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Objective This study describes parenting experiences at the beginning of the COVID‐19 pandemic and examines differences across parent gender and family income level. Background The COVID‐19 pandemic had unprecedented impacts on families. Many parents faced employment changes, including job loss, reduced pay, and working remotely, while simultaneously experiencing increased childcare responsibilities due to school and childcare closures. Research is needed to document the ongoing impact of these changes on parents and families. Method An online convenience sample of parents (N = 1,009) reported on their parenting experiences during the beginning of the COVID‐19 pandemic (April 2020) in an online survey. Results Parents reported high levels of depression, anxiety, and parental burnout. Further, many parents reported increased negative emotions, such as anger and worry, while simultaneously feeling closer to their children and offering more comfort and soothing. Differences across gender and income levels are presented. Conclusion These results align with other emerging findings of increased impacts to mental health and well‐being for parents and children and document the disproportionate effects on women and low‐income families. Implications Implications include needing additional support (e.g., financial, caregiving) for parents and families as we continue to face the impacts and consequences of COVID‐19.

There is limited knowledge on shared and syndrome-specific attentional profiles in autism spectrum disorder (ASD) and Williams syndrome (WS). Using eye-tracking, we examined attentional profiles of 35 preschoolers with ASD, 22 preschoolers with WS and 20 typically developing children across social and non-social dimensions of attention. Children with ASD and those with WS presented with overlapping deficits in spontaneous visual engagement with the target of others’ attention and in sustained attention. Children with ASD showed syndrome-specific abnormalities in monitoring and following a person’s referential gaze, as well as a lack of preferential attention to social stimuli. Children with ASD and WS present with shared as well as syndrome-specific abnormalities across social and non-social dimensions of attention.

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn’s disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles. Inflammatory bowel disease (IBD) has been linked to host-microbiota interactions. Here, the authors investigate mucosa-associated microbiota using endoscopically-targeted biopsies from inflamed and non-inflamed colon in patients with Crohn’s disease and ulcerative colitis, finding associations with inflammation and host epigenomic alterations.

Over the last few decades, rising greenhouse gas emissions have promoted poleward expansion of the large-scale atmospheric Hadley circulation that dominates the Tropics, thereby affecting behavior of the Intertropical Convergence Zone (ITCZ) and North Atlantic Oscillation (NAO). Expression of these changes in tropical marine ecosystems is poorly understood because of sparse observational datasets. We link contemporary ecological changes in the southern Caribbean Sea to global climate change indices. Monthly observations from the CARIACO Ocean Time-Series between 1996 and 2010 document significant decadal scale trends, including a net sea surface temperature (SST) rise of ∼1.0 ± 0.14 °C (±SE), intensified stratification, reduced delivery of upwelled nutrients to surface waters, and diminished phytoplankton bloom intensities evident as overall declines in chlorophyll a concentrations (ΔChl a = −2.8 ± 0.5%⋅y ⁻¹) and net primary production (ΔNPP = −1.5 ± 0.3%⋅y ⁻¹). Additionally, phytoplankton taxon dominance shifted from diatoms, dinoflagellates, and coccolithophorids to smaller taxa after 2004, whereas mesozooplankton biomass increased and commercial landings of planktivorous sardines collapsed. Collectively, our results reveal an ecological state change in this planktonic system. The weakening trend in Trade Winds (−1.9 ± 0.3%⋅y ⁻¹) and dependent local variables are largely explained by trends in two climatic indices, namely the northward migration of the Azores High pressure center (descending branch of Hadley cell) by 1.12 ± 0.42°N latitude and the northeasterly progression of the ITCZ Atlantic centroid (ascending branch of Hadley cell), the March position of which shifted by about 800 km between 1996 and 2009.

The oriented peptide library technique was used to investigate the peptide-binding specificities of nine PDZ domains. Each PDZ domain selected peptides with hydrophobic residues at the carboxyl terminus. Individual PDZ domains selected unique optimal motifs defined primarily by the carboxyl terminal three to seven residues of the peptides. One family of PDZ domains, including those of the Discs Large protein, selected peptides with the consensus motif Glu-(Ser/Thr)-Xxx-(Val/Ile) (where Xxx represents any amino acid) at the carboxyl terminus. In contrast, another family of PDZ domains, including those of LIN-2, p55, and Tiam-1, selected peptides with hydrophobic or aromatic side chains at the carboxyl terminal three residues. On the basis of crystal structures of the PSD-95-3 PDZ domain, the specificities observed with the peptide library can be rationalized.

Advancements in the rapidity, cost efficacy, and sensitivity of next‐generation sequencing (NGS) have facilitated molecular risk stratification and precision medicine‐based treatment for pediatric leukemia. The benefit of uniform cytomolecular analyses for clinical trial risk assignment is clear. However, the clinical impact of comprehensive NGS for pediatric leukemias at an institutional level is not well described. We report the genomic spectrum of one of the largest cohorts of pediatric and adolescent/young adult (AYA) acute leukemias examined to date (n = 1442) via institutional NGS testing from our large tertiary care center. We evaluated the clinical utility of genomic results for informing prognosis and treatment. We identified high utility of the comprehensive DNA‐based mutational panel and RNA‐fusion panel, which detected leukemia‐associated variants in 99% of specimens. We observed 65% of B‐cell acute lymphoblastic leukemia cases and 69% of patients with acute myeloid leukemia harbored a prognostic molecular alteration. In total, 325 of 1134 patients (29%) harbored potentially targetable molecular biomarkers, and 23% of cases with follow‐up data received precision medicine‐based therapy. Paired diagnostic and relapsed leukemia samples aided in differentiation between treatment‐related leukemia versus lineage drift/switch. These findings demonstrate the broad utility of comprehensive molecular sequencing for pediatric/AYA leukemia at an institutional level to improve outcomes.

