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Background Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as "long COVID". Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC. Methods Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses. Results Of 6942 records, 52 studies with at least 100 patients were analysed; ~70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28 days after hospital discharge. At 1-4 months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8 months (73.1% (95% CI 44.2-90.3%)) and 8--12 months (75.0% (95% CI 56.4-87.4%)). Conclusions A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC. [ABSTRACT FROM AUTHOR]

Background: Despite growing use, questions remain surrounding the utility, acceptability and feasibility of chemical adherence testing (CAT) as part of hypertension management in clinical practice. Objectives: This scoping review aimed to (i) identify and summarise studies using CAT in hypertension management, and (ii) describe and critically evaluate how CAT is currently being used in the clinical management of hypertension. Eligibility criteria: Peer-reviewed and published studies in English, reporting original research in any setting, with any study design, were included. Search concepts included hypertension, medication adherence, CAT, and their synonyms. Sources of evidence: Searches were carried out using Ovid Medline, EMBASE, and PsycInfo (EBSCO), alongside manual searching of reference lists. Using Covidence software, we screened titles and abstracts, followed by full-text articles. Data from the included articles were tabulated and summarised. Results: Of the 618 studies identified, 48 were included. The studies cover diverse clinical settings, and were mostly observational in design. 7 studies reporting adherence analyses within clinical trials for hypertension therapies. The use of theoretical frameworks to guide reporting was rare, and there was considerable variation in key terminology and definitions, most notably in the definition of adherence. Conclusion: The current body of evidence demonstrates considerable variability in the approach to implementing CAT for hypertension management in clinical practice, and a paucity of randomised controlled trials to evaluate its impact. Future research could (i) adopt a cohesive theoretical framework including clear operational definitions to standardise the approach to this important topic; (ii) further explore the impact of CAT on clinical outcomes using RCTs. [ABSTRACT FROM AUTHOR]

Postacute infection syndromes like Long Covid disproportionately affect females, differing in prevalence, symptoms, and potential causes from males. This Viewpoint highlights these sex differences, gaps in current understanding, and the critical need for sex-based research. [ABSTRACT FROM AUTHOR]

Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition. [ABSTRACT FROM AUTHOR]

Sex differences have been observed in acute coronavirus disease 2019 (COVID-19) and Long Covid (LC) outcomes, with greater disease severity and mortality during acute infection in males and greater proportions of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to LC pathogenesis. To investigate the immunologic underpinnings of LC development and symptom persistence, we performed multiomic analyses on blood samples obtained during acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 3 and 12 months after infection in a cohort of 45 participants who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Males who would later develop LC exhibited increases in transforming growth factor–β (TGF-β) signaling during acute infection, whereas females who would go on to develop LC had reduced TGFB1 expression. Females who developed LC demonstrated increased expression of XIST, an RNA gene implicated in autoimmunity, during acute infection compared with females who recovered. Many immune features of LC were also conserved across sexes, such as alterations in monocyte phenotype and activation state. Nuclear factor κB (NF-κB) transcription factors were up-regulated in many cell types at acute and convalescent time points. Those with ongoing LC demonstrated reduced ETS1 expression across lymphocyte subsets and elevated intracellular IL-4 in T cell subsets, suggesting that ETS1 alterations may drive aberrantly elevated T helper cell 2–like responses in LC. Altogether, this study describes multiple innate and adaptive immune correlates of LC, some of which differ by sex, and offers insights toward the pursuit of tailored therapeutics. Editor's summary: Sex differences have been reported for both acute coronavirus disease 2019 (COVID-19) and Long Covid (LC), with males typically having more severe acute disease and females being more likely to develop LC. Here, Hamlin et al. performed multiomics on peripheral blood samples from a prospective cohort of individuals to understand why. The authors identified immune pathways during acute infection that were associated with later development of LC. Some pathways, such as alterations in monocyte activation, were shared between the sexes; others were unique to males or females. This study both highlights the heterogeneity of LC and suggests that immunomodulatory treatments need to be tailored to the individual. —Courtney Malo [ABSTRACT FROM AUTHOR]

The recognition of Long Covid has renewed efforts to understand other infection-associated chronic conditions (IACCs). Here, we describe how studies of Long Covid and other IACCs might inform one another. We argue for the importance of a coordinated research agenda addressing these debilitating illnesses. [ABSTRACT FROM AUTHOR]

