corona Is Required for Higher-Order Assembly of Transverse Filaments into Full-Length Synaptonemal Complex in Drosophila Oocytes

The synaptonemal complex (SC) is an intricate structure that forms between homologous chromosomes early during the meiotic prophase, where it mediates homolog pairing interactions and promotes the formation of genetic exchanges. In Drosophila melanogaster, C(3)G protein forms the transverse filaments (TFs) of the SC. The N termini of C(3)G homodimers localize to the Central Element (CE) of the SC, while the C-termini of C(3)G connect the TFs to the chromosomes via associations with the axial elements/lateral elements (AEs/LEs) of the SC. Here, we show that the Drosophila protein Corona (CONA) co-localizes with C(3)G in a mutually dependent fashion and is required for the polymerization of C(3)G into mature thread-like structures, in the context both of paired homologous chromosomes and of C(3)G polycomplexes that lack AEs/LEs. Although AEs assemble in cona oocytes, they exhibit defects that are characteristic of c(3)G mutant oocytes, including failure of AE alignment and synapsis. These results demonstrate that CONA, which does not contain a coiled coil domain, is required for the stable ‘zippering’ of TFs to form the central region of the Drosophila SC. We speculate that CONA's role in SC formation may be similar to that of the mammalian CE proteins SYCE2 and TEX12. However, the observation that AE alignment and pairing occurs in Tex12 and Syce2 mutant meiocytes but not in cona oocytes suggests that the SC plays a more critical role in the stable association of homologs in Drosophila than it does in mammalian cells

Clinical Characteristics and Post-Operative Outcomes in Children with Very Severe Obstructive Sleep Apnea

Available information on clinical characteristics and post-operative outcomes in children with very severe obstructive sleep apnea (OSA) is limited. Our study evaluates the clinical features and polysomnographic (PSG) variables that predict post-operative outcomes in children with an obstructive apneal hypopnea index (AHI) of more than 25 events/hr. In this study from a single tertiary care center, we performed a retrospective chart review of patients with an AHI > 25/hr, who underwent tonsillectomy and adenoidectomy (T&A) between January 2016 and September 2021. In total, 50 children were included in the study: 26.0% (13/50) of children experienced post-operative respiratory events and four children needed intubation and ventilator support. Compared with children without respiratory events, children requiring post-operative respiratory interventions were younger (4.4 ± 5.2 vs. 8.0 ± 5.2 years; p = 0.04), had higher pre-operative AHI (73.6 ± 27.4 vs. 44.8 ± 24.9; p < 0.01), lower oxygen nadirs (70.0 ± 13.0% vs. 83.0 ± 7.0%; p < 0.01), and had lower body metabolic index Z-scores (−0.51 ± 2.1 vs. 0.66 ± 1.5; p < 0.04). Moderate to severe residual OSA was identified in 70% (24/34) of children with available post-operative PSG; younger children had better PSG outcomes. Our study shows that post-operative respiratory events are frequent in children with very severe OSA, particularly with an AHI > 40/h, younger children (<2 years of age), lower oxygen saturation (SpO2), and poor nutritional status, necessitating close monitoring

Risk Stratification and Personal Protective Equipment Use in Pediatric Endoscopy During the Coronavirus Disease 2019 Outbreak: A Single-center Protocol.

SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic. Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces. Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease. Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route. We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis. We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients

Risk Stratification and Personal Protective Equipment Use in Pediatric Endoscopy During the Coronavirus Disease 2019 Outbreak: A Single-center Protocol.

SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic. Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces. Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease. Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route. We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis. We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients

Macrophages protect against loss of adipose tissue during cancer cachexia

Background Cancer cachexia represents a central obstacle in medical oncology as it is associated with poor therapy response and reduced overall survival. Systemic inflammation is considered to be a key driver of cancer cachexia; however, clinical studies with anti-inflammatory drugs failed to show distinct cachexia-inhibiting effects. To address this contradiction, we investigated the functional importance of innate immune cells for hepatocellular carcinoma (HCC)-associated cachexia. Methods A transgenic HCC mouse model was intercrossed with mice harbouring a defect in myeloid cell-mediated inflammation. Body composition of mice was analysed via nuclear magnetic resonance spectroscopy and microcomputed tomography. Quantitative PCR was used to determine adipose tissue browning and polarization of adipose tissue macrophages. The activation state of distinct areas of the hypothalamus was analysed via immunofluorescence. Multispectral immunofluorescence imaging and immunoblot were applied to characterize sympathetic neurons and macrophages in visceral adipose tissue. Quantification of pro-inflammatory cytokines in mouse serum was performed with a multiplex immunoassay. Visceral adipose tissue of HCC patients was quantified via the L3 index of computed tomography scans obtained during routine clinical care. Results We identified robust cachexia in the HCC mouse model as evidenced by a marked loss of visceral fat and lean mass. Computed tomography-based analyses demonstrated that a subgroup of human HCC patients displays reduced visceral fat mass, complementing the murine data. While the myeloid cell-mediated inflammation defect resulted in reduced expression of pro-inflammatory cytokines in the serum of HCC-bearing mice, this unexpectedly did not translate into diminished but rather enhanced cachexia-associated fat loss. Defective myeloid cell-mediated inflammation was associated with decreased macrophage abundance in visceral adipose tissue, suggesting a role for local macrophages in the regulation of cancer-induced fat loss. Conclusions Myeloid cell-mediated inflammation displays a rather unexpected beneficial function in a murine HCC model. These results demonstrate that immune cells are capable of protecting the host against cancer-induced tissue wasting, adding a further layer of complexity to the pathogenesis of cachexia and providing a potential explanation for the contradictory results of clinical studies with anti-inflammatory drugs

A Systematic Framework to Rapidly Obtain Data on Patients with Cancer and COVID-19: CCC19 Governance, Protocol, and Quality Assurance

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments. When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments