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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease-causing pathogen of the COVID-19 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe COVID-19 disease and are at higher risk for preterm birth compared to uninfected pregnant women. Despite this evidence, the immunological effects of SARS-CoV-2 infection during pregnancy remain understudied. Objective To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women. Study Design Immune responses to SARS-CoV-2 were analyzed using samples from pregnant (n=33) and non-pregnant (n=17) women who had either tested positive (pregnant n=22; non-pregnant n=17) or negative for SARS-CoV-2 (pregnant n=11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we evaluated anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood. Results SARS-COV-2 positive pregnant women expressed more IL1β , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of SARS-CoV-2 nAb was inhibited by infection during pregnancy. Conclusions SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.

Defects in the phosphoinositide 3-kinase (PI3K) pathway are shared characteristics in several brain disorders, including the inherited intellectual disability and autism spectrum disorder, fragile X syndrome (FXS). PI3K signaling therefore could serve as a therapeutic target for FXS and other brain disorders. However, broad inhibition of such a central signal transduction pathway involved in essential cellular functions may produce deleterious side effects. Pharmacological strategies that selectively correct the overactive components of the PI3K pathway while leaving other parts of the pathway intact may overcome these challenges. Here, we provide the first evidence that disease mechanism-based PI3K isoform-specific inhibition may be a viable treatment option for FXS. FXS is caused by loss of the fragile X mental retardation protein (FMRP), which translationally represses specific messenger RNAs, including the PI3K catalytic isoform p110β. FMRP deficiency increases p110β protein levels and activity in FXS mouse models and in cells from subjects with FXS. Here, we show that a novel, brain-permeable p110β-specific inhibitor, GSK2702926A, ameliorates FXS-associated phenotypes on molecular, cellular, behavioral, and cognitive levels in two different FMRP-deficient mouse models. Rescued phenotypes included increased PI3K downstream signaling, protein synthesis rates, and dendritic spine density, as well as impaired social interaction and higher-order cognition. Several p110β-selective inhibitors, for example, a molecule from the same chemotype as GSK2702926A, are currently being evaluated in clinical trials to treat cancer. Our results suggest that repurposing p110β inhibitors to treat cognitive and behavioral defects may be a promising disease-modifying strategy for FXS and other brain disorders.

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Introduction With the increased occurrence of methicillin resistant S. aureus (MRSA), the consumption of vancomycin, the drug of choice, has also increased. As a consequence, strains of S. aureus resistant to vancomycin have started to emerge. This study aimed to evaluate the level of vancomycin resistance among clinical and nasal S. aureus isolates in a rural town in Egypt. MethodsThis cross-sectional study was held in the general hospital at the rural town of Kafr Eldawar in Egypt, during the period from January 2013 to January 2014. S. aureus isolates were collected from clinical samples and from nasal swabs. Results Two hundred S. aureus isolates were collected, 80 (40%) from clinical samples and 120 (60%) from nasal carriage samples. Vancomycin resistant S. aureus (VRSA) was only detected in clinical samples, all collected from the outpatient clinic. Eleven VRSA isolates (13.8% of total S. aureus clinical isolates) and one strain of vancomycin-intermediate S. aureus (from nasal carriage) were detected. VRSA isolates were most resistant to ciprofloxacin (90.9%) and erythromycin (81.8%). Five isolates were resistant to all tested antibiotics: ciprofloxacin, clindamycin, erythromycin, linezolid, oxacillin, penicillin and trimethoprim-sulfamethoxazole. MRSA was found to constitute 43.8% of clinical S. aureus isolates. The MRSA colonization rate among community individuals was 43.6%, 42.9% among healthcare workers and 51.4% among patients. Conclusion The prevalence of VRSA was high in clinical samples suggesting that there is a high level of VRSA strains in Egypt that goes undetected since most laboratories only use disk diffusion for detection of vancomycin resistance. Keywords Antibiotic resistance, methicillin resistant S. aureus, vancomycin resistant S. aureus

Attention-deficit/hyperactivity disorder (ADHD), the most common pediatric neurobehavioral disorder, frequently presents with coexisting reading disorders (RDs). Despite this, it is unclear whether medication improves symptoms and function in children with comorbid ADHD and RD. We present a systematic review of studies investigating the effects of ADHD medications on ADHD symptoms, academic outcomes, and neuropsychological measures in this important group.

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