) epilepsy (CF 4/12 versus 12/450, p<0.001; MR 54/1000 person years versus 2.7/1000 person year; SMR 46.55 versus 7.22). Given that only 1/8 early onset epilepsy deaths was seizure-related, mortality appears to be more affected by underlying etiology. PMID:23582606

Development and initial validation of the Classification of Early-Onset Scoliosis (C-EOS).

PubMed

Williams, Brendan A; Matsumoto, Hiroko; McCalla, Daren J; Akbarnia, Behrooz A; Blakemore, Laurel C; Betz, Randal R; Flynn, John M; Johnston, Charles E; McCarthy, Richard E; Roye, David P; Skaggs, David L; Smith, John T; Snyder, Brian D; Sponseller, Paul D; Sturm, Peter F; Thompson, George H; Yazici, Muharrem; Vitale, Michael G

2014-08-20

Early-onset scoliosis is a heterogeneous condition, with highly variable manifestations and natural history. No standardized classification system exists to describe and group patients, to guide optimal care, or to prognosticate outcomes within this population. A classification system for early-onset scoliosis is thus a necessary prerequisite to the timely evolution of care of these patients. Fifteen experienced surgeons participated in a nominal group technique designed to achieve a consensus-based classification system for early-onset scoliosis. A comprehensive list of factors important in managing early-onset scoliosis was generated using a standardized literature review, semi-structured interviews, and open forum discussion. Three group meetings and two rounds of surveying guided the selection of classification components, subgroupings, and cut-points. Initial validation of the system was conducted using an interobserver reliability assessment based on the classification of a series of thirty cases. Nominal group technique was used to identify three core variables (major curve angle, etiology, and kyphosis) with high group content validity scores. Age and curve progression ranked slightly lower. Participants evaluated the cases of thirty patients with early-onset scoliosis for reliability testing. The mean kappa value for etiology (0.64) was substantial, while the mean kappa values for major curve angle (0.95) and kyphosis (0.93) indicated almost perfect agreement. The final classification consisted of a continuous age prefix, etiology (congenital or structural, neuromuscular, syndromic, and idiopathic), major curve angle (1, 2, 3, or 4), and kyphosis (-, N, or +) variables, and an optional progression modifier (P0, P1, or P2). Utilizing formal consensus-building methods in a large group of surgeons experienced in treating early-onset scoliosis, a novel classification system for early-onset scoliosis was developed with all core components demonstrating

A new clinical feature associated with familial early-onset of dystonic-guttural tics: An unusual diagnosis of PANDAS.

PubMed

Vitaliti, Giovanna; Trifiletti, Rosario R; Falsaperla, Raffaele; Parano, Enrico; Spalice, Alberto; Pavone, Piero

2014-01-01

Until today there is a large debate about the existence of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually have dramatic, "overnight" onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. In addition to these symptoms, children may also have comorbid features of associated disorders. Herein, we report a family with an early onset of tics, with exclusively dystonic and guttural tics. All patients had a particularly strong excitement trigger. Two of the patients were shown to have signs suggestive of PANDAS and all family members were Group A beta-hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group of disorders. We have described a PANDAS variant, in which the family seems to share common autoimmune pattern and may be viewed in the large spectrum of PANDAS.

Neural abnormalities in early-onset and adolescence-onset conduct disorder.

PubMed

Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

2010-07-01

Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for

Early-onset dementias: diagnostic and etiological considerations

PubMed Central

2013-01-01

This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect. PMID:24565469

Early-Onset Physical Frailty in Adults with Diabesity and Peripheral Neuropathy.

PubMed

Tuttle, Lori J; Bittel, Daniel C; Bittel, Adam J; Sinacore, David R

2017-12-07

Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy. We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m 2 ); 13 with diabesity only (53 years of age, BMI 34 kg/m 2 ) and 10 obese controls (67 years of age, BMI 32 kg/m 2 ). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry. Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty. Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Guillain-Barré Syndrome Associated With Zika Virus Infection in Martinique in 2016: A Prospective Study.

PubMed

Rozé, Benoît; Najioullah, Fatiha; Fergé, Jean-Louis; Dorléans, Frédérique; Apetse, Kossivi; Barnay, Jose-Luis; Daudens-Vaysse, Elise; Brouste, Yannick; Césaire, Raymond; Fagour, Laurence; Valentino, Ruddy; Ledrans, Martine; Mehdaoui, Hossein; Abel, Sylvie; Leparc-Goffart, Isabelle; Signate, Aissatou; Cabié, André

2017-10-16

Guillain-Barré syndrome (GBS) has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies, mostly on the basis of serological tests, with the problematic cross-reacting antibodies of the Flavivirus genus. Some GBS cases do not exhibit a high level of diagnostic certainty. This prospective study aimed to describe the clinical profiles and the frequency of GBS associated with ZIKV during the ZIKV outbreak in Martinique in 2016. We recorded prospective data from GBS meeting levels 1 or 2 of diagnostic certainty for the Brighton Collaboration, with proof of recent ZIKV infection and negative screening for etiologies of GBS. Of the sample of 34 patients with suspected GBS during the outbreak, 30 had a proven presence of GBS, and 23 had a recent ZIKV infection. The estimated GBS incidence rate ratio (2016 vs 2006-2015) was 4.52 (95% confidence interval, 2.80-7.64; P = .0001). Recent ZIKV infection was confirmed by urine reverse-transcription polymerase chain reaction (RT-PCR) analysis in 17 cases and by serology in 6 cases. Patients, 65% of whom were male, had a median age of 61 years (interquartile range, 56-71 years) and experienced severe GBS. Electrophysiological tests were consistent with the primary demyelinating form of the disease. ZIKV infection is usually benign, when symptomatic, but in countries at risk of ZIKV epidemics, adequate intensive care bed capacity is required for management of severe GBS cases. Arbovirus RNA detection by RT-PCR should be part of the management of GBS cases. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The impact of early-onset cannabis use on functional brain correlates of working memory.

PubMed

Becker, Benjamin; Wagner, Daniel; Gouzoulis-Mayfrank, Euphrosyne; Spuentrup, Elmar; Daumann, Jörg

2010-08-16

Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Streptococcus agalactiae isolates of serotypes Ia, III and V from human and cow are able to infect tilapia.

PubMed

Chen, Ming; Wang, Rui; Luo, Fu-Guang; Huang, Yan; Liang, Wan-Wen; Huang, Ting; Lei, Ai-Ying; Gan, Xi; Li, Li-Ping

2015-10-22

Recent studies have shown that group B streptococcus (GBS) may be infectious across hosts. The purpose of this study is to investigate the pathogenicity of clinical GBS isolates with serotypes Ia, III and V from human and cow to tilapia and the evolutionary relationship among these GBS strains of different sources. A total of 27 clinical GBS isolates from human (n=10), cow (n=2) and tilapia (n=15) were analyzed using serotyping, multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Among them, 15 isolates were tested for their pathogenicity to tilapia. The results showed that five human GBS strains (2 serotype III, 2 serotype Ia and 1 serotype V) infected tilapia with mortality rate ranging from 56.67% to 100%, while the other five human GBS strains tested were unable to infect tilapia. In addition, two cow GBS strains C001 and C003 of serotype III infected tilapia. However, they had significantly lower pathogenicity than the five human strains. Furthermore, human GBS strains H005 and H008, which had very strong ability to infect tilapia, had the same PFGE pattern. MLST analysis showed that the five human and the two cow GBS strains that were able to infect tilapia belonged to clonal complexes CC19, CC23 and CC103. The study for the first time confirmed that human or cow GBS clonal complexes CC19, CC23 and CC103 containing strains with serotypes Ia, III and V could infect tilapia and induce clinical signs under experimental conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Distinct breast cancer subtypes in women with early-onset disease across races

PubMed Central

Singh, Mandeep; Ding, Yi; Zhang, Li-Ying; Song, Dong; Gong, Yun; Adams, Sylvia; Ross, Dara S; Wang, Jin-Hua; Grover, Shruti; Doval, Dinesh Chandra; Shao, Charles; He, Zi-Li; Chang, Victor; Chin, Warren W; Deng, Fang-Ming; Singh, Baljit; Zhang, David; Xu, Ru-Liang; Lee, Peng

2014-01-01

Background: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. Methods: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). Results: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. Conclusions: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients. PMID:25057437

GBS: Global 3D simulation of tokamak edge region

NASA Astrophysics Data System (ADS)

Zhu, Ben; Fisher, Dustin; Rogers, Barrett; Ricci, Paolo

2012-10-01

A 3D two-fluid global code, namely Global Braginskii Solver (GBS), is being developed to explore the physics of turbulent transport, confinement, self-consistent profile formation, pedestal scaling and related phenomena in the edge region of tokamaks. Aimed at solving drift-reduced Braginskii equations [1] in complex magnetic geometry, the GBS is used for turbulence simulation in SOL region. In the recent upgrade, the simulation domain is expanded into close flux region with twist-shift boundary conditions. Hence, the new GBS code is able to explore global transport physics in an annular full-torus domain from the top of the pedestal into the far SOL. We are in the process of identifying and analyzing the linear and nonlinear instabilities in the system using the new GBS code. Preliminary results will be presented and compared with other codes if possible.[4pt] [1] A. Zeiler, J. F. Drake and B. Rogers, Phys. Plasmas 4, 2134 (1997)

Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

PubMed

Immanuel, Jincy; Simmons, David

2017-10-02

We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

The neutralizing role of IgM during early Chikungunya virus infection

PubMed Central

Chua, Chong-Long; Chiam, Chun-Wei; Chan, Yoke-Fun

2017-01-01

The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays. PMID:28182795

Mothers' experience of caring for a child with early onset scoliosis: A qualitative descriptive study.

PubMed

Lauder, Bonnie; Sinclair, Peter M; Maguire, Jane

2018-04-01

This study aimed to identify and describe the experience of parents of children diagnosed with early onset scoliosis living in Australia. Chronic childhood disease has a major impact on health-related quality of life. Caring for a child with a chronic illness is well documented but the specific experiences of parents who care for children with early onset scoliosis, a rare but devastating illness, has not been explored. Numerous studies have described the interrelated psychological, financial, social, physical and logistical factors that impact the experience of the caregiver role with various diseases, but in the case of early onset scoliosis, limited studies have been conducted about the parental experience. A qualitative descriptive design was used. A snowball sampling technique assisted in the recruitment. Parents invited to the study included mothers, fathers and guardians. Data were collected through semistructured interviews and transcribed verbatim. Transcripts were analysed thematically. Data collection complied with the Consolidated criteria for reporting qualitative research guidelines. Twelve mothers of children with early onset scoliosis were interviewed, as only mothers consented to participate. Four major themes emerged: emotional rollercoaster ride, a lack of resources, money talks and pervasive burden. Factors that impacted on the participants' ability to confront, manage and endure caring for a child with early onset scoliosis emerged from the data. The findings suggest there are multiple factors that influence the experience of mothers' caring for a child with early onset scoliosis. The recognition and appropriate management of these factors by healthcare professionals have the potential to improve the quality of life of parents who care for a child with early onset scoliosis. Healthcare professionals have first-line contact with parents of children with early onset scoliosis and are well placed to provide parents with evidence-based education

GBS 1.0

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

2010-09-30

The Umbra gbs (Graph-Based Search) library provides implementations of graph-based search/planning algorithms that can be applied to legacy graph data structures. Unlike some other graph algorithm libraries, this one does not require your graph class to inherit from a specific base class. Implementations of Dijkstra's Algorithm and A-Star search are included and can be used with graphs that are lazily-constructed.

Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns).

PubMed

Stocker, Martin; van Herk, Wendy; El Helou, Salhab; Dutta, Sourabh; Fontana, Matteo S; Schuerman, Frank A B A; van den Tooren-de Groot, Rita K; Wieringa, Jantien W; Janota, Jan; van der Meer-Kappelle, Laura H; Moonen, Rob; Sie, Sintha D; de Vries, Esther; Donker, Albertine E; Zimmerman, Urs; Schlapbach, Luregn J; de Mol, Amerik C; Hoffman-Haringsma, Angelique; Roy, Madan; Tomaske, Maren; Kornelisse, René F; van Gijsel, Juliette; Visser, Eline G; Willemsen, Sten P; van Rossum, Annemarie M C

2017-08-26

Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932. Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844

Brain Structure Changes Visualized in Early- and Late-Onset Blind Subjects

PubMed Central

Leporé, Natasha; Voss, Patrice; Lepore, Franco; Chou, Yi-Yu; Fortin, Madeleine; Gougoux, Frédéric; Lee, Agatha D.; Brun, Caroline; Lassonde, Maryse; Madsen, Sarah K.; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

We examine 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor-based morphometry, we map volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject’s structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and hypertrophy in the isthmus. Gains in the isthmus and non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID:19643183

Barriers and facilitators related to the uptake of four strategies to prevent neonatal early-onset group B haemolytic streptococcus disease: a qualitative study.

PubMed

Kolkman, Diny G E; Fleuren, Margot A H; Wouters, Maurice G A J; de Groot, Christianne J M; Rijnders, Marlies E B

2017-05-09

Actions to prevent early onset disease in neonates are based on different strategies including administering antibiotic prophylaxis during labour in case of 1) maternal GBS colonisation (screening strategy), 2) identified risk factors (risk-based strategy) or 3) a combination of these two conditions (maternal GBS colonisation and identified risk factors: combination strategy and the Dutch guideline). Low adherence to guidelines preventing EOGBS has been reported. Each strategy has drawbacks and clinical outcomes are affected by care providers' and women's adherence. The actual impact of any preventive strategy is the product of efficacy of the strategy and the level of implementation. In order to reduce neonatal death due to EOGBS by developing the optimal guideline, we analysed barriers and facilitators of current used strategies. Focus group and personal interviews with care providers and women were performed. Impeding and enhancing factors in adherence to the preventive strategies were discussed and scored using the Measurement Instrument for Determinants of Innovations (MIDI) and analysed by two independent researchers. Overall, care providers identified 3.6 times more factors that would impede (n = 116) rather than facilitate (n = 32) adherence to the preventive strategies. 28% facilitative factors were reported in relation to the combination strategy and 86% impeding factors in relation to the Dutch guideline. The most preferred strategy was the combination strategy by 74% of the care providers and by 86% of the women. We obtained a detailed understanding of factors that influence adherence to preventive strategies. This insight can be used to develop implementation activities to improve the uptake of new strategies. The trial is registered in the Dutch Trial Register NTR3965 .

Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer's disease.

PubMed

Schöll, Michael; Ossenkoppele, Rik; Strandberg, Olof; Palmqvist, Sebastian; Jögi, Jonas; Ohlsson, Tomas; Smith, Ruben; Hansson, Oskar

2017-09-01

Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher 18F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher 18F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher 18F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease. © The Author (2017). Published by Oxford

Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

ERIC Educational Resources Information Center

Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.

2010-01-01

Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…

Low-cost and miniaturized 100-Gb/s (2 × 50 Gb/s) PAM-4 TO-packaged ROSA for data center networks.

PubMed

Kang, Sae-Kyoung; Huh, Joon Young; Lee, Jie Hyun; Lee, Joon Ki

2018-03-05

We design and implement a cost-effective and compact 100-Gb/s (2 × 50 Gb/s) PAM-4 receiver optical sub-assembly (ROSA) by using a TO-can package instead of an expensive box-type package. It consists of an optical demultiplexer, two PIN-PDs and a 2-channel linear transimpedance amplifier. The components are passively aligned and assembled using alignment marks engraved on each part. With a real-time PAM-4 DSP chip, we measured the back-to-back receiver sensitivities of the 100-Gb/s ROSA based on TO-56 to be less than -13.2 dBm for both channels at a bit error rate of 2.4e-4. The crosstalk penalty due to the adjacent channel interference was observed around 0.1 dB.

Comparison of the effect of penicillins versus erythromycin in preventing neonatal group B streptococcus infection in active carriers following preterm prelabor rupture of membranes.

PubMed

Yeung, Sik Wing; Sahota, Daljit Singh; Leung, Tak Yeung

2014-06-01

To compare the incidence of neonatal group B streptococcus (GBS) infection in active GBS carriers with preterm prelabor rupture of membranes (PPROMs) after penicillins and erythromycin prophylaxis. Patients diagnosed to have PPROM between 2004 and 2009 inclusive were treated using erythromycin (erythromycin group), ampicillin, amoxicillin or co-amoxiclav (penicillin group), or no antibiotics (control group) according to department protocols depending on their gestation and their GBS status at the time of presentation. Patients receiving both erythromycin and penicillins were included in the penicillin group. The incidence of neonatal GBS infection was compared between groups categorized according to the antibiotic regime received. A total of 680 women were diagnosed to have PPROM of which 85 (12.5%) were active GBS carriers. GBS isolates were 100% sensitive to penicillins but only 35% were sensitive to erythromycin. There were 16, 22, and 47 patients in the penicillin, erythromycin, and control groups, respectively. The incidence of neonatal GBS infection in the three groups was 0%, 36%, and 13%, respectively, and was statistically significant (p = 0.023). Penicillins are more effective than erythromycin in preventing neonatal GBS infection in women with PPROM who were active GBS carriers. Because most women do not know their GBS status at the time of PPROM and it is practically difficult to identify the active carriers before delivery, ampicillin/amoxicillin should be used as a prophylactic antibiotic for active GBS carriers and women with unknown GBS carriage status to prevent neonatal GBS infection following PPROM. Copyright © 2014. Published by Elsevier B.V.

Severity and frequency of community-onset Clostridium difficile infection on an Australian tertiary referral hospital campus.

PubMed

Clohessy, Penny; Merif, Juan; Post, Jeffrey John

2014-12-01

Clostridium difficile infection (CDI) is increasingly being found in populations without traditional risk factors. We compared the relative frequency, risk factors, severity, and outcomes of community-onset CDI with hospital-acquired infection. This was a retrospective, observational study of CDI at a tertiary hospital campus in Sydney, Australia. Patients aged 15 years and older with a first episode of CDI from January 1 to December 31, 2011 were included. CDI was defined as the presence of diarrhoea with a positive enzyme immunoassay in conjunction with a positive cell cytotoxicity assay, toxin culture, or organism culture. Main outcome measures were onset of infection (hospital or community), risk factors, markers of severity, and outcomes for the two groups. One hundred and twenty-nine cases of CDI infection were identified, of which 38 (29%) were community-onset. The community-onset infection group were less likely to have a recent history of antibiotic use (66% vs. 98%; p<0.001) or proton pump inhibitor use (38% vs. 69%; p=0.03) than the hospital-acquired infection group. Markers of severity and outcomes were similar in the two groups, with an overall mortality of 9%. Community-onset CDI accounts for a large proportion of C. difficile infections and has a similar potential for severe disease as hospital-acquired infection. Using a history of previous antibiotic use, proton pump inhibitor use, or recent hospitalization to predict cases is unreliable. We recommend that patients with diarrhoea being investigated in emergency departments and community practice are tested for Clostridium difficile infection. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Early Assessment of Pancreatic Infections and Overall Prognosis in Severe Acute Pancreatitis by Procalcitonin (PCT)

PubMed Central

Rau, Bettina M.; Kemppainen, Esko A.; Gumbs, Andrew A.; Büchler, Markus W.; Wegscheider, Karl; Bassi, Claudio; Puolakkainen, Pauli A.; Beger, Hans G.

2007-01-01

Background: Pancreatic infections and sepsis are major complications in severe acute pancreatitis (AP) with significant impact on management and outcome. We investigated the value of Procalcitonin (PCT) for identifying patients at risk to develop pancreatic infections in severe AP. Methods: A total of 104 patients with predicted severe AP were enrolled in five European academic surgical centers within 96 hours of symptom onset. PCT was measured prospectively by a semi-automated immunoassay in each center, C-reactive protein (CRP) was routinely assessed. Both parameters were monitored over a maximum of 21 consecutive days and in weekly intervals thereafter. Results: In contrast to CRP, PCT concentrations were significantly elevated in patients with pancreatic infections and associated multiorgan dysfunction syndrome (MODS) who all required surgery (n = 10) and in nonsurvivors (n = 8) early after onset of symptoms. PCT levels revealed only a moderate increase in patients with pancreatic infections in the absence of MODS (n = 7), all of whom were managed nonoperatively without mortality. A PCT value of ≥3.5 ng/mL on 2 consecutive days was superior to CRP ≥430 mg/L for the assessment of infected necrosis with MODS or nonsurvival as determined by ROC analysis with a sensitivity and specificity of 93% and 88% for PCT and 40% and 100% for CRP, respectively (P < 0.01). The single or combined prediction of the two major complications was already possible on the third and fourth day after onset of symptoms with a sensitivity and specificity of 79% and 93% for PCT ≥3.8 ng/mL compared with 36% and 97% for CRP ≥430 mg/L, respectively (P = 0.002). Conclusion: Monitoring of PCT allows early and reliable assessment of clinically relevant pancreatic infections and overall prognosis in AP. This single test parameter significantly contributes to an improved stratification of patients at risk to develop major complications. PMID:17457167

ASSESSMENT OF OXIDATIVE STRESS IN EARLY AND LATE ONSET PRE-ECLAMPSIA AMONG GHANAIAN WOMEN.

PubMed

Tetteh, P W; Adu-Bonsaffoh, K; Antwi-Boasiako, C; Antwi, D A; Gyan, B; Obed, S A

2015-01-01

Pre-eclampsia is a multisystem pregnancy-related disorder with multiple theories regarding its aetiology resulting in lack of reliable screening tests and well-established measures for primary prevention. However, oxidative stress is increasingly being implicated in the pathogenesi of pre-eclampsia although conflicting findings have been reported. To determine and compare the levels of oxidative stress in early and late onset pre-eclampsia by measuring urinary excretion of isoprostane and total antioxidant power (TAP) in a cohort of pre-eclamptic women at Korle Bu Teaching Hospital. This was a cross-sectional study conducted at Korle-Bu Teaching Hospital, Accra, Ghana involving pre-eclamptic women between the ages 18 and 45 years who gave written informed consent. Urinary isoprostane levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit whereas the Total Anti-oxidant Power in urine samples was determined using Total Antioxidant Power Colorimetric Microplate Assay kit. The data obtained were analyzed using MEGASTAT statistical software package. We included 102 pre-eclamptic women comprising 68 (66.7%) and 34 (33.3%) with early-onset and late-onset pre-eclampsia respectively. There were no statistically significant differences between the mean maternal age, haematological indices, serum ALT, AST, ALT, albumin, urea, creatinine uric acid and total protein at the time of diagnosis. The mean gestational age at diagnosis of early and late onset pre-eclampsia were 31.65 ± 0.41 and 38.03 ± 0.21 respectively (p ˂ 0.001). Also, there were statistically significant differences between the diastolic blood pressure (BP), systolic BP and mean arterial pressure (MAP) at diagnosis of pre-eclampsia in the two categories. The mean urinary Isoprostane excretion was significantly higher in the early onset pre-eclamptic group (3.04 ± 0.34 ng/mg Cr) compared to that of the late onset pre-eclamptic group (2.36 ± 0.45 ng/mg Cr), (p=0.019). Urinary total

Clinical features of adult-onset chronic active Epstein-Barr virus infection: a retrospective analysis.

PubMed

Arai, Ayako; Imadome, Ken-Ichi; Watanabe, Yuko; Yoshimori, Mayumi; Koyama, Takatoshi; Kawaguchi, Takeharu; Nakaseko, Chiaki; Fujiwara, Shigeyoshi; Miura, Osamu

2011-05-01

We performed a retrospective analysis of patients with adult-onset chronic active Epstein-Barr virus infection (CAEBV). First, we analyzed five patients (aged 28-72) diagnosed at our hospitals with EBV-infected clonally proliferating T cells. Four patients were administered cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) chemotherapy, but no remarkable decrease of viral load was observed in three of the patients. The other patient died 19 days after initiation of CHOP treatment due to disease progression. Addition of high-dose cytarabine to the regimens of two of the patients was discontinued shortly after administration, due to the development of grade 4 pericardial effusion. Together, these regimens may be insufficient for treating adult-onset CAEBV. We next reviewed 23 adult-onset CAEBV patients, adding 18 previously reported patients to the five patients described in the present study. T cells were frequently infected (87%), whereas NK- and T-cell types are known to be almost equally prevalent in childhood-onset cases. The time duration from the onset of disease to initiation of treatment averaged 20 months. Reports showed that 12 patients died; seven patients died at an average of 8 months after initiation of treatment. Patients' disease courses seemed to be rapidly progressive and more aggressive than those of childhood-onset cases. More cases must be studied to clarify clinical features and establish an optimal treatment strategy.

