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Background The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Methods Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. Results In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40–4.26), Beta (HR 2.85, 95% CI 1.56–5.23), Delta (HR 2.28 95% CI 1.56–3.34), or Alpha (HR 1.64, 95% CI 1.29–2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56–1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. Conclusions Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.One Sentence SummaryAnalysis of SARS-CoV-2 genomes in King County, Washington show that diverse areas in the same metropolitan region can have different epidemic dynamics.

Concurrent sexual partnerships (i.e., relationships that overlap in time) contribute to higher HIV acquisition risk. Social capital, defined as resources and connections available to individuals is hypothesized to reduce sexual HIV risk behavior, including sexual concurrency. Additionally, we do not know whether any association between social capital and sexual concurrency is moderated by gender. Multivariable logistic regression tested the association between social capital and sexual concurrency and effect modification by gender. Among 1445 African Americans presenting for care at an urban STI clinic in Jackson, Mississippi, mean social capital was 2.85 (range 1–5), mean age was 25 (SD = 6), and 62% were women. Sexual concurrency in the current year was lower for women compared to men (45% vs. 55%, χ2(df = 1) = 11.07, p = .001). Higher social capital was associated with lower adjusted odds of sexual concurrency for women compared to men (adjusted Odds Ratio [aOR] = 0.62 (95% CI 0.39–0.97), p = 0.034), controlling for sociodemographic and psychosocial covariates. Interventions that add social capital components may be important for lowering sexual risk among African Americans in Mississippi.

Summary Despite the known causality of copy-number variations (CNVs) to human neurodevelopmental disorders, the mechanisms behind each gene’s contribution to the constellation of neural phenotypes remain elusive. Here, we investigated the 7q11.23 CNV, whose hemideletion causes Williams syndrome (WS), and uncovered that mitochondrial dysfunction participates in WS pathogenesis. Dysfunction is facilitated in part by the 7q11.23 protein DNAJC30, which interacts with mitochondrial ATP-synthase machinery. Removal of Dnajc30 in mice resulted in hypofunctional mitochondria, diminished morphological features of neocortical pyramidal neurons, and altered behaviors reminiscent of WS. The mitochondrial features are consistent with our observations of decreased integrity of oxidative phosphorylation supercomplexes and ATP-synthase dimers in WS. Thus, we identify DNAJC30 as an auxiliary component of ATP-synthase machinery and reveal mitochondrial maladies as underlying certain defects in brain development and function associated with WS.

In medicine, micro-electro-mechanical systems (MEMS) perform several specific functions. The design of bio-packages for MEMS to be implanted into the human body has been an increasing challenge in the last years. Mechanical, chemical and thermal resistance, as well as excellent bonding to silicon surfaces, are needed. Furthermore, ideal bio-packages should minimize post-operative complications and be well accepted by the host. To reach this goal, two different morphology-controlled hydroxyapatite-based porous biomaterials were synthesized, implanted in rats and evaluated mechanically and histologically. The novel biomaterials were prepared at room temperature using synthetic hydroxyapatite micro-particles, silica nanoparticles and water-based resin and compared with a standard hydroxyapatite biomaterial. The morphology (porosity) was controlled to obtain interconnected pores with appropriated pore size and pore volume fraction. All biomaterials were implanted in rats at the dorsal area near the third thoracic vertebra. The rats were killed 2, 7 and 21 days after surgery. Histological analysis revealed that the implants were well accepted by the host and minimal local inflammation was observed. The acute inflammatory response disappeared 21 days after surgery for both novel biomaterials. Additionally, organic matter (collagen) was produced in the interior of the porous biomaterial, indicating that an incipient vascularization process was in progress after 21 days of implantation. Both new biomaterials showed high abrasion resistance, high Young modulus, the appropriate porosity to allow possible vascularization, and good bonding to silicon surfaces.

We evaluated the performance of a novel dual pulse lithotriptor for extracorporeal lithotripsy.A piezoelectric lithotriptor was modified to produce pairs of successive (tandem) shock waves. Four kidney stone models were exposed in vitro to 500 single shock waves with a standard lithotriptor. Another set of stones was exposed 1 at a time to 250 pairs of shock waves with the tandem lithotriptor. The time delay between the first and second shock waves was increased in steps of 50 microseconds between 100 and 600 microseconds. Four stones were used per delay, ie 44 phantoms were fractured with the tandem system. Rabbits were used in vivo to demonstrate that the novel device does not produce more tissue trauma. Five rabbits were exposed to shock waves generated by the new device, 5 were treated with the standard system and 5 served as the sham treated group. Renal damage caused by the 2 systems was compared 1 week after shock wave application.Enhanced fragmentation efficiency was achieved at a delay of 250 microseconds. In vivo results indicate that the dual pulse shock wave generator does not produce more kidney tissue damage.Tandem lithotriptors may improve the quality and rate of stone comminution without increasing tissue damage. The device enhances cavitation induced damage to kidney stones. Extensive in vivo experiments will be important to evaluate the new design.