Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets.

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein-protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as "causative" for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration-approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

Dementia in-patient units in psychiatric hospitals: research priority setting.

AIMS AND METHOD: Dementia in-patient units (DIU) are mental health wards that care for people living with dementia (PLWD) whose symptoms are causing severe distress or potential risk. DIUs look after some of the most vulnerable and unwell people in society, yet they are environments that are underresearched: a recent systematic review revealed only 36 articles worldwide relating to DIUs. To better understand research priorities in DIUs, we undertook a two-round online Delphi survey of PLWD with experience of DIUs, their carers and professionals who work in DIUs. RESULTS: Ten research priorities were described and ranked. The top three were how to use non-pharmacological techniques to manage non-cognitive symptoms of dementia, supporting families and better understanding of how to discharge PLWD safely and healthily. CLINICAL IMPLICATIONS: This is the first Delphi consensus to describe DIU research priorities. This paper will help researchers focus on the areas that matter most to people who use DIUs.

Cell size, density, and nutrient dependency of unicellular algal gravitational sinking velocities.

Eukaryotic phytoplankton, also known as algae, form the basis of marine food webs and drive marine carbon sequestration. Algae must regulate their motility and gravitational sinking to balance access to light at the surface and nutrients in deeper layers. However, the regulation of gravitational sinking remains largely unknown, especially in motile species. Here, we quantify gravitational sinking velocities according to Stokes' law in diverse clades of unicellular marine microalgae to reveal the cell size, density, and nutrient dependency of sinking velocities. We identify a motile algal species, Tetraselmis sp., that sinks faster when starved due to a photosynthesis-driven accumulation of carbohydrates and a loss of intracellular water, both of which increase cell density. Moreover, the regulation of cell sinking velocities is connected to proliferation and can respond to multiple nutrients. Overall, our work elucidates how cell size and density respond to environmental conditions to drive the vertical migration of motile algae.

Vitifolignans, 3,4-dibenzyltetrahydrofuran lignans from Anemone vitifolia Buch.-Ham.

Anemone vitifolia is a small herb found in Asia that is used to treat a range of diseases in Chinese traditional medicine. GNPS-based molecular networking of an Anemone vitifolia specimen revealed the presence of a network containing numerous ions indicating the presence of lignans, several of which suggested that there might be previously undescribed compounds in the extract. Fractionation of the organic extract yielded five undescribed lignans, the vitifolignans, together with one known. The structures were identified based on extensive spectroscopic data analysis (NMR, HR-ESI-MS, and UV), coupling constant calculation and comparison with reported data. Their absolute configurations were determined by comparison of experimental ECD spectra with calculated spectra. Compounds 4/5 showed weak inhibition of LPS-induced NO production in mouse mononuclear macrophages.

Myological and osteological approaches to gape and bite force reconstruction in Smilodon fatalis.

Masticatory gape and bite force are important behavioral and ecological variables. While much has been written about the highly derived masticatory anatomy of Smilodon fatalis, there remains a great deal of debate about their masticatory behaviors. To that end, we establish osteological proxies for masticatory adductor fascicle length (FL) based on extant felids and apply these along with previously validated techniques to S. fatalis to provide estimates of fascicle lengths, maximum osteological gapes, and bite force. While the best correlated FL proxies in extant felids do not predict particularly long fascicles, these proxies may be of value for less morphologically distinct felids. A slightly less well correlated proxy predicts a temporalis FL 15% longer than that of Panthera tigris. While angular maximum bony gape is significantly larger in S. fatalis than it is in extant felids, linear gape at the canine tip and carnassial notch were not significantly different from those of extant felids. Finally, we produce anatomical bite force estimates of 1283.74 N at the canine and 4671.41 N at the carnassial, which are similar in magnitude to estimates not of the largest felids but of the much smaller P. onca, with S. fatalis producing slightly less force at the canines and more at the carnassials. These estimates align with previous predictions that S. fatalis may have killed large prey with canine shearing bites produced, in part, by force contributions of the postcranial muscles.

Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004-2019).

BACKGROUND: Interest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies. This investigation examined the temporal trajectories of MRFs for dementia in England. METHODS: We used data from the English Longitudinal Study of Ageing, a panel study over eight waves collected between 2004 and 2019 (76,904 interviews in total). We calculated the PAFs for twelve MRFs (including six early- to mid-life factors and six late-life factors), as recommended by the Lancet Commission, and the individual weighted PAFs (IW-PAFs) for each risk factor. Temporal trends were analysed to understand the changes in the overall PAF and IW-PAF over the study period. Subgroup analyses were conducted by sex and socioeconomic status (SES). RESULTS: The overall PAF for dementia MRFs changed from 46.73% in 2004/2005 to 36.79% in 2018/2019, though this trend was not statistically significant. During 2004-2019, hypertension, with an average IW-PAF of 8.21%, was the primary modifiable determinant of dementia, followed by obesity (6.16%), social isolation (5.61%), hearing loss (4.81%), depression (4.72%), low education (4.63%), physical inactivity (3.26%), diabetes mellitus (2.49%), smoking (2.0%), excessive alcohol consumption (1.16%), air pollution (0.42%), and traumatic brain injury (TBI) (0.26%). During 2004-2019, only IW-PAFs of low education, social isolation, and smoking showed significant decreasing trends, while IW-PAFs of other factors either did not change significantly or increased (including TBI, diabetes mellitus, and air pollution). Upon sex-specific disaggregation, a higher overall PAF for MRFs was found among women, predominantly associated with later-life risk factors, most notably social isolation, depression, and physical inactivity. Additionally, hearing loss, classified as an early- to mid-life factor, played a supplementary role in the identified sex disparity. A comparable discrepancy was evident upon PAF evaluation by SES, with lower income groups experiencing a higher dementia risk, largely tied to later-life factors such as social isolation, physical inactivity, depression, and smoking. Early- to mid-life factors, in particular, low education and obesity, were also observed to contribute to the SES-associated divergence in dementia risk. Temporal PAF and IW-PAF trends, stratified by sex and SES, revealed that MRF PAF gaps across sex or SES categories have persisted or increased. CONCLUSIONS: In England, there was little change over time in the proportion of dementia attributable to known modifiable risk factors. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them.

Recommendations for Tumor Mutational Burden Assay Validation and Reporting: A Joint Consensus Recommendation of the Association for Molecular Pathology, College of American Pathologists, and Society for Immunotherapy of Cancer.

Tumor mutational burden (TMB) has been recognized as a predictive biomarker for immunotherapy response in several tumor types. Several laboratories offer TMB testing, but there is significant variation in how TMB is calculated, reported, and interpreted among laboratories. TMB standardization efforts are underway, but no published guidance for TMB validation and reporting is currently available. Recognizing the current challenges of clinical TMB testing, the Association for Molecular Pathology convened a multidisciplinary collaborative working group with representation from the American Society of Clinical Oncology, the College of American Pathologists, and the Society for the Immunotherapy of Cancer to review the laboratory practices surrounding TMB and develop recommendations for the analytical validation and reporting of TMB testing based on survey data, literature review, and expert consensus. These recommendations encompass pre-analytical, analytical, and postanalytical factors of TMB analysis, and they emphasize the relevance of comprehensive methodological descriptions to allow comparability between assays.

Respiratory Syncytial Virus-Associated Hospitalizations in Children <5 Years: 2016-2022.