Tumor necrosis factor (TNF)-like cytokine 1A (TL1A)/TNF superfamily member 15 (TNFSF15) is a proinflammatory cytokine and TNFα superfamily member that is linked preclinically and clinically to inflammatory bowel disease (IBD). By homology and function, TNFα is its closest family member. In this study, we investigated the mechanism of TL1A-induced inflammation in CD4+ T cells and compared it with the TNFα pathway. We found that TL1A induces proinflammatory cytokines, including TNFα, from isolated human CD4+CD161+ T cells, whereas these cells were resistant to TNFα treatment. Anti-TNFα failed to block TL1A-induced cytokine production, indicating that the effects of TL1A are direct. Lastly, CD161 and TL1A expression were significantly and selectively increased in gut tissue biopsies, but not in the peripheral blood, from IBD patients. Thus, TLIA not only functions upstream of TNFα, driving its expression from CD161+ T cells, but is also independent of TNFα. These findings may have therapeutic IBD implications.

The junction-associated protein zonula occludens-1 (ZO-1) is a member of a family of membrane-associated guanylate kinase homologues thought to be important in signal transduction at sites of cell-cell contact. We present evidence that under certain conditions of cell growth, ZO-1 can be detected in the nucleus. Two different antibodies against distinct portions of the ZO-1 polypeptide reveal nuclear staining in subconfluent, but not confluent, cell cultures. An exogenously expressed, epitope-tagged ZO-1 can also be detected in the nuclei of transfected cells. Nuclear accumulation can be stimulated at sites of wounding in cultured epithelial cells, and immunoperoxidase detection of ZO-1 in tissue sections of intestinal epithelial cells reveals nuclear labeling only along the outer tip of the villus. These results suggest that the nuclear localization of ZO-1 is inversely related to the extent and/or maturity of cell contact. Since cell-cell contacts are specialized sites for signaling pathways implicated in growth and differentiation, we suggest that the nuclear accumulation of ZO-1 may be relevant for its suggested role in membrane-associated guanylate kinase homologue signal transduction.

Although laparoscopic repair of type 3 paraesophageal hernias is safe and results in symptomatic relief, recent data have questioned the anatomic integrity of the laparoscopic approach. The reports document an asymptomatic recurrence rate as high as 42% with radiologic follow-up evaluation for type 3 paraesophageal hernias repaired laparoscopically. This disturbingly high recurrence rate has prompted the addition of an anterior gastropexy to our standard laparoscopic paraesophageal hernia repair. A prospective series of 28 patients underwent laparoscopic repair of large type 3 hiatal hernias between July 2000 and January 2002 at the Cleveland Clinic Foundation by one surgeon. All the patients underwent reduction of the hernia, sac excision, crural repair, antireflux procedure, and anterior gastropexy. They all had a video esophagram 24 h after surgery, then at 3-, 6-, and 12-month follow-up visits and annually thereafter. Symptomatic outcomes were assessed with a standard questionnaire at each follow-up visit. In this study, 21 women and 7 men with a mean age of 67 years (range, 35-82 years) underwent successful laparoscopic paraesophageal hernia repair. The mean operative time was 146 min (range, 101-186 min), and the average blood loss was 71 ml (range, 10-200 ml). One intraoperative complication occurred: A small esophageal mucosal tear occurred during esophageal dissection and was repaired laparoscopically. At 24 h, upper gastrointestinal examination identified no leaks. At this writing, all the patients have undergone video esophagram at a 3-month follow-up visit. All were asymptomatic and all examinations were normal. Of the 28 patients, 27 have undergone follow-up assessment at 6 months. At this writing, all the patients have undergone video esophagram at 3, 6, and 12 months follow up visits. All were asymptomatic and all examinations were normal. Ten patients have completed 2 year follow up barium swallows with no recurrences. With up to 2 years of follow-up evaluation, the addition of an anterior gastropexy to the laparoscopic repair of type 3 hiatal hernias resulted in no recurrences. These encouraging results necessitate further follow-up evaluation to document the long-term effects of anterior gastropexy in reducing postoperative recurrence after laparoscopic repair of paraesophageal hernias.

Tight junctions form an intercellular barrier between epithelial cells, serve to separate tissue compartments, and maintain cellular polarity. Paracellular sealing properties vary among cell types and are regulated by undefined mechanisms. Sequence of the full-length cDNA for human ZO-1, the first identified tight junction component, predicts a protein of 1736 aa. The N-terminal 793 aa are homologous to the product of the lethal(1)discs-large-1 (dlg) tumor suppressor gene of Drosophila, located in septate junctions, and to a 95-kDa protein located in the postsynaptic densities of rat brain, PSD-95. All three proteins contain both a src homology region 3 (SH3 domain), previously identified in membrane proteins involved in signal transduction, and a region homologous to guanylate kinase. ZO-1 contains an additional 943-aa C-terminal domain that is proline-rich (14.1%) and contains an alternatively spliced domain, whose expression was previously shown to correlate with variable properties of tight junctions. dlg mutations result in loss of apical-basolateral epithelial cell polarity and in neoplastic growth. These results suggest a protein family specialized for signal transduction on the cytoplasmic surface of intercellular junctions. These results also provide biochemical evidence for similarity between invertebrate septate and vertebrate tight junctions. The C-terminal domain of ZO-1, and its alternatively spliced region, appears to confer variable properties unique to tight junctions.