Abstract
Background
Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) ...(PLWH), as do initial responses to a third dose.
Methods
We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls.
Results
Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post–third-dose humoral responses substantially exceeded post–second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post–third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post–third-dose responses.
Conclusion
PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.
People living with human immunodeficiency virus with well-controlled viral loads on antiretroviral therapy and preserved CD4+ T-cell counts mount strong, functional antibody responses to 2- and 3-dose coronavirus disease 2019 vaccination, including to Omicron. Monitoring responses over time remains important.
•New technology to understanding the interactions of polyphenols and complex protein matrices was proposed.•Mimic global interactions of wine polyphenols and saliva matrix applied to wine ...astringency.•The sensor response correlates well to astringency by sensorial analysis.•Showed that astringency could not be evaluated based on analysis of individual polyphenols.•Insight into the role of individual polyphenols in the context of wine astringency.
Wine astringency was evaluated based on the interaction of two complex matrices (red wine and saliva) by combining localized surface plasmon resonance (LSPR) and molecular imprinted polymers (MIP) at gold nanodisks as an alternative to sensorial analysis. The main objective of the work was to simulate wine astringency inside the mouth by mimicking this biological system. The LSPR/MIP sensor provided a linear response for astringency expressed in pentagalloyl glucose (PGG) units in concentrations ranging from 1 to 140μmol/L. The sensor was also applied to wine samples correlating well with sensorial analysis obtained by a trained panel. The correlation of astringency and wine composition was also evaluated showing that anthocyanins may have an important role, not only for pigmentation but also in astringency.
Objective
There is limited literature describing the overlap of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), and the studies have employed a range of case definitions. Our study ...used the new EULAR/American College of Rheumatology (ACR) SLE classification criteria to define SSc‐SLE cases among our center's SSc cohort.
Methods
This is a single‐center, retrospective study of a previously described cohort of patients with SSc. Patient data were re‐ed to evaluate for fulfillment of the 2019 EULAR/ACR classification criteria for SLE. Demographic, laboratory, clinical features, and mortality were compared among patients with SSc‐SLE and patients with SSc alone.
Results
Among the 402 patients with SSc that were analyzed, 40 (10%) fulfilled the 2019 EULAR/ACR SLE classification criteria. Neuropsychiatric and renal involvement were rare. An initial SLE diagnosis was purported in 43% of the patients with SSc‐SLE and 7% of patients with SSc alone (P < 0.001). Patients with SSc‐SLE were more likely to be female, African American, and with limited cutaneous SSc. Anti–U1‐RNP antibody positivity prevalence was 30% among patients with SSc‐SLE and 6.6% among patients with SSc alone (P < 0.001). Death during follow‐up occurred in 12 patients (30%) with SSc‐SLE and in 81 patients (22%) with SSc alone, but there was no difference in survival among the groups per log rank test (P = 0.404).
Conclusion
Ten percent of patients with SSc fulfill the 2019 EULAR/ACR classification criteria for SLE. These patients comprise a distinct demographic, serologic, and clinical phenotype but have similar severe SSc‐specific end‐organ damage and mortality as patients with SSc alone. Patients with SLE with Raynaud phenomenon should be evaluated for SSc‐specific autoantibodies and scleroderma organ involvement.
Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing ...countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.
•Overall, epilepsy-related deaths have not increased during the COVID-19 pandemic.•There may have been an isolated spike in the number of epilepsy-related deaths in women during the COVID-19 ...pandemic.•Around 14% of epilepsy-related deaths also list COVID-19 as a cause, with 11% specifically listing it as the underlying cause.•COVID-19 is a common underlying cause of both epilepsy-related deaths and deaths unrelated to epilepsy.
To examine whether epilepsy-related deaths increased during the COVID-19 pandemic and if the proportion with COVID-19 listed as the underlying cause is different between people experiencing epilepsy-related deaths and those experiencing deaths unrelated to epilepsy.
This was a Scotland-wide, population-based, cross-sectional study of routinely-collected mortality data pertaining to March–August of 2020 (COVID-19 pandemic peak) compared to the corresponding periods in 2015–2019. ICD-10-coded causes of death of deceased people of any age were obtained from a national mortality registry of death certificates in order to identify those experiencing epilepsy-related deaths (coded G40–41), deaths with COVID-19 listed as a cause (coded U07.1–07.2), and deaths unrelated to epilepsy (death without G40–41 coded). The number of epilepsy-related deaths in 2020 were compared to the mean observed through 2015–2019 on an autoregressive integrated moving average (ARIMA) model (overall, men, women). Proportionate mortality and odds ratios (OR) for deaths with COVID-19 listed as the underlying cause were determined for the epilepsy-related deaths compared to deaths unrelated to epilepsy, reporting 95% confidence intervals (CIs).
