The neuropeptide Pth2 dynamically senses others via mechanosensation.

Species that depend on membership in social groups for survival exhibit changes in neuronal gene expression and behaviour when they face restricted social interactions or isolation1-3. Here we show that, across the lifespan of zebrafish (Danio rerio), social isolation specifically decreased the level of transcription of pth2, the gene that encodes the vertebrate-specific neuropeptide Pth2. However, 30 minutes of exposure to conspecifics was sufficient to initiate a significant rescue of pth2 transcript levels in previously isolated zebrafish. Transcription of pth2 exhibited bidirectional dynamics; following the acute isolation of socially reared fish, a rapid reduction in the levels of pth2 was observed. The expression of pth2 tracked not only the presence of other fish but also the density of the group. The sensory modality that controls the expression of pth2 was neither visual nor chemosensory in origin but instead was mechanical, induced by the movements of neighbouring fish. Chemical ablation of the mechanosensitive neuromast cells within the lateral line of fish prevented the rescue of pth2 levels that was induced by the social environment. In addition, mechanical perturbation of the water at frequencies similar to the movements of the zebrafish tail was sufficient to rescue the levels of pth2 in previously isolated fish. These data indicate a previously underappreciated role for the relatively unexplored neuropeptide Pth2 in both tracking and responding to the population density of the social environment of an animal.

RIM and RIM-binding protein localize synaptic CaV2 channels to differentially regulate transmission in neuronal circuits.

At chemical synapses, voltage-gated Ca2+-channels (VGCCs) translate electrical signals into a trigger for synaptic vesicle (SV) fusion. VGCCs and the Ca2+ microdomains they elicit must be located precisely to primed SVs, to evoke rapid transmitter release. Localization is mediated by Rab3 interacting molecule (RIM) and RIM-binding proteins (RIM-BPs), which interact and bind to the C-terminus of the CaV2 VGCC α-subunit. We studied this machinery at the mixed cholinergic/GABAergic neuromuscular junction (NMJ) of Caenorhabditis elegans hermaphrodites. rimb-1 mutants had mild synaptic defects, through loosening the anchoring of UNC-2/CaV2 and delaying the onset of SV fusion. UNC-10/RIM deletion much more severely affected transmission. Even though postsynaptic depolarization was reduced, rimb-1 mutants had increased cholinergic (but reduced GABAergic) transmission, to compensate for the delayed release. This did not occur when the excitation-inhibition balance was altered by removing GABA transmission. Further analyses of GABA defective mutants and GABAA or GABAB receptor deletions, as well as cholinergic rescue of RIMB-1, emphasized that GABA neurons may be more affected than cholinergic neurons. Thus RIMB-1 function differentially affects excitation/inhibition balance in the different motor neurons, and RIMB-1 thus may differentially regulate transmission in mixed circuits. Untethering the UNC-2/CaV2 channel by removing its C-terminal PDZ ligand exacerbated the rimb-1 defects, and similar phenotypes resulted from acute degradation of the CaV2 ß-subunit CCB-1. Therefore, untethering of the CaV2 complex is as severe as its elimination, yet does not abolish transmission, likely due to compensation by CaV1. Thus, robustness and flexibility of synaptic transmission emerges from VGCC regulation.Significance statement The machinery for chemical synaptic transmission is organized in a precise spatial arrangement in order to enable efficient and temporally accurate coupling of action potentials with the rise of the Ca2+ concentration through CaV2 P/Q-type voltage gated Ca2+ channels. This triggers the fusion of synaptic vesicles with the plasma membrane and the release of transmitters. Here, we analyzed the molecular and functional interplay of proteins of the active zone scaffold, RIM and RIM-binding protein (RIMB-1), with the CaV2 channel in the C. elegans neuromuscular junction, a tripartite synapse with cholinergic and GABAergic neuronal input. Our work shows a differential requirement of RIMB-1 in cholinergic vs. GABAergic neurons, that affects the regulation of excitation-inhibition balance at circuit, cellular and ultrastructural levels.

Comparison of Bivalent and Monovalent mRNA Vaccine Boosters.

In this cohort study conducted in Hong Kong where both bivalent and monovalent formulations of BNT162b2 were available, there were no significant differences in the mortality or hospitalization between those who received bivalent and monovalent mRNA as second boosters. Bivalent and monovalent mRNA boosters appear equally protective against clinical outcomes.