The prevention of early-onset neonatal group B streptococcal disease.

PubMed

Money, Deborah; Allen, Victoria M

2013-10-01

To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal disease. The key revisions in this updated guideline include changed recommendations for regimens for antibiotic prophylaxis, susceptibility testing, and management of women with pre-labour rupture of membranes. Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use. Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated. Published literature was retrieved through searches of MEDLINE, CINAHL, and The Cochrane Library from January 1980 to July 2012 using appropriate controlled vocabulary and key words (group B streptococcus, antibiotic therapy, infection, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). The recommendations in this guideline are designed to help clinicians identify and manage pregnancies at risk for neonatal group B streptococcal disease to optimize maternal and perinatal outcomes. No cost-benefit analysis is provided. There is good evidence based on randomized control trial data that in women with pre-labour rupture of membranes at term who are colonized with group B streptococcus, rates of neonatal infection are

Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases.

PubMed

Chen, Qi; Wang, Yao; Zhao, Min; Hyett, Jonathan; da Silva Costa, Fabricio; Nie, Guiying

2016-07-01

Preeclampsia is a pregnancy specific disorder affecting 3-5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation. Serum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n=16, late-onset n=18) and 66 gestation-age-matched controls, and sera at 11-13weeks of pregnancy from women who later did (n=36) or did not (n=33) develop late-onset preeclampsia, were examined for GDF15 by ELISA. Serum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11-13weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia. Serum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Indoor tanning and risk of early-onset basal cell carcinoma

PubMed Central

Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

2011-01-01

Background Despite a rise in incidence of basal cell carcinoma (BCC) among young people and the ubiquity of indoor tanning in this population, few epidemiologic studies have investigated this exposure-disease relationship. Objective Evaluate the association between indoor tanning and early-onset BCC. Methods BCC cases (n=376) and controls with minor benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on ever indoor tanning, age of initiation, frequency, duration, burns while tanning, and type of tanning device during an in-person interview. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariate logistic regression with never indoor tanners as the referent group. Results Ever indoor tanning was associated with a 69% increased risk of early-onset BCC (95% CI=1.15-2.48). This association was stronger among women (OR=2.14, 95% CI=1.31-3.47), for multiple BCCs (OR=2.16, 95% CI=1.26-3.70), and for BCCs on the trunk and extremities (OR=2.81, 95% CI=1.57-5.02). Risk increased dose-dependently with years used regular indoor tanning devices (p-trend=0.003), number of overall burns (p-trend=<0.001) and burns to biopsy site (p-trend=<0.001) from indoor tanning. Approximately one-quarter (27%) of early-onset BCCs (or 43% among women) could be prevented if individuals never tanned indoors. Limitations Potential recall bias of indoor tanning by cases and generalizability of the control population suggest replication in other studies is warranted. Conclusions Indoor tanning was a strong risk factor for early-onset BCC, particularly among women. Indoor tanning should continue to be targeted by both policy-based and behavioral interventions, as the impact on BCC-associated morbidity may be substantial. PMID:22153793

Early Onset Diabetes - Genetic And Hormonal Analysis In Pakistani Population.

PubMed

Wahid, Maryam; Kamran, Mohammad

2016-01-01

Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population.

In vivo intratumoral Epstein-Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications.

PubMed

Gonzalez-Farre, Blanca; Rovira, Jordina; Martinez, Daniel; Valera, Alexandra; Garcia-Herrera, Adriana; Marcos, Maria Angeles; Sole, Carla; Roue, Gael; Colomer, Dolors; Gonzalvo, Elena; Ribera-Cortada, Imma; Araya, Monica; Lloreta, Josep; Colomo, Luis; Campo, Elias; Lopez-Guillermo, Armando; Martinez, Antonio

2014-12-01

Post-transplant lymphoproliferative disorders are life-threatening complications following hematopoietic or solid organ transplantation. They represent a spectrum of mostly EBV-driven lymphoplasmacytic proliferations. While the oncogenic effect of EBV is related to latent infection, lytic infection also has a role in lymphomagenesis. In vitro, EBV replication is linked to plasma cell differentiation and XBP1 activation, although this phenomenon has never been addressed in vivo. We analyzed for the first time latent and lytic intratumoral EBV infection in a series of 35 adult patients with a diagnosis of post-transplant lymphoproliferative disorder (26M/9F, median age 54 years). A complete EBV study was performed including the analysis of the latent EBER, latent membrane protein-11, and EBV nuclear antigens as well as the immediate-early BZLF1/ZEBRA and early BMRF1/EADE31 lytic genes. XBP1 activation was assessed by nuclear protein expression. EBV infection was observed in 28 (80%) cases being latency II and III the most frequently observed 22 (79%). Intratumoral EBV replication was detected in 17 (60%) cases. Among these, XBP1 activation was observed in 11/12 evaluable cases associated with strong cytoplasmic immunoglobulin expression consistent with plasma cell differentiation. Intriguingly, the combination of latency III infection and EBV replication identified a high-risk subgroup of patients with significantly shorter survival (overall survival at 1 year 18% vs 48%) and early-onset (median of 7 vs 26 months) post-transplant lymphoproliferative disorder. Moreover, these patients appear to be more heavily immunosuppressed, so they exhibit lower rates of rejection and graft vs host disease but higher rates of cytomegalovirus reactivation. In conclusion, EBV replication is associated with plasma cell differentiation and XBP1 activation with prognostic implications. Both latency III and lytic EBV infection are related to aggressive and early-onset post

Does theory of mind performance differ in children with early-onset and regressive autism?

PubMed

Matthews, Nicole L; Goldberg, Wendy A; Lukowski, Angela F; Osann, Kathryn; Abdullah, Maryam M; Ly, Agnes R; Thorsen, Kara; Spence, M Anne

2012-01-01

A deficit in theory of mind (ToM), or the ability to infer the mental states of others, has been implicated as one of the major characteristics of Autism Spectrum Disorder (ASD); however, little attention has been devoted to possible differences in ToM ability within ASD. The current study examined ToM performance in children with early-onset autism and regressive autism in comparison to typically developing children. Results indicated that children in the regressive autism group performed significantly better than the early-onset autism group on the non-verbal appearance-reality task. Additionally, Fisher's exact tests indicated a pattern of lowest scores in the early-onset group and highest scores in the typically developing group, whereas the regressive autism group tended to score in between the early-onset and typically developing groups. The apparent heterogeneity in ToM performance within ASD could account for the lack of universality in ToM ability found in previous studies. © 2011 Blackwell Publishing Ltd.

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

PubMed Central

Lawn, Joy E; Bianchi-Jassir, Fiorella; Russell, Neal J; Kohli-Lynch, Maya; Tann, Cally J; Hall, Jennifer; Madrid, Lola; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Heath, Paul T; Ip, Margaret; Le Doare, Kirsty; Madhi, Shabir A; Rubens, Craig E; Saha, Samir K; Schrag, Stephanie; Sobanjo-ter Meulen, Ajoke; Vekemans, Johan; Seale, Anna C

2017-01-01

Abstract Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination. PMID:29117323

Early hospital discharge of infants born to group B streptococci-positive mothers: a decision analysis.

PubMed

Berger, M B; Xu, X; Williams, J A; Van de Ven, C J M; Mozurkewich, E L

2012-03-01

To compare the cost-effectiveness of an additional 24-hour inpatient observation for asymptomatic term neonates born to group B streptococcus (GBS)-colonised mothers with adequate intrapartum antibiotic prophylaxis (IAP) after an initial 24-hour in-hospital observation. Cost-effectiveness analysis from a societal perspective. United States. Asymptomatic term neonates born to GBS-colonised mothers with IAP after an initial 24-hour in-hospital observation. Monte Carlo simulation for a decision tree model incorporating the following chance events: development of GBS sepsis during the second 24 hours of life, development of GBS sepsis between 48 hours and 7 days of life, prompt versus delayed treatment for sepsis, neonatal mortality and long-term health sequelae. Expected cost and quality-adjusted life years (QALYs), Incremental cost-effectiveness ratio (ICER). Delayed, versus early, hospital discharge results in similar mean expected QALYs, but substantially higher expected cost. The mean difference in QALY is 0.00016 (95% CI 0.00005-0.00040), whereas the mean difference in cost is $1170.96 (95% CI $750.13-1584.32). The ICER is estimated to be $9,771,520.87 per QALY (95% CI $2,573,139.89-24,407,017.82). The proportion of early-onset GBS that develops during the second 24 hours of life, the cost of 24 hours of inpatient observation, and the probability of long-term sequelae following prompt versus delayed treatment play important roles in determining the cost-effectiveness of delayed hospital discharge. Cost-effectiveness analysis suggests that with adequate IAP, discharging asymptomatic term neonates to home after 24 hours is the preferred approach compared with 48 hours inpatient observation. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Isolated early onset anemia after rh isoimmunization: a unique presentation in 3 neonates.

PubMed

Louis, Deepak; Oberoi, Sapna; Sundaram, Venkataseshan; Trehan, Amita

2010-08-01

Rh isoimmunization manifesting as isolated early onset neonatal anemia has not been reported. We describe the presentation of 3 infants who manifested with isolated early severe anemia. All the infants presented early (3 to 7 d of age) with severe pallor. None had clinically significant jaundice. Evidence for hemolysis was present in all and their direct antiglobulin test was positive. To reduce the hemolysis, immunoglobulin was administered after which their hemoglobin improved. This report highlights the possibility of early onset anemia without significant jaundice as the sole manifestation of Rh isoimmunization and the possible beneficial role of immunoglobulin in them.

Neutral endopeptidase (EC 3.4.24.11) downregulates the onset of intestinal inflammation in the nematode infected mouse.

PubMed

Barbara, G; De Giorgio, R; Stanghellini, V; Corinaldesi, R; Cremon, C; Gerard, N; Gerard, C; Grady, E F; Bunnett, N W; Blennerhassett, P A; Collins, S M

2003-10-01

Substance P (SP) release from sensory nerves induces neurogenic inflammation. Neutral endopeptidase (NEP) degrades SP, thereby limiting its proinflammatory effects. Intestinal inflammation following Trichinella spiralis infection markedly downregulates NEP, resulting in diminished SP degradation, with unknown functional consequences. We hypothesised that diminished expression of NEP would exacerbate T spiralis induced enteritis. NEP knockout (NEP-/-) and wild-type (NEP+/+) mice were infected with T spiralis and studied at 6, 12, 24, and 48 hours post infection (PI). Tissue inflammation was quantified by computerised cell counting and myeloperoxidase activity (MPO). The leucocyte adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), and SP were assessed by immunohistochemistry. Before infection, the lack of NEP was not associated with changes in mucosal cellularity or MPO activity. Twelve hours PI, NEP-/- mice showed a 2.5-fold increase in MPO activity at a time when values in NEP+/+ mice were still within normal limits. MPO activity and cellularity peaked at 24 hours PI. This was accompanied by increased staining for both ICAM-1 and SP in NEP-/- mice. Infusion of rhNEP to NEP-/- mice significantly reduced MPO activity 24 hours PI. These findings demonstrate that NEP downregulates the early onset of nematode intestinal inflammation and that increased bioavailability of SP and overexpression of ICAM-1 in NEP-/- mice likely play a role in the earlier onset of intestinal inflammation.

Cytokine expression during early and late phase of acute Puumala hantavirus infection

PubMed Central

2011-01-01

Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

Variants of early-onset restrictive eating disturbances in middle childhood.

PubMed

Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

2016-01-01

This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. © 2015 Wiley Periodicals, Inc.

Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease

PubMed Central

Sheng, Ke; Fang, Weidong; Zhu, Yingcheng; Shuai, Guangying; Zou, Dezhi; Su, Meilan; Han, Yu; Cheng, Oumei

2016-01-01

HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans.Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state.Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset. Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age. Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset. PMID:27462265

Guillain Barré Syndrome is induced in Non-Obese Diabetic (NOD) mice following Campylobacter jejuni infection and is exacerbated by antibiotics.

PubMed

St Charles, J L; Bell, J A; Gadsden, B J; Malik, A; Cooke, H; Van de Grift, L K; Kim, H Y; Smith, E J; Mansfield, L S

2017-02-01

Campylobacter jejuni is a leading cause of bacterial gastroenteritis linked to several serious autoimmune sequelae such as the peripheral neuropathies Guillain Barré syndrome (GBS) and Miller Fisher syndrome (MFS). We hypothesized that GBS and MFS can result in NOD wild type (WT) mice or their congenic interleukin (IL)-10 or B7-2 knockouts secondary to C. jejuni infection. Mice were gavaged orally with C. jejuni strains HB93-13 and 260.94 from patients with GBS or CF93-6 from a patient with MFS and assessed for clinical neurological signs and phenotypes, anti-ganglioside antibodies, and cellular infiltrates and lesions in gut and peripheral nerve tissues. Significant increases in autoantibodies against single gangliosides (GM1, GQ1b, GD1a) occurred in infected NOD mice of all genotypes, although the isotypes varied (NOD WT had IgG1, IgG3; NOD B7-2 -/- had IgG3; NOD IL-10 -/- had IgG1, IgG3, IgG2a). Infected NOD WT and NOD IL-10 -/- mice also produced anti-ganglioside antibodies of the IgG1 isotype directed against a mixture of GM1/GQ1b gangliosides. Phenotypic tests showed significant differences between treatment groups of all mouse genotypes. Peripheral nerve lesions with macrophage infiltrates were significantly increased in infected mice of NOD WT and IL-10 -/- genotypes compared to sham-inoculated controls, while lesions with T cell infiltrates were significantly increased in infected mice of the NOD B7-2 -/- genotype compared to sham-inoculated controls. In both infected and sham inoculated NOD IL-10 -/- mice, antibiotic treatment exacerbated neurological signs, lesions and the amount and number of different isotypes of antiganglioside autoantibodies produced. Thus, inducible mouse models of post-C. jejuni GBS are feasible and can be characterized based on evaluation of three factors-onset of GBS clinical signs/phenotypes, anti-ganglioside autoantibodies and nerve lesions. Based on these factors we characterized 1) NOD B-7 -/- mice as an acute

CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

PubMed

Elia, M; Falco, M; Ferri, R; Spalletta, A; Bottitta, M; Calabrese, G; Carotenuto, M; Musumeci, S A; Lo Giudice, M; Fichera, M

2008-09-23

To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations. Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis. We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep. This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

Stabilization in early adult-onset myopia with corneal refractive therapy.

PubMed

González-Méijome, José M; Carracedo, Gonzalo; Lopes-Ferreira, Daniela; Faria-Ribeiro, Miguel A; Peixoto-de-Matos, Sofia C; Queirós, António

2016-02-01

To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between -1.50 and -2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ) lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January-December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Global and Temporal Cortical Folding in Patients with Early-Onset Schizophrenia

ERIC Educational Resources Information Center

Penttila, Jani; Paillere-Martinot, Marie-Laure; Martinot, Jean-Luc; Mangin, Jean-Francois; Burke, Lisa; Corrigall, Richard; Frangou, Sophia; Cachia, Arnaud

2008-01-01

Disturbances in the temporal lobes and alterations in cortical folding in adult on-set schizophrenia are studied using magnetic resonance T1 images of 51 patients. The study showed that patients with early on-set schizophrenia had lower global sulcal indices in both hemispheres and the left collateral sulcus has a lower sulcal index irrespective…

Atypical antipsychotics in the treatment of early-onset schizophrenia

PubMed Central

Hrdlicka, Michal; Dudova, Iva

2015-01-01

Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226

Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

PubMed

Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

2004-09-30

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

Early Identification of Autism: Early Characteristics, Onset of Symptoms, and Diagnostic Stability

ERIC Educational Resources Information Center

Webb, Sara Jane; Jones, Emily J. H.

2009-01-01

In the first year of life, infants who later go on to develop autistic spectrum disorders (ASD) may exhibit subtle disruptions in social interest and attention, communication, temperament, and head circumference growth that occur prior to the onset of clinical symptoms. These disruptions may reflect the early course of ASD development and may also…

Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.

PubMed

Sikich, Linmarie; Frazier, Jean A; McClellan, Jon; Findling, Robert L; Vitiello, Benedetto; Ritz, Louise; Ambler, Denisse; Puglia, Madeline; Maloney, Ann E; Michael, Emily; De Jong, Sandra; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie; Pierson, Leslie; McNamara, Nora K; Delporto-Bedoya, Denise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2008-11-01

Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia

Social Status of Adolescents with an Early Onset of Externalizing Behavior: The SNARE Study

ERIC Educational Resources Information Center

Franken, Aart; Harakeh, Zeena; Veenstra, Rene; Vollebergh, Wilma; Dijkstra, Jan Kornelis

2017-01-01

This study investigated the social status (i.e., popularity, likeability, and friendships) of adolescents with an early onset of externalizing behavior (i.e., alcohol use, tobacco use, and antisocial behavior). Building on Moffitt's dual-taxonomy model, it was hypothesized that early onset adolescents were more popular, but not necessarily more…

Impact of Topically Administered Steroids, Antibiotics, and Sodium Hyaluronate on Bleb-Related Infection Onset: The Japan Glaucoma Society Survey of Bleb-Related Infection Report 4

PubMed Central

Yamamoto, Tetsuya; Imaizumi, Kimihiro; Sekiryu, Tetsuju

2017-01-01

Purpose To investigate the impact of topically administered ophthalmic medications on the onset and severity of bleb-related infections. Methods Data obtained from 104 eyes of 104 patients with bleb-related infections were analyzed. We assigned an infection stage to each eye (stage 1–4) and analyzed the onset severity. Results Steroids and antibiotics were routinely administered to 13 (12.5%) and 42 (40.4%) eyes, respectively. The median stage of steroid-administered eyes was 3 versus 1 for eyes without steroid administration (P = 0.012). The median duration from surgery to infection for the steroid-administered eyes was 2.0 years versus 5.8 years for eyes without steroid administration (P = 0.030). The median duration from surgery to infection for the antibiotic-administered eyes was 6.4 years versus 3.9 years for eyes without antibiotic administration (P = 0.025). Multiple logistic regression analysis revealed that infections were severe in the steroid-administered eyes (odds ratio: 4.57). No infections developed within 16 weeks postoperatively. No relationship was detected between sodium hyaluronate and the analyzed factors. Conclusions Topical steroid administration beyond the immediate postoperative period may affect severe and earlier onset bleb-related infections. Conversely, topical antibiotic administration may be effective in suppressing earlier onset bleb-related infections. PMID:29138694

Cognitive ability in young adulthood predicts risk of early-onset dementia in Finnish men.

PubMed

Rantalainen, Ville; Lahti, Jari; Henriksson, Markus; Kajantie, Eero; Eriksson, Johan G; Räikkönen, Katri

2018-06-06

To test if the Finnish Defence Forces Basic Intellectual Ability Test scores at 20.1 years predicted risk of organic dementia or Alzheimer disease (AD). Dementia was defined as inpatient or outpatient diagnosis of organic dementia or AD risk derived from Hospital Discharge or Causes of Death Registers in 2,785 men from the Helsinki Birth Cohort Study, divided based on age at first diagnosis into early onset (<65 years) or late onset (≥65 years). The Finnish Defence Forces Basic Intellectual Ability Test comprises verbal, arithmetic, and visuospatial subtests and a total score (scores transformed into a mean of 100 and SD of 15). We used Cox proportional hazard models and adjusted for age at testing, childhood socioeconomic status, mother's age at delivery, parity, participant's birthweight, education, and stroke or coronary heart disease diagnosis. Lower cognitive ability total and verbal ability (hazard ratio [HR] per 1 SD disadvantage >1.69, 95% confidence interval [CI] 1.01-2.63) scores predicted higher early-onset any dementia risk across the statistical models; arithmetic and visuospatial ability scores were similarly associated with early-onset any dementia risk, but these associations weakened after covariate adjustments (HR per 1 SD disadvantage >1.57, 95% CI 0.96-2.57). All associations were rendered nonsignificant when we adjusted for participant's education. Cognitive ability did not predict late-onset dementia risk. These findings reinforce previous suggestions that lower cognitive ability in early life is a risk factor for early-onset dementia. © 2018 American Academy of Neurology.

Early-Onset Psychosis in Youth with Intellectual Disability

ERIC Educational Resources Information Center

Friedlander, R. I.; Donnelly, T.

2004-01-01

Accurate diagnosis of psychotic disorders may be very difficult in youth with intellectual disabilities. The authors reviewed the assessment, treatment and follow-up of 21 youths with ID referred because of early onset of psychotic symptoms. Just over one half of the patients had a diagnosis of schizophrenia or schizo-affective disorder. One third…

Mapping callosal morphology in early- and late-onset elderly depression: an index of distinct changes in cortical connectivity.

PubMed

Ballmaier, Martina; Kumar, Anand; Elderkin-Thompson, Virginia; Narr, Katherine L; Luders, Eileen; Thompson, Paul M; Hojatkashani, Cornelius; Pham, Daniel; Heinz, Andreas; Toga, Arthur W

2008-06-01

There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are region-specific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age = 68.00, SD+/-5.83), 22 patients with late-onset depression (mean age = 74.50, SD+/-8.09) and 34 elderly control subjects (mean age = 72.38; SD+/-6.93) were studied. Using 3D MRI data, novel mesh-based geometrical modeling methods were applied to compare the midsagittal thickness of the corpus callosum at high spatial resolution between groups. Neuropsychological correlates of midsagittal callosal area differences were additionally investigated in a subsample of subjects. Depressed patients exhibited significant callosal thinning in the genu and splenium compared to controls. Significant callosal thinning was restricted to the genu in early-onset patients, but patients with late-onset depression exhibited significant callosal thinning in both the genu and splenium relative to controls. The splenium of the corpus callosum was also significantly thinner in subjects with late- vs early-onset depression. Genu and splenium midsagittal areas significantly correlated with memory and attention functioning among late-onset depressed patients, but not early-onset depressed patients or controls. Circumscribed structural alterations in callosal morphology may distinguish late- from early-onset depression in the elderly. These findings suggest distinct abnormalities of cortical connectivity in late- and early-onset elderly depression with possible influence on the course of illness. Patients with a late onset of depression may be at higher risk of illness progression and eventually dementia conversion than early-onset depression, with potentially important implications for research and therapy.

[Treatment of early onset scoliosis : How far can we go?].

PubMed

Studer, D; Hasler, C C; Schulze, A

2015-11-01

Recently, inconsistent definitions of early onset scoliosis (EOS) and a wide variety of treatment options have been observed. To clearly define the term EOS, to depict non-operative and operative treatment options, and to present the limitations of the boundaries of these techniques. Review of the literature, including conference presentations and expert opinions, in addition to personal experiences. Early onset scoliosis (EOS) refers to spine deformity that is present before 10 years of age, regardless of etiology. All existing operative treatment options share a high risk of complications. Therefore, non-operative treatment should act as a time-buying approach to postpone surgery. Awareness of treatment options and their specific indications, in addition to respecting each patient's individual needs and feasibilities, are crucial for the optimal outcome.

Global Broadcast Service (GBS)

DTIC Science & Technology

2014-12-01

Frequency Follow-On ( UFO ) satellites, leased commercial satellite transponders, and the Wideband Global SATCOM constellation. Theater Injection Point...each IOC: IOC 1: - PIPs operational on UFO satellites 8, 9, 10. - Full Satellite Broadcast Manager capability. - Field 20% of JPO Receive Suites (19...Independently assess system capabilities. - Augment UFO GBS with leased commercial satellite services to cover gaps over CONUS. - Demonstrate smart push and

Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.