Preexisting anti–interferon-α (anti–IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti–IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti–IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti–IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti–SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti–IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti–IFN-α response. In contrast, systemic IgG1 anti–IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti–IFN-α in the immunopathology of COVID-19 and suggest that anti–IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa. Editor's summary: Autoantibodies targeting interferon-α (IFN-α) have been found in the circulation of those with severe COVID-19 and are considered a bad sign for disease progression. However, less is known about IFN-α–specific autoantibodies in other tissues, such as the mucosa. Here, Babcock et al. used a multiparameter flow cytometry technique called FlowBEAT to show that IgA1 autoantibodies targeting IFN-α could be found in the nasal mucosa and were associated with improved responses to SARS-CoV-2. The induction of these anti–IFN-α autoantibodies was temporally linked to a decline in IFN-α itself, suggesting that elicitation of these autoantibodies may be a mechanism to temper inflammation in the respiratory mucosa. These data suggest that there is a complex, location-dependent, role for antibodies against IFN-α and that these antibodies may tip the balance between protection and pathology. —Courtney Malo [ABSTRACT FROM AUTHOR]

The endothelial cells of the blood circulation are exposed to hemodynamic forces, such as cyclic strain, hydrostatic forces, and shear stress caused by the blood fluid's frictional force. Endothelial cells perceive mechanical forces via mechanosensors and thus elicit physiological reactions such as alterations in vessel width. The mechanosensors considered comprise ion channels, structures linked to the plasma membrane, cytoskeletal spectrin scaffold, mechanoreceptors, and junctional proteins. This review focuses on endothelial mechanosensors and how they alter the vascular functions of endothelial cells. The current state of knowledge on the dysregulation of endothelial mechanosensitivity in disease is briefly presented. The interplay in mechanical perception between endothelial cells and vascular smooth muscle cells is briefly outlined. Finally, future research avenues are highlighted, which are necessary to overcome existing limitations. [ABSTRACT FROM AUTHOR]

Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet‐derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element‐binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC‐mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC‐induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Epigenetic regulation of metabolism profoundly influences cell fate commitment. During osteoclast differentiation, the activation of RANK signaling is accompanied by metabolic reprogramming, but the epigenetic mechanisms by which RANK signaling induces this reprogramming remain elusive. By transcriptional sequence and ATAC analysis, this study identifies that activation of RANK signaling upregulates PRMT6 by epigenetic modification, triggering a metabolic switching from fatty acids oxidation toward glycolysis. Conversely, Prmt6 deficiency reverses this shift, markedly reducing HIF‐1α‐mediated glycolysis and enhancing fatty acid oxidation. Consequently, PRMT6 deficiency or inhibitor impedes osteoclast differentiation and alleviates bone loss in ovariectomized (OVX) mice. At the molecular level, Prmt6 deficiency reduces asymmetric dimethylation of H3R2 at the promoters of genes including Ppard, Acox3, and Cpt1a, enhancing genomic accessibility for fatty acid oxidation. PRMT6 thus emerges as a metabolic checkpoint, mediating metabolic switch from fatty acid oxidation to glycolysis, thereby supporting osteoclastogenesis. Unveiling PRMT6's critical role in epigenetically orchestrating metabolic shifts in osteoclastogenesis offers a promising target for anti‐resorptive therapy. [ABSTRACT FROM AUTHOR]

The success of immunotherapy for cancer treatment is limited by the presence of an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this immunosuppressive TME and enhance immunotherapy efficacy is essential. In this study, enrichment analysis based on publicly available single‐cell and bulk RNA sequencing data from gastric cancer patients are conducted, and found that tumor‐intrinsic interferon (IFN) plays a central role in TME regulation. The results shows that KDM3A over‐expression suppresses the tumor‐intrinsic IFN response and inhibits KDM3A, either genomically or pharmacologically, which effectively promotes IFN responses by activating endogenous retroviruses (ERVs). KDM3A ablation reconfigures the dsRNA‐MAVS‐IFN axis by modulating H3K4me2, enhancing the infiltration and function of CD8 T cells, and simultaneously reducing the presence of regulatory T cells, resulting in a reshaped TME in vivo. In addition, combining anti‐PD1 therapy with KDM3A inhibition effectively inhibited tumor growth. In conclusions, this study highlights KDM3A as a potential target for TME remodeling and the enhancement of antitumor immunity in gastric cancer through the regulation of the ERV‐MAVS‐IFN axis. [ABSTRACT FROM AUTHOR]