Proteomic analysis of boar seminal plasma: Putative markers for fertility based on capacity of semen preservation at 17°C.

Boar seminal plasma (SP) proteins were associated with differences on sperm resistance to cooling at 17°C. However, information about seminal plasma proteins in boars classified by capacity of semen preservation and in vivo fertility remains lacking. Thus, the objective was to evaluate the SP proteome in boars classified by capacity of semen preservation and putative biomarkers for fertility. The ejaculates from high-preservation (HP) showed higher progressive motility during all 5 days than the low-preservation (LP) boars. There was no difference for farrowing rate between ejaculates from LP (89.7%) and HP boars (88.4%). The LP boars presented lower total piglets born (14.0 ± 0.2) than HP (14.8 ± 0.2; p < 0.01). A total of 257 proteins were identified, where 184 were present in both classes of boar, and 41 and 32 were identified only in LP and HP boars, respectively. Nine proteins were differently expressed: five were more abundant in HP (SPMI, ZPBP1, FN1, HPX, and C3) and four in LP boars (B2M, COL1A1, NKX3-2, and MPZL1). The HP boars had an increased abundance of SP proteins related to sperm resistance and fecundation process which explains the better TPB. LP boars had a higher abundance of SP proteins associated with impaired spermatogenesis.

Building an HIV Learning Health Care Community for Youth in Florida: Opportunities and Challenges.

In Florida, 33% of new HIV infections among men and 21% of new infections among women are among those younger than 29 years of age. We describe the development of a Learning Health Care Community for youth (Y-LHCC) in Orange County, FL. Its core implementation team (iTeam) was composed of representatives from community agencies and academics, whose work was informed by data from the Florida Department of Health (FDOH) and regional research, in-depth interviews (IDIs) with agency representatives, and a pilot implementation of Tailored Motivational Interviewing (TMI) to improve service provision. IDIs revealed limited programming specifically for youth, significant structural challenges providing them with PrEP, and differences in use of evidence-based behavioral interventions to improve HIV services. FDOH provided data on new HIV infections, linkage to care, viral suppression, and PrEP coverage, however, limitations such as minimal data on PrEP referrals and use, agency level data, and inability to generate data quarterly (which would facilitate program improvement) were encountered. Thirty staff members from five agencies serving youth in Orange County participated in TMI training. About half the agency staff (n = 16) completed at least three of the four online training sessions. MI skills improved from pre- (n = 28; M = 1.96) to post TMI training (n = 11; M = 2.48, SD = 0.57); (t(37) = - 3.14, p = 0.0033). The iTeam held seven remote meetings and two in-person half-day meetings at the end of the study, during which they reassessed areas of focus for improving youth services. They also reiterated their commitment to continuing to meet beyond the study period and to engage other agencies in the newly established coalition. Findings highlight the potential of creating a Y-LHCC in Florida as well as some of the challenges that will need to be overcome to achieve ending the HIV Epidemic goals for young people in the region.

RESUMEN: En Florida, el 33% y 21% de las nuevas infecciones del VIH entre hombres y mujeres, respectivamente, fueron entre personas menores de 29 años de edad. Describimos el desarrollo de una Comunidad de Aprendizaje de Atención Médica para jóvenes (Y-LHCC) en el Condado de Orange, FL. Su equipo central de implementación (iTeam) estuvo compuesto de representantes de agencias comunitarias y académicos, cuyo trabajo se basó en datos del Departamento de Salud de Florida (FDOH) e investigaciones regionales, entrevistas en profundidad con representantes de agencias y un programa piloto de implementación de la Entrevista Motivacional a la Medida (TMI) para mejorar la prestación de servicios. Las entrevistas revelaron poca programación específica para los jóvenes, desafíos estructurales significativos para proporcionarles PrEP, y diferencias en el uso de intervenciones conductuales basadas en evidencia para mejorar los servicios de VIH. El FDOH proporcionó datos sobre nuevas infecciones por el VIH, vinculación con la atención médica, supresión viral y cobertura de PrEP. Sin embargo, se encontraron limitaciones en la data, tales como datos limitados sobre derivaciones u uso de PrEP, falta de datos a nivel de agencia, e incapacidad para generar datos trimestrales (lo que facilitaría la mejora de programas en la agencia). Treinta miembros del personal de cinco agencias que atienden a jóvenes en el Condado de Orange participaron en la capacitación de TMI. Aproximadamente la mitad del personal de la agencia (n = 16) completó al menos tres de las cuatro sesiones de capacitación remota. Las habilidades de MI mejoraron desde antes (n = 28; M = 1.96, SD = .042) hasta después del entrenamiento de TMI (n = 11; M = 2.48, SD = 0.57); (t(37) = − 3.14, p = 0.0033). El iTeam realizó siete reuniones remotas y dos reuniones en persona de medio día al final del estudio, durante las cuales reevaluaron las áreas de enfoque para mejorar los servicios para jóvenes. También reiteraron su compromiso de continuar reuniéndose más allá del período de estudio y de involucrar a otras agencias en la coalición recién establecida. Los hallazgos destacan el potencial de crear un Y-LHCC en Florida, así como algunos de los desafíos que deberán superarse para lograr los objetivos de terminar con la epidemia de VIH para los jóvenes de la región.