A mean number of 164 epilepsy-related deaths occurred through March–August of 2015–2019 (of which a mean of 71 were in women and 93 in men). There were subsequently 189 epilepsy-related deaths during the pandemic March–August 2020 (89 women, 100 men). This was 25 more epilepsy-related deaths (18 women, 7 men) compared to the mean through 2015–2019. The increase in women was beyond the mean year-to-year variation seen in 2015–2019. Proportionate mortality with COVID-19 listed as the underlying cause was similar between people experiencing epilepsy-related deaths (21/189, 11.1%, CI 7.0–16.5%) and deaths unrelated to epilepsy (3,879/27,428, 14.1%, CI 13.7–14.6%), OR 0.76 (CI 0.48–1.20). Ten of 18 excess epilepsy-related deaths in women had COVID-19 listed as an additional cause.
There is little evidence to suggest there have been any major increases in epilepsy-related deaths in Scotland during the COVID-19 pandemic. COVID-19 is a common underlying cause of both epilepsy-related and unrelated deaths.
Rapid cellular zinc influx regulates early mammalian development during the oocyte-to-egg transition through modulation of the meiotic cell cycle. Despite the physiological necessity of this zinc ...influx, the molecular mechanisms that govern such accumulation are unknown. Here we show that the fully grown mammalian oocyte does not employ a transcriptionally based mechanism of zinc regulation involving metal response element-binding transcription factor-1 (MTF-1), as demonstrated by a lack of MTF-1 responsiveness to environmental zinc manipulation. Instead, the mammalian oocyte controls zinc uptake through two maternally derived and cortically distributed zinc transporters, ZIP6 and ZIP10. Targeted disruption of these transporters using several approaches during meiotic maturation perturbs the intracellular zinc quota and results in a cell cycle arrest at a telophase I-like state. This arrest phenocopies established models of zinc insufficiency during the oocyte-to-egg transition, indicating the essential function of these maternally expressed transporters. Labile zinc localizes to punctate cytoplasmic structures in the human oocyte, and ZIP6 and ZIP10 are enriched in the cortex. Altogether, we demonstrate a mechanism of metal regulation required for female gamete development that may be evolutionarily conserved.
Premature fusion of the cranial sutures (craniosynostosis), affecting 1 in 2000 newborns, is treated surgically in infancy to prevent adverse neurologic outcomes. To identify mutations contributing ...to common non-syndromic midline (sagittal and metopic) craniosynostosis, we performed exome sequencing of 132 parent-offspring trios and 59 additional probands. Thirteen probands (7%) had damaging de novo or rare transmitted mutations in
, an inhibitor of BMP - induced osteoblast differentiation (p<10
).
mutations nonetheless showed striking incomplete penetrance (<60%). Genotypes of a common variant near
that is strongly associated with midline craniosynostosis explained nearly all the phenotypic variation in these kindreds, with highly significant evidence of genetic interaction between these loci via both association and analysis of linkage. This epistatic interaction of rare and common variants defines the most frequent cause of midline craniosynostosis and has implications for the genetic basis of other diseases.
Geothermal springs are model ecosystems to investigate microbial biogeography as they represent discrete, relatively homogenous habitats, are distributed across multiple geographical scales, span ...broad geochemical gradients, and have reduced metazoan interactions. Here, we report the largest known consolidated study of geothermal ecosystems to determine factors that influence biogeographical patterns. We measured bacterial and archaeal community composition, 46 physicochemical parameters, and metadata from 925 geothermal springs across New Zealand (13.9-100.6 °C and pH < 1-9.7). We determined that diversity is primarily influenced by pH at temperatures <70 °C; with temperature only having a significant effect for values >70 °C. Further, community dissimilarity increases with geographic distance, with niche selection driving assembly at a localised scale. Surprisingly, two genera (Venenivibrio and Acidithiobacillus) dominated in both average relative abundance (11.2% and 11.1%, respectively) and prevalence (74.2% and 62.9%, respectively). These findings provide an unprecedented insight into ecological behaviour in geothermal springs, and a foundation to improve the characterisation of microbial biogeographical processes.
Identification of habitable planets beyond our solar system is a key goal of current and future space missions. Yet habitability depends not only on the stellar irradiance, but equally on constituent ...parts of the planetary atmosphere. Here we show, for the first time, that radiatively active mineral dust will have a significant impact on the habitability of Earth-like exoplanets. On tidally-locked planets, dust cools the day-side and warms the night-side, significantly widening the habitable zone. Independent of orbital configuration, we suggest that airborne dust can postpone planetary water loss at the inner edge of the habitable zone, through a feedback involving decreasing ocean coverage and increased dust loading. The inclusion of dust significantly obscures key biomarker gases (e.g. ozone, methane) in simulated transmission spectra, implying an important influence on the interpretation of observations. We demonstrate that future observational and theoretical studies of terrestrial exoplanets must consider the effect of dust.
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