Clinical assessment of HNF1A and GCK variants and identification of a novel mutation causing MODY2

A child with impaired fasting glucose was found to be heterozygous for a novel variant at c.659G>A in GCK and a variant at c.1663C>T in HNF1A. Structural modeling and clinical correlation suggests that the GCK variant causes monogenic diabetes while the variant in HNF1A is unlikely to be pathogenic.     

Secondhand smoke exposure,illness severity,and resource utilization in pediatric emergency department patients with respiratory illnesses

Objective: Hospital-based data reveal that children who have secondhand smoke exposure (SHSe) experience severe respiratory illnesses and greater resource utilization. Our objective was to assess the relationship between SHSe and illness severity/resource utilization among children presenting to the pediatric emergency department (PED) with three common respiratory conditions—asthma, bronchiolitis, and pneumonia. Methods: A retrospective review of a yearlong consecutive sample of PED patients with SHSe status documentation and asthma, bronchiolitis, or pneumonia diagnoses was performed. PED illness severity/resource utilization variables included triage categorization, initial oxygen saturation, evaluation/testing (influenza A & B, respiratory syncytial virus, chest X-ray), procedures/interventions performed (supplemental oxygen, suctioning, intubation), medications administered, and disposition. Logistic and linear regression models were conducted to determine differences in each diagnosis group while controlling for sociodemographics, medical history, seasonality, and insurance type. Results: There were 3,229 children with documentation of SHSe status and an asthma (41%), bronchiolitis (36%), or pneumonia (23%) diagnosis. Across diagnosis groups, approximately 1/4 had positive documentation of SHSe. Asthmatic children with SHSe were more likely to receive corticosteroids (odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.19, 2.44) and/or magnesium sulfate (OR = 1.66, 95% CI = 1.14, 2.40). Children with SHSe and bronchiolitis were more likely to receive racemic epinephrine (OR = 2.48, 95% CI = 1.21, 5.08), have a chest X-ray (OR = 1.36, 95% CI = 1.00, 1.85), and/or be admitted (OR = 1.46, 95% CI = 1.09, 1.95). No differences in illness severity/resource utilization were identified for children with pneumonia. Conclusions: SHS-exposed children with asthma or bronchiolitis have greater illness severity/resource utilization. Our findings highlight the importance of SHSe assessment, cessation, and research efforts in the PED setting.     

Using a social ecological framework to characterize the correlates of HIV among men who have sex with men in Lomé, Togo

In the mixed and concentrated HIV epidemics of West Africa, the relative disproportionate burden of HIV among men who have sex with men (MSM) compared to other reproductive-age men is higher than that observed in Southern and Eastern Africa. Our aim is to describe the correlates of HIV infection among MSM living in Lomé, Togo, using the Modified Social Ecological Model (MSEM). A total of 354 MSM?≥18 years of age were recruited using respondent driven sampling (RDS) for a cross-sectional survey in Lomé, Togo. Participants completed a structured questionnaire and were tested for HIV and syphilis. Statistical analyses included RDS-weighted proportions, bootstrapped confidence intervals (CI), and logistic regression models. Mean age of participants was 22 years; 71.5% were between 18 and 24 years. RDS-weighted HIV prevalence was 9.2% (95% CI=5.4–13.2). In RDS-adjusted (RDSa) bivariate analysis, HIV infection was associated with disclosure of sexual orientation to a family member, discriminatory remarks made by family members, forced sex, ever being blackmailed because of being MSM, community and social stigma and discrimination, and health service stigma and discrimination. In the multivariable model, HIV infection was associated with being 25 years or older (RDSa adjusted OR (aOR)=4.3, 95% CI=1.5–12.2), and having sex with a man before age 18 (RDSa aOR=0.3, 95% CI=0.1–0.9). HIV prevalence was more than seven times higher than that estimated among adults aged 15–49 living in Togo. Using the MSEM, network, community, and policy-level factors were associated with HIV infection among MSM in Lomé, Togo. Through the use of this flexible risk framework, a structured assessment of the multiple levels of HIV risk was characterized, highlighting the need for evidence-based and human-rights affirming combination HIV prevention and treatment programs that address these various risk levels for MSM in Lomé.     

