Sustained Increase Research Articles

Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction

AbstractTherapies involving the use of stem Leydig cells (SLCs), as testicular mesenchymal stromal cells, have shown great promise in the treatment of Leydig cell (LC) dysfunction in aging males. However, the outcomes of these therapies are not satisfactory. In this study, it is demonstrated that the aging microenvironment of the testicular interstitium impairs the function of SLCs, leading to poor regeneration of LCs and, consequently, inefficient functional restoration. The study develops a decellularized testicular extracellular matrix (dTECM) hydrogel from young pigs and evaluates its safety and feasibility as a supportive niche for the expansion and differentiation of SLCs. dTECM hydrogel facilitates the steroidogenic differentiation of SLCs into LCs, the primary producers of testosterone. The combination of SLCs with a dTECM hydrogel leads to a significant and sustained increase in testosterone levels, which promotes the restoration of spermatogenesis and fertility in an LC‐deficient and aged mouse model. Mechanistically, collagen 1 within the dTECM is identified as a key factor contributing to these effects. Notably, symptoms associated with testosterone deficiency syndrome are significantly alleviated in aged mice. These findings may aid the design of therapeutic interventions for patients with testosterone deficiency in the clinic.

Calcium dynamics of skin-resident macrophages during homeostasis and tissue injury.

Immune cells depend on rapid changes in intracellular calcium activity to modulate cell function. Skin contains diverse immune cell types and is critically dependent on calcium signaling for homeostasis and repair, yet the dynamics and functions of calcium in skin immune cells remain poorly understood. Here, we characterize calcium activity in Langerhans cells, skin-resident macrophages responsible for surveillance and clearance of cellular debris after tissue damage. Langerhans cells reside in the epidermis and extend dynamic dendrites in close proximity to adjacent keratinocytes and somatosensory peripheral axons. We find that homeostatic Langerhans cells exhibit spontaneous and transient changes in calcium activity, with calcium flux occurring primarily in the cell body and rarely in the dendrites. Triggering somatosensory axon degeneration increases the frequency of calcium activity in Langerhans cell dendrites. By contrast, we show that Langerhans cells exhibit a sustained increase in intracellular calcium following engulfment of damaged keratinocytes. Altering intracellular calcium activity leads to a decrease in engulfment efficiency of keratinocyte debris. Our findings demonstrate that Langerhans cells exhibit context-specific changes in calcium activity and highlight the utility of skin as an accessible model for imaging calcium dynamics in tissue-resident macrophages. [Media: see text] [Media: see text] [Media: see text] [Media: see text].

Dynamic reorganization of multivesicular bodies and exosome production impacted by sonoporation

Naturally occurring cell-derived extracellular vesicles (EVs) have emerged as attractive nanocarriers for drug delivery. However, production of large quantities of EVs for clinical applications in a scalable manner remains a significant challenge. This study investigated at the single cell level how sonoporation, or membrane poration produced by ultrasound-induced microbubble cavitation, impacts EV production using mouse macrophage RAW 264.7 cells stably expressing CD63-GFP as a model system. Real-time fluorescence videomicroscopy detected rapid changes in CD63-GFP, a tetraspanin family member highly enriched in intraluminal vesicles tagged with GFP, to track changes in multivesicular bodies (MVBs), which are the cellular compartments where exosomes originate within the cells. Our results revealed distinct dynamic changes in CD63-GFP intensity and distribution in RAW 264.7 cells in terms of response time and duration depending on whether the cells were directly or indirectly impacted by sonoporation, suggesting reorganization of MVBs in response to direct and indirect mechanisms resulted from the mechanical impact of ultrasound pulse on the cells. Analysis of the supernatant from sonoporation-treated RAW 264.7 cells expressing CD63-GFP demonstrated a delayed and sustained increase in the production of CD63-GFP-positive EVs. These results show the robust and detailed effect of sonoporation and reveal insights into sonoporation-induced EV release useful for guiding the application of sonoporation to enhance large-scale EV production.

Rising incidence of gonorrhea in Taiwan amid the COVID-19 pandemic: a nationwide surveillance study.