Background: One of the most important causes of cardiovascular disease is hypertension. Lifestyle modification has been emphasized in preventing and controlling blood pressure. This research aimed to determine the effect of educational intervention by application of PRECEDE‐PROCEED model on lifestyle change in hypertensive patients in the villages of Fasa City, Fars Province, Iran. Methods: This research is a quasi‐experimental study that was conducted on 300 hypertensive patients in 2020–2021. Data gathering tools were a demographic information questionnaire, a questionnaire based on the PRECEDE‐PROCEED model, and a lifestyle questionnaire (LSQ). The educational intervention consisted of ten sessions lasting 45 or 50 min. Before and 6 months after the educational intervention, the two groups each completed a questionnaire. The systolic and diastolic blood pressure (DBP) levels, as well as physical exercise and health variables, nutrition and weight control, mental health, and spiritual health were measured before and 6 months after the educational intervention. Results: The results showed that there was no significant difference between the two groups before in cues of PRECEDE‐PROCEED model; however, the experimental group had a significant increase in cues of PRECEDE‐PROCEED model 6 months after the intervention. The results showed that the experimental group had a significant increase 6 months after the intervention in terms of physical exercise and health variables, nutrition and weight control, mental health, and spiritual health. The mean blood pressure (both diastolic and systolic) in the experimental group was significantly reduced after the intervention. Conclusions: The study's results showed the effectiveness of an educational intervention based on the PRECEDE‐PROCEED model on lifestyle change in hypertensive patients. It also highlights the need to pay further attention to the education aimed at controlling hypertension through a healthy lifestyle and correct behavioral habits. [ABSTRACT FROM AUTHOR]

Background. Uncontrolled hypertension is a major public health challenge in low‐ and middle‐income countries. The Hypertension Control Program in Argentina (HCPIA) showed that a community health worker‐led multicomponent intervention was effective for blood pressure (BP) reduction in resource‐limited settings, but whether the intervention was equally effective across participant subgroups is unknown. Objective. To identify participants who benefit the most from the HCPIA BP control intervention. Methods. This secondary analysis used data from HCPIA, a successful 18‐month cluster‐randomized trial in 18 health centers with 1,432 low‐income hypertensive patients in Argentina. Fifteen baseline characteristics were used to define subgroups. The proportion of controlled BP (<140/90 mmHg) was estimated using generalized linear mixed models with arm‐by‐subgroup interaction terms. The distribution of trial BP response among intervention patient subgroups was assessed. Results. Participants were 53.0% female, a mean age of 56 years, and 17.4% controlled BP at baseline. After the intervention, 72.9% of intervention and 52.2% of control participants had controlled BP. The intervention was more effective in physically inactive patients (OR = 2.76, 95% CI: 1.82 and 4.21; p for interaction = 0.04), moderately active patients (OR = 3.08, 95% CI: 1.90 and 4.99; p for interaction = 0.03), and those with uncontrolled BP at baseline (OR = 2.77, 95% CI: 2.15 and 3.57; p for interaction = 0.05). Among intervention participants, 20.2% had no BP response (BP change < −4 mmHg), 41.3% had a moderate BP response (BP change: −4 mmHg to −24 mmHg), and 38.5% had a high BP response (BP change > −24 mmHg). Women (p = 0.01), those who were physically inactive (p = 0.03), and those not taking antihypertensive medications at baseline (p = 0.001) had the greatest BP response. Conclusion. The effect of the intervention was consistent across many subgroups with some key groups showing a particularly strong intervention effect. These findings could be useful for planning future hypertension control programs in low‐ and middle‐income countries. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of different single and combined preadmission antihypertensive drug regimens on the prognosis of critically ill patients. Methods: We performed a retrospective cohort study using data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. All initial ICU admission records of patients with hypertension and previous antihypertensive exposure before ICU admission were included. Our primary outcome was 90-day mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to balance the distribution of baseline characteristics. Logistic regression analysis and subgroup analysis were performed to determine the independent effect of different single and combined antihypertensive drug regimens on 90-day mortality. Results: A total of 13,142 patients were included in the final analysis. The 90-day mortality rate in the combined groups is lower than that in the single therapy group (10.94% vs 11.12%), but no statistical significance was found in the original cohort (p = 0.742). After adjustment for potential confounders, the significantly decreased 90-day mortality rate was found in the combined groups (10.78% vs 12.65%, p = 0.004 in PSM; 10.34% vs 11.90%, p = 0.007). Patients who were exposed to either ACEIs or ARBs had a better prognosis than those not exposed (7.19% vs 17.08%, p < 0.001 in single antihypertensive groups; 8.14% vs18.91%, p < 0.001 in combined antihypertensive groups). The results keep robustness in the PSM and IPTW cohorts. In the logistic regression model analysis, combined therapy was associated with a 12%-20% reduced risk of 90-day death after adjusting potential confounders (OR 0.80-0.88, all p < 0.05), while exposure to ACEIs or ARBs was associated with the decreased risk of 90-day death by 52%-62% (OR 0.38-0.48, all p < 0.001) and 40%-62% (OR 0.38-0.60, all p < 0.001) in the single and combined therapy groups, respectively. The results were still robust to subgroup analysis. Conclusions: Pre-admission combined antihypertensive therapy is associated with a significantly lower risk of death than exposure to single antihypertensives in critically ill patients. Meanwhile, either ACEIs or ARBs seem to be the optimal candidates for both single and combined therapy. Further high-quality trials are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: β-thalassemia (β-TH) is a hereditary hemolytic anemia that results in deficient hemoglobin (Hb) synthesis. It is characterized by ineffective erythropoiesis, anemia, splenomegaly, and systemic iron overload. Exploration new potential biomarkers and drug candidates is important to facilitate the prevention and treatment of β-TH. Methods: We applied quasi-targeted metabolomics between wild type (Wt) and heterozygous β-TH mice (Th3/+), a model of non-transfusion-dependent β-TH intermedia, in plasma and peripheral blood (PB) cells. Futher data was deeply mined by Kyoto Encyclopedia of Genomes (KEGG) and machine algorithms methods. Results: Using KEGG enrichment analysis, we found that taurine and hypotaurine metabolism disorders in plasma and alanine, aspartate and glutamate metabolism disorders in PB cells. After systematically anatomize the metabolites by machine algorithms, we confirmed that alpha-muricholic acidUP and N-acetyl-DL-phenylalanineUP in plasma and Dl-3-hydroxynorvalineUP, O-acetyl-L-serineUP, H-abu-OHUP, S-(Methyl) glutathioneUP, sepiapterinDOWN, and imidazoleacetic acidDOWN in PB cells play key roles in predicting the occurrence of β-TH. Furthermore, Sepiapterin, Imidazoleacetic acid, Methyl alpha-Dglucopyranoside and alpha-ketoglutaric acid have a good binding capacity to hemoglobin E through molecular docking and are considered to be potential drug candidates for β-TH. Conclusion: Those results may help in identify useful molecular targets in the diagnosis and treatment of β-TH and lays a strong foundation for further research. [ABSTRACT FROM AUTHOR]