Academic Detailing to Teach Aging and Geriatrics

Geriatric education is a required component of internal medicine training. Work hour rules and hectic schedules have challenged residency training programs to develop and utilize innovative teaching methods. In this study, the authors examined the use of academic detailing as a teaching intervention in their residents’ clinic and on the general medicine inpatient wards to improve clinical knowledge and skills in geriatric care. The authors found that this teaching method enables efficient, directed education without disrupting patient care. We were able to show improvements in medical knowledge as well as self-efficacy across multiple geriatric topics.     

Parental Perceptions, Early Maladaptive Schemas, and Depressive Symptoms in Young Adults

Cognitive models of depression propose that negative schemas contribute to depressive symptoms. Early experiences, particularly parenting, have been proposed to influence cognitive schemas and have also been shown to correlate with depression. This study explores the concurrent relationship between retrospective reports of parenting, Early Maladaptive Schemas (EMSs) described by J. E. Young (1994), and symptoms of depression in a sample of undergraduate students (N = 194). The EMSs of defectiveness/shame, insufficient self-control, vulnerability, and incompetence/inferiority were associated with perceptions of parenting and depressive symptomatology. There was evidence that these four EMSs partially mediate the relationship between parental perceptions and depressive symptomatology. Results are discussed in relation to previous findings, theory, and the measurement of EMSs.     

Performance of a histidine-rich protein 2 rapid diagnostic test, Paracheck Pf®, for detection of malaria infections in Ugandan pregnant women

Improved laboratory diagnosis is critical to reduce the burden of malaria in pregnancy. Peripheral blood smears appear less sensitive than Plasmodium falciparum histidine-rich protein 2-based rapid diagnostic tests (RDTs) for placental malaria infections in studies conducted at delivery. In this study, 81 women in Uganda in the second or third trimester of pregnancy were followed-up until delivery. At each visit, peripheral blood was tested by blood smear, RDT, and nested species-specific polymerase chain reaction (PCR). Sensitivity and specificity of the tests was calculated with PCR, which detected 22 infections of P. falciparum, as the gold standard. The sensitivity and specificity of blood smears were 36.4% (95% confidence interval [CI] = 18.0-59.2%) and 99.6% (95% CI = 97.7-100%), respectively. The corresponding values for RDT were 31.8% (95% CI = 14.7-54.9%) and 100% (95% CI = 98.3-100%). The RDTs could replace blood smears for diagnosis of malaria in pregnancy by virtue of their relative ease of use. Field-based sensitive tests for malaria in pregnancy are urgently needed.     

X-ray crystal structure of the streptococcal specific phage lysin PlyC

Bacteriophages deploy lysins that degrade the bacterial cell wall and facilitate virus egress from the host. When applied exogenously, these enzymes destroy susceptible microbes and, accordingly, have potential as therapeutic agents. The most potent lysin identified to date is PlyC, an enzyme assembled from two components (PlyCA and PlyCB) that is specific for streptococcal species. Here the structure of the PlyC holoenzyme reveals that a single PlyCA moiety is tethered to a ring-shaped assembly of eight PlyCB molecules. Structure-guided mutagenesis reveals that the bacterial cell wall binding is achieved through a cleft on PlyCB. Unexpectedly, our structural data reveal that PlyCA contains a glycoside hydrolase domain in addition to the previously recognized cysteine, histidine-dependent amidohydrolases/peptidases catalytic domain. The presence of eight cell wall-binding domains together with two catalytic domains may explain the extraordinary potency of the PlyC holoenyzme toward target bacteria.     

Junín Virus Pathogenesis and Virus Replication

Junín virus, the etiological agent of Argentine hemorrhagic fever, causes significant morbidity and mortality. The virus is spread through the aerosolization of host rodent excreta and endemic to the humid pampas of Argentina. Recently, significant progress has been achieved with the development of new technologies (e.g. reverse genetics) that have expanded knowledge about the pathogenesis and viral replication of Junín virus. We will review the pathogenesis of Junín virus in various animal models and the role of innate and adaptive immunity during infection. We will highlight current research regarding the role of molecular biology of Junín virus in elucidating virus attenuation. We will also summarize current knowledge on Junín virus pathogenesis focusing on the recent development of vaccines and potential therapeutics.