PubMed

Belcastro, Vincenzo; Caraballo, Roberto Horacio; Romeo, Antonino; Striano, Pasquale

2013-12-01

Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia.

PubMed

Boyd, Heather A; Tahir, Hassaan; Wohlfahrt, Jan; Melbye, Mads

2013-12-01

Preeclampsia encompasses multiple conditions of varying severity. We examined the recurrence and familial aggregation of preeclampsia by timing of onset, which is a marker for severity. We ascertained personal and family histories of preeclampsia for women who delivered live singletons in Denmark in 1978-2008 (almost 1.4 million pregnancies). Using log-linear binomial regression, we estimated risk ratios for the associations between personal and family histories of preeclampsia and the risk of early-onset (before 34 weeks of gestation, which is typically the most severe), intermediate-onset (at 34-36 weeks of gestation), and late-onset (after 36 weeks of gestation) preeclampsia. Previous early-, intermediate-, or late-onset preeclampsia increased the risk of recurrent preeclampsia with the same timing of onset 25.2 times (95% confidence interval (CI): 21.8, 29.1), 19.7 times (95% CI: 17.0, 22.8), and 10.3 times (95% CI: 9.85, 10.9), respectively, compared with having no such history. Preeclampsia in a woman's family was associated with a 24%-163% increase in preeclampsia risk, with the strongest associations for early- and intermediate-onset preeclampsia in female relatives. Preeclampsia in the man's family did not affect a woman's risk of early-onset preeclampsia and was only weakly associated with her risks of intermediate- and late-onset preeclampsia. Early-onset preeclampsia appears to have the largest genetic component, whereas environmental factors likely contribute most to late-onset preeclampsia. The role of paternal genes in the etiology of preeclampsia appears to be limited.

CHANGES IN HUMORAL IMMUNITY OCCURRING DURING THE EARLY STAGES OF EXPERIMENTAL PNEUMOCOCCUS INFECTION

PubMed Central

Terrell, Edward E.

1930-01-01

A study was made of the changes in humoral immunity occurring during the early phases of experimental pneumococcus infection in the dog and cat. The methods devised by Robertson and Sia were employed to demonstrate the presence of anti-pneumococcus properties in the serum of animals naturally resistant to this micro-organism. It was found that with a generalized and overwhelming infection accompanied by early blood invasion, there was a prompt and rapid decrease in the concentration of natural humoral immune bodies which frequently disappeared entirely by the time of death. This same early diminution of humoral immune substances, opsonins, agglutinins, and pneumococcidal-promoting bodies was observed in animals that survived a moderately severe generalized infection but the concentration of immune bodies rose again with the onset of recovery. The decrease in concentration of humoral immune substances during a severe generalized infection appeared to be due to the combination of "S" substance with the normal immune bodies. When the pneumococcus infection was more localized as in the case of true lobar pneumonia a quite different sequence of events was observed to occur. Several animals, in which extensive lobar pneumonia was produced, showed the presence in quantity of humoral immune bodies in the blood throughout the course of an infection terminating fatally. These findings suggest that after the inception of pneumococcus infection in the dog and cat the chief function of natural anti-pneurnococcus substances in the blood is to limit or prevent blood invasion. When pneumococcic infection is localized these circulating antibodies appear to have little effect either in preventing the spread of the process or determining the outcome of the disease. PMID:19869701

Exome Sequencing Frequently Reveals the Cause of Early-Onset Chronic Kidney Disease

PubMed Central

Vivante, Asaf; Hildebrandt, Friedhelm

2016-01-01

The primary causes of chronic kidney disease (CKD) in children differ from those of adult onset CKD. In the United States the most common diagnostic groups of CKD that manifests before 25 years of age are: i) congenital anomalies of the kidneys and urinary tract (CAKUT) (49.1%), ii) steroid-resistant nephrotic syndrome (SRNS) (10.4%), iii) chronic glomerulonephritis (8.1%), and iv) renal cystic ciliopathies (5.3 %), encompassing >70% of CKD together. Recent findings suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. High-throughput sequencing has very recently rendered identification of causative mutations in this high number of genes feasible. Molecular genetic diagnostics in early onset-CKD (before the age of 25 years) will, i) provide patients and families with a molecular genetic diagnosis, ii) generate new insights into diseases mechanisms, iii) allow etiology-based classification of patient cohorts for clinical studies and, iv) may have consequences for personalized treatment and prevention of CKD. In this review, we will discuss the implications of next-generation sequencing for clinical genetic diagnostics and discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and therapeutic implications. PMID:26750453

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

PubMed

Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

2017-12-01

To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

Neutral endopeptidase (EC 3.4.24.11) downregulates the onset of intestinal inflammation in the nematode infected mouse

PubMed Central

Barbara, G; De Giorgio, R; Stanghellini, V; Corinaldesi, R; Cremon, C; Gerard, N; Gerard, C; Grady, E F; Bunnett, N W; Blennerhassett, P A; Collins, S M

2003-01-01

Background and aims: Substance P (SP) release from sensory nerves induces neurogenic inflammation. Neutral endopeptidase (NEP) degrades SP, thereby limiting its proinflammatory effects. Intestinal inflammation following Trichinella spiralis infection markedly downregulates NEP, resulting in diminished SP degradation, with unknown functional consequences. We hypothesised that diminished expression of NEP would exacerbate T spiralis induced enteritis. Methods: NEP knockout (NEP−/−) and wild-type (NEP+/+) mice were infected with T spiralis and studied at 6, 12, 24, and 48 hours post infection (PI). Tissue inflammation was quantified by computerised cell counting and myeloperoxidase activity (MPO). The leucocyte adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), and SP were assessed by immunohistochemistry. Results: Before infection, the lack of NEP was not associated with changes in mucosal cellularity or MPO activity. Twelve hours PI, NEP−/− mice showed a 2.5-fold increase in MPO activity at a time when values in NEP+/+ mice were still within normal limits. MPO activity and cellularity peaked at 24 hours PI. This was accompanied by increased staining for both ICAM-1 and SP in NEP−/− mice. Infusion of rhNEP to NEP−/− mice significantly reduced MPO activity 24 hours PI. Conclusions: These findings demonstrate that NEP downregulates the early onset of nematode intestinal inflammation and that increased bioavailability of SP and overexpression of ICAM-1 in NEP−/− mice likely play a role in the earlier onset of intestinal inflammation. PMID:12970139

Comparison of Neuropsychological Functioning Between Adults With Early- and Late-Onset DSM-5 ADHD.

PubMed

Lin, Yu-Ju; Gau, Susan Shur-Fen

2017-09-01

We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and non-ADHD controls. We divided the participants, aged 17 to 40 years, into three groups-(a) ADHD, onset <7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls ( n = 148)-and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing Automated Battery. Both ADHD groups had deficits in attention and signal detectability, spatial working memory, and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups in neuropsychological functioning. DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

Whole Exome Analysis of Early Onset Alzheimer’s Disease

DTIC Science & Technology

2016-04-01

Early Onset Alzheimer’s Disease 5a. CONTRACT NUMBER W81XWH-12-1-0013 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Margaret A. Pericak...relationship between SORL1, AD, and Parkinsonism . 16 Appendix V: ABCA7 Frameshift Deletion Associated with Alzheimer’s Disease in African Americans...onset Alzheimer disease identified using whole-exome sequencing G. W. Beecham1, B. W. Kunkle1, B. Vardarajan2, P. L. Whitehead1, S . Rolati1, E. R

Evidence for apolipoprotein E {epsilon}4 association in early-onset Alzheimer`s patients with late-onset relatives

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

Perez-Tur, J.; Delacourte, A.; Chartier-Harlin, M.C.

1995-12-18

Recently several reports have extended the apolipoprotein E (APOE) {epsilon}4 association found in late-onset Alzheimer`s disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset {<=}60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE {epsilon}A allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that, for an individual, bearing at least one {epsilon}4 allele increases both the risk of AD beforemore » age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases. 19 refs., 3 tabs.« less

Acute and chronic neurological consequences of early-life Zika virus infection in mice.

PubMed

Nem de Oliveira Souza, Isis; Frost, Paula S; França, Julia V; Nascimento-Viana, Jéssica B; Neris, Rômulo L S; Freitas, Leandro; Pinheiro, Daniel J L L; Nogueira, Clara O; Neves, Gilda; Chimelli, Leila; De Felice, Fernanda G; Cavalheiro, Ésper A; Ferreira, Sergio T; Assunção-Miranda, Iranaia; Figueiredo, Claudia P; Da Poian, Andrea T; Clarke, Julia R

2018-06-06

Although congenital Zika virus (ZIKV) exposure has been associated with microcephaly and other neurodevelopmental disorders, long-term consequences of perinatal infection are largely unknown. We evaluated short- and long-term neuropathological and behavioral consequences of neonatal ZIKV infection in mice. ZIKV showed brain tropism, causing postnatal-onset microcephaly and several behavioral deficits in adulthood. During the acute phase of infection, mice developed frequent seizures, which were reduced by tumor necrosis factor-α (TNF-α) inhibition. During adulthood, ZIKV replication persisted in neonatally infected mice, and the animals showed increased susceptibility to chemically induced seizures, neurodegeneration, and brain calcifications. Altogether, the results show that neonatal ZIKV infection has long-term neuropathological and behavioral complications in mice and suggest that early inhibition of TNF-α-mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

PubMed

Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

2015-01-01

After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis.

PubMed

Randis, Tara M; Rice, Madeline Murguia; Myatt, Leslie; Tita, Alan T N; Leveno, Kenneth J; Reddy, Uma M; Varner, Michael W; Thorp, John M; Mercer, Brian M; Dinsmoor, Mara J; Ramin, Susan M; Carpenter, Marshall W; Samuels, Philip; Sciscione, Anthony; Tolosa, Jorge E; Saade, George; Sorokin, Yoram

2018-05-23

To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16-5.08)] and confirmed [OR 4.93 (1.65-14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70-2.61)], respiratory distress [OR 3.14 (2.16-4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01-3.60)] and 4-7 [OR 1.71 (1.43-2.04)] and 5 min Apgar score of 4-7 [OR 1.67 (1.17-2.37)] (vs. 8-10). Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis.

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

PubMed

Lawn, Joy E; Bianchi-Jassir, Fiorella; Russell, Neal J; Kohli-Lynch, Maya; Tann, Cally J; Hall, Jennifer; Madrid, Lola; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Heath, Paul T; Ip, Margaret; Le Doare, Kirsty; Madhi, Shabir A; Rubens, Craig E; Saha, Samir K; Schrag, Stephanie; Sobanjo-Ter Meulen, Ajoke; Vekemans, Johan; Seale, Anna C

2017-11-06

Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Estimating time since infection in early homogeneous HIV-1 samples using a poisson model

PubMed Central

2010-01-01

Background The occurrence of a genetic bottleneck in HIV sexual or mother-to-infant transmission has been well documented. This results in a majority of new infections being homogeneous, i.e., initiated by a single genetic strain. Early after infection, prior to the onset of the host immune response, the viral population grows exponentially. In this simple setting, an approach for estimating evolutionary and demographic parameters based on comparison of diversity measures is a feasible alternative to the existing Bayesian methods (e.g., BEAST), which are instead based on the simulation of genealogies. Results We have devised a web tool that analyzes genetic diversity in acutely infected HIV-1 patients by comparing it to a model of neutral growth. More specifically, we consider a homogeneous infection (i.e., initiated by a unique genetic strain) prior to the onset of host-induced selection, where we can assume a random accumulation of mutations. Previously, we have shown that such a model successfully describes about 80% of sexual HIV-1 transmissions provided the samples are drawn early enough in the infection. Violation of the model is an indicator of either heterogeneous infections or the initiation of selection. Conclusions When the underlying assumptions of our model (homogeneous infection prior to selection and fast exponential growth) are met, we are under a very particular scenario for which we can use a forward approach (instead of backwards in time as provided by coalescent methods). This allows for more computationally efficient methods to derive the time since the most recent common ancestor. Furthermore, the tool performs statistical tests on the Hamming distance frequency distribution, and outputs summary statistics (mean of the best fitting Poisson distribution, goodness of fit p-value, etc). The tool runs within minutes and can readily accommodate the tens of thousands of sequences generated through new ultradeep pyrosequencing technologies. The tool

A case report: a dog with acute onset of Hepatozoon canis infection.

PubMed

Sakuma, Masato; Nakahara, Yoshitaka; Suzuki, Hiroyuki; Uchimura, Masato; Sekiya, Zin; Setoguchi, Asuka; Endo, Yasuyuki

2009-06-01

We present a clinical overview of a dog with acute onset of Hepatozoon canis infection. A stray female beagle dog of unknown age was referred to Kagoshima University showing anemia. Blood tests revealed the presence of anemia, thrombocytopenia, hyperproteinemia, polyclonal gammopathy, hypoalbuminemia, and elevated creatine kinase and alkaline phosphatase activities. In addition, capsule-like organisms were detected in the cytoplasm of approximately 50% of neutrophils in blood smears. H. canis infection was confirmed by polymerase chain reaction and DNA sequencing analyses. Amplified DNA fragments revealed 100% identity to the 18S ribosomal RNA gene of H. canis. The clinical symptoms improved after the administration of antibiotics. Hepatozoonosis in dogs is rare, but veterinarians should be alert to its possible acute onset.

Human Milk Oligosaccharides Exhibit Antimicrobial and Antibiofilm Properties against Group B Streptococcus.

PubMed

Ackerman, Dorothy L; Doster, Ryan S; Weitkamp, Jörn-Hendrik; Aronoff, David M; Gaddy, Jennifer A; Townsend, Steven D

2017-08-11

Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults. During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillbirth, and neonatal sepsis. Recently, breastfeeding has been thought to represent a potential mode of GBS transmission from mother to newborn, which might increase the risk for late-onset sepsis. Little is known, however, about the molecular components of breast milk that may support or prevent GBS colonization. In this study, we examine how human milk oligosaccharides (HMOs) affect the pathogenesis of GBS. HMOs from discrete donor samples were isolated and profiled by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Growth and biofilm assays show that HMOs from mothers of specific milk groups can modulate the growth and biofilm formation of GBS. High-resolution field-emission gun scanning electron microscopy (SEM) and confocal laser scanning microscopy confirmed the quantitative biofilm assays and demonstrated cell arrangement perturbations in bacterial cultures treated with specific oligosaccharides. These findings demonstrate that HMOs affect the growth and cell biology of GBS. Finally, this study provides the first example of HMOs functioning as antibiofilm agents against GBS.

Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

PubMed

Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

2018-01-01

To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

ERIC Educational Resources Information Center

Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.

2009-01-01

Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

The common single-nucleotide polymorphism rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

PubMed

Wan, Ji-Peng; Wang, Hong; Li, Chang-Zhong; Zhao, Han; You, Li; Shi, Dong-Hong; Sun, Xiu-Hua; Lv, Hong; Wang, Fei; Wen, Ze-Qing; Wang, Xie-Tong; Chen, Zi-Jiang

2014-11-01

Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. © The Author(s) 2014.

Preventing group B streptococcal infections in newborns.

PubMed

Porta, Kelly; Rizzolo, Denise

2015-03-01

Despite advances in intrapartum antibiotic prophylaxis (IAP), group B streptococcal infection continues to be a predominant cause of early-onset disease in neonates. About 2% of neonates exposed to group B Streptococcus develop clinical manifestations including sepsis, pneumonia, and meningitis. Screening in late pregnancy reduces the incidence of early-onset sepsis by more than 80%. Clinicians must be able to identify the risk factors and clinical manifestations of group B streptococcal infection and to understand management and prevention guidelines.

Cross-reactive antibodies against GM2 and CMV-infected fibroblasts in Guillain-Barré syndrome.

PubMed

Ang, C W; Jacobs, B C; Brandenburg, A H; Laman, J D; van der Meché, F G; Osterhaus, A D; van Doorn, P A

2000-04-11

To investigate whether anti-GM2 antibodies in patients with Guillain-Barré syndrome (GBS) are induced by molecular mimicry with cytomegalovirus (CMV). Antibodies against ganglioside GM2 are frequently present in the serum from GBS patients with an antecedent infection with CMV. The authors detected inhibition of anti-GM2 reactivity after incubation of GM2-reactive serum samples with fibroblasts infected with a GBS-associated CMV strain. Control sera consisted of GQ1b-reactive samples, and control antigens included uninfected fibroblasts and fibroblasts that were infected with other herpes viruses. Serum immunoglobulin M reactivity with GM2 was decreased in a dose-dependent manner after incubation with CMV-infected fibroblasts. Incubation of anti-GM2-positive serum samples with uninfected fibroblasts and fibroblasts infected with varicella zoster virus did not inhibit anti-GM2 reactivity, whereas this reactivity was slightly decreased after incubation with herpes simplex virus type 1 in one patient. Antibodies against ganglioside GQ1b did not react with CMV-infected fibroblasts. CMV-infected fibroblasts express gangliosidelike epitopes that recognize specifically anti-GM2 antibodies. These results support the hypothesis that antiganglioside antibodies in CMV-infected GBS patients are induced by molecular mimicry between GM2 and antigens that are induced by a CMV infection.

Early-onset scoliosis: current treatment.

PubMed

Cunin, V

2015-02-01

Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with

Neurological complications of Zika virus infection.

PubMed

Carod-Artal, Francisco Javier

2018-05-01

Zika virus (ZIKV) disease is a vector-borne infectious disease transmitted by Aedes mosquitoes. Recently, ZIKV has caused outbreaks in most American countries. Areas covered: Publications about neurological complications of ZIKV infection retrieved from pubmed searchers were reviewed, and reference lists and relevant articles from review articles were also examined. Vertical/intrauterine transmission leads to congenital infection and causes microcephaly and congenital ZIKV syndrome. ZIKV preferentially infects human neural progenitor cells and triggers cell apoptosis. ZIKV RNA has been identified in foetal brain tissue and brains of microcephalic infants who died; amniotic fluid and placentas of pregnant mothers; and umbilical cord, cerebro-spinal fluid and meninges of newborns. The increase in the number of Guillain-Barre syndrome (GBS) cases during the ZIKV outbreak in the Americas provides epidemiological evidence for the link between ZIKV infection and GBS. Less frequently reported ZIKV neurological complications include encephalitis/meningoencephalitis, acute disseminated encephalomyelitis, myelitis, cerebrovascular complications (ischemic infarction; vasculopathy), seizures and encephalopathy, sensory polyneuropathy and sensory neuronopathy. Analysis of GBS incidence could serve as an epidemiological 'marker' or sentinel for ZIKV disease and other neurological complications associated to ZIKV. Expert commentary: An expanding spectrum of neurological complications associated with ZIKV infection is being recognised.

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

PubMed

Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

2016-12-01

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms.

PubMed

Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin; Black, Kathleen; Fernandez, Maria Victoria; Budde, John; Ibanez, Laura; Deming, Yuetiva; Kapoor, Manav; Tosto, Giuseppe; Mayeux, Richard P; Holtzman, David M; Fagan, Anne M; Morris, John C; Bateman, Randall J; Goate, Alison M; Harari, Oscar

2018-02-01

To determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD). Polygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk. We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. The highest association of the PRS and risk (odds ratio [OR] = 2.27; P = 1.29 × 10 -7 ) was observed in sEOAD, followed by fLOAD (OR = 1.75; P = 1.12 × 10 -7 ) and sLOAD (OR = 1.40; P = 1.21 × 10 -3 ). The PRS was associated with cerebrospinal fluid ptau 181 -Aβ 42 on eADAD (P = 4.36 × 10 -2 ). Our analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The Role of Chronic Mesh Infection in Delayed-Onset Vaginal Mesh Complications or Recurrent Urinary Tract Infections: Results From Explanted Mesh Cultures.

PubMed

Mellano, Erin M; Nakamura, Leah Y; Choi, Judy M; Kang, Diana C; Grisales, Tamara; Raz, Shlomo; Rodriguez, Larissa V

2016-01-01

Vaginal mesh complications necessitating excision are increasingly prevalent. We aim to study whether subclinical chronically infected mesh contributes to the development of delayed-onset mesh complications or recurrent urinary tract infections (UTIs). Women undergoing mesh removal from August 2013 through May 2014 were identified by surgical code for vaginal mesh removal. Only women undergoing removal of anti-incontinence mesh were included. Exclusion criteria included any women undergoing simultaneous prolapse mesh removal. We abstracted preoperative and postoperative information from the medical record and compared mesh culture results from patients with and without mesh extrusion, de novo recurrent UTIs, and delayed-onset pain. One hundred seven women with only anti-incontinence mesh removed were included in the analysis. Onset of complications after mesh placement was within the first 6 months in 70 (65%) of 107 and delayed (≥6 months) in 37 (35%) of 107. A positive culture from the explanted mesh was obtained from 82 (77%) of 107 patients, and 40 (37%) of 107 were positive with potential pathogens. There were no significant differences in culture results when comparing patients with delayed-onset versus immediate pain, extrusion with no extrusion, and de novo recurrent UTIs with no infections. In this large cohort of patients with mesh removed for a diverse array of complications, cultures of the explanted vaginal mesh demonstrate frequent low-density bacterial colonization. We found no differences in culture results from women with delayed-onset pain versus acute pain, vaginal mesh extrusions versus no extrusions, or recurrent UTIs using standard culture methods. Chronic prosthetic infections in other areas of medicine are associated with bacterial biofilms, which are resistant to typical culture techniques. Further studies using culture-independent methods are needed to investigate the potential role of chronic bacterial infections in delayed vaginal mesh

Community-Onset Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Invasive Infections in Children in a University Hospital in France.

PubMed

Toubiana, Julie; Timsit, Sandra; Ferroni, Agnès; Grasseau, Marie; Nassif, Xavier; Lortholary, Olivier; Zahar, Jean-Ralph; Chalumeau, Martin

2016-03-01

Limited data is available on pediatric community-onset infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), but such infections may affect both the efficacy of empiric antibiotic therapy and the rational use of antibiotics.We retrospectively analyzed data from 2007 to 2012 for all children ≤16 years old with a positive ESBL-PE strain from usually sterile sites within 48 hours of admission in a tertiary hospital in France. We analyzed healthcare- and community-associated infections among community-onset infections. In total, 3612 Enterobacteriaceae isolates were collected; the prevalence of ESBL-PE infection increased over the study period, from 2.4% to 5.1% (P < 0.001). Among the 90 children with a first community-onset ESBL-PE infection, 58% (n = 52) had a healthcare-associated infection, and 87% of isolates were susceptible to amikacin. As compared with patients with community-associated infections, those with healthcare-associated infections had fewer urinary tract infections (UTIs) (86% vs 97%) and Escherichia coli infections (35% vs 84%) and more Klebsiella pneumoniae infections (46% vs 8%). Inappropriate empiric treatment was prescribed for 54 patients (64%), but a favorable outcome was observed in 46 of 49 (94%) and 1 of 5 (20%) patients with UTIs and non-UTIs, respectively (P < 0.001). Among patients with community-associated infections, 85% had at least 1 risk factor for ESBL-PE infections. In conclusion, the prevalence of community-onset ESBL-PE infections doubled during the study period. These infections mainly occurred among children with healthcare-associated criteria or identified risk factors. Amikacin is an alternative to carbapenems for empiric treatment because most of these infections involved urinary tract and susceptible isolates.

