A Diagnosis You Cannot Afford to MIS-C: Multisystem Inflammatory Syndrome in Children Within the Active Duty Population.

Multisystem inflammatory syndrome in children (MIS-C), which is associated with coronavirus disease 2019 (COVID-19) and occurs in the immediately post-infectious period, has never-before been reported within the active duty population. It typically affects children, aged 5-13 years, but has been shown to affect those up to 20 years old. We present an 18-year-old active duty male that arrived at a military treatment facility emergency department with headache, neck pain, and shock without evidence of meningoencephalitis on cerebrospinal fluid analysis and with a negative COVID-19 test. He developed significant abdominal pain and cardiomyopathy. Chest computed tomography showed evidence of ground glass infiltrates, and repeat testing was positive for the COVID-19 virus. Multisystem inflammatory syndrome in children (MIS-C) was diagnosed and treated with a rapid improvement in the patient's condition. It is a rare but potentially fatal condition that has been shown to affect patients up to the age of 20, encompassing a large part of the junior enlisted population. Multisystem inflammatory syndrome in children (MIS-C) can lead to death, yet mimic other diseases leading to delay of care. Thus, it should be considered when faced with the appropriate constellation of symptoms.

Chromobacterium violaceum in a U.S. Marine: A Case Report.

Chromobacterium violaceum is associated with severe sepsis leading to cutaneous and visceral organ abscesses, with mortality rates up to 73%. Around 200 cases of C. violaceum infection have been reported globally. We report a case of a 27-year-old female U.S. Marine recruit who presented with fever, chills, myalgias, arthralgias, headache, and nodules on her extremities. Physical examination revealed multiple small skin abscesses on her extremities. Abdominal imaging with contrast revealed large liver abscesses requiring drainage. Both blood and wound cultures grew C. violaceum. The patient was successfully treated with meropenem and ciprofloxacin. At 3 months, symptoms had resolved, and labs and imaging were normal. Though rare, C. violaceum infection rates are increasing. Severe infection develops rapidly and invasive disease is not uncommon. Early detection and appropriate antibiotic treatment are key in preventing mortality.

Methylation of High-Risk Human Papillomavirus Genomes Are Associated with Cervical Precancer in HIV-Positive Women.

BACKGROUND: HIV-positive women are at substantial risk of HPV-associated cervical neoplasia caused by high-risk (HR) HPVs. Methylation of the HPV genome is associated with cervical intraepithelial neoplasia grade 3 (CIN3) in HIV-negative women, yet it is unknown whether this holds true for HIV-positive women. METHODS: We designed a case-control study within the Women's Interagency HIV Study (WIHS) cohort comparing HIV-positive CIN3 cases (N = 72) to HIV-positive controls without detectable CIN2+. The unit of analysis and matching was HPV-type infection. Cases with ≥2 HR-HPV types (N = 23; 32%) had a separate control for each HR-HPV type. We developed and utilized next-generation sequencing (NGS) methylation assays for 12 different HR-HPVs, focusing on CpG sites in the L1/L2 regions. RESULTS: Significant case-control differences in individual CpG site methylation levels were observed for multiple alpha-9 (HPV16/31/35/58) and alpha-7 HPV (HPV18/39/45) types, based on dichotomization of tertile levels (T3 vs. T1 and T2). Analyses combining homologous CpG sites [e.g., HPV16-L1-5608/HPV31-L1-5521/HPV35-L2L1-5570; OR = 7.28; 95% confidence interval (CI): 2.75-19.3], and (e.g., HPV18-L1-7062/HPV45-L1-7066; OR = 6.94; 95% CI: 1.23-39.3) were significant in separate case-control comparisons. In cases with multiple HR-HPVs, we tested and confirmed the hypothesis that one HR-HPV type would have higher methylation than other types detected, consistent with there being a single HR-HPV causally related to a lesion. CONCLUSIONS: CIN3 is associated with elevated L1/L2 CpG methylation levels in HIV-positive women. IMPACT: HPV DNA CpG methylation is a promising triage option in HIV-positive women testing positive for HR-HPV types and provides risk attribution in women with multiple HPV type infections.

Coordination of Heparan Sulfate Proteoglycans with Wnt Signaling To Control Cellular Migrations and Positioning in Caenorhabditis elegans.

Heparan sulfates (HS) are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as cofactors for multiple signaling pathways, including the Wnt-signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts. Double mutant analyses reveal distinct redundancies among HSPGs for different migration events, and different cellular migrations require distinct heparan sulfate modification patterns. Our studies reveal that the transmembrane HSPG SDN-1/Syndecan functions within the migrating cell to promote cellular migrations, while the GPI-linked LON-2/Glypican functions cell nonautonomously to establish the final cellular position. Genetic analyses with the Wnt-signaling system show that (1) a given HSPG can act with different Wnts and Frizzled receptors, and that (2) a given Wnt/Frizzled pair acts with different HSPGs in a context-dependent manner. Lastly, we find that distinct HSPG and Wnt/Frizzled combinations serve separate functions to promote cellular migration and establish position of specific neurons. Our studies suggest that HSPGs use structurally diverse glycans in coordination with Wnt-signaling pathways to control multiple cellular behaviors, including cellular and axonal migrations and, cellular positioning.

The Atg6/Vps30/Beclin 1 ortholog BEC-1 mediates endocytic retrograde transport in addition to autophagy in C. elegans.

Autophagy and endocytosis are dynamic and tightly regulated processes that contribute to many fundamental aspects of biology including survival, longevity, and development. However, the molecular links between autophagy and endocytosis are not well understood. Here, we report that BEC-1, the C. elegans ortholog of Atg6/Vps30/Beclin1, a key regulator of the autophagic machinery, also contributes to endosome function. In particular we identify a defect in retrograde transport from endosomes to the Golgi in bec-1 mutants. MIG-14/Wntless is normally recycled from endosomes to the Golgi through the action of the retromer complex and its associated factor RME-8. Lack of retromer or RME-8 activity results in the aberrant transport of MIG-14/Wntless to the lysosome where it is degraded. Similarly, we find that lack of bec-1 also results in mislocalization and degradation of MIG-14::GFP, reduced levels of RME-8 on endosomal membranes, and the accumulation of morphologically abnormal endosomes. A similar phenotype was observed in animals treated with dsRNA against vps-34. We further identify a requirement for BEC-1 in the clearance of apoptotic corpses in the hermaphrodite gonad, suggesting a role for BEC-1 in phagosome maturation, a process that appears to depend upon retrograde transport. In addition, autophagy genes may also be required for cell corpse clearance, as we find that RNAi against atg-18 or unc-51 also results in a lack of cell corpse clearance.