BACKGROUND: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities. METHODS: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses. We estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 prepandemic seasons (2016-2020) to those hospitalized in 2021 or 2022. RESULTS: There was no difference in median age or age distribution between prepandemic and 2021 seasons. Median age of children hospitalized with RSV was higher in 2022 (9.6 months vs 6.0 months, P < .001). RSV-associated hospitalization rates were higher in 2021 and 2022 than the prepandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37-2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in prepandemic seasons (P < .001 and P = .003, respectively), but there was no difference in the proportion hypoxemic, mechanically ventilated, or admitted to intensive care. CONCLUSIONS: The atypical 2021 and 2022 RSV seasons resulted in higher hospitalization rates with similar disease severity to prepandemic seasons.

Surgical Approach Does Not Influence Instability Risk in Revision Total Hip Arthroplasty.

BACKGROUND: Although the direct anterior (DA) approach has increased in popularity for primary total hip arthroplasty (THA), there is limited evidence regarding its use for revision THA. It is unknown whether the dislocation benefit seen in the primary setting translates to revision cases. METHODS: This retrospective review compared the dislocation rates of revision THA performed through DA versus postero-lateral (PL) approaches at a single institution (2011 to 2021). Exclusion criteria included revision for instability, ≥ 2 prior revisions, approaches other than DA or PL, and placement of dual-mobility or constrained liners. There were 182 hips in 173 patients that met the inclusion criteria. The average follow-up was 6.5 years (range, 2 to 8 years). RESULTS: There was a trend toward more both-component revisions being performed through the PL approach. There were no differences in dislocation rates between the DA revision and PL revision cohorts, which were 8.1% (5 of 72) and 7.5% (9 of 120), respectively (P = .999). Dislocation trended lower when the revision approach was discordant from the primary approach compared to cases where primary and revision had a concordant approach (4.9 versus 8.5%), but this was not statistically significant (P = .740). No significant differences were found in return to operating room, 90-day emergency department visits, or 90-day readmissions. However, the length of stay was significantly shorter in patients who had DA revisions after a primary PL procedure (P = .021). CONCLUSIONS: Dislocation rates following revision THA did not differ between the DA and PL approaches irrespective of the primary approach. Surgeons should choose their revision approach based on their experience and the specific needs of the patient.

Belowground plant allocation regulates rice methane emissions from degraded peat soils.

Carbon-rich peat soils have been drained and used extensively for agriculture throughout human history, leading to significant losses of their soil carbon. One solution for rewetting degraded peat is wet crop cultivation. Crops such as rice, which can grow in water-saturated conditions, could enable agricultural production to be maintained whilst reducing CO2 and N2O emissions from peat. However, wet rice cultivation can release considerable methane (CH4). Water table and soil management strategies may enhance rice yield and minimize CH4 emissions, but they also influence plant biomass allocation strategies. It remains unclear how water and soil management influences rice allocation strategies and how changing plant allocation and associated traits, particularly belowground, influence CH4-related processes. We examined belowground biomass (BGB), aboveground biomass (AGB), belowground:aboveground ratio (BGB:ABG), and a range of root traits (root length, root diameter, root volume, root area, and specific root length) under different soil and water treatments; and evaluated plant trait linkages to CH4. Rice (Oryza sativa L.) was grown for six months in field mesocosms under high (saturated) or low water table treatments, and in either degraded peat soil or degraded peat covered with mineral soil. We found that BGB and BGB:AGB were lowest in water saturated conditions where mineral soil had been added to the peat, and highest in low-water table peat soils. Furthermore, CH4 and BGB were positively related, with BGB explaining 60% of the variation in CH4 but only under low water table conditions. Our results suggest that a mix of low water table and mineral soil addition could minimize belowground plant allocation in rice, which could further lower CH4 likely because root-derived carbon is a key substrate for methanogenesis. Minimizing root allocation, in conjunction with water and soil management, could be explored as a strategy for lowering CH4 emissions from wet rice cultivation in degraded peatlands.

Longitudinal Evaluation of Atrial Function in Patients with Tetralogy of Fallot.