Community-Onset Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Invasive Infections in Children in a University Hospital in France

PubMed Central

Toubiana, Julie; Timsit, Sandra; Ferroni, Agnès; Grasseau, Marie; Nassif, Xavier; Lortholary, Olivier; Zahar, Jean-Ralph; Chalumeau, Martin

2016-01-01

Abstract Limited data is available on pediatric community-onset infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), but such infections may affect both the efficacy of empiric antibiotic therapy and the rational use of antibiotics. We retrospectively analyzed data from 2007 to 2012 for all children ≤16 years old with a positive ESBL-PE strain from usually sterile sites within 48 hours of admission in a tertiary hospital in France. We analyzed healthcare- and community-associated infections among community-onset infections. In total, 3612 Enterobacteriaceae isolates were collected; the prevalence of ESBL-PE infection increased over the study period, from 2.4% to 5.1% (P < 0.001). Among the 90 children with a first community-onset ESBL-PE infection, 58% (n = 52) had a healthcare-associated infection, and 87% of isolates were susceptible to amikacin. As compared with patients with community-associated infections, those with healthcare-associated infections had fewer urinary tract infections (UTIs) (86% vs 97%) and Escherichia coli infections (35% vs 84%) and more Klebsiella pneumoniae infections (46% vs 8%). Inappropriate empiric treatment was prescribed for 54 patients (64%), but a favorable outcome was observed in 46 of 49 (94%) and 1 of 5 (20%) patients with UTIs and non-UTIs, respectively (P < 0.001). Among patients with community-associated infections, 85% had at least 1 risk factor for ESBL-PE infections. In conclusion, the prevalence of community-onset ESBL-PE infections doubled during the study period. These infections mainly occurred among children with healthcare-associated criteria or identified risk factors. Amikacin is an alternative to carbapenems for empiric treatment because most of these infections involved urinary tract and susceptible isolates. PMID:27015202

Delayed onset infections after lower third molar germectomy could be related to the space distal to the second molar.

PubMed

Monaco, G; Cecchini, S; Gatto, M R; Pelliccioni, G A

2017-03-01

The onset of delayed infection after lower third molar germectomy is influenced by the amount of distal space. This retrospective study aimed to determine whether the incidence of delayed onset infection is related to the space distal to the second molar. The ratio between the distal space and the crown width, measured according to the Ganss protocol on panoramic radiographs, was obtained for 218 surgical germectomies performed for orthodontic reasons in 134 patients. A delayed onset infection occurred following 20 germectomies at between 2 and 8 weeks after surgery; purulent exudates from the alveolus and swelling were present. In 16 of the 20 cases of infection, a Ganss ratio of <0.5 showed the almost complete absence of space distal to the second molar. This study found that the distal space was significantly and inversely correlated with delayed onset infection (P=0.004). From a clinical point of view, it is important for the surgeon to be aware that a higher Ganss ratio may indicate that a delayed onset infection is less likely to occur and that a lower Ganss ratio could indicate a greater likelihood of this type of infection, so that the patient can be properly informed. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Deferred and immediate imitation in regressive and early onset autism

PubMed Central

Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

2010-01-01

Deferred imitation has long held a privileged position in early cognitive development, considered an early marker of representational thought with links to language development and symbolic processes. Children with autism have difficulties with several abilities generally thought to be related to deferred imitation: immediate imitation, language, and symbolic play. However, few studies have examined deferred imitation in early autism. The present study examined both deferred, spontaneous imitation and immediate, elicited imitation on a set of carefully matched tasks in 36 young children with autism: 16 with early onset autism, 20 with regressive autism and two contrast groups, younger typically developing children (n = 20) and age matched children with significant developmental delays (n = 21). Analyses of co-variance controlling for differences in verbal mental age revealed significant main effects for task, but no main effect of group and no interaction of task by group. Deferred imitation scores were lower than immediate imitation scores for all groups. Imitation performance was related to overall intellectual functioning for all groups, and there were moderate and significant relations between imitation in the immediate elicited condition and in the spontaneous deferred condition for all groups. Finally, there were no differences between onset subgroups in imitation scores, suggesting that the two share a similar phenotype involving both types of imitation. PMID:18221343

First impression at stroke onset plays an important role in early hospital arrival.

PubMed

Iguchi, Yasuyuki; Wada, Kuniyasu; Shibazaki, Kensaku; Inoue, Takeshi; Ueno, Yuji; Yamashita, Shinji; Kimura, Kazumi

2006-01-01

Treatment for acute ischemic stroke should be administered as soon as possible after symptom onset. The aim of this study was to investigate whether or not the patient's and bystander's first impression at stroke onset was associated with hospital arrival time. To investigate the factors influencing the prehospital delay, we prospectively interviewed consecutive stroke patients and bystanders about their first impression at the stroke onset and assessed the methods of transportation, and clinical characteristics. Early arrival was defined as a hospital arrival of within 2 h from stroke onset. One hundred thirty patients were enrolled: 82% were ischemic stroke and 18% were cerebral hemorrhage. The median interval between symptom onset and the hospital arrival was 7.5 h and 30% of patients presented within 2 h of stroke onset. First impression of stroke (odds ratios [OR] 4.56, 95% confidence interval [CI] 1.54-13.5, p=0.006), presence of consciousness disturbance (OR 4.29, CI 1.39-13.3, p=0.011), arrival through other facilities (OR 0.25, CI 0.08-0.76, p=0.015), a history of diabetes (OR 0.23, CI 0.06-0.80, p=0.028) and nocturnal onset (OR 0.19, CI 0.04-0.88, p=0.042) independently contributed to the early arrival. The first impression of patients and bystanders at stroke onset is important in order to reach hospital earlier in Japan. Public educational systems such as those, which advertise stroke warning signs, are necessary.

[Early onset pneumonia after successful resuscitation : Incidence after mild invasive hypothermia therapy].

PubMed

Erath, J W; Hodrius, J; Bushoven, P; Fichtlscherer, S; Zeiher, A M; Seeger, F H; Honold, J

2017-09-01

Targeted temperature management (TTM) represents an effective therapy to improve neurologic outcome in patients who survive an out-of-hospital cardiac arrest (OHCA). First publications about this therapy reported a higher incidence of infections in patients who underwent TTM induced by external cooling devices. Whether intravascular cooling devices are also associated with an increased infection rate has not been investigated so far. In a single center retrospective study, the incidence of early onset pneumonia (EOP) in OHCA patients with or without intravascular TTM at 33 °C target temperature for 24 h who survived at least 24 h after admission was analyzed. A total of 68 OHCA survivors (mean age 65 ± 15 years) were included in this analysis. The most common causes of OHCA were myocardial infarction (35 %), primary ventricular fibrillation (24 %), asystole (15 %), and pulmonary embolism (7 %). Of those, 32 patients (48 %) received TTM. The overall incidence of EOP was 38 %. Incidence of EOP did not differ significantly between groups, was more frequent in the group without TTM (42 % vs. 34 %, p = 0.57) and had no impact on mortality (hazard ratio = 1.02; 95 % confidence interval 0.25-4.16; p = 0.97). Intravascular TTM at 33 °C with a cooling catheter is not associated with more infective complications in OHCA patients. This finding underscores the safety of TTM.

Early Detection of Infection in Pigs through an Online Monitoring System.

PubMed

Martínez-Avilés, M; Fernández-Carrión, E; López García-Baones, J M; Sánchez-Vizcaíno, J M

2017-04-01

Late detection of emergency diseases causes significant economic losses for pig producers and governments. As the first signs of animal infection are usually fever and reduced motion that lead to reduced consumption of water and feed, we developed a novel smart system to monitor body temperature and motion in real time, facilitating the early detection of infectious diseases. In this study, carried out within the framework of the European Union research project Rapidia Field, we tested the smart system on 10 pigs experimentally infected with two doses of an attenuated strain of African swine fever. Biosensors and an accelerometer embedded in an eartag captured data before and after infection, and video cameras were used to monitor the animals 24 h per day. The results showed that in 8 of 9 cases, the monitoring system detected infection onset as an increase in body temperature and decrease in movement before or simultaneously with fever detection based on rectal temperature measurement, observation of clinical signs, the decrease in water consumption or positive qPCR detection of virus. In addition, this decrease in movement was reliably detected using automatic analysis of video images therefore providing an inexpensive alternative to direct motion measurement. The system can be set up to alert staff when high fever, reduced motion or both are detected in one or more animals. This system may be useful for monitoring sentinel herds in real time, considerably reducing the financial and logistical costs of periodic sampling and increasing the chances of early detection of infection. © 2015 Blackwell Verlag GmbH.

Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

PubMed

Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

2018-04-01

Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

10 Gb/s operation of photonic crystal silicon optical modulators.

PubMed

Nguyen, Hong C; Sakai, Yuya; Shinkawa, Mizuki; Ishikura, Norihiro; Baba, Toshihiko

2011-07-04

We report the first experimental demonstration of 10 Gb/s modulation in a photonic crystal silicon optical modulator. The device consists of a 200 μm-long SiO2-clad photonic crystal waveguide, with an embedded p-n junction, incorporated into an asymmetric Mach-Zehnder interferometer. The device is integrated on a SOI chip and fabricated by CMOS-compatible processes. With the bias voltage set at 0 V, we measure a V(π)L < 0.056 V∙cm. Optical modulation is demonstrated by electrically driving the device with a 2(31) - 1 bit non-return-to-zero pseudo-random bit sequence signal. An open eye pattern is observed at bitrates of 10 Gb/s and 2 Gb/s, with and without pre-emphasis of the drive signal, respectively.

Early onset marfan syndrome: Atypical clinical presentation of two cases

PubMed Central

Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

2015-01-01

Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

Early-onset Major Depressive Disorder in men is associated with childlessness.

PubMed

Yates, William R; Meller, William H; Lund, Brian C; Thurber, Steve; Grambsch, Patricia L

2010-07-01

The self-reported number of children was compared for men and women from the National Epidemiologic Survey of Alcoholism and Related Conditions Survey (NESARC). Subjects with a diagnosis of major depressive disorder or bipolar disorder were compared to those without an axis I disorder. The effect of age, gender, marriage and diagnostic status on number of children was completed using multivariate analyses. Men with a history of major depressive disorder but not bipolar disorder reported higher rates of childlessness and lower mean number of children. This reduced number of children was related to an early age of onset of MDD. Thirty percent of men with an age of onset of MDD before 22 were childless compared to only 18.9% of men without an axis I disorder (Odds ratio=1.82, 95% CI=1.45-2.27). No effect of mood disorder on number of children was found in women with major depression or bipolar disorder. This study suggests that an early age of onset of major depressive disorder contributes to childlessness in men.

Functional Connectivity of the Amygdala in Early Childhood Onset Depression

PubMed Central

Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

2011-01-01

Objective Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early childhood onset MDD. Method Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777

A practical approach to implementing new CDC GBS guidelines.

PubMed

Hill, Shawna M; Bridges, Margie A; Knudsen, Alexis L; Vezeau, Toni M

2013-01-01

Group beta streptococcus (GBS) is a well-documented pathogen causing serious maternal and fetal morbidity and mortality. The CDC guidelines for managing clients who test positive for GBS in pregnancy were revised and published in 2010. However, CDC and extant literature provide limited guidance on implementation strategies for these new recommendations. Although several algorithms are included in the CDC (2010) document, none combine the maternal risk factors for practical and consistent implementation from pregnancy to newborn. In response to confusion upon initial education of these guidelines, we developed an algorithm for maternal intrapartum management. In addition, we clarified the CDC (2010) newborn algorithm in response to provider request. Without altering the recommendations, both algorithms provide clarification of the CDC (2010) guidelines. The nursing process provides an organizational structure for the discussion of our efforts to translate the complex guidelines into practice. This article could provide other facilities with tools for dealing with specific aspects of the complex clinical management of perinatal GBS.

Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy

PubMed Central

Nair, Umesh; Malhotra, Sony; Meyer, Esther; Trump, Natalie; Gazina, Elena V.; Papandreou, Apostolos; Ngoh, Adeline; Ackermann, Sally; Ambegaonkar, Gautam; Appleton, Richard; Desurkar, Archana; Eltze, Christin; Kneen, Rachel; Kumar, Ajith V.; Lascelles, Karine; Montgomery, Tara; Ramesh, Venkateswaran; Samanta, Rajib; Scott, Richard H.; Tan, Jeen; Whitehouse, William; Poduri, Annapurna; Scheffer, Ingrid E.; Chong, W.K. “Kling”; Cross, J. Helen; Topf, Maya; Petrou, Steven

2018-01-01

Objective To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset KCNT1 epilepsy. Methods We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified KCNT1 variants on local diagnostic multiple gene panel testing were also included. When possible, we performed homology modeling to predict the putative effects of variants on protein structure and function. We undertook electrophysiologic assessment of mutant KCNT1 channels in a xenopus oocyte model system. Results We identified pathogenic variants in KCNT1 in 12 patients, 4 of which are novel. Most variants occurred de novo. Ten patients had a clinical diagnosis of EIMFS, and the other 2 presented with early-onset severe nocturnal frontal lobe seizures. Three patients had a trial of quinidine with good clinical response in 1 patient. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. Conclusions Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Currently, genotype-phenotype correlations are unclear, although clinical outcome is poor for the majority of cases. Further elucidation of disease mechanisms may facilitate the development of targeted treatments, much needed for this pharmacoresistant genetic epilepsy. PMID:29196579

Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

ERIC Educational Resources Information Center

Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

2016-01-01

This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

[The relationship between accommodative accuracy at different near-work distances and early-onset myopia].

PubMed

Yu, Q W; Zhang, P; Zhou, S B; Hu, Y; Ji, M X; Luo, Y C; You, H L; Yao, Z X

2016-07-01

To observe the accommodative accuracy of children with early-onset myopia at different near-work distances, and discuss the relationship between accommodative accuracy and early-onset myopia. This was a case-control study. Thirty-seven emmetropic children, 41 early-onset myopic children without correction, and 39 early-onset myopic children with spectacles, aged 7 to 13 years, were included. Measures of refractive errors and accommodative accuracy at four near-work distances, including 50 cm, 40 cm, 30 cm, and 20 cm, were made using the binocular fusion cross cylinder (FCC) of an automatic phoropter. Most candidates showed accommodative lags, including the children with emmetropia. The ratio of lags in all candidates at different near-work distances was 75.21% (50 cm), 87.18% (40 cm), 92.31% (30 cm), and 98.29% (20 cm), respectively. All accommodative accuracies became worse, and the accommodative lag ratio and values of FCC increased, along with the shortening of the distance. The difference in accommodative accuracy among groups was statistically significant at 30 cm (χ(2)=7.852, P= 0.020) and 20 cm (χ(2)=6.480, P=0.039). The values of FCC among groups were significantly different at 30 cm (F=3.626, P=0.030) and 20 cm (F=3.703, P=0.028), but not at 50 cm and 40 cm (P>0.05). In addition, the FCC values of 30 cm and 20 cm had a statistically significant difference between myopic children without correction [(1.25±0.44) D and (1.76±0.43) D] and emmetropic children [(0.95±0.52) D and (1.41±0.58) D] (P=0.012, 0.008). The correlation between diopters of myopia and accommodative accuracy at different nearwork distances was not statistically significant (P>0.05). However, the correlation between diopters of myopia and the accommodative lag value (FCC) at 20 cm was statistically significant (r=0.246, P=0.028). The closer the near-work distance is, the worse the accommodative accuracy is. This is more significant in early-onset myopia, especially myopia without

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

PubMed Central

Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

2011-01-01

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

An assessment of public health surveillance of Zika virus infection and potentially associated outcomes in Latin America.

PubMed

Bautista, Leonelo E; Herrera, Víctor M

2018-05-24

We evaluated whether outbreaks of Zika virus (ZIKV) infection, newborn microcephaly, and Guillain-Barré syndrome (GBS) in Latin America may be detected through current surveillance systems, and how cases detected through surveillance may increase health care burden. We estimated the sensitivity and specificity of surveillance case definitions using published data. We assumed a 10% ZIKV infection risk during a non-outbreak period and hypothetical increases in risk during an outbreak period. We used sensitivity and specificity estimates to correct for non-differential misclassification, and calculated a misclassification-corrected relative risk comparing both periods. To identify the smallest hypothetical increase in risk resulting in a detectable outbreak we compared the misclassification-corrected relative risk to the relative risk corresponding to the upper limit of the endemic channel (mean + 2 SD). We also estimated the proportion of false positive cases detected during the outbreak. We followed the same approach for microcephaly and GBS, but assumed the risk of ZIKV infection doubled during the outbreak, and ZIKV infection increased the risk of both diseases. ZIKV infection outbreaks were not detectable through non-serological surveillance. Outbreaks were detectable through serologic surveillance if infection risk increased by at least 10%, but more than 50% of all cases were false positive. Outbreaks of severe microcephaly were detected if ZIKV infection increased prevalence of this condition by at least 24.0 times. When ZIKV infection did not increase the prevalence of severe microcephaly, 34.7 to 82.5% of all cases were false positive, depending on diagnostic accuracy. GBS outbreaks were detected if ZIKV infection increased the GBS risk by at least seven times. For optimal GBS diagnosis accuracy, the proportion of false positive cases ranged from 29 to 54% and from 45 to 56% depending on the incidence of GBS mimics. Current surveillance systems have a

The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

PubMed

Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

2018-05-16

To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

PubMed Central

Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; Souza, Fábio Gomes de Matos e

2015-01-01

Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear. PMID:26097750

Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

PubMed

Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

2005-08-01

Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

Study protocol: EXERcise and cognition in sedentary adults with early-ONset dementia (EXERCISE-ON).

PubMed

Hooghiemstra, Astrid M; Eggermont, Laura H P; Scheltens, Philip; van der Flier, Wiesje M; Bakker, Jet; de Greef, Mathieu H G; Koppe, Peter A; Scherder, Erik J A

2012-08-16

Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. The present study is registered within The Netherlands National Trial Register (ref: NTR2124).

Challenges in reducing group B Streptococcus disease in African settings.

PubMed

Nishihara, Yo; Dangor, Ziyaad; French, Neil; Madhi, Shabir; Heyderman, Robert

2017-01-01

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis in high-income settings and is associated with high rates of neonatal mortality and morbidity. There is now increasing evidence to suggest that there is a high GBS disease burden in resource-limited countries, and it is therefore critically important to identify suitable and practical preventive strategies. In Europe and North America, intrapartum antibiotic prophylaxis (IAP) has led to a dramatic reduction of early-onset GBS disease. However, the methods for identifying pregnant women who should receive IAP and how to reduce late-onset GBS disease are not without controversy and are challenging for most sub-Saharan African countries. GBS vaccines are approaching phase III trials but are still under development. This review aims to explore the current evidence related to strategies for reducing invasive GBS disease in an African setting, the development of a GBS vaccine and whether preventative measures against GBS disease can be practically implemented. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Psychological differences between early- and late-onset psoriasis: a study of personality traits, anxiety and depression in psoriasis.

PubMed

Remröd, C; Sjöström, K; Svensson, A

2013-08-01

Onset of psoriasis may occur at any age. Early negative experiences often influence personality development, and may lead to physical disease, anxiety and depression in adulthood. Knowledge about onset of psoriasis and psychopathology is limited. To examine whether patients with early-onset psoriasis differ psychologically from patients with late-onset psoriasis, regarding personality traits, anxiety and depression. A descriptive cross-sectional study was conducted among 101 consecutively recruited outpatients with psoriasis. A psychosocial interview was performed followed by self-assessment of validated questionnaires: Swedish Universities Scales of Personality (SSP), Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory. Psoriasis severity was assessed by the Psoriasis Area and Severity Index. Patients with early-onset psoriasis (age < 20 years) were significantly more anxious and depressed than patients with late-onset psoriasis. In multiple linear regression models, younger age at onset of psoriasis was a significant determinant of higher scores of four personality traits: SSP-embitterment, -trait irritability, -mistrust and -verbal trait aggression. Our results indicate that early detection of psychological vulnerability when treating children and adolescents with psoriasis seems to be of great importance. Traits of psychological vulnerability and pessimistic personality traits were found to be significantly associated with the early onset of psoriasis, but not with disease duration in this study. These traits may be seen as a consequence of psoriasis, and/or as individual traits modulating and impairing clinical course and efforts to cope with psoriasis. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

EARLY ONSET OF DELINQUENCY AND THE TRAJECTORY OF ALCOHOL-IMPAIRED DRIVING AMONG YOUNG MALES*

PubMed Central

Zhang, Lening; Wieczorek, William F.; Welte, John W.

2011-01-01

Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. PMID:21831528

Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

PubMed

Passeron, Thierry; Salhi, Aicha; Mazer, Jean-Michel; Lavogiez, Céline; Mazereeuw-Hautier, Juliette; Galliot, Chrystèle; Collet-Villette, Anne-Marie; Labreze, Christine; Boon, Laurence; Hardy, Jean-Philippe; Fayard, Virginie; Livideanu, Cristina Bulai; Toubel, Gérard; Georgescou, Gabriela; Gral, Nathalie; Maza, Aude; Lacour, Jean-Philippe

2016-07-01

There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). We sought to characterize patients with hypertrophic PWS presenting during childhood. Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Alcohol intake and early-onset basal cell carcinoma in a case-control study

PubMed Central

Zhang, Y; Ferrucci, L.M.; Cartmel, B.; Molinaro, A.M.; Leffell, D.J.; Bale, A.E.; Mayne, S.T.

2014-01-01

Background Previous epidemiologic studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) light, this has not been evaluated in existing epidemiologic studies. Objective To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Methods BCC cases (n=380) and controls with benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage during an in-person interview. Self-report data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional multivariate logistic regression in the full sample and in women only. Results There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall (above median intake vs. no regular alcohol intake OR 1.10, 95% CI 0.69-1.73) or in women only (OR 1.21, 95% CI 0.73-2.01). Similarly, intake of red wine, white wine, beer or hard liquor and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (pinteraction=0.003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping confidence intervals. Conclusions Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. PMID:25059635

Early Onset Bipolar Spectrum Disorder: Psychopharmacological, Psychological, and Educational Management

ERIC Educational Resources Information Center

McIntosh, David E.; Trotter, Jeffrey S.

2006-01-01

Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…

Accuracy of a rapid real-time polymerase chain reaction assay for diagnosis of group B Streptococcus colonization in a cohort of HIV-infected pregnant women.

PubMed

Gouvea, Maria Isabel S; Joao, Esau C; Teixeira, Maria de Lourdes B; Read, Jennifer S; Fracalanzza, Sergio E L; Souza, Claudia T V; Souza, Maria José de; Torres Filho, Helio M; Leite, Cassiana C F; do Brasil, Pedro E A A

2017-05-01

There are limited data regarding Xpert performance to detect Group B Streptococcus (GBS) in HIV-infected pregnant women. We evaluated the accuracy of a rapid real-time polymerase chain reaction (PCR) test in a cohort of HIV-infected women. At 35-37 weeks of pregnancy, a pair of combined rectovaginal swabs were collected for two GBS assays in a cohort of sequentially included HIV-infected women in Rio de Janeiro: (1) culture; and (2) real-time PCR assay [GeneXpert GBS (Cepheid, Sunnyvale, CA)]. Using culture as the reference, sensitivity, specificity, positive and negative-likelihood ratios were estimated. From June 2012 to February 2015, 337 pregnant women met inclusion criteria. One woman was later excluded, due to failure to obtain a result in the index test; 336 were included in the analyses. The GBS colonization rate was 19.04%. Sensitivity and specificity of the GeneXpert GBS assay were 85.94% (95% CI: 75.38-92.42) and 94.85% (95% CI: 91.55-96.91), respectively. Positive and negative predictive values were 79.71% (95% CI: 68.78-87.51) and 96.63% (95% CI: 93.72-98.22), respectively. GeneXpert GBS is an acceptable test for the identification of GBS colonization in HIV-infected pregnant women and represents a reasonable option to detect GBS colonization in settings where culture is not feasible.