Depression Among Pregnant and Breastfeeding Persons Participating in Two Randomized Trials of the Dapivirine Vaginal Ring and Oral Pre-Exposure Prophylaxis (PrEP) in Malawi, South Africa, Uganda, and Zimbabwe.

Depression is associated with lower adherence to oral pre-exposure prophylaxis (PrEP) to prevent HIV, but data are not currently available on how depression may affect use of other HIV prevention methods including the dapivirine vaginal ring (DVR). We conducted a mixed methods study using data from the Microbicide Trials Network (MTN) 042/DELIVER (n = 558) and MTN-043/B-PROTECTED (n = 197) studies to describe the prevalence of depressive symptoms and explore how depressive symptoms may have influenced attitudes about use of the monthly DVR and once-daily oral PrEP tablet among pregnant and breastfeeding persons, respectively, in Malawi, South Africa, Uganda, and Zimbabwe. Eleven participants had high Edinburgh Postnatal Depression scores ≥ 10 in MTN-042/DELIVER (2%) and four participants (2%) in MTN-043/B-PROTECTED. In interviews with 9 participants who had high scores (6 DVR, 3 oral PrEP), those with depressive symptoms described overlapping stressors which were magnified by job loss and economic instability during the COVID-19 pandemic, and by experiences of pregnancy/postpartum. These participants experienced a lack of support from partners or family members, and conflict with partners related to trust, and infidelity. While we did not find evidence of a change in product adherence, there was a strong sense of commitment and motivation to use the study products for protection from HIV for participants themselves and their baby. Although lack of social support is usually an obstacle to adherence, in this study, the participants' lives and relationships seemed to have reinforced the need for HIV prevention and motivated women to protect themselves and their babies from HIV.

History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

The 2023 report of the MJA-Lancet Countdown on health and climate change: sustainability needed in Australia's health care sector.

The MJA-Lancet Countdown on health and climate change in Australia was established in 2017 and produced its first national assessment in 2018 and annual updates in 2019, 2020, 2021 and 2022. It examines five broad domains: health hazards, exposures and impacts; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In this, the sixth report of the MJA-Lancet Countdown, we track progress on an extensive suite of indicators across these five domains, accessing and presenting the latest data and further refining and developing our analyses. Our results highlight the health and economic costs of inaction on health and climate change. A series of major flood events across the four eastern states of Australia in 2022 was the main contributor to insured losses from climate-related catastrophes of $7.168 billion - the highest amount on record. The floods also directly caused 23 deaths and resulted in the displacement of tens of thousands of people. High red meat and processed meat consumption and insufficient consumption of fruit and vegetables accounted for about half of the 87 166 diet-related deaths in Australia in 2021. Correction of this imbalance would both save lives and reduce the heavy carbon footprint associated with meat production. We find signs of progress on health and climate change. Importantly, the Australian Government released Australia's first National Health and Climate Strategy, and the Government of Western Australia is preparing a Health Sector Adaptation Plan. We also find increasing action on, and engagement with, health and climate change at a community level, with the number of electric vehicle sales almost doubling in 2022 compared with 2021, and with a 65% increase in coverage of health and climate change in the media in 2022 compared with 2021. Overall, the urgency of substantial enhancements in Australia's mitigation and adaptation responses to the enormous health and climate change challenge cannot be overstated. Australia's energy system, and its health care sector, currently emit an unreasonable and unjust proportion of greenhouse gases into the atmosphere. As the Lancet Countdown enters its second and most critical phase in the leadup to 2030, the depth and breadth of our assessment of health and climate change will be augmented to increasingly examine Australia in its regional context, and to better measure and track key issues in Australia such as mental health and Aboriginal and Torres Strait Islander health and wellbeing.