Atrial function provides insight into ventricular diastolic function. Invasive assessment of left ventricular (LV) diastolic function correlates with development of sustained ventricular tachyarrhythmias in patients with repaired tetralogy of Fallot (rTOF). Non-invasive assessment of atrial function may prove key towards assessment of diastolic function. We longitudinally evaluated the progression of biatrial function in patients with rTOF, regardless of pulmonary valve replacement (PVR). Patients with rTOF who had multiple CMR were identified. CMR examinations were retrospectively reviewed. Left (LA) and right (RA) atrial size and function were measured in the two and four-chamber views and assessed over time and after PVR. Left and right atrial reservoir, conduit, pump strain and strain rates were determined using tissue tracking. Thirty-six patients with rTOF were identified (64% male), ten (28%) had PVR during the study. Median age of PVR was 16.5 years. No improvement in RA or LA function was observed after PVR. A decline in RA reservoir strain rate (p < 0.05) and RA pump strain (p < 0.05) were observed despite improvements in right ventricular systolic function (p < 0.05). In patients who had multiple CMR without PVR, RA reservoir strain rate (p < 0.05) and pump strain rate (p < 0.05) worsened over time. LA pump strain decreased over time in all patients. There is progressive decline of several RA functional parameters over time. No significant improvement in LA or RA function after PVR was observed. Additional studies are needed to understand how these changes may relate to poor outcomes and potentially better guide timing of PVR.

Disruption in glutathione metabolism and altered energy production in the liver and kidney after ischemic acute kidney injury in mice.

Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8-10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981. Mechanistically, TAK-981 de-SUMOylates the cBAF subunit SMARCE1, stabilizing and restoring cBAF on chromatin, shifting away from SS18::SSX-ncBAF-driven transcription, associated with DNA damage and cell death and resulting in tumor inhibition across both human and mouse SS tumor models. TAK-981 synergized with cytotoxic chemotherapy through increased DNA damage, leading to tumor regression. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX-ncBAF transcriptome, identifying a therapeutic vulnerability in SS, positioning the in-clinic TAK-981 to treat SS.

Longitudinal Changes in Kidney Solute Clearance in a Prospective Cohort of Patients Initiating Chronic Hemodialysis.

Introduction: Longitudinal changes in residual kidney function have not been well-examined in patients starting chronic hemodialysis (HD). Methods: We analyzed urine volume and kidney solute clearances from timed urine collections and corresponding plasma samples from 42 patients randomized to incremental HD (n = 21) and conventional HD (n = 21) in the TwoPlus pilot study. Samples were collected before HD initiation (baseline); and at 6, 12, 24, and 48 weeks. We assessed temporal trends in urine volume, kidney urea and creatinine clearance, and correlations between urine volume and kidney solute clearance. Results: Residual kidney function parameters in all patients declined over time; the pattern of decline differed between urine volume and kidney solute clearances. Urine volume declined at a steady rate with median (quartile 1, quartile 3) percentage change relative to baseline of -10% (-36 to 29) at week 6 and -47% (-76 to 5) by week 48. Kidney urea and creatinine clearances exhibited a larger decline than urine volume at week 6, -32% (-61 to 8) and -47% (-57 to -20), respectively. The rate of decline subsequently slowed, reaching about 61% decline for both solutes by week 48. Conventional HD demonstrated larger declines in urine volume and kidney urea clearance than incremental HD at week 6. Urine volume showed moderate correlation with urea (R = 0.47) and weaker correlation with creatinine (R = 0.34). Conclusion: Despite gradual decrement in urine volume and kidney solute clearances, residual kidney function persists nearly 1 year after HD initiation. This knowledge could motivate increased practice of individualizing HD prescriptions by incorporating residual kidney function.

Mitigating Toxic Metal Exposure Through Leafy Greens: A Comprehensive Review Contrasting Cadmium and Lead in Spinach.