Diagnosis of neonatal group B Streptococcus sepsis by nested-PCR of residual urine samples

PubMed Central

Cezarino, Bruno Nicolino; Yamamoto, Lidia; Del Negro, Gilda Maria Barbaro; Rocha, Daisy; Okay, Thelma Suely

2008-01-01

Group B streptococcus (GBS) remains the most common cause of early-onset sepsis in newborns. Laboratory gold-standard, broth culture methods are highly specific, but lack sensitivity. The aim of this study was to validate a nested-PCR and to determine whether residue volumes of urine samples obtained by non invasive, non sterile methods could be used to confirm neonatal GBS sepsis. The nested-PCR was performed with primers of the major GBS surface antigen. Unavailability of biological samples to perform life supporting exams, as well as others to elucidate the etiology of infections is a frequent problem concerning newborn patients. Nevertheless, we decided to include cases according to strict criteria: newborns had to present with signs and symptoms compatible with GBS infection; at least one of the following biological samples had to be sent for culture: blood, urine, or cerebrospinal fluid; availability of residue volumes of the samples sent for cultures, or of others collected on the day of hospitalization, prior to antibiotic therapy prescription, to be analyzed by PCR; favorable outcome after GBS empiric treatment. In only one newborn GBS infection was confirmed by cultures, while infection was only presumptive in the other three patients (they fulfilled inclusion criteria but were GBS-culture negative). From a total of 12 biological samples (5 blood, 3 CSF and 4 urine specimen), eight were tested by culture methods (2/8 were positive), and 8 were tested by PCR (7/8 were positive), and only 4 samples were simultaneously tested by both methods (1 positive by culture and 3 by PCR). In conclusion, although based on a restricted number of neonates and samples, our results suggest that the proposed nested-PCR might be used to diagnose GBS sepsis as it has successfully amplified the three types of biological samples analyzed (blood, urine and cerebrospinal fluid), and was more sensitive than culture methods as PCR in urine confirmed diagnosis in all four patients

Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration.

PubMed

Seo, Sang Won; Thibodeau, Marie-Pierre; Perry, David C; Hua, Alice; Sidhu, Manu; Sible, Isabel; Vargas, Jose Norberto S; Gaus, Stephanie E; Rabinovici, Gil D; Rankin, Katherine D; Boxer, Adam L; Kramer, Joel H; Rosen, Howard J; Gorno-Tempini, Maria Luisa; Grinberg, Lea T; Huang, Eric J; DeArmond, Stephen J; Trojanowski, John Q; Miller, Bruce L; Seeley, William W

2018-03-20

To examine clinicopathologic correlations in early vs late age at onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD). All patients were clinically evaluated and prospectively diagnosed at the UCSF Memory and Aging Center. Two consecutive series were included: (1) patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort 1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of the clinical syndrome (cohort 2). These series were divided by age at symptom onset (cutoff 65 years). In cohort 1, 48 (25.3%) were 65 years or older at symptom onset. Pathologic causes of behavioral variant FTD (bvFTD) were similar in the early age at onset (EO) and late age at onset (LO) bvFTD groups. In corticobasal syndrome (CBS), however, the most common pathologic substrate differed according to age at onset: progressive supranuclear palsy (42.9%) in LO-CBS and Alzheimer disease (AD; 40.7%) in EO-CBS. In cohort 2, 57 (28.4%) were classified as LO-FTLD. Regarding FTLD major molecular classes, FTLD with transactive response DNA-binding protein of 43 kDa was most common in EO-FTLD (44.4%), whereas FTLD-tau (58.3%) was most common in LO-FTLD. Antemortem diagnosis of a non-FTD syndrome, usually AD-type dementia, was more frequent in LO-FTLD than EO-FTLD (19.3% vs 7.7%, p = 0.017). LO-FTLD was also associated with more prevalent comorbid pathologic changes. Of these, moderate to severe AD neuropathologic change and argyrophilic grain disease were overrepresented among patients who received an antemortem diagnosis of AD-type dementia. Patients with FTD and FTLD often develop symptoms after age 65, and age at onset represents an important consideration when making antemortem neuropathologic predictions. © 2018 American Academy of Neurology.

Early-onset restrictive eating disturbances in primary school boys and girls.

PubMed

Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

2015-07-01

This study sought to determine the distribution of early-onset restrictive eating disturbances characteristic of the new DSM-5 diagnosis, avoidant/restrictive food intake disorder (ARFID) in middle childhood, as well as to evaluate the screening instrument, Eating Disturbances in Youth-Questionnaire (EDY-Q). A total of 1,444 8- to 13-year-old children were screened in regular schools (3rd to 6th grade) in Switzerland using the self-report measure EDY-Q, consisting of 12 items based on the DSM-5 criteria for ARFID. 46 children (3.2%) reported features of ARFID in the self-rating. Group differences were found for body mass index, with underweight children reporting features of ARFID more often than normal and overweight children. The EDY-Q revealed good psychometric properties, including adequate discriminant and convergent validity. Early-onset restrictive eating disturbances are commonly reported in middle childhood. Because of possible negative short- and long-term impact, early detection is essential. Further studies with structured interviews and parent reports are needed to confirm this study's findings.

[Dermohypodermitis and gut translocation Escherichia coli septicemia in a newborn infant].

PubMed

Gouache, E; Chantier, E; Hubert, N; Rivière, M-F

2013-01-01

The burden of neonatal bacterial infections continues. They remain a significant cause of death and morbidity, despite recommendations for prevention. The epidemiology of these infections has changed. Currently the two most causative pathogens for early-onset neonatal sepsis and for late-onset sepsis in term infants are Group B streptococci (GBS) and Escherichia coli. E. coli's role is increasingly important since the widespread use of intrapartum antibiotic prophylaxis. In late-onset infections, one of the suggested pathophysiological mechanisms is microbial translocation in the gut secondary to digestive colonization, particularly when E. coli is isolated in blood cultures. This can occur either before or after birth. Bacterial sepsis can be associated with various non-specific peripheral manifestations involving skin and soft tissues. We report the case of a full-term, 26-day-old newborn admitted to the hospital for fever. She presented with dermohypodermitis of the left trunk and was diagnosed with E. coli septicemia. She was discharged in good condition after appropriate intravenous antibiotic therapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

In vitro activity of an aqueous allicin extract and a novel allicin topical gel formulation against Lancefield group B streptococci.

PubMed

Cutler, Ronald R; Odent, Michel; Hajj-Ahmad, Hussein; Maharjan, Sunil; Bennett, Norman J; Josling, Peter D; Ball, Vanessa; Hatton, Paulette; Dall'Antonia, Martino

2009-01-01

Studies have shown the efficacy of intra-partum antibiotics in preventing early-onset group B streptococcal sepsis. This approach results in a high intra-partum antibiotic use. Worryingly, the same antibiotics used in prophylaxis are also first-line treatment for neonatal sepsis, and antibiotic exposure in the peri-natal period has been shown to be a risk factor for late-onset serious bacterial infections and allergic disease. Antibiotic exposure in the peri-natal period is becoming a major public health issue; alternative strategies are needed. Garlic has been traditionally used to treat vaginal infections. Allicin is the main antibacterial agent isolated from garlic. The aim of the study was to investigate the in vitro activity of a novel allicin extract in aqueous and gel formulation against 76 clinical isolates of Lancefield group B streptococci (GBS). MICs and MBCs of allicin were determined for 76 GBS isolates by agar dilution and microtitre plate methods. Killing kinetics were determined for a selected 16 of the 76 strains. Agar diffusion tests were compared for allicin liquid and gel (500 mg/L). MICs and MBCs of allicin liquid were 35 to 95 mg/L and 75 to 315 mg/L, respectively. Time/dose kill curves produced a 2-3 log reduction in cfu/mL within 3 h and no detectable growth at 8 and 24 h. A novel 500 mg/L allicin gel produced an average zone size of 23+/-6 mm compared with 21+/-6 mm for allicin in water. Aqueous allicin is bactericidal against GBS isolates and maintains activity in a novel gel formulation.

Comparison of early versus late onset familial Mediterranean fever.

PubMed

Yasar Bilge, Nazife Sule; Sari, Ismail; Solmaz, Dilek; Senel, Soner; Emmungil, Hakan; Kilic, Levent; Yilmaz Oner, Sibel; Yildiz, Fatih; Yilmaz, Sedat; Ersozlu Bozkirli, Duygu; Aydin Tufan, Muge; Yilmaz, Sema; Yazisiz, Veli; Pehlivan, Yavuz; Bes, Cemal; Yildirim Cetin, Gozde; Erten, Sukran; Gonullu, Emel; Sahin, Fezan; Akar, Servet; Aksu, Kenan; Kalyoncu, Umut; Direskeneli, Haner; Erken, Eren; Sayarlioglu, Mehmet; Cınar, Muhammed; Kasifoglu, Timucin

2018-04-01

Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. One of the common characteristics of this disease is its young age predominance. Nearly 90% of patients experience disease flares during early adult age periods. Currently there are limited data for the comparison of early versus late onset FMF and therefore the primary aim of this study was to investigate these two subsets with regard to their certain demographic, clinical and genetic differences. Early (≤ 20 years, Group 1) and late (> 20 years, Group 2) onset FMF patients were identified from the national FMF registry that involves 2246 patients from 15 adult rheumatology clinics located in different geographical areas of Turkey. Of the 2246 patients, 1633 (72.7%) were aged ≤ 20 years old (Group 1) and the remaining 613 were older than 20 years (Group 2). Delay in diagnosis was longer in Group 1 and fever, peritonitis, pleuritis, erysipelas-like erythema (ELE), arthritis, family history of FMF and amyloidosis were more common in Group 1. On the other hand, sex distribution, rates of amyloidosis, vasculitis and kidney failure were not different between the groups. Among patients with available genotypes, homozygous and heterozygous M694V mutations were significantly higher and heterozygous E148Q mutation was significantly lower in Group 1 compared to Group 2. Patients with FMF whose symptoms start before 20 years of age seem to have severe symptoms and M694V mutation may be responsible for the early expression of the disease. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity.

PubMed

Mazen, I; El-Gammal, M; Abdel-Hamid, M; Farooqi, I S; Amr, K

2011-04-01

Congenital deficiency of the leptin receptor is a very rare cause of severe early-onset obesity. To date, only 9 families have been reported in the literature to have mutations in the leptin receptor gene. The clinical features include severe early onset obesity, severe hyperphagia, hypogonadotropic hypogonadism, and T cell and neuroendocrine/metabolic dysfunction. Here we report two cousins with severe early onset obesity and recurrent respiratory tract infections. Their serum leptin levels were elevated but they were within the range predicted by the elevated fat mass in both cousins. Direct sequencing of the entire coding sequence of the leptin receptor gene revealed a novel homozygous missense mutation in exon 6, P316T. The mutation was found in the homozygous form in both cousins and in the heterozygote state in their parents. This mutation was not found in 200 chromosomes from 100 unrelated normal weight control subjects of Egyptian origin using PCR-RFLP analysis. In conclusion, finding this new mutation in the LEPR beside our previous mutation in the LEP gene implies that monogenic obesity syndromes may be common in the Egyptian population owing to the high rates of consanguineous marriages. Further screening of more families for mutations in LEP, LEPR, and MC4 might confirm this assumption. Copyright © 2010 Elsevier Inc. All rights reserved.

Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort

PubMed Central

2013-01-01

Background To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort. Methods We studied serial serum samples collected prospectively at 12 + 0 - 14 + 0, 18 + 0 - 20 + 0, and 26 + 0 - 28 + 0 weeks + days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls. Results Serum PlGF concentrations were lower at 18 + 0 to 20 + 0, and 26 + 0 to 28 + 0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p < 0.05 for all comparisons). At 18 + 0 to 20 + 0 weeks of gestation area under the receiver-operating characteristic curve (AUC) for serum PlGF was 99.8% (p = 0.0007, 95% CI 99.0-100.0). At 26 + 0 to 28 + 0 weeks of gestation serum sFlt-1/PlGF ratio explicitly detects those women who developed early-onset preeclampsia (AUC 100.0%, p = 0.0007, 95% CI 100–100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N = 8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p = 0.004, p = 0.006, and p = 0.003, respectively) compared to women with non-severe form (N = 13). Conclusions Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset

Alcohol intake and early-onset basal cell carcinoma in a case-control study.

PubMed

Zhang, Y; Ferrucci, L M; Cartmel, B; Molinaro, A M; Leffell, D J; Bale, A E; Mayne, S T

2014-12-01

Previous epidemiological studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) radiation, this has not been evaluated in existing epidemiological studies. To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Basal cell carcinoma cases (n = 380) and controls with benign skin conditions (n = 390) under 40 years of age were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage, during an in-person interview. Self-reported data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression in the full sample and in women only. There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall [above median intake vs. no regular alcohol intake (OR 1·10, 95% CI 0·69-1·73)] or in women only (OR 1·21, 95% CI 0·73-2·01). Similarly, intake of red wine, white wine, beer or spirits and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (P(interaction) = 0·003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping CIs. Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. © 2014 British Association of Dermatologists.

Functional Connectivity of the Amygdala in Early-Childhood-Onset Depression

ERIC Educational Resources Information Center

Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

2011-01-01

Objective: Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD. Method: A total of 51 children 7 through 11 years of age who had…

Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis

ERIC Educational Resources Information Center

Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso

2011-01-01

Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…

A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.

PubMed

Saitsu, Hirotomo; Osaka, Hitoshi; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi

2012-05-01

Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Early onset of delinquency and the trajectory of alcohol-impaired driving among young males.

PubMed

Zhang, Lening; Wieczorek, William F; Welte, John W

2011-12-01

Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q

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

Baldwin, C.T.; Farrer, L.A.; Adair, R.

Calcium pyrophosphate-deposition disease (CPDD), also called {open_quotes}chondrocalcinosis{close_quotes} or {open_quotes}pseudogout{close_quotes}, is a disorder characterized by the deposition of calcium-containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2nd and 5th decades of life. Inmore » this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family. 29 refs., 2 figs., 1 tab.« less

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

PubMed Central

2012-01-01

Background Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. Methods/Design One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. Discussion The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. Trial registration The present study is registered within The Netherlands

Guillain-Barré Syndrome (GBS) and Flu Vaccine

MedlinePlus

... million doses of flu vaccine administered. How do public health authorities investigate cases of GBS? CDC and the Food and Drug Administration (FDA) closely monitor the safety of vaccines approved ...

Triggers for Preeclampsia Onset: a Case-Crossover Study.

PubMed

Ford, Jane B; Schemann, Kathrin; Patterson, Jillian A; Morris, Jonathan; Herbert, Robert D; Roberts, Christine L

2016-11-01

Risk factors for preeclampsia are well established, whereas, the triggers associated with timing of preeclampsia onset are not. The aim of this study was to establish whether recent infection or other triggers were associated with timing of preeclampsia onset. We used a case-crossover design with preeclampsia cases serving as their own controls. Women with singleton pregnancies of ≥20 weeks gestation presenting at three hospitals were eligible for inclusion. Exposures to potential triggers were identified via guided questionnaire. Infective episodes included symptoms lasting >24 h. Preeclampsia was defined as hypertension (BP ≥140 mmHg and/or ≥90 mmHg) and proteinuria (protein/creatinine ratio ≥30 mg/mmol). Conditional logistic regression was used to compare the odds of exposure to potential triggers in the case windows (1-7 days preceding diagnosis of preeclampsia) and control windows (8-14 days prior to diagnosis); unadjusted odds ratios (ORs) are reported. Among 286 recruited women, 25 (8.7%) reported a new infection in the 7 days prior to preeclampsia onset and 21 (7.3%) in the 8-14 days prior. There was no significant association between onset of infection in the 7 days prior and preeclampsia diagnosis (OR 1.24, 95% CI 0.65, 2.34). Consumption of caffeine (OR 0.51, 95% CI 0.33, 0.77), spicy food (OR 0.49, 95% CI 0.30, 0.81), and alcohol (OR 0.26, 95% CI 0.10, 0.71) were strongly inversely associated with preeclampsia onset. Recent infection does not appear to trigger preeclampsia. Decreased consumption of caffeine, spicy food, and alcohol may be prodromal markers. Such behaviours may be early markers of imminent preeclampsia. © 2016 John Wiley & Sons Ltd.

Childhood abuse and late-life depression: Mediating effects of psychosocial factors for early- and late-onset depression.

PubMed

Wielaard, Ilse; Hoyer, Mathijs; Rhebergen, Didi; Stek, Max L; Comijs, Hannie C

2018-03-01

Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (<60 years), and 125 with a late-onset (≥60 years) depression. Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression. Copyright © 2018 John Wiley & Sons, Ltd.

Maturation, Peer Context, and Indigenous Girls' Early-Onset Substance Use

ERIC Educational Resources Information Center

Walls, Melissa L.; Whitbeck, Les B.

2011-01-01

This article examines a biosocial model of the impact of puberty on indigenous girls' early-onset substance use by considering the potential mediating role of peer context (i.e., mixed-sex peer groups and substance use prototypes) on the puberty and substance use relationship. Data include responses from 360 girls of a common indigenous cultural…

Birdshot Retinochoroidopathy: Differences in Clinical Characteristics between Patients with Early and Late Age of Onset.

PubMed

Silpa-Archa, Sukhum; Cao, Jennifer H; Boonsopon, Sutasinee; Lee, Joan; Preble, Janine M; Foster, C Stephen

2017-10-01

To describe differences in the clinical characteristics of birdshot retinochoroidopathy (BSRC) patients diagnosed early and later in life. This is a retrospective cohort study. Age was primarily analyzed and 50 years of age at diagnosis was selected as a cut-off point. A total of 144 patients (288 eyes) were included; 68 with early-onset and 76 with late-onset BSRC. The younger group had a statistically significant higher rate of more severe iritis (p = 0.04); an average number of non-steroidal immunosuppressants and biologic agents (NSIB) (p = 0.04); and a prolonged time to initiation of NSIB (p = 0.01). There were only four patients (3%) who had >0.5+ cells in the anterior chamber. Patients with early-onset BSRC carried a higher risk for anterior segment inflammation, had a more prolonged delay to initiation of treatment with NSIB, and required a greater number of NSIBs to achieve remission.

Distinct Immunoglobulin Class and Immunoglobulin G Subclass Patterns against Ganglioside GQ1b in Miller Fisher Syndrome following Different Types of Infection

PubMed Central

Schwerer, Beatrix; Neisser, Andrea; Bernheimer, Hanno

1999-01-01

We studied serum antibodies against gangliosides GQ1b and GM1 in 13 patients with Miller Fisher syndrome (MFS) and in 18 patients with Guillain-Barré syndrome (GBS) with cranial nerve involvement. Anti-GQ1b titers were elevated in all patients with MFS cases (immunoglobulin G [IgG] > IgA, IgM), and in 8 of the 18 with GBS. Lower frequencies of increased anti-GM1 titers were observed in MFS patients (3 of 13), as well as in GBS patients (5 of 18). During the course of MFS, anti-GQ1b titers of all Ig classes decreased within 3 weeks after onset. By contrast, anti-GM1 titers (mainly IgM) transiently increased during the course of MFS in five of six patients, suggesting a nonspecific secondary immune response. In patients with MFS following respiratory infections, IgG was the major anti-GQ1b Ig class (six of six patients) and IgG3 was the major subclass (five of six). In contrast, four of five patients with MFS following gastrointestinal infections showed predominance of anti-GQ1b IgA or IgM over IgG and predominance of the IgG2 subclass; anti-GQ1b IgG (IgG3) prevailed in one patient only. These distinct Ig patterns strongly suggest that different infections may trigger different mechanisms of anti-GQ1b production, such as via T-cell-dependent as opposed to T-cell-independent pathways. Thus, the origin of antibodies against GQ1b in MFS may be determined by the type of infectious agent that precipitates the disease. PMID:10225903

Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

ERIC Educational Resources Information Center

Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

2005-01-01

Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

Demonstration of an 8*10-Gb/s OTDM system

NASA Astrophysics Data System (ADS)

Huo, Li; Yang, Yanfu; Lou, Caiyun; Gao, Yizhi

2005-03-01

An 8*10 Gb/s optical time-division-multiplexing (OTDM) system was demonstrated with an electroabsorption modulator (EAM) based short pulse generator followed by a two-stage nonlinear compression scheme which generated stable 10-GHz, 2-ps full-width at half-maximum (FWHM) pulse train, an opto-electronic oscillator (OEO) that extracted 10-GHz clock with a timing jitter of 300 fs from 80-Gb/s OTDM signal and a self cascaded EAM which produced a switching window of about 10 ps. A back-to-back error free demultiplexing experiment with a power penalty of 3.25 dB was carried out to verify the system performance.

Depression and Anxiety Symptoms: Onset, Developmental Course and Risk Factors during Early Childhood

ERIC Educational Resources Information Center

Cote, Sylvana M.; Boivin, Michel; Liu, Xuecheng; Nagin, Daniel S.; Zoccolillo, Mark; Tremblay, Richard E.

2009-01-01

Background: Depressive and anxiety disorders are among the top ten leading causes of disabilities. We know little, however, about the onset, developmental course and early risk factors for depressive and anxiety symptoms (DAS). Objective: Model the developmental trajectories of DAS during early childhood and to identify risk factors for atypically…

Functional and Radiographic Outcomes Following Growth-Sparing Management of Early-Onset Scoliosis.

PubMed

Johnston, Charles E; Tran, Dong-Phuong; McClung, Anna

2017-06-21

In this study, we sought to evaluate radiographic, functional, and quality-of-life outcomes of patients who have completed growth-sparing management of early-onset scoliosis. This prospective study involved patients with early-onset scoliosis who underwent growth-sparing treatment and either "final" fusion or observation for ≥2 years since the last lengthening procedure. Demographics, radiographic parameters, pulmonary function test (PFT) values, and scores of patient-reported assessments (Early-Onset Scoliosis Questionnaire [EOSQ] and Scoliosis Research Society [SRS]-30) were obtained. At the most recent follow-up, patients performed 2 additional functional outcome tests: step-activity monitoring and a treadmill exercise-tolerance test. Twelve patients were evaluated as "graduates" of growth-sparing management of early-onset scoliosis (mean of 37 months since the most recent surgery). The major scoliosis curve measurement averaged 88° before treatment and 47° at the most recent follow-up. T1-S1 height increased from a mean of 22.3 cm to 34.7 cm and T1-T12 height, from 13.3 to 22.3 cm. At the most recent follow-up, the mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) as a percentage of the predicted volume were 52.1% and 55.3%, respectively, and were essentially unchanged from the earliest PFT that patients could perform (FEV1 = 53.8% of predicted and FVC = 53.5% of predicted). There was no difference between graduates and controls with respect to activity time or total steps in step-activity monitoring, and in the exercise-tolerance test, graduates walked at the same speed but at a higher heart rate and at a significantly higher (p <0.001) VO2 cost (rate of oxygen consumed per distance traveled). The EOSQ mean score was 102.2 of a possible 120 points, and the SRS mean score was 4.1 of a possible 5 points. A realistic long-term goal for the management of early-onset scoliosis appears to be spine elongation and maintenance of

Early onset of bilateral brachial plexopathy during mantle radiotherapy for Hodgkin's disease.

PubMed

Churn, M; Clough, V; Slater, A

2000-01-01

We report a case of brachial plexus neuropathy occurring in a 50-year-old man treated with standard mantle radiotherapy for early-stage Hodgkin's disease. A dose of 35 Gy in 20 fractions was given to the mantle field, following by a boost to the right side of the neck (8 Gy in four fractions). The onset of symptoms was early in the course of treatment and a gradual and almost full recovery was observed over 3 years after completion ofradiotherapy. The diagnosis was supported by electromyography. The temporal relationship of the radiotherapy and the onset of the brachial plexus neuropathy suggests a cause and effect, but this association is rarely reported after mantle radiotherapy. We review the aetiology of this condition and postulate possible mechanisms in this patient.

Alertness and cognitive control: Testing the early onset hypothesis.