A prospective study of the proteome of equine pre-implantation embryo.

The present study was conducted to investigate the global proteome of 8-day-old equine blastocysts. Follicular dynamics of eight adult mares were monitored by ultrasonography and inseminated 24 h after the detection of a preovulatory follicle. Four expanded blastocysts were recovered, pooled, and subjected to protein extraction and mass spectrometry. Protein identification was conducted based on four database searches (PEAKS, Proteome Discoverer software, SearchGUI software, and PepExplorer). Enrichment analysis was performed using g:Profiler, Panther, and String platforms. After the elimination of identification redundancies among search tools (at three levels, based on identifiers, peptides, and cross-database mapping), 1977 proteins were reliably identified in the samples of equine embryos. Proteomic analysis unveiled robust metabolic activity in the 8-day equine embryo, highlighted by an abundance of proteins engaged in key metabolic pathways like the TCA cycle, ATP biosynthesis, and glycolysis. The prevalence of chaperones among highly abundant proteins suggests that regulation of protein folding, and degradation is a key process during embryo development. These findings pave the way for developing new strategies to improve equine embryo media and optimize in vitro fertilization techniques.

Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study.

BACKGROUND: Little is known about the real-world effectiveness of oral antivirals against the SARS-CoV-2 omicron (B.1.1.529) variant. We aimed to assess the clinical effectiveness of two oral antiviral drugs among community-dwelling COVID-19 outpatients in Hong Kong. METHODS: In this observational study, we used data from the Hong Kong Hospital Authority to identify an unselected, territory-wide cohort of non-hospitalised patients with an officially registered diagnosis of SARS-CoV-2 infection between Feb 26 and June 26, 2022, during the period in which the omicron subvariant BA.2.2 was dominant in Hong Kong. We used a retrospective cohort design as primary analysis, and a case-control design as sensitivity analysis. We identified patients with COVID-19 who received either molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir plus ritonavir (nirmatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days, or nirmatrelvir 150 mg and ritonavir 100 mg if estimated glomerular filtration rate was 30-59 mL/min per 1·73 m2). Outpatient oral antiviral users were matched with controls using propensity score (1:10) according to age, sex, date of SARS-CoV-2 infection diagnosis, Charlson Comorbidity Index score, and vaccination status. Study outcomes were death, COVID-19-related hospitalisation, and in-hospital disease progression (in-hospital death, invasive mechanical ventilation, or intensive care unit admission). Hazard ratios (HRs) were estimated by Cox regression for the primary analysis, and odds ratios in oral antiviral users compared with non-users by logistic regression for the sensitivity analysis. FINDINGS: Among 1 074 856 non-hospitalised patients with COVID-19, 5383 received molnupiravir and 6464 received nirmatrelvir plus ritonavir in the community setting. Patients were followed up for a median of 103 days in the molnupiravir group and 99 days in the nirmatrelvir plus ritonavir group. Compared with nirmatrelvir plus ritonavir users, those on molnupiravir were older (4758 [85·9%] vs 4418 [88.7%] aged >60 years) and less likely to have been fully vaccinated (1850 [33·4%] vs 800 [16·1%]). Molnupiravir use was associated with lower risks of death (HR 0·76 [95% CI 0·61-0·95]) and in-hospital disease progression (0·57 [0·43-0·76]) than non-use was, whereas risk of hospitalisation was similar in both groups (0·98 [0·89-1·06]). Nirmatrelvir plus ritonavir use was associated with lower risks of death (0·34 [0·22-0·52]), hospitalisation (0·76 [0·67-0·86]), and in-hospital disease progression (0·57 [0·38-0·87]) than non-use was. We consistently found reduced risks of mortality and hospitalisation associated with early oral antiviral use among older patients. The findings from the case-control analysis broadly supported those from the primary analysis. INTERPRETATION: During Hong Kong's wave of SARS-CoV-2 omicron subvariant BA.2.2, among non-hospitalised patients with COVID-19, early initiation of novel oral antivirals was associated with reduced risks of mortality and in-hospital disease progression. Nirmatrelvir plus ritonavir use was additionally associated with a reduced risk of hospitalisation. FUNDING: Health and Medical Research Fund, Health Bureau, Government of Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Landscape-scale forest cover drives the predictability of forest regeneration across the Neotropics.