This study focuses on examining and ascertaining the impact of various elements of industry 4.0, namely the internet of things (IoT) and -physical-cyber systems, on the human factors concerning operators in the Refinery industry. The primary objective of this study is to analyze the relationship between these variables and human factors. In this study, a quantitative approach employing partial least square-structural equation modeling (PLS-SEM) was utilized as the research methodology. The study sample consisted of 70 respondents who were specifically chosen from the Indonesian oil and gas sector operators. The findings of this research demonstrate a positive and significant influence of Industry 4.0 on human factors. Moreover, a significant correlation between the Internet of Things and human factors was identified. Additionally, the study also revealed a noteworthy association between the physical-cyber system and human factors. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension (HTN) is a common disease. A close relationship between HTN and high salt diet (HS) is recorded. Reduction of dietary HS in hypertensive patients causes improvements in blood pressure (BP) and cardiac architecture. Sodium--glucose cotransporter-2 inhibitors (SGLT2i) are oral anti diabetic drugs. Empagliflozin (EMPA) is one of these inhibitors. EMPA is an anti-hyperglycemic agent and reduces BP in patients with and without diabetes mellitus. Aim of the Work: The aim was to assess the EMPA therapy effects on the hypertensive Wister adult male albino rat's myocardium and the regenerative role of telocytes. Materials and Methods: Fifty adult male albino rats were utilized and divided into 2 main groups: group I (Control): included 20 rats and subdivided into subgroups IA (Standard diet & placebo) and IB (Standard diet & EMPA) and group II (HTN induced): involved 30 rats which took HS diet for eight weeks then subdivided into subgroup IIA (HS diet ), IIB (HS diet & EMPA) and IIC (Low salt diet) for another 8 weeks. Systolic BP was measured at the start, 8 and 16 weeks following the experiment's start. Specimens from the myocardium left ventricle were prepared for Picrosirius Red, CD34 immunostaining and electron microscopic examination. SBP, telocytes number and percentage of collagen fibers were analyzed statistically. Results: Subgroup IIA showed disrupted histological architecture of the myocardium but it was preserved in subgroups IIB and IIC. Systolic BP and collagen fibers deposition were high in IIA subgroup but showed levels near those of the control group in IIB and IIC subgroups. Area percentage of telocytes was high in IIB and IIC with marked decrease in IIA subgroups. Conclusion: Relation between hypertension and HS diet intake is proved. HS diet has deleterious effects on the myocardium architecture. This study revealed that EMPA and dietary salt restriction preserve rat's myocardium architecture. [ABSTRACT FROM AUTHOR]