PubMed

Schneider, Darryl W

2018-05-01

Previous research has revealed a peculiar interaction between alertness and cognitive control in selective-attention tasks: Congruency effects are larger on alert trials (on which an alerting cue is presented briefly in advance of the imperative stimulus) than on no-alert trials, despite shorter response times (RTs) on alert trials. One explanation for this finding is the early onset hypothesis, which is based on the assumptions that increased alertness shortens stimulus-encoding time and that cognitive control involves gradually focusing attention during a trial. The author tested the hypothesis in 3 experiments by manipulating alertness and stimulus quality (which were intended to shorten and lengthen stimulus-encoding time, respectively) in an arrow-based flanker task involving congruent and incongruent stimuli. Replicating past findings, the alerting manipulation led to shorter RTs but larger congruency effects on alert trials than on no-alert trials. The stimulus-quality manipulation led to longer RTs and larger congruency effects for degraded stimuli than for intact stimuli. These results provide mixed support for the early onset hypothesis, but the author discusses how data and theory might be reconciled if stimulus quality affects stimulus-encoding time and the rate of evidence accumulation in the decision process. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Preterm Infants Have Deficient Monocyte and Lymphocyte Cytokine Responses to Group B Streptococcus▿

PubMed Central

Currie, Andrew J.; Curtis, Samantha; Strunk, Tobias; Riley, Karen; Liyanage, Khemanganee; Prescott, Susan; Doherty, Dorota; Simmer, Karen; Richmond, Peter; Burgner, David

2011-01-01

Group B streptococcus (GBS) is an important cause of early- and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS (HKGBS) of preterm infants (gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor (TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants (GA, <30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection. PMID:21300777

Guillain-Barré Syndrome During Ongoing Zika Virus Transmission - Puerto Rico, January 1-July 31, 2016.

PubMed

Dirlikov, Emilio; Major, Chelsea G; Mayshack, Marrielle; Medina, Nicole; Matos, Desiree; Ryff, Kyle R; Torres-Aponte, Jomil; Alkis, Rebecca; Munoz-Jordan, Jorge; Colon-Sanchez, Candimar; Salinas, Jorge L; Pastula, Daniel M; Garcia, Myriam; Segarra, Marangely Olivero; Malave, Graciela; Thomas, Dana L; Rodríguez-Vega, Gloria M; Luciano, Carlos A; Sejvar, James; Sharp, Tyler M; Rivera-Garcia, Brenda

2016-09-02

Guillain-Barré syndrome (GBS) is a postinfectious autoimmune disorder characterized by bilateral flaccid limb weakness attributable to peripheral nerve damage (1). Increased GBS incidence has been reported in countries with local transmission of Zika virus, a flavivirus transmitted primarily by certain Aedes species mosquitoes (2). In Puerto Rico, three arthropod-borne viruses (arboviruses) are currently circulating: Zika, dengue, and chikungunya. The first locally acquired Zika virus infection in Puerto Rico was reported in December 2015 (3). In February 2016, the Puerto Rico Department of Health (PRDH), with assistance from CDC, implemented the GBS Passive Surveillance System (GBPSS) to identify new cases of suspected GBS (4). Fifty-six suspected cases of GBS with onset of neurologic signs during January 1-July 31, 2016, were identified. Thirty-four (61%) patients had evidence of Zika virus or flavivirus infection; the median age of these patients was 55 years (range = 21-88 years), and 20 (59%) patients were female. These 34 patients were residents of seven of eight PRDH public health regions. All 34 patients were hospitalized and treated with intravenous immunoglobulin G (IVIg), the standard treatment for GBS; 21 (62%) required intensive care unit admission, including 12 (35%) who required endotracheal intubation and mechanical ventilation. One patient died of septic shock after treatment for GBS. Additionally, 26 cases of neurologic conditions other than GBS were reported through GBPSS, including seven (27%) in patients with evidence of Zika virus or flavivirus infection. Residents of and travelers to Puerto Rico and countries with active Zika virus transmission should follow recommendations for prevention of Zika virus infections.* Persons with signs or symptoms consistent with GBS should promptly seek medical attention. Health care providers in areas with ongoing local transmission seeing patients with neurologic illnesses should consider GBS and report

Group B Streptococcal Cellulitis and Necrotizing Fasciitis in Infants: A Systematic Review.

PubMed

Wojtera, Monika; Cheng, Horace; Fiorini, Kyle; Coughlin, Kevin; Barton, Michelle; Strychowsky, Julie

2018-02-07

There is no consensus regarding approaches to infantile group B streptococcal (GBS) head and neck cellulitis and necrotizing fasciitis. We present a case of GBS necrotizing cellulitis and summarizes the literature regarding the presentation and management of infantile head and neck GBS cellulitis and necrotizing fasciitis. The literature was searched using PubMed, Web of Science, EMBASE, and Medline (inception to April 2017) by two independent review authors. Inclusion criteria encompassed case reports or case series of infants less than 12 months of age with GBS cellulitis of the head and neck, or with GBS necrotizing fasciitis without restriction to the head and neck. Data were extracted using tables developed a priori by two independent review authors, and discrepancies were resolved by consensus. An infant presenting at 33 days of age with GBS facial necrotizing fasciitis was successfully treated conservatively with antibiotics. Our literature search identified 40 infants with GBS head and neck cellulitis. Late-onset (98%), male gender (65%), and prematurity (58%) predominated. Penicillins were the main therapy used (97%). The 12 identified cases of necrotizing fasciitis were associated with polymicrobial etiology (36%) and broad-spectrum antibiotic use. Seventy-five percent required debridement, including four of five (80%) cases involving the head and neck. Skin and soft tissue involvement is an uncommon manifestation of late-onset GBS infection which requires antibiotic therapy and possibly surgical debridement cases with necrotizing fasciitis.

Fatigue-induced early onset of anticipatory postural adjustments in non-fatigued muscles: support for a centrally mediated adaptation.

PubMed

Strang, Adam J; Berg, William P; Hieronymus, Mathias

2009-08-01

Muscle fatigue has been shown to result in early onset of anticipatory postural adjustments (APAs) relative to those produced in a non-fatigued state. This adaptation is thought to reflect an attempt to preserve postural stability during a focal movement performed in a fatigued state. It remains unclear, however, whether this adaptation is of central (e.g., central nervous system motor command) or peripheral (e.g., muscle contractile properties), origin. One way to confirm that this adaptation is centrally driven is to identify fatigued-induced early APA onsets in non-fatigued muscles. In this study, APAs were obtained using a rapid bilateral reaching maneuver and recorded via surface electromyography before and after conditions of rest (n = 25) or fatigue (n = 25). Fatigue was generated using isokinetic exercise of the right leg. Results showed that fatigue-induced early APA onsets occurred in fatigued and non-fatigued muscles, confirming that fatigue-induced early APA onset is a centrally mediated adaptation.

Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion.

PubMed

Hakonen, Anna H; Isohanni, Pirjo; Paetau, Anders; Herva, Riitta; Suomalainen, Anu; Lönnqvist, Tuula

2007-11-01

Twinkle is a mitochondrial replicative helicase, the mutations of which have been associated with autosomal dominant progressive external ophthalmoplegia (adPEO), and recessively inherited infantile onset spinocerebellar ataxia (IOSCA). We report here a new phenotype in two siblings with compound heterozygous Twinkle mutations (A318T and Y508C), characterized by severe early onset encephalopathy and signs of liver involvement. The clinical manifestations included hypotonia, athetosis, sensory neuropathy, ataxia, hearing deficit, ophthalmoplegia, intractable epilepsy and elevation of serum transaminases. The liver showed mtDNA depletion, whereas the muscle mtDNA was only slightly affected. Alpers-Huttenlocher syndrome has previously been associated with mutations of polymerase gamma, a replicative polymerase of mtDNA. We show here that recessive mutations of the close functional partner of the polymerase, the Twinkle helicase, can also manifest as early encephalopathy with liver involvement, a phenotype reminiscent of Alpers syndrome, and are a new genetic cause underlying tissue-specific mtDNA depletion.

ABCC6 mutations and early onset stroke: Two cases of a typical Pseudoxanthoma Elasticum.

PubMed

Bertamino, Marta; Severino, Mariasavina; Grossi, Alice; Rusmini, Marta; Tortora, Domenico; Gandolfo, Carlo; Pederzoli, Silvia; Malattia, Clara; Picco, Paolo; Striano, Pasquale; Ceccherini, Isabella; Di Rocco, Maja

2018-04-12

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by fragmented and mineralized elastic fibers in the mid-dermis of the skin, eye, digestive tract and cardiovascular system. Clinical presentation includes typical skin lesions, ocular angioid streaks, and multisystem vasculopathy. The age of onset varies considerably from infancy to old age, but the diagnosis is usually made in young adults due to frequent absence of pathognomonic skin and ocular manifestations in early childhood. We report two children with PXE presenting with isolated multisystem vasculopathy and early-onset stroke. In the first patient, diagnosis was delayed until typical dermatologic alterations appeared; in the second patient, next-generation sequencing (NGS) study led to early diagnosis and specific follow-up, underlying the crucial role in idiopathic pediatric stroke of early genetic testing using NGS-based panels. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Self-passivation Rule and the Effect of Post-treatment in GBs of Solar Cell Materials

NASA Astrophysics Data System (ADS)

Liu, Chengyan; Chen, Shiyou; Xiang, Hongjun; Gong, Xingao

Grain boundaries (GBs) existing in polycrystalline semiconductors alloys inducing a great deal of deep defect levels are usually harmful to cells' photovoltaic performance. Experimental and theoretical investigations verified that these defect levels come from the GBs' dangling bonds. We find that, the defect levels in anion core of GB can be passivated by its cations, called by self-passivation. For instance, the post-treated by CdCl2, Cd can eliminate the defect levels by saturating Te dangling bonds in the grain boundary of CdTe. We verify that the idea of self-passivation rule can perfectly explain the benign GBs of CISe and CZTS by sodium treatment. The present work reveals a general mechanism about how dopants in GBs eliminate the defect states through passivating the dangling bonds in covalent polycrystalline semiconductors, and sheds light on how to passivate dangling bonds in GBs with alterative processes. National Science Foundation of China, international collaboration project of MOST, Pujiang plan, Program for Professor of Special Appointment (Eastern Scholar), and Shanghai Rising-star program.

[Knowledge of Andalusian pediatricians and parents about early-onset tooth decay].

PubMed

González, E; Pérez-Hinojosa, S; Alarcón, J A; Peñalver, M A

2015-01-01

To determine the level of knowledge of pediatricians and parents from Andalucía (southern Spain) about early-onset tooth decay, and to assess if pediatricians provide information to parents about pediatric oral care and visits to the pediatric dentist. A random sample of 113 pediatricians and 112 parents with children under 3 years of age received an anonymous questionnaire comprising 14 items for pediatricians and 16 items for parents, grouped into five blocks: visits to the dentist, oral hygiene, caries, nutritional habits, and treatment of caries. The chi-squared test was used to assess differences between groups. Pediatricians showed deficiencies in their knowledge about visits to the dentist and treatment of caries, however their level of knowledge on oral hygiene, tooth decay and nutritional habits were adequate. Parents showed a low level of knowledge in all aspects of the study, mainly about the treatment of tooth decay. There were no significant differences between pediatricians and parents in the knowledge about visits to the dentist, however pediatricians had more knowledge than the parents about hygiene, tooth decay, nutritional habits and treatment (P<0.001). Most of the parents indicated that pediatricians did not provide them detailed information on oral care, and about the possibility of visiting a pediatric dentist. Andalusian pediatricians should improve their knowledge about early-onset tooth decay, and provide more information to parents about the oral care and the possibility of visiting a pediatric dentist. Parents have a very low level of knowledge about early-onset tooth decay, and particularly about treatment. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Outcomes of subsequent pregnancy after first pregnancy with early-onset preeclampsia.

PubMed

van Rijn, Bas B; Hoeks, Lette B; Bots, Michiel L; Franx, Arie; Bruinse, Hein W

2006-09-01

The aim of this study was to report outcome of subsequent pregnancy after early-onset preeclampsia in first pregnancy, and to evaluate potential risk factors for recurrence of preeclampsia and preterm delivery. Reproductive follow-up data were obtained for women with a history of early-onset preeclampsia, resulting in delivery before 34 weeks of gestation at the University Medical Center Utrecht, The Netherlands, between July 1993 and September 2002. The relative contributions of demographic data, outcome variables of first pregnancy, and common thrombophilias to the recurrence risk of preeclampsia and preterm delivery in subsequent pregnancy, were estimated by Cox proportional hazard models. Subsequent pregnancy outcome data were available for 120 women. Overall, preeclampsia reoccurred in the second pregnancy in 30 women (25%). However, 6 women delivered before 34 weeks of gestation (5%), 20 women between 34 and 37 weeks of gestation (17%), and 94 women after 37 weeks of gestation (78%). Forty-one women (34%) had an uneventful pregnancy. Recurrence rates for preeclampsia or preterm delivery were not related to severity of first pregnancy complications, including delivery before 28 weeks of gestation, occurrence of hemolysis, elevated liver enzymes, and low platelet count syndrome, small-for-gestational age infants, and to hereditary or acquired thrombophilias. Chronic hypertension was related to a higher recurrence risk of preeclampsia in the second pregnancy (hazard ratio 2.1, 95% CI 1.0-4.4), and smoking was related to a higher recurrence risk of preterm birth (hazard ratio 2.4, 95% CI 1.1-5.6). Outcomes of subsequent pregnancy after first pregnancy with early-onset preeclampsia is generally favorable.

Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia.

PubMed

Liang, Mengmeng; Niu, Jianmin; Zhang, Liang; Deng, Hua; Ma, Jian; Zhou, Weiping; Duan, Dongmei; Zhou, Yuheng; Xu, Huikun; Chen, Longding

2016-04-01

Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; <34 weeks), and late-onset (n = 8; >36 weeks) preeclampsia and their controls who delivered preterm (n = 5; <34 weeks) or at term (n = 5; >36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value < 0.05. Quantitative real-time reverse transcriptase PCR was used to verify the results. Western blotting was performed to verify the expressions of secreted genes at the protein level. Six hundred twenty-seven genes were differentially expressed in early-compared with late-onset preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early

Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk.

PubMed

Veltman-Verhulst, Susanne M; van Rijn, Bas B; Westerveld, H Egbertine; Franx, Arie; Bruinse, Hein W; Fauser, Bart C J M; Goverde, Angelique J

2010-01-01

Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable metabolic constitution in women may present itself early in life as a reproductive complication, such as polycystic ovary syndrome (PCOS) and preeclampsia. We evaluated the cardiovascular risk of women with a history of early-onset preeclampsia and women with PCOS and assessed their need for implementation of early risk factor-reduction strategies. We performed a standardized evaluation of 240 women with a history of early-onset preeclampsia and 456 women diagnosed with PCOS for established major CVD risk factors. Metabolic syndrome characteristics were analyzed per body mass index category. Mean age was 30.6 and 29.0 years for women with preeclampsia and PCOS, respectively. High percentages of metabolic syndrome were found in both groups (preeclampsia group, 14.6%; and PCOS group, 18.4%), with an incidence of greater than 50% in both groups of women if body mass index was greater than 30 kg/m. Overall, more than 90% of the women qualified for either lifestyle or medical intervention according to the American Heart Association guideline for CVD prevention in women. Women with PCOS and early-onset preeclampsia already show an unfavorable cardiovascular risk profile with high need for lifestyle or medical intervention at a young age. We therefore recommend an active role of the gynecologist in routine screening and follow-up of women with reproductive conditions linked to future cardiovascular risk.

Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

PubMed

Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

2016-01-01

The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

Improved outcome with early rifampicin combination treatment in methicillin-sensitive Staphylococcus aureus bacteraemia with a deep infection focus - a retrospective cohort study.

PubMed

Forsblom, Erik; Ruotsalainen, Eeva; Järvinen, Asko

2015-01-01

Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection. Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality. Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin ≥14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy ≥14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy ≥14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p<0.01) during 90 days follow-up. Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.

High Prevalence of ESBL-Producing Klebsiella pneumoniae Causing Community-Onset Infections in China

PubMed Central

Zhang, Jing; Zhou, Kai; Zheng, Beiwen; Zhao, Lina; Shen, Ping; Ji, Jinru; Wei, Zeqing; Li, Lanjuan; Zhou, Jianying; Xiao, Yonghong

2016-01-01

The aim of this work was to investigate the epidemiological and genetic characteristics of ESBL-producing Klebsiella pneumoniae (ESBL-Kp) causing community-onset infections. K. pneumoniae isolates were collected from 31 Chinese secondary hospitals between August 2010 and 2011. Genes encoding ESBL and AmpC beta-lactamases were detected by PCR. The isolates were assigned to sequence types (STs) using multi-locus sequence typing (MLST). Eleven ESBL-Kp strains were selected for whole-genome sequencing (WGS) for investigating the genetic environment and plasmids encoding ESBL genes. A total of 578 K. pneumoniae isolates were collected, and 184 (31.8%) carried ESBL genes. The prevalence of ESBL-Kp varied from different geographical areas of China (10.2–50.3%). The three most prevalent ESBL genes were blaCTX-M-14 (n = 74), blaCTX-M-15 (n = 60), and blaCTX-M-3 (n = 40). MLST assigned 127 CTX-M-14 and CTX-M-15 producers to 54 STs, and CC17 was the most prevalent population (12.6%). STs (23, 37, and 86) that were known frequently associated with hypervirulent K. pneumoniae (hvKP) account for 14.1% (18/127). Phylogenetic analysis by concatenating the seven loci of MLST revealed the existence of ESBL-producing K. quasipneumoniae (two strains) and K. varricola (one strain), which was further confirmed by WGS. This study highlights the challenge of community-onset infections caused by ESBL-Kp in China. The prevalence of STs frequently associating with hvKP should be of concern. Surveillance of ESBL-KP causing community-onset infections now appears imperative. PMID:27895637

Definition, clinical profile, microbiological spectrum, and prognostic factors of early-onset prosthetic valve endocarditis.

PubMed

López, Javier; Revilla, Ana; Vilacosta, Isidre; Villacorta, Eduardo; González-Juanatey, Carlos; Gómez, Itziar; Rollán, María Jesús; San Román, José Alberto

2007-03-01

There is no agreement in the best cutoff time to distinguish between early- and late- onset prosthetic valve endocarditis (PVE). Our objectives are to define early-onset PVE according to the microbiological spectrum and to analyse the profile and short-term prognosis of this entity. The microbiological profile of 172 non-drug users, who were patients with PVE, were compared according to the time elapsed from surgery among 640 endocarditis diagnosed between 1996 and 2004. There were no differences in the microbiological profile of patients with PVE occurred within 2 months of valve replacement and those accounting between 2 and 12 months. The proportion of coagulase-negative Staphylococci (CNS) was higher during the first year post-intervention (37 vs. 18%, P = 0.005) and Streptococci viridans were more common after 1 year (18 vs. 1%, P = 0.001). The percentage of methicilin-resistant CNS strains was higher before 1 year (77 vs. 30%, P = 0.004). Early-onset PVE represented 38% of all episodes of PVE, CNS being the most frequent isolated microorganisms (37%), most of them methicilin resistant (77%). In-hospital mortality of patients who needed urgent surgery was 46% and elective surgery 25%. Overall, in-hospital mortality was 38% and no differences were seen between surgical and medical groups (32 vs. 45%, P = 0.30). Periannular complications were associated with higher in-hospital mortality (60 vs. 27%, P = 0.007). According to the microbiological profile, the most appropriate cutoff time to distinguish between early- and late-onset PVE was 1 year. Methicilin-resistant CNS are the most frequent pathogens and periannular complications, the only risk factor for in-hospital mortality.

Psychiatric comorbidities of adults with early- and late-onset attention-deficit/hyperactivity disorder.

PubMed

Lin, Yu-Ju; Yang, Li-Kuang; Gau, Susan Shur-Fen

2016-06-01

We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset <7 years (early-onset); (2) attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental

Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD.

PubMed

Mendez, Mario F

2012-11-01

Patients with Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ∼4-5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer's research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22-64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein Eɛ4 (APOE ɛ4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

PubMed Central

Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

2014-01-01

To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

PubMed

Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

2016-06-01

It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases. © The Author(s) 2016.

Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early-onset schizophrenia patients.

PubMed

Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine; Christensen, Anne Marie Raaberg; Nordentoft, Merete; Mortensen, Erik Lykke

2013-10-01

Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early-onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual-construction, aspects of visual and verbal memory, and executive functions in chronic, early-onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early-onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual-construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early-onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms. © 2013 The Scandinavian Psychological Associations.

New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

PubMed

Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

2017-05-01

The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

Premature adrenarche: novel lessons from early onset androgen excess.

PubMed

Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

2011-08-01

Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

Effects of comorbidity and early age of onset in young people with Bipolar Disorder on self harming behaviour and suicide attempts.

PubMed

Moor, Stephanie; Crowe, Marie; Luty, Sue; Carter, Janet; Joyce, Peter R

2012-02-01

The age of the first episode of illness in Bipolar Disorder has been shown to be an important predictor of outcome with early onset, particularly onset before puberty, associated with greater comorbidity, a poorer quality of life and greatest impairment in functioning. Baseline data from a psychotherapy study was used to examine the prevalence of other comorbid psychiatric conditions and the impact of onset at an early age on both self harming behaviour and suicide attempts in young people with Bipolar Disorder. This study of 100 adolescents and young adults (aged 15-36 years) with Bipolar Disorder showed that comorbid conditions were very common, even at the start of their bipolar illness. Comorbidity increased as the age of onset decreased with very early onset (<13 years) patients bearing the greatest burden of disease. Greater comorbidity also significantly increased the risk of having self harmed and attempted suicide with high lethal intent. Self harming behaviour was predicted by having a lifetime diagnoses of Borderline Personality Disorder and Panic Disorder along with an early age of onset of Bipolar Disorder. In contrast, previous suicide attempts were predicted by greater comorbidity and not by very early (<13 years) age of onset. Copyright © 2011 Elsevier B.V. All rights reserved.

Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency.

PubMed

Peng, Kaiyue; Qian, Xiaowen; Huang, Zhiheng; Lu, Junping; Wang, Yuhuan; Zhou, Ying; Wang, Huijun; Wu, Bingbing; Wang, Ying; Chen, Lingli; Zhai, Xiaowen; Huang, Ying

2018-05-18

Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post-transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced-intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001.

Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline.

PubMed

Da Cunha, Violette; Davies, Mark R; Douarre, Pierre-Emmanuel; Rosinski-Chupin, Isabelle; Margarit, Immaculada; Spinali, Sebastien; Perkins, Tim; Lechat, Pierre; Dmytruk, Nicolas; Sauvage, Elisabeth; Ma, Laurence; Romi, Benedetta; Tichit, Magali; Lopez-Sanchez, Maria-José; Descorps-Declere, Stéphane; Souche, Erika; Buchrieser, Carmen; Trieu-Cuot, Patrick; Moszer, Ivan; Clermont, Dominique; Maione, Domenico; Bouchier, Christiane; McMillan, David J; Parkhill, Julian; Telford, John L; Dougan, Gordan; Walker, Mark J; Holden, Matthew T G; Poyart, Claire; Glaser, Philippe

2014-08-04

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates.

Association between polymorphisms in cancer-related genes and early onset of esophageal adenocarcinoma.

PubMed

Wu, I-Chen; Zhao, Yang; Zhai, Rihong; Liu, Geoffrey; Ter-Minassian, Monica; Asomaning, Kofi; Su, Li; Liu, Chen-Yu; Chen, Feng; Kulke, Matthew H; Heist, Rebecca S; Christiani, David C

2011-04-01

There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ≤ 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (≤55 vs >55 years, all P < .05 after adjusting for co-variates and false discovery rate). Among them, five SNPs in the NOS3, BCL2, TNFRSF10A, and CASP8 genes were known to be involved in apoptosis processes. In Kaplan-Meier analyses, rs2070744 of NOS3, rs720321 of BCL2, and rs1035142 of CASP8 were also significantly associated with early onset of EA. Moreover, there was a higher risk of developing EA at a younger age when one had more risk genotypes. In conclusion, polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner.