Abandonment of agricultural lands promotes the global expansion of secondary forests, which are critical for preserving biodiversity and ecosystem functions and services. Such roles largely depend, however, on two essential successional attributes, trajectory and recovery rate, which are expected to depend on landscape-scale forest cover in nonlinear ways. Using a multi-scale approach and a large vegetation dataset (843 plots, 3511 tree species) from 22 secondary forest chronosequences distributed across the Neotropics, we show that successional trajectories of woody plant species richness, stem density and basal area are less predictable in landscapes (4 km radius) with intermediate (40-60%) forest cover than in landscapes with high (greater than 60%) forest cover. This supports theory suggesting that high spatial and environmental heterogeneity in intermediately deforested landscapes can increase the variation of key ecological factors for forest recovery (e.g. seed dispersal and seedling recruitment), increasing the uncertainty of successional trajectories. Regarding the recovery rate, only species richness is positively related to forest cover in relatively small (1 km radius) landscapes. These findings highlight the importance of using a spatially explicit landscape approach in restoration initiatives and suggest that these initiatives can be more effective in more forested landscapes, especially if implemented across spatial extents of 1-4 km radius.

Update on artificial insemination: Semen, techniques, and sow fertility.

Over the years, reproductive efficiency in the swine industry has focused on reducing the sperm cell number required per sow. Recent advances have included the identification of subfertile boars, new studies in extended semen quality control, new catheters and cannulas for intrauterine artificial insemination (AI), and fixed-time AI under commercial use. Therefore, it is essential to link field demands with scientific studies. In this review, we intend to discuss the current status of porcine AI, pointing out challenges and opportunities to improve reproductive efficiency.

Type 1 diabetes could begin with alterations in innate anti-viral immunity, which are already at this stage associated with HLA risk haplotypes.

AIMS: To investigate if HLA risk haplotypes and HbA1c levels are associated with the expression levels of innate anti-viral immune pathway genes in type 1 diabetes. MATERIALS AND METHODS: We investigated RNA expression levels of innate anti-viral immune pathway genes in laser-dissected islets from two to five tissue sections per donor from the Diabetes Virus Detection study and the network of Pancreatic Organ Donors in relation to HLA risk haplotypes (non-predisposed and predisposed) and HbA1c levels (normal, elevated, and high). RESULTS: The expression of innate anti-viral immune genes (TLR7, OAS1, OAS3 etc.) was significantly increased in individuals with predisposing vs non-predisposing HLA haplotypes. Also, the expression of several of the innate anti-viral immune genes from the HLA risk haplotype analysis was significantly increased in the group with high vs normal HbA1c. Furthermore, the gene expression of OAS2 was significantly increased in the group with high HbA1c vs elevated HbA1c. CONCLUSIONS: Expression of innate anti-viral immune pathway genes was increased in individuals with predisposing HLA risk haplotypes and those with high HbA1c. This indicates that type 1 diabetes might well begin with alterations in innate anti-viral immunity, and already at this stage be associated with HLA risk haplotypes.

Discharge of postoperative patients with an opioid prescription is associated with increased persistent opioid use, healthcare expenditures and mortality: a retrospective cohort study.

BACKGROUND: The risk factors for persistent opioid use after surgical discharge and the association between opioid prescription at discharge and postoperative emergency department visits, readmission, and mortality are unclear. METHODS: This population-based retrospective cohort study involved opioid-naive patients who underwent surgical procedures from January 1, 2000 to November 30, 2020. The data source was Hong Kong Hospital Authority Clinical Management System electronic health record. The primary outcome was the incidence of new persistent opioid use. Other study outcomes included 30-day emergency department visits, 30-day readmission, and 30-day all-cause mortality. Multivariable logistic regression models were used to estimate the association between opioid prescription at discharge and persistent opioid use, emergency department visits, readmission, and all-cause mortality. RESULTS: Over a median follow-up of 1 month with 36 104 person-years, 438 128 patients (opioid prescription: 32 932, no opioid prescription: 405 196) who underwent surgical procedures were analysed, of whom 15 112 (3.45%) had persistent opioid use after discharge. Prescribing opioids on discharge was associated with increased risks of developing persistent opioid use (odds ratio [OR]: 2.30, 95% confidence interval [CI]: 2.19-2.40, P<0.001), 30-day emergency department visits (OR: 1.28, 95% CI: 1.23-1.33, P<0.001), 30-day readmission (OR: 1.17, 95% CI: 1.13-1.20, P<0.001), and 30-day all-cause mortality (OR: 1.68, 95% CI: 1.53-1.86, P<0.001). CONCLUSIONS: In this large cohort of patients undergoing surgery, an opioid prescription on discharge was associated with a higher chance of persistent opioid use and increased risks of postoperative emergency department visits, readmission, and mortality. Minimising opioid prescriptions on discharge could improve perioperative patient outcomes.