Background The protracted battle against coronavirus disease 2019 (COVID-19) has had a profound impact on various facets of society. The epidemiology of several diseases underwent alterations following the implementation of social restrictive strategies and non-pharmaceutical interventions (NPI). Methods In response to these changes, we conducted a retrospective nationwide surveillance study to investigate the prevalence of sexually transmitted infections during the pandemic. Weekly incidences of gonorrhea, syphilis, human immunodeficiency virus (HIV), and enterovirus were extracted from the national surveillance database. Results Over the period from 2015 to 2022, a sustained increase in gonorrhea notifications was evident (linear trend with a rising slope of 0.24 and an R-squared value of 0.62). When comparing the pre-pandemic period (2017-2019) with the pandemic period (2020-2022), a significant surge in gonorrhea notifications was observed (85 notifications per week pre-pandemic vs 143 notifications during the pandemic, representing a 68% increase, P Conclusions Our study highlights a significant rise in gonorrhea notifications during the pandemic. Despite disruptions to gonorrhea testing and medical services, and the implementation of NPI, there was no significant decrease in the incidence of gonorrhea in Taiwan. Gonorrhea emerged as a critical public health concern during the pandemic.

Understanding public opinion and discussion dynamics of digital humans on social media: an analysis of sentiment, themes and user characteristics

PurposeThe emergence of artificial intelligence-generated content (AIGC) technology has markedly enhanced the capabilities of digital human content generation and natural language processing, thus further advancing the development of digital humans. To enable enterprises and governments to effectively address the challenges and opportunities arising from the rapid development of digital humans, it is imperative to understand the public opinion and discussion dynamics of digital humans.Design/methodology/approachThis study initially analyzed the trends and distribution patterns of public attention to digital humans. By utilizing word cloud technology, we explored the primary focal points of public interest and conducted a topic analysis using latent Dirichlet allocation (LDA) techniques. Subsequently, content analysis was conducted on the popular application domains of digital humans. Finally, this study examined the influence of user characteristics on emotional scores toward digital humans and the presence of differences in focus across user groups.FindingsThe results indicate a sustained increase in public attention toward digital humans, accompanied by notable geographic disparities in the distribution of discussions. Discussions on Weibo are primarily focused on four domains, whereas areas within the digital human application domain that provoke widespread discussion include live streaming, service, cultural entertainment and digital avatars. Significant impacts of user characteristics on sentiment scores were observed, revealing divergent focal points of interest among different user groups toward digital humans.Originality/valueThrough the deep analysis of Weibo data, this study offers new insights into the digital human industry, enabling governments and businesses to understand industry trends and develop targeted digital human customization strategies based on customer characteristics.

Understanding the Role of Serendipity and Savoring on Travelers’ Life Satisfa

This study challenges the top-down theory’s view that travel does not lead to sustained increases in life satisfaction. The impact of travel experience factors on life satisfaction before, during, and after travel was longitudinally evaluated among 252 young travelers (aged 20‐30 years). The survey results showed that expectations before the trip, serendipity during the trip, and savoring after the trip affected life satisfaction directly or indirectly. In particular, the influence of savoring after travel on life satisfaction was much higher than that associated with travel satisfaction. In addition, the effect of travel satisfaction on savoring was nonsignificant, while that of serendipity was significant. Thus, beyond travel satisfaction, serendipity and savoring offer alternative paths to amplify life satisfaction derived from travel experiences.

Research trends of biomechanics in scoliosis from 1999 to 2023: a bibliometric analysis.

Despite the abundance of research on the biomechanics of scoliosis, there is a lack of a comprehensive bibliometric analysis. This study utilizes bibliometric methods to elucidate the research trends and hotspots within this domain. The data for this study were obtained from the Web of Science Core Collection and then analyzed using the open-source Bibliometrix R package and Citespace. The analysis encompassed 410 publications published from 1999 to 2023. There is a sustained increase in the number of publications within the field. Utilizing citation analysis and keyword analysis, the study identified key research focuses. Burst keyword analysis identified 19 keywords. The period from 1999 to 2023 has witnessed significant research attention on the biomechanics of scoliosis. The demographic shift towards an aging population has recently increased interest in ASD. Proximal biomechanical changes and transitional zones in PJK and PJF are hotspots in research, offering emerging scholars in this discipline