Prevention of hospital-onset Clostridium difficile infection in the New York metropolitan region using a collaborative intervention model.

PubMed

Koll, Brian S; Ruiz, Rafael E; Calfee, David P; Jalon, Hillary S; Stricof, Rachel L; Adams, Audrey; Smith, Barbara A; Shin, Gina; Gase, Kathleen; Woods, Maria K; Sirtalan, Ismail

2014-01-01

The incidence, severity, and associated costs of Clostridium difficile (C. difficile) infection (CDI) have dramatically increased in hospitals over the past decade, indicating an urgent need for strategies to prevent transmission of C. difficile. This article describes a multifaceted collaborative approach to reduce hospital-onset CDI rates in 35 acute care hospitals in the New York metropolitan region. Hospitals participated in a comprehensive CDI reduction intervention and formed interdisciplinary teams to coordinate their efforts. Standardized clinical infection prevention and environmental cleaning protocols were implemented and monitored using checklists. Monthly data reports were provided to hospitals for facility-specific performance evaluation and comparison to aggregate data from all participants. Hospitals also participated in monthly teleconferences to review data and highlight successes, challenges, and strategies to reduce CDI. Incidence of hospital-onset CDI per 10,000 patient days was the primary outcome measure. Additionally, the incidence of nonhospital-associated, community-onset, hospital-associated, and recurrent CDIs were measured. The use of a collaborative model to implement a multifaceted infection prevention strategy was temporally associated with a significant reduction in hospital-onset CDI rates in participating New York metropolitan regional hospitals. © 2013 National Association for Healthcare Quality.

[Acute inflammatory polyradiculoneuropathy and membranous glomerulonephritis following Epbstein-Barr virus primary infection in a 12-year-old girl].

PubMed

Meyer, P; Soëte, S; Raynaud, P; Henry, V; Morin, D; Rodière, M; Rivier, F; Roubertie, A

2010-11-01

Acute inflammatory polyradiculoneuropathy, or Guillain-Barré syndrome (GBS), is characterized by peripheral nerve demyelination, which leads to rapidly progressive weakness, loss of sensation, and loss of deep tendon reflexes. It is a prototype of postinfectious autoimmune disease, whose pathophysiology is well described in the forms provoked by certain bacteria (molecular mimicry with Campylobacter jejuni), but remains unclear for the forms related to other organisms (cytomegalovirus, Epstein-Barr virus and other herpes group viruses, Mycoplasma pneumoniae). Glomerular lesions can be associated with the neurological symptoms and have also been described after various infections, independently of any signs of polyradiculoneuropathy. We report the observation of a 12-year-old girl who presented with Guillain-Barré syndrome with facial diplegia, ataxia, and intracranial hypertension following Epstein-Barr virus (EBV) primary infection. During the course of the neurological disease, membranous glomerulonephritis (MGN) was diagnosed. The neurological impairment was regressive within 6 months after intravenous immunoglobulin treatment followed by intravenous then oral corticosteroid administration. Viremia remained high more than 6 months after the onset of symptoms. Glomerulopathy progressed independently and finally required immunosuppressant medication with cyclosporine. EBV might be the factor that triggered the autoimmune disorders, as previously reported for systemic lupus erythematosus and multiple sclerosis in children. To the best of our knowledge, this association of 3 conditions (GBS, MGN, and EBV primary infection) has never been reported in the literature. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

STIMULUS: End-System Network Interface Controller for 100 Gb/s Wide Area Networks

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

Zarkesh-Ha, Payman

2014-09-12

The main goal of this research grant is to develop a system-level solution leveraging novel technologies that enable network communications at 100 Gb/s or beyond. University of New Mexico in collaboration with Acadia Optronics LLC has been working on this project to develop the 100 Gb/s Network Interface Controller (NIC) under this Department of Energy (DOE) grant.

Invasive group B streptococcal infections in adults, France (2007-2010).

PubMed

Tazi, A; Morand, P C; Réglier-Poupet, H; Dmytruk, N; Billoët, A; Antona, D; Trieu-Cuot, P; Poyart, C

2011-10-01

Group B streptococcus (GBS) has emerged as an important cause of invasive infection in adults. Here, we report the clinical and microbiological characteristics of 401 non-redundant GBS strains causing adult invasive infections collected during a 4-year period (2007-2010). Bacteraemia without focus (43.4%) and bone and joint infections (18.7%) were the main clinical manifestations. The distribution of capsular polysaccharide (CPS) type showed that types Ia, III, and V accounted for 71.8% of all strains. Resistance to erythromycin increased from 20.2% in 2007 to 35.3% in 2010, and was mainly associated with CPS type V harbouring the erm(B) resistant determinant. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Predictors of Early-Onset Permanent Hearing Loss in Malnourished Infants in Sub-Saharan Africa

ERIC Educational Resources Information Center

Olusanya, Bolajoko O.

2011-01-01

The objective of this study was to determine the predictors of early-onset permanent hearing loss (EPHL) among undernourished infants in a low-income country where routine screening for developmental disabilities in early childhood is currently unattainable. All infants attending four community-based clinics for routine immunization who met the…

Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

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

Mullan, M.; Bennett, C.; Figueredo, C.

1995-02-27

Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onsetmore » disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.« less

Growing rod erosion through the lamina causing spinal cord compression in an 8-year-old girl with early-onset scoliosis.

PubMed

Abduljabbar, Fahad H; Waly, Feras; Nooh, Anas; Ouellet, Jean

2016-09-01

Early-onset scoliosis often occurs by the age of 5 years and is attributed to many structural abnormalities. Syndromic early-onset scoliosis is considered one of the most aggressive types of early-onset scoliosis. Treatment starts with serial casting and bracing, but eventually most of these patients undergo growth-sparing procedures, such as a single growing rod, dual growing rods, or a vertical expandable titanium prosthetic rib. This case report aimed to describe an unusual complication of erosion of a growing rod through the lamina that caused spinal cord compression in an 8-year-old girl with early-onset scoliosis. This is a case report. A retrospective chart review was used to describe the clinical course and radiographic findings of this case after rod erosion into the spinal canal. The patient underwent successful revision surgery removing the rod without neurologic complications. Patients with syndromic early-onset scoliosis are more prone to progressive curves and severe rotational deformity. We believe that the severe kyphotic deformity in addition to the dysplastic nature of the deformity in this population may predispose them to this unusual complication. Copyright © 2016 Elsevier Inc. All rights reserved.

Serial elongation-derotation-flexion casting for children with early-onset scoliosis.

PubMed

Canavese, Federico; Samba, Antoine; Dimeglio, Alain; Mansour, Mounira; Rousset, Marie

2015-12-18

Various early-onset spinal deformities, particularly infantile and juvenile scoliosis (JS), still pose challenges to pediatric orthopedic surgeons. The ideal treatment of these deformities has yet to emerge, as both clinicians and surgeons still face multiple challenges including preservation of thoracic motion, spine and cage, and protection of cardiac and lung growth and function. Elongation-derotation-flexion (EDF) casting is a technique that uses a custom-made thoracolumbar cast based on a three-dimensional correction concept. EDF can control progression of the deformity and - in some cases-coax the initially-curved spine to grow straighter by acting simultaneously in the frontal, sagittal and coronal planes. Here we provide a comprehensive review of how infantile and JS can affect normal spine and thorax and how serial EDF casting can be used to manage these spinal deformities. A fresh review of the literature helps fully understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in patients with early-onset spinal deformities, particularly infantile and juvenile scolisois.

Serial elongation-derotation-flexion casting for children with early-onset scoliosis

PubMed Central

Canavese, Federico; Samba, Antoine; Dimeglio, Alain; Mansour, Mounira; Rousset, Marie

2015-01-01

Various early-onset spinal deformities, particularly infantile and juvenile scoliosis (JS), still pose challenges to pediatric orthopedic surgeons. The ideal treatment of these deformities has yet to emerge, as both clinicians and surgeons still face multiple challenges including preservation of thoracic motion, spine and cage, and protection of cardiac and lung growth and function. Elongation-derotation-flexion (EDF) casting is a technique that uses a custom-made thoracolumbar cast based on a three-dimensional correction concept. EDF can control progression of the deformity and - in some cases-coax the initially-curved spine to grow straighter by acting simultaneously in the frontal, sagittal and coronal planes. Here we provide a comprehensive review of how infantile and JS can affect normal spine and thorax and how serial EDF casting can be used to manage these spinal deformities. A fresh review of the literature helps fully understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in patients with early-onset spinal deformities, particularly infantile and juvenile scolisois. PMID:26716089

Family history of skin cancer is associated with early-onset basal cell carcinoma independent of MC1R genotype.

PubMed

Berlin, Nicholas L; Cartmel, Brenda; Leffell, David J; Bale, Allen E; Mayne, Susan T; Ferrucci, Leah M

2015-12-01

As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual's risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80-3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74-3.35). Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90-7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC. Copyright © 2015. Published by Elsevier Ltd.

Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study

ERIC Educational Resources Information Center

Frazier, Jean A.; Giuliano, Anthony J.; Johnson, Jacqueline L.; Yakutis, Lauren; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.; Hooper, Stephen R.

2012-01-01

Objective: To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method: Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated…

Community-onset carbapenem-resistant Klebsiella pneumoniae urinary tract infections in infancy following NICU hospitalisation.

PubMed

Vergadi, Eleni; Bitsori, Maria; Maraki, Sofia; Galanakis, Emmanouil

2017-10-01

Urinary tract infection (UTI) is a common bacterial infection in childhood with favourable outcome. However, the recent emergence of UTI caused by multidrug-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae (CRE), has become a great concern worldwide. CRE are mainly responsible for nosocomial infections and community-onset CRE infections in healthy individuals are rare. In this study, we report a series of infants without substantial genitourinary abnormalities that were admitted with community-onset urinary tract infections (UTIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and we discuss their aetiology. We retrospectively reviewed the medical records of nine infants who presented from community to the paediatric ward with CRKP urinary tract infections, as well as all affected neonates of a concomitant CRKP outbreak that occurred in the neonatal intensive care unit (NICU) in a tertiary hospital (period from April 2009 to July 2012). We further retrieved all culture-proven CRKP infections of any site from 2007 to 2015 in our paediatric department. Over a 33-month period, nine infants, all males, aged 0.9-19.3 (median 4.0) months, were admitted to the Department of Paediatrics with UTI caused by CRKP. Three of them were diagnosed with urinary tract abnormalities but only one had vesicoureteral reflux (VUR), which was a UTI-associated one. History revealed that they had all been hospitalised in the same NICU during a concurrent long-lasting CRKP outbreak for a median of 17 (2-275) days and thereafter presented with CRKP UTI 15 to 207 (median 41) days after NICU discharge. The antibiotic susceptibility and phenotypic characteristics were identical among all isolates in NICU and the paediatric ward. The summary Figure shows a timeline of NICU hospitalisation indicative of its duration and subsequent CRKP UTI of study participants is presented. These cases illustrate that UTI caused by multidrug-resistant pathogens does not

Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease.

PubMed

Chaudhury, Sultan; Patel, Tulsi; Barber, Imelda S; Guetta-Baranes, Tamar; Brookes, Keeley J; Chappell, Sally; Turton, James; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew; Hardy, John; Mann, David; Morgan, Kevin

2018-02-01

Sporadic early-onset Alzheimer's disease (sEOAD) exhibits the symptoms of late-onset Alzheimer's disease but lacks the familial aspect of the early-onset familial form. The genetics of Alzheimer's disease (AD) identifies APOEε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRSs) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls. A cohort of sEOAD cases was genotyped on the NeuroX array, and PRSs were generated using PRSice. The target data set consisted of 408 sEOAD cases and 436 controls. The base data set was collated by the International Genomics of Alzheimer's Project consortium, with association data from 17,008 late-onset Alzheimer's disease cases and 37,154 controls, which can be used for identifying sEOAD cases due to having shared phenotype. PRSs were generated using all common single nucleotide polymorphisms between the base and target data set, PRS were also generated using only single nucleotide polymorphisms within a 500 kb region surrounding the APOE gene. Sex and number of APOE ε2 or ε4 alleles were used as variables for logistic regression and combined with PRS. The results show that PRS is higher on average in sEOAD cases than controls, although there is still overlap among the whole cohort. Predictive ability of identifying cases and controls using PRSice was calculated with 72.9% accuracy, greater than the APOE locus alone (65.2%). Predictive ability was further improved with logistic regression, identifying cases and controls with 75.5% accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

Whole Exome Analysis of Early Onset Alzheimer’s Disease

DTIC Science & Technology

2013-04-01

FTD), FTD with Parkinsonism , and early-onset Alzheimer Disease (EOAD)-like presentations. Using whole exome capture with subsequent sequencing, we...dementia. The MAPT R406W mutation is associated with EOAD-like symptoms and Parkinsonism without FTD, as well as distinct cognitive courses. KEY...OUTCOMES: Carney RM, Kohli MA, Kunkle BW, Naj AC, Gilbert JR, Züchner S, PERICAK-VANCE MA, Parkinsonism and distinct dementia patterns in a

Identifying anomalously early spring onsets in the CESM large ensemble project

NASA Astrophysics Data System (ADS)

Labe, Zachary; Ault, Toby; Zurita-Milla, Raul

2017-06-01

Seasonal transitions from winter to spring impact a wide variety of ecological and physical systems. While the effects of early springs across North America are widely documented, changes in their frequency and likelihood under the combined influences of climate change and natural variability are poorly understood. Extremely early springs, such as March 2012, can lead to severe economical losses and agricultural damage when these are followed by hard freeze events. Here we use the new Community Earth System Model Large Ensemble project and Extended Spring Indices to simulate historical and future spring onsets across the United States and in the particular the Great Lakes region. We found a marked increase in the frequency of March 2012-like springs by midcentury in addition to an overall trend towards earlier spring onsets, which nearly doubles that of observational records. However, changes in the date of last freeze do not occur at the same rate, therefore, causing a potential increase in the threat of plant tissue damage. Although large-scale climate modes, such as the Pacific Decadal Oscillation, have previously dominated decadal to multidecadal spring onset trends, our results indicate a decreased role in natural climate variability and hence a greater forced response by the end of the century for modulating trends. Without a major reduction in greenhouse gas emissions, our study suggests that years like 2012 in the US could become normal by mid-century.

Early pubertal onset and its relationship with sexual risk taking, substance use and anti-social behaviour: a preliminary cross-sectional study

PubMed Central

2009-01-01

Background In many countries age at pubertal onset has declined substantially. Relatively little attention has been paid to how this decline may affect adolescent behaviours such as substance use, violence and unprotected sex and consequently impact on public health. Methods In the UK, two opportunistic samples (aged 16-45 years), paper-based (n = 976) and online (n = 1117), examined factors associated with earlier pubertal onset and whether earlier age of onset predicted sexual risk-taking, substance use and anti-social behaviours during early adolescence. Results Overall, 45.6% of females reported menarche ≤ 12 years and 53.3% of males were categorised as having pubertal onset ≤ 11 years. For both sexes earlier pubertal onset was associated with poorer parental socio-economic status. Other pre-pubertal predictors of early onset were being overweight, more childhood illnesses (females) and younger age at time of survey (males). For both sexes earlier puberty predicted having drunk alcohol, been drunk, smoked and used drugs <14 years as well as having a sexual debut and unprotected sex <16 years. Males with earlier pubertal onset were more likely to report fighting and aggressive responses to emotional upset during early adolescence while females were more likely to report being bullied and having taken more time off school. Conclusion Results provide sufficient evidence for changes in age of pubertal onset to be further explored as a potential influence on trends in adolescent risk behaviours. Further insight into the relationship between early puberty and both obesity and socio-economic status may help inform early interventions to tackle the development of risk behaviours and health inequalities during early adolescence. PMID:19958543

Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

PubMed

Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

2016-02-01

To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd

High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

PubMed

Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

2018-01-01

Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

Guillain-Barre syndrome caused by hepatitis E infection: case report and literature review.

PubMed

Zheng, Xiaoqin; Yu, Liang; Xu, Qiaomai; Gu, Silan; Tang, Lingling

2018-01-23

Hepatitis E infection is a global disorder that causes substantial morbidity. Numerous neurologic illnesses, including Guillain-Barre syndrome (GBS), have occurred in patients with hepatitis E virus (HEV) infection. We report a 58 year-old non-immunocompromised man who presented with progressive muscle weakness in all extremities during an episode of acute HEV infection, which was confirmed by measuring the anti-HEV IgM antibodies in the serum. Both cerebrospinal fluid examination and electrophysiological study were in agreement with the diagnosis of HEV-associated GBS. Following the treatment with intravenous immunoglobulin, the patient's neurological condition improved rapidly. HEV infection should be strongly considered in patients with neurological symptoms, especially those with elevated levels of liver enzymes.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

PubMed

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-03-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

Demonstration of 20Gb/s polarization-insensitive wavelength switching system for high-speed free-space optical network

NASA Astrophysics Data System (ADS)

Qian, Feng-chen; Ye, Ya-lin; Wen, Yu; Duan, Tao; Feng, Huan

2015-10-01

A 20Gb/s polarization-insensitive all-optical wavelength switching system for high-speed free-space optical communication (FSO) network is experimentally demonstrated All-optical wavelength conversion (AOWC) is implemented using four-wave mixing (FWM) by highly-nonlinear fiber (HNLF). In the experimental setup, a simple actively mode-locked fiber ring laser (AML-FRL) with repetition frequency from 1 to 15 GHz is used to generate eight 2.5Gb/s tributary signals, which are multiplexed into one 20Gb/s optical data stream. At the receiver, the 20 Gb/s OTDM data stream is demultiplexed down to 2.5 Gb/s via a polarization-insensitive FWM scheme. The whole space communication distance is over 10 meters in building hallway. The experimental results show that this system can stably run over 24 hours at 10-9 BER level, thus the proposed architecture can work at higher rate with wavelength-division multiplexing (WDM) and high order modulation schemes.

Is early-onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

PubMed

Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N

2008-02-15

Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.

Evidence for an agitated-aggressive syndrome in early-onset psychosis correlated with antisocial personality disorder, forensic history, and substance use disorder.

PubMed

Huber, Christian G; Hochstrasser, Lisa; Meister, Klara; Schimmelmann, Benno G; Lambert, Martin

2016-08-01

Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of Eugenol against Streptococcus agalactiae and Synergistic Interaction with Biologically Produced Silver Nanoparticles

PubMed Central

Perugini Biasi-Garbin, Renata; Saori Otaguiri, Eliane; Fernandes da Silva, Mayara; Belotto Morguette, Ana Elisa; Armando Contreras Lancheros, César; Kian, Danielle; Perugini, Márcia Regina Eches; Durán, Nelson; Nakamura, Celso Vataru; Yamauchi, Lucy Megumi; Yamada-Ogatta, Sueli Fumie

2015-01-01

Streptococcus agalactiae (group B streptococci (GBS)) is an important infections agent in newborns associated with maternal vaginal colonization. Intrapartum antibiotic prophylaxis in GBS-colonized pregnant women has led to a significant reduction in the incidence of early neonatal infection in various geographic regions. However, this strategy may lead to resistance selecting among GBS, indicating the need for new alternatives to prevent bacterial transmission and even to treat GBS infections. This study reported for the first time the effect of eugenol on GBS isolated from colonized women, alone and in combination with silver nanoparticles produced by Fusarium oxysporum (AgNPbio). Eugenol showed a bactericidal effect against planktonic cells of all GBS strains, and this effect appeared to be time-dependent as judged by the time-kill curves and viability analysis. Combination of eugenol with AgNPbio resulted in a strong synergistic activity, significantly reducing the minimum inhibitory concentration values of both compounds. Scanning and transmission electron microscopy revealed fragmented cells and changes in bacterial morphology after incubation with eugenol. In addition, eugenol inhibited the viability of sessile cells during biofilm formation and in mature biofilms. These results indicate the potential of eugenol as an alternative for controlling GBS infections. PMID:25945115

Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study.

PubMed

Ghaderi, Sara; Gunnes, Nina; Bakken, Inger Johanne; Magnus, Per; Trogstad, Lill; Håberg, Siri Eldevik

2016-01-01

Vaccinations and infections are possible triggers of Guillain-Barré syndrome (GBS). However, studies on GBS after vaccinations during the influenza A(H1N1)pmd09 pandemic in 2009, show inconsistent results. Only few studies have addressed the role of influenza infection. We used information from national health data-bases with information on the total Norwegian population (N = 4,832,211). Cox regression analyses with time-varying covariates and self-controlled case series was applied. The risk of being hospitalized with GBS during the pandemic period, within 42 days after an influenza diagnosis or pandemic vaccination was estimated. There were 490 GBS cases during 2009-2012 of which 410 cases occurred after October 1, 2009 of which 46 new cases occurred during the peak period of the influenza pandemic. An influenza diagnosis was registered for 2.47% of the population and the vaccination coverage was 39.25%. The incidence rate ratio of GBS during the pandemic peak relative to other periods was 1.46 [95% confidence interval (CI) 1.08-1.98]. The adjusted hazard ratio (HR) of GBS within 42 days after a diagnosis of pandemic influenza was 4.89 (95% CI 1.17-20.36). After pandemic vaccination the adjusted HR was 1.11 (95% CI 0.51-2.43). Our results indicated that there was a significantly increased risk of GBS during the pandemic season and after pandemic influenza infection. However, vaccination did not increase the risk of GBS. The small number of GBS cases in this study warrants caution in the interpretation of the findings.

Group B Streptococci Colonization in Pregnant Guatemalan Women: Prevalence, Risk Factors, and Vaginal Microbiome.

PubMed

Rick, Anne-Marie; Aguilar, Angie; Cortes, Rosita; Gordillo, Remei; Melgar, Mario; Samayoa-Reyes, Gabriela; Frank, Daniel N; Asturias, Edwin J

2017-01-01

Infection causes 1 of every 5 neonatal deaths globally. Group B Streptococcus (GBS) is the most significant pathogen, although little is known about its epidemiology and risk in low-income countries. A cross-sectional study in 2015 at a public hospital in Guatemala City enrolled women ≥35 weeks' gestation. Vaginal and rectal swabs were processed using Lim broth and GBS CHROMagar then agglutination testing. Risk factors were assessed using multivariate analysis. Vaginal microbiota were profiled by 16S ribosomal ribonucleic acid sequencing in a subset of 94 women. Of 896 pregnant women, 155 (17.3%; 95% confidence interval [CI], 14.9-19.9) were GBS colonized. Colonization was associated with history of previous infant with poor outcome (odds ratio [OR], 1.94; 95% CI, 1.15-3.27) and increasing maternal age (OR, 1.05; 95% CI, 1.02-1.09). Multiparity was protective (OR, .39; 95% CI, .21-.72). Four (6%) GBS-exposed infants had early-onset neonatal sepsis. Vaginal microbiome composition was associated with previous antibiotic exposure ( P = .003) and previous low birth weight infant ( P = .03), but not GBS colonization ( P = .72). Several individual taxa differed in abundance between colonized and noncolonized women. Group B Streptococcus is prevalent in pregnant women from Guatemala with different risk factors than previously described. Although the vaginal microbiome was not altered significantly in GBS-colonized women, use of antibiotics had an effect on its composition. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Maternal colonisation with Streptococcus agalactiae, and associated stillbirth and neonatal disease in coastal Kenya

PubMed Central

Seale, Anna C; Koech, Angela C; Sheppard, Anna E; Barsosio, Hellen C; Langat, Joyce; Anyango, Emily; Mwakio, Stella; Mwarumba, Salim; Morpeth, Susan C; Anampiu, Kirimi; Vaughan, Alison; Giess, Adam; Mogeni, Polycarp; Walusuna, Leahbell; Mwangudzah, Hope; Mwanzui, Doris; Salim, Mariam; Kemp, Bryn; Jones, Caroline; Mturi, Neema; Tsofa, Benjamin; Mumbo, Edward; Mulewa, David; Bandika, Victor; Soita, Musimbi; Owiti, Maureen; Onzere, Norris; Walker, A Sarah; Schrag, Stephanie J; Kennedy, Stephen H; Fegan, Greg; Crook, Derrick W; Berkley, James A

2016-01-01

Streptococcus agalactiae (Group B Streptococcus, GBS) causes neonatal disease and stillbirth, but its burden in sub-Saharan Africa is uncertain. We assessed maternal recto-vaginal GBS colonisation (7967 women), stillbirth and neonatal disease. Whole genome sequencing was used to determine serotypes, sequence types (ST), and phylogeny. We found low maternal GBS colonisation prevalence (934/7967, 12%), but comparatively high incidence of GBS-associated stillbirth and early onset neonatal disease (EOD) in hospital (0.91(0.25-2.3)/1000 births; 0.76(0.25-1.77)/1000 live-births respectively). However, using a population denominator, EOD incidence was considerably reduced (0.13(0.07-0.21)/1000 live-births). Treated cases of EOD had very high case fatality (17/36, 47%), especially within 24 hours of birth, making under-ascertainment of community-born cases highly likely, both here and in similar facility-based studies. Maternal GBS colonisation was less common in women with low socio-economic status, HIV infection and undernutrition, but when GBS-colonised, they were more likely colonised by the most virulent clone, CC17. CC17 accounted for 267/915(29%) of maternal colonising (265/267(99%) serotype III, 2/267(0.7%) serotype IV), and 51/73(70%) of neonatal disease cases (all serotype III). Trivalent (Ia/II/III) and pentavalent (Ia/Ib/II/III/V) vaccines would cover 71/73(97%) and 72/73(99%) of disease-causing serotypes respectively. Serotype IV should be considered for inclusion, with evidence of capsular switching in CC17 strains. PMID:27572968

Football and dementia: A qualitative investigation of a community based sports group for men with early onset dementia.