Metals and metalloids (hereafter, metal(loid)s) in plant-based foods are a source of exposure to humans, but not all metal(loid)-food interactions are the same. Differences exist between metal(loid)s in terms of their behavior in soils and in how they are taken up by plants and stored in the edible plant tissue/food. Thus, there cannot be one consistent solution to reducing toxic metal(loid)s exposure to humans from foods. In addition, how metal(loid)s are absorbed, distributed, metabolized, and excreted by the human body differs based on both the metal(loid), other elements and nutrients in the food, and the nutritional status of the human. Initiatives like the United States Food and Drug Administration's Closer to Zero initiative to reduce the exposure of young children to the toxic elements cadmium, lead, arsenic, and mercury from foods warrant careful consideration of each metal(loid) and plant interaction. This review explores such plant-metal(loid) interactions using the example of spinach and the metals cadmium and lead. This review highlights differences in the magnitude of exposure, bioavailability, and the practicality of mitigation strategies while outlining research gaps and future needs. A focus on feasibility and producer needs, informed via stakeholder interviews, emphasizes the need for better analytical testing facilities and grower and consumer education. More research should focus on minimization of chloride inputs for leafy greens to lessen plant-availability of Cd and the role of oxalate in reducing Cd bioavailability from spinach. These findings are applicable to other leafy greens (e.g., kale, lettuce), but not for other plants or metal(loid)s.

Teleneurology and Artificial Intelligence in Clinical Practice.

ABSTRACT: As teleheath becomes integrated into the practice of medicine, it is important to understand the benefits, limitations, and variety of applications. Telestroke was an early example of teleneurology that arose from a need for urgent access to neurologists for time-sensitive treatments for stroke. It made a scarce resource widely available via video conferencing technologies. Additionally, applications such as outpatient video visits, electronic consultation (e-consult), and wearable devices developed in neurology, as well. Telehealth dramatically increased during the COVID-19 pandemic when offices were closed and hospitals were overwhelmed; a multitude of both outpatient and inpatient programs developed and matured during this time. It is helpful to explore what has been learned regarding the quality of telehealth, disparities in care, and how artificial intelligence can interact with medical practices in the teleneurology context.

Early Effects of the COVID-19 Pandemic on Patients in a Virtual Multicenter Spontaneous Coronary Artery Dissection (SCAD) Registry.

Background: The COVID-19 pandemic effects among patients with a history of spontaneous coronary artery dissection (SCAD), a cause of acute coronary syndrome associated with emotional and physical stress, are unknown. Methods: For this cross-sectional cohort study, participants of the Mayo Clinic "Virtual" Multicenter SCAD Registry were surveyed about the COVID-19 pandemic. Results: Among 1352 participants, 727 (53.8%) completed surveys between June 2, 2021 and September 29, 2021. The majority of respondents (96.7%) were female, with a mean age of 54.9 ± 9.4 years. At the time of completing the survey, which was early in the pandemic, 91 respondents (12.6%) reported having prior COVID-19 symptoms, with < 1% experiencing hospitalization (n = 4) or cardiac complications (n = 6). A total of 14% had ≥ moderate anxiety symptoms, per the General Anxiety Disorder-7 item survey, and 11.8% had ≥ moderate depressive symptoms, per the Patient Health Questionnaire-9 item. Higher stress scores on the Likert scale were correlated with pandemic-related reduction in work hours and/or pay and/or unemployment (P = 0.013), remote work and/or change of job (P < 0.001), and loss of insurance and/or medical coverage (P = 0.025). A higher anxiety level, as measured on the Likert scale, was correlated with pandemic-related remote work and/or change of job (P = 0.007) and loss of insurance and/or medical coverage (P = 0.008). Since the start of the pandemic, 54% of respondents reported having at least monthly chest pain. Chest pain and COVID symptoms were each associated with higher scores on the General Anxiety Disorder-7 item survey and the Patient Health Questionnaire-9 item. Conclusions: Early in the pandemic, COVID-19 symptoms, hospitalization, and cardiac complications were uncommon among SCAD patients. The burden of anxiety and depressive symptoms was minimal to mild, similar to that in prior reports. Likert-scale measures of stress and anxiety were higher among persons with work and/or pay reduction and/or unemployment, remote work and/or change of job, and loss of insurance and/or medical coverage. Over half of respondents reported experiencing chest pain, which was correlated with depressive and anxiety symptoms, highlighting an overarching clinical need.