Transgender Women's Experiences Using SMARTtest, a Smartphone Application to Facilitate Self- and Partner-HIV/Syphilis Testing Using the INSTI Multiplex.

We present experiences of transgender women (TW) who have sex with men with SMARTtest, a smartphone app to accompany the INSTI Multiplex®, a one-minute, dual blood-based HIV/syphilis rapid test. TW participants (N = 11) received 10 INSTI Multiplex® tests to take home for self- and/or partner-testing and installed the SMARTtest app on their phones. The SMARTtest app aimed to support INSTI Multiplex users in correctly performing the test, interpreting the results, and connecting with care following a positive HIV or syphilis screening. After 3 months, users completed in-depth interviews on their experiences. A total of 9 TW used SMARTtest with partners. App feedback was positive, but refining is necessary. Specifically, TW reported that SMARTtest is easy to use and convenient; instructions on how to use the INSTI Multiplex presented on the app were helpful to complete procedures correctly; the most frequently used feature on SMARTtest was the information on clinics that offered confirmatory testing; and participants and their partners were not concerned about app privacy but reported that this could change if INSTI Multiplex detected an HIV-positive result. Further, participants provided recommendations on how to improve SMARTtest, and changes were mostly related to features, content, functionality, navigation, and overall "look" of the app. SMARTtest is promising to facilitate INSTI Multiplex® use in TW. User feedback should be integrated in future versions.

Comparative Assessment of Biomechanical Parameters in Subjects With Multiple Cerebral Aneurysms Using Fluid-Structure Interaction Simulations.

Cerebral aneurysm progression is a result of a complex interplay of the biomechanical and clinical risk factors that drive aneurysmal growth and rupture. Subjects with multiple aneurysms are unique cases wherein clinical risk factors are expected to affect each aneurysm equally, thus allowing for disentangling the effect of biomechanical factors on aneurysmal growth. Toward this end, we performed a comparative computational fluid-structure interaction analysis of aneurysmal biomechanics in image-based models of stable and growing aneurysms in the same subjects, using the cardiovascular simulation platform simvascular. We observed that areas exposed to low shear and the median peak systolic arterial wall displacement were higher by factors of 2 or more and 1.5, respectively, in growing aneurysms as compared to stable aneurysms. Furthermore, we defined a novel metric, the oscillatory stress index (OStI), which indicates locations of oscillating arterial wall stresses. We observed that growing aneurysms were characterized by regions of combined low wall shear and high OStI, which we hypothesize to be associated with regions of collagen degradation and remodeling. Such regions were either absent or below 5% of the surface area in stable aneurysms. Our results lay the groundwork for future studies in larger cohorts of subjects, to evaluate the statistical significance of these biomechanical parameters in cerebral aneurysm growth.

Differential patterns of fish sensitization in Asian populations: Implication for precision diagnosis.

BACKGROUND: The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern in fish allergic subjects from two distinct populations in Asia. METHODS: One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients' sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80 °C were evaluated by SDS-PAGE and mass spectrometry. RESULTS: Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens. CONCLUSIONS: Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients' allergic manifestations.

Clinical Improvement, Outcomes, Antiviral Activity, and Costs Associated With Early Treatment With Remdesivir for Patients With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Evidence remains inconclusive on any significant benefits of remdesivir in patients with mild-to-moderate COVID-19. This study explored the disease progression, various clinical outcomes, changes in viral load, and costs associated with early remdesivir treatment among COVID-19 patients. METHODS: A territory-wide retrospective cohort of 10 419 patients with COVID-19 hospitalized from 21 January 2020 to 31 January 2021 in Hong Kong was identified. Early remdesivir users were matched with controls using propensity-score matching in a ratio ≤1:4. Study outcomes were time to clinical improvement of at least 1 point on WHO clinical progression scale, hospital discharge, recovery, viral clearance, low viral load, positive IgG antibody, in-hospital death, and composite outcomes of in-hospital death requiring invasive ventilation or intensive care. RESULTS: After multiple imputation and propensity-score matching, median follow-up was 14 days for both remdesivir (n = 352) and control (n = 1347) groups. Time to clinical improvement was significantly shorter in the remdesivir group than that of control (HR: 1.14; 95% CI: 1.01-1.29; P = .038), as well as for achieving low viral load (1.51; 1.24-1.83; P < .001) and positive IgG antibody (1.50; 1.31-1.70; P < .001). Early remdesivir treatment was associated with lower risk of in-hospital death (HR: .58; 95% CI: .34-.99; P = .045), in addition to a significantly shorter length of hospital stay (difference: -2.56 days; 95% CI: -4.86 to -.26; P = .029), without increasing risks of composite outcomes for clinical deterioration. CONCLUSIONS: Early remdesivir treatment could be extended to hospitalized patients with moderate COVID-19 not requiring oxygen therapy on admission.

Optimal Timing of Remdesivir Initiation in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Administered With Dexamethasone.

BACKGROUND: Evidence is lacking about any additional benefits of introducing remdesivir on top of dexamethasone, and the optimal timing of initiation. METHODS: In a territory-wide cohort of 10 445 coronavirus disease 2019 (COVID-19) patients from Hong Kong who were hospitalized between 21 January 2020 and 31 January 2021, 1544 had received dexamethasone during hospitalization. The exposure group consisted of patients who had initiated remdesivir prior to dexamethasone (n = 93) or co-initiated the 2 drugs simultaneously (n = 373), whereas the nonexposure group included patients who were given remdesivir after dexamethasone (n = 149) or those without remdesivir use (n = 929). Multiple imputation and inverse probability of treatment weighting for propensity score were applied and hazard ratios (HRs) of event outcomes were estimated using Cox regression models. RESULTS: Time to clinical improvement (HR = 1.23; 95% CI, 1.02-1.49; P = .032) and positive IgG antibody (HR = 1.22; 95% CI, 1.02-1.46; P = .029) were significantly shorter in the exposure group than that of nonexposure. The exposure group had a shorter hospital length of stay by 2.65 days among survivors, lower WHO clinical progression scale scores from 5 days of follow-up onwards, and lower risks of in-hospital death (HR = .59; 95% CI, .36-.98; P = .042) and composite outcomes; and without experiencing an increased risk of acute respiratory distress syndrome. Differences in the cumulative direct medical costs between groups were no longer significant from 17 days of follow-up onwards. CONCLUSIONS: Initiation of remdesivir prior to or simultaneously with dexamethasone was associated with significantly shorter time to clinical improvement and positive IgG antibody, lower risk of in-hospital death, in addition to shorter length of hospital stay in patients with moderate COVID-19.

How in vitro maturation changes the proteome of ovine cumulus-oocyte complexes?

The present study evaluated the effects of in vitro maturation (IVM) on the proteome of cumulus-oocyte complexes (COCs) from ewes. Extracted COC proteins were analyzed by LC-MS/MS. Differences in protein abundances (p < 0.05) and functional enrichments in immature versus in vitro-matured COCs were evaluated using bioinformatics tools. There were 2550 proteins identified in the COCs, with 89 and 87 proteins exclusive to immature and mature COCs, respectively. IVM caused downregulation of 84 and upregulation of 34 proteins. Major upregulated proteins in mature COCs were dopey_N domain-containing protein, structural maintenance of chromosomes protein, ubiquitin-like modifier-activating enzyme 2. Main downregulated proteins in mature COCs were immunoglobulin heavy constant mu, inter-alpha-trypsin inhibitor heavy chain 2, alpha-2-macroglobulin. Proteins exclusive to mature COCs and upregulated after IVM related to immune response, complement cascade, vesicle-mediated transport, cell cycle, and extracellular matrix organization. Proteins of immature COCs and downregulated after IVM were linked to metabolic processes, immune response, and complement cascade. KEGG pathways and miRNA-regulated genes attributed to downregulated and mature COC proteins related to complement and coagulation cascades, metabolism, humoral response, and B cell-mediated immunity. Thus, IVM influenced the ovine COC proteome. This knowledge supports the future development of efficient IVM protocols for Ovis aries.