PubMed

Carone, Laura; Tischler, Victoria; Dening, Tom

2016-11-01

This study investigates the impact of a weekly group providing sport and physical activities for men with early onset dementia established by Notts County Football in the Community (NCFC). There were three aims: to investigate the effect of early onset dementia on individuals with the condition and their carers; to examine the perceptions of current levels of service provision for people with early onset dementia; and to analyse the impact of the group. Men with dementia (n = 5) attending the sessions, their carers (n = 5), NCFC coaching staff (n = 5) and people organizing/facilitating the sessions (n = 5) were interviewed. Semi-structured interviews explored the participants' experiences of dementia, their opinions on current service provisions and on the sessions. Data were analysed using thematic analysis. Four main themes were found: loss related to the condition of dementia and its impact on relationships ('Loss'); lack of age-appropriate services for people with early onset dementia ('Lack of Resources'); enjoyment and positive anticipation related to the group for all involved ('Enjoyment and Anticipation'); and 'the Notts County Effect' which attributed the success of the sessions to the strong brand of the football club, and to personalized service in a "dementia-free" environment. The NCFC sessions provided a safe low-cost intervention with positive effects upon quality of life for both people with early onset dementia, their carers and the staff involved. This suggests that the service may be valuable to a wider range of people living in different areas. © The Author(s) 2014.

Early-Onset Vemurafenib-Induced DRESS Syndrome.

PubMed

Munch, Marion; Peuvrel, Lucie; Brocard, Anabelle; Saint Jean, Mélanie; Khammari, Amir; Dreno, Brigitte; Quereux, Gaelle

2016-01-01

Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma in patients with BRAF mutations. Vemurafenib is frequently toxic, but the toxicity is often not serious. The third case of vemurafenib-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The case is unusual in that the onset was early, with symptoms emerging as of day 8 of treatment. Treatment of DRESS syndrome is not currently based on precise recommendations, but systemic corticosteroid therapy is effective in serious cases. Severe toxidermias under vemurafenib are exceptional; immediate discontinuation of treatment upon diagnosis is imperative. Switching from vemurafenib to dabrafenib then seems to constitute an interesting therapeutic alternative, since its efficacy is the same but with fewer cutaneous adverse reactions. This case highlights the importance of awareness of the risk of DRESS syndrome associated with vemurafenib and monitoring for warning signs from treatment initiation. © 2015 S. Karger AG, Basel.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

2007-01-01

Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

Neurological soft signs in juvenile patients with Asperger syndrome, early-onset psychosis, and healthy controls.

PubMed

Mayoral, María; Merchán-Naranjo, Jessica; Rapado, Marta; Leiva, Marta; Moreno, Carmen; Giráldez, Marisa; Arango, Celso; Parellada, Mara

2010-11-01

The study of neurological soft signs (NSS) in patients with Asperger syndrome may help us to elucidate the neurological basis of this disorder and to clarify its relationship with other neurodevelopmental disorders. The goal of this study was to compare the prevalence of NSS in a sample of patients with Asperger syndrome, early-onset psychosis and healthy controls. NSS were assessed by means of the Neurological Evaluation Scale in a sample of 29 patients with Asperger syndrome (mean age = 12.86 ± 2.58 years), 30 patients with first-episode early-onset psychoses (mean age 14.17 ± 1.02 years) and 30 healthy controls (mean age 12.33 ± 2.69 years). Significant group differences were found between Asperger syndrome patients and healthy controls both in all the Neurological Evaluation Scale subscales and in the Neurological Evaluation Scale total score. There were no significant differences between both groups of patients in any of the Neurological Evaluation Scale scores. NSS are more prevalent in Asperger syndrome than in healthy controls. The NSS profile was not disorder-specific in our samples of patients with Asperger syndrome and early-onset psychoses. © 2010 Blackwell Publishing Asia Pty Ltd.

Robustness of 40 Gb/s ASK modulation formats in the practical system infrastructure

NASA Astrophysics Data System (ADS)

Pincemin, Erwan; Tan, Antoine; Bezard, Aude; Tonello, Alessandro; Wabnitz, Stefano; Ania-Castañòn, Juan-Diego; Turitsyn, Sergei

2006-12-01

In this work, we theoretically and experimentally analyzed the resilience of 40 Gb/s amplitude shift keying modulation formats to transmission impairments in standard single-mode fiber lines as well as to optical filtering introduced by the optical add/drop multiplexer cascade. Our study is a pre-requisite to assess the implementation of cost-effective 40 Gb/s modulation technology in next generation high bit-rate robust optical transport networks.

Diphtheritic polyneuropathy: a clinical study and comparison with Guillain-Barré syndrome

PubMed Central

Logina, I.; Donaghy, M.

1999-01-01

OBJECTIVES AND METHODS—Clinical features of 50 adults with diphtheritic polyneuropathy (DP) were studied in Riga, Latvia and compared with 21 patients with Guillain-Barré syndrome (GBS).
RESULTS—Neurological complications occurred in 15% of patients admitted to hospital with diphtheria and usually after severe pharyngeal infection. Bulbar dysfunction occurred in 98% of patients with DP and only 10% of patients with GBS. Limb weakness was mild or absent in 30% of patients with DP. Ventilation dependent respiratory failure occurred in 20% of patients with DP. The first symptoms of DP occurred 2-50 days after the onset of local diphtheria infection. Neurological deterioration in DP continued for a median of 49(range 15-83) days and improvement started 73 (range 20-115) days after onset. In 66% of patients with DP, the neuropathy was biphasic with a secondary worsening after 40 days. By contrast patients with GBS worsened for only 10 days on average (range 2-28 days) and improved after 21 (range 4-49) days. Eight patients with DP died, four from severe cardiomyopathy and four from multiple diphtheritic organ failure. Prolonged distal motor latencies (DMLs) were common to both DP and GBS, and more pronounced than motor conduction slowing. Limb symptoms continued after 1 year in 80% of the patients with DP, 6% were unable to walk independently, but independent respiratory and bulbar function had returned in all survivors. By comparison no patients with GBS died and none were severely disabled after 1 year. No death, in patients with DP occurred after antitoxin on days 1 or 2 after onset of diphtheria symptoms, whereas identical rates of death and peak severity of DP were seen both in those who received antitoxin on days 3-6 and those who did not receive it at all.
CONCLUSION—Diphtheric polyneuropathy is much more likely than GBS to have a bulbar onset, to lead to respiratory failure, to evolve more slowly, to take a biphasic course, and to cause death or long

Does Diagnostic Classification of Early-Onset Psychosis Change over Follow-Up?

ERIC Educational Resources Information Center

Fraguas, David; de Castro, Maria J.; Medina, Oscar; Parellada, Mara; Moreno, Dolores; Graell, Montserrat; Merchan-Naranjo, Jessica; Arango, Celso

2008-01-01

Objective: To examine the diagnostic stability and the functional outcome of patients with early-onset psychosis (EOP) over a 2-year follow-up period. Methods: A total of 24 patients (18 males (75%) and 6 females (25%), mean age [plus or minus] SD: 15.7 [plus or minus] 1.6 years) with a first episode of EOP formed the sample. Psychotic symptoms…

Group B Streptococcal Colonization Among Pregnant Women in Delhi, India.

PubMed

Chaudhary, Manu; Rench, Marcia A; Baker, Carol J; Singh, Pushpa; Hans, Charoo; Edwards, Morven S

2017-07-01

Little is known regarding maternal group B streptococcal (GBS) colonization prevalence and capsular (CPS) serotype distribution among pregnant women in India. The objective of this prospective cohort study was to determine GBS recto-vaginal colonization prevalence in pregnant women at Dr. Ram Manohar Lohia Hospital in Delhi, India. Literature review identified reports from India assessing GBS colonization prevalence in pregnant women. Rectal and vaginal swabs were inoculated into Strep B Carrot Broth (Hardy Diagnostics, Santa Maria, CA) and subcultured onto GBS Detect plates (Hardy Diagnostics, Santa Maria, CA). Isolates were serotyped using ImmuLex Strep-B latex kits (Statens Serum Institut, Copenhagen, Denmark). Thirteen studies were identified citing GBS colonization prevalence during pregnancy as 0.47%-16%. Among 300 pregnant women (mean age: 26.9 years; mean gestation: 34 weeks) enrolled (August 2015 to April 2016), GBS colonization prevalence was 15%. Fifteen percent of women had vaginal only, 29% had rectal only and 56% had both sites colonized. CPS types were Ia (13.3%), Ib (4.4%), II (20%), III (22.2%), V (20%) and VII (6.7%); 13.3% were nontypable. Fetal loss in a prior pregnancy at ≥20-weeks gestation was more common in colonized than noncolonized women (15.6% vs. 3.5%; P = 0.004). Employing recent census data for the birth cohort and estimating that 1%-2% of neonates born to colonized women develop early-onset disease, at least 39,000 cases of early-onset disease may occur yearly in India. Using optimal methods, 15% of third trimester pregnant women in India are GBS colonized. A multivalent vaccine containing 6 CPS types (Ia, Ib, II, III, V and VII) would encompass ~87% of GBS carried by pregnant women in India.

113Gb/s (10 x 11.3Gb/s) ultra-low power EAM driver array.

PubMed

Vaernewyck, Renato; Bauwelinck, Johan; Yin, Xin; Pierco, Ramses; Verbrugghe, Jochen; Torfs, Guy; Li, Zhisheng; Qiu, Xing-Zhi; Vandewege, Jan; Cronin, Richard; Borghesani, Anna; Moodie, David

2013-01-14

This paper presents an ultra-low power SiGe BiCMOS IC for driving a 10 channel electro-absorption modulator (EAM) array at 113Gb/s for wavelength division multiplexing passive optical network (WDM-PON) applications. With an output swing of 2.5V(pp), the EAM driver array consumes only 2.2W or 220mW per channel, 50% below the state of the art. Both the output swing and bias are configurable between 1.5 and 3.0V(pp) and 0.75-2.15V respectively.

Risk factors for late onset gram-negative infections: a case-control study.

PubMed

Samanta, Srabani; Farrer, Kate; Breathnach, Aodhan; Heath, Paul T

2011-01-01

To determine the incidence, mortality and risk factors for neonatal late onset gram-negative sepsis and meningitis (LOGNS). Retrospective case-control study. Tertiary neonatal unit in London. Consecutive inborn infants with late onset (>48 h of life) invasive gram-negative infections diagnosed between 1999 and 2005. Controls were healthy infants matched for gestation and time of admission to the neonatal unit. Clinical and risk factor data. 73 cases of LOGNS were identified of which 48 were inborn and included in the study (incidence 1.85/1000 live births). Enterobacter spp. (28%), Escherichia coli (27%) and Klebsiella spp. (21%) were the most common pathogens. The majority of infants were of very low birthweight (VLBW; 79%), and cases and controls were well matched (median gestation 26 weeks). Overall case death was 27% in cases versus 13.5% in controls (p=0.08). There was no significant difference between cases and controls regarding maternal risk factors. Mechanical ventilation, total parenteral nutrition (TPN) and its duration, presence of a central venous line and its duration, use of specific antibiotics and the occurrence of necrotising enterocolitis at or before the first positive culture were all significantly associated with case status in univariate analysis. In multivariate logistic regression analysis, only duration of TPN at or before first positive blood culture remained independently associated with LOGNS (p<0.001). LOGNS occurs predominantly in VLBW infants. When the influence of gestational age is accounted for, the only independent risk factor found for late onset gram-negative neonatal infections is the duration of TPN.

Should Israel screen all mothers-to-be to prevent early-onset of neonatal group B streptococcal disease? A cost-utility analysis.

PubMed

Ginsberg, Gary M; Eidelman, Arthur I; Shinwell, Eric; Anis, Emilia; Peyser, Reuven; Lotan, Yoram

2013-02-20

In Israel, an average of 37 children are born each year with sepsis and another four with meningitis as a result of Group B Streptococcal (GBS) disease. Israel currently only screens mothers with defined risk factors (around 15% of all pregnancies) in order to identify candidates for Intrapartum Antiobiotic Prophyhlaxis (IAP) of GBS. This paper presents a cost-utility analysis of implementing an alternative strategy, which would expand the current protocol to one aiming to screen all pregnant women at 35-37 weeks gestation based on taking a vaginal culture for GBS. A spreadsheet model was built incorporating technical, epidemiological, health service costs, demographic and economic data based primarily on Israeli sources. The intervention of universal screening (compared with the current scenario) would increase screening costs from 580,000 NIS to 3,278,000 million NIS. In addition, the intervention would also increase penicillin costs from 39,000 NIS to 221,000 NIS. Current culture screening of approximately 15% of mothers-to-be with high risk factors resulted in 42 GBS births in 2008-9 (0.253/1000 births). Expanding culture screening to 85% of mothers-to-be, will decrease the number of GBS births to 17.3 (0.104/1000 births). The initial 2.9 million NIS incremental intervention costs are offset by decreased treatment costs of 1.9 million NIS and work productivity gains of 811,000 NIS as a result of a decrease in neurological sequelae from GBS caused meningitis. Thus the resultant net cost of the intervention is only around 134,000 NIS. Culture based screening will reduce the burden of disease by 12.6 discounted Quality Adjusted Life Years (QALYS), giving a very cost effective baseline incremental cost per QALY (cf. risk factor screening) of 10,641 NIS per QALY. The data was very sensitive to rates of anaphylactic shock and changes in the percentage of meningitis cases that had associated long term-sequelae. It is recommended that Israel adopt universal culture

Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis.

PubMed

Cusmai, Raffaella; Moavero, Romina; Bombardieri, Roberta; Vigevano, Federico; Curatolo, Paolo

2011-12-01

In tuberous sclerosis complex, early seizure onset is associated with high risk of intractable epilepsy and cognitive/behavioral impairment. We retrospectively evaluated the long-term outcome of 44 infants presenting with seizures in the first 12 months who received vigabatrin, and were followed up for at least 3.5 years. At the final evaluation 55% of patients were still having seizures, 80% had intellectual disability, and 30% had autism. Sixty-five percent of children who had been treated earlier with vigabatrin after seizure onset achieved seizure freedom, compared with 24% of subjects who received vigabatrin treatment later (P<0.01). Intellectual disability was present in 61% of the children treated early (group A) and in 100% of the children treated later (group B). Nine percent of group A and 52% of group B had autism (P≈0.001). A shorter gap between seizure onset and start of treatment could reduce the risk of epileptic encephalopathy, minimizing the deleterious effect of seizures, but is not able to completely reverse the tuberous sclerosis complex-associated cognitive impairment. Copyright © 2011 Elsevier Inc. All rights reserved.

Two Novel Mutations in the GDAP1 and PRX Genes in Early Onset Charcot-Marie-Tooth Syndrome

PubMed Central

Auer-Grumbach, M.; Fischer, C.; Papić, L.; John, E.; Plecko, B.; Bittner, R. E.; Bernert, G.; Pieber, T. R.; Miltenberger, G.; Schwarz, R.; Windpassinger, C.; Grill, F.; Timmerman, V.; Speicher, M. R.; Janecke, A. R.

2011-01-01

Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested. PMID:18504680

Grain Boundary Sliding (GBS) as a Plastic Instability Leading to Coeval Pseudotachylyte Development in Mylonites: an EBSD Study of the Seismic Cycle in Brittle-Ductile Transition Rocks of the South Mountains Core Complex, Arizona, USA

NASA Astrophysics Data System (ADS)

Miranda, E.; Stewart, C.

2017-12-01

Exposures of coeval pseudotachylytes and mylonites are relatively rare, but are crucial for understanding the seismic cycle in the vicinity of the brittle-ductile transition (BDT). We use both field observations and electron backscatter diffraction (EBSD) analysis to investigate the coeval pseudotachylytes and granodiorite mylonites exposed in the footwall of the South Mountains core complex, Arizona, to evaluate how strain is localized both prior to and during pseudotachylyte development at the BDT. In the field, we observe numerous pseudotachylyte veins oriented parallel to mylonitic foliation; the veins have synthetic shear sense with adjacent mylonites, and are < 2 cm thick, laterally discontinuous, and confined to a few m in structural thickness. EBSD analysis reveals that deformation is strongly partitioned into quartz in mylonites, where quartz shows subgrain rotation overprinted by bulging recrystallization microstructures and lattice preferred orientation (LPO) patterns indicative of dislocation creep. Foliation-parallel zones of finely recrystallized, (< 5 μm diameter) bulge-nucleated grains in the mylonites show four-grain junctions and randomized LPO patterns consistent with grain boundary sliding (GBS). Pseudotachylyte veins have elongate polycrystalline quartz survivor clasts that also exhibit GBS traits, suggesting that pseudotachylytes form within GBS zones in mylonites. We interpret the onset of GBS as a triggering mechanism for coeval pseudotachylyte development, where the accompanying decrease in effective viscosity and increase in strain rate initiated seismic slip and pseudotachylyte formation within GBS zones. Strain became localized within the pseudotachylyte until crystallization of melt impeded flow, inducing pseudotachylyte development in other GBS zones. We associate the pseudotachylyte veins and host mylonites with the coseismic and interseismic parts of the seismic cycle, respectively, where the abundance and lateral discontinuity of

Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.

PubMed

Sanchez, Lauren A; Maggadottir, Solrun Melkorka; Pantell, Matthew S; Lugar, Patricia; Rundles, Charlotte Cunningham; Sullivan, Kathleen E

2017-08-01

Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older). Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups. After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients. These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for

The stochastic dance of early HIV infection

NASA Astrophysics Data System (ADS)

Merrill, Stephen J.

2005-12-01

The stochastic nature of early HIV infection is described in a series of models, each of which captures aspects of the dance of HIV during the early stages of infection. It is to this highly variable target that the immune response must respond. The adaptability of the various components of the immune response is an important aspect of the system's operation, as the nature of the pathogens that the response will be required to respond to and the order in which those responses must be made cannot be known beforehand. As HIV infection has direct influence over cells responsible for the immune response, the dance predicts that the immune response will be also in a variable state of readiness and capability for this task of adaptation. The description of the stochastic dance of HIV here will use the tools of stochastic models, and for the most part, simulation. The justification for this approach is that the early stages and the development of HIV diversity require that the model to be able to describe both individual sample path and patient-to-patient variability. In addition, as early viral dynamics are best described using branching processes, the explosive growth of these models both predicts high variability and rapid response of HIV to changes in system parameters.In this paper, a basic viral growth model based on a time dependent continuous-time branching process is used to describe the growth of HIV infected cells in the macrophage and lymphocyte populations. Immigration from the reservoir population is added to the basic model to describe the incubation time distribution. This distribution is deduced directly from the modeling assumptions and the model of viral growth. A system of two branching processes, one in the infected macrophage population and one in the infected lymphocyte population is used to provide a description of the relationship between the development of HIV diversity as it relates to tropism (host cell preference). The role of the immune

Nervous System Injury and Neuroimaging of Zika Virus Infection.

PubMed

Wu, Shanshan; Zeng, Yu; Lerner, Alexander; Gao, Bo; Law, Meng

2018-01-01

In 2016, World Health Organization announced Zika virus infection and its neurological sequalae are a public health emergency of global scope. Preliminary studies have confirmed a relationship between Zika virus infection and certain neurological disorders, including microcephaly and Guillain-Barre syndrome (GBS). The neuroimaging features of microcephaly secondary to Zika virus infection include calcifications at the junction of gray-white matter and subcortical white matter with associated cortical abnormalities, diminution of white matter, large ventricles with or without hydrocephalus, cortical malformations, hypoplasia of cerebellum and brainstem, and enlargement of cerebellomedullary cistern. Contrast enhancement of the cauda equine nerve roots is the typical neuroimaging finding of GBS associated with Zika virus. This review describes the nervous system disorders and associated imaging findings seen in Zika virus infection, with the aim to improve the understanding of this disease. Imaging plays a key role on accurate diagnosis and prognostic evaluation of this disease.

Cardiopulmonary morbidity of streptococcal infections in a PICU.

PubMed

Hon, Kam-Lun E; Fu, Antony; Leung, Ting Fan; Poon, Terence C W; Cheung, Wai Hung; Fong, Chor Yiu; Ho, Yee Ting Christina; Lee, Tsui Yin Jamie; Ng, Tam Man; Yu, Wai Ling; Cheung, Kam Lau; Lee, Vivian; Ip, Margaret

2015-01-01

The streptococci are important bacteria that cause serious childhood infections. We investigated cardiopulmonary morbidity associated with streptococcal infection and pediatric intensive care unit (PICU) admission. A retrospective study between 2002 and 2013 of all children with a laboratory isolation of streptococcus. There were 40 (2.3%) PICU patients with streptococcal isolations including Streptococcus pyogenes (Group A streptococcus, GAS, n = 7), Streptococcus agalactiae (Group B streptococcus, GBS, n = 5), Streptococcus pneumoniae (SP, n = 20), alpha-hemolytic (n = 4), beta-hemolytic (n = 2) and gama-hemolytic (n = 2) streptococci. Comparing among GAS, GBS and SP, respiratory isolates were more likely positive for GAS or SP (P = 0.033), whereas cerebrospinal fluid was more likely positive for GBS (P = 0.002). All GAS and GBS, and the majority of SP (90%) were sensitive to penicillin. All SP specimens were sensitive to cefotaxime and vancomycin. These infections were associated with high PICU mortality of 43%, 20% and 25%, respectively. Isolation of streptococci was associated with a 30% mortality and high rates of need for mechanical ventilatory and inotropic supports. Patients with GAS, SP or any streptococcal isolation had relative risks [95% confidence interval (CI), P value] of PICU deaths of 7.5 (CI 3.1-18.1, P < 0.0001), 4.5 (CI 2.0-9.8, P < 0.0002) and 5.7 (CI 3.4-9.5, P < 0.0001), respectively. In SP, older children had significantly higher prevalence of premorbid conditions such as malignancy, mental retardation/cerebral palsy ± seizure disorders, chromosomal or genetic disorders (P = 0.003) than children <5 years of age. Serotypes were available for some of these specimens that included 19A, 6B, 3 and 6C. There were four SP deaths with multiorgan system failure and hemolytic uremic syndrome (two 19A and two serotype 3). Severe streptococcal infections are associated with significant morbidity and