Contexte: On ne connaît pas les effets de la pandémie de COVID-19 sur les personnes ayant des antécédents de dissection spontanée de l'artère coronaire (DSAC), une cause du syndrome coronarien aigu qui est une source de stress physique et émotionnel. Méthodologie: Pour les besoins de cette étude de cohorte transversale, les participants au registre « virtuel ¼ multicentrique sur la DSAC de la clinique Mayo ont été interrogés dans le cadre d'une enquête sur la pandémie de COVID-19. Résultats: Parmi les 1 352 participants au registre, 727 (53,8 %) ont répondu à l'enquête entre le 2 juin et le 29 septembre 2021. La majorité des répondants (96,7 %) étaient des femmes, et l'âge moyen était de 54,9 ± 9,4 ans. Au moment de l'enquête, réalisée au début de la pandémie, 91 répondants (12,6 %) avaient indiqué avoir déjà présenté des symptômes de COVID-19, et < 1 % avaient été hospitalisés (n = 4) ou avaient présenté des complications cardiaques (n = 6). Au total, 14 % des participants présentaient des symptômes d'anxiété à tout le moins modérés d'après le questionnaire GAD-7 (General Anxiety Disorder-7 item) et 11,8 %, des symptômes dépressifs à tout le moins modérés d'après le questionnaire PHQ-9 (Patient Health Questionnaire-9 item). Une corrélation a été établie entre un score de stress plus élevé sur une échelle de Likert et une réduction des heures de travail et/ou du salaire, une période de chômage (p = 0,013), le télétravail et/ou un changement d'emploi (p < 0,001) et la perte de l'assurance et/ou de la couverture médicale (p = 0,025) en lien avec la pandémie. Une corrélation a également été établie entre un niveau d'anxiété plus élevé mesuré sur une échelle de Likert et le télétravail et/ou un changement d'emploi (p = 0,007) et la perte de l'assurance et/ou de la couverture médicale (p = 0,008) en lien avec la pandémie. Depuis le début de la pandémie, 54 % des répondants ont indiqué ressentir une douleur thoracique au moins une fois par mois. La douleur thoracique et les symptômes de la COVID-19 ont par ailleurs été associés à des scores plus élevés aux questionnaires GAD-7 et PHQ-9. Conclusions: Au début de la pandémie, les symptômes de la COVID-19, les hospitalisations et les complications cardiaques n'étaient pas fréquents chez les patients présentant une DSAC. Le fardeau des symptômes anxieux et dépressifs allait de minime à léger, comme en faisaient état les rapports précédents. L'anxiété et le stress mesurés sur une échelle de Likert ont été plus élevés chez les personnes ayant connu une réduction des heures de travail et/ou du salaire ou une période de chômage, ayant dû recourir au télétravail et/ou changer d'emploi, ou ayant perdu leur assurance et/ou couverture médicale. Plus de la moitié des répondants ont indiqué ressentir une douleur thoracique, laquelle a été mise en corrélation avec les symptômes d'anxiété et de dépression, ce qui souligne l'existence d'un besoin clinique important.

Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

Beyond co-expression: pathway discovery for plant pharmaceuticals.

Plant natural products have been an important source of medicinal molecules since ancient times. To gain access to the whole diversity of these molecules for pharmaceutical applications, it is important to understand their biosynthetic origins. Whilst co-expression is a reliable tool for identifying gene candidates, a variety of complementary methods can aid in screening or refining candidate selection. Here, we review recently employed plant biosynthetic pathway discovery approaches, and highlight future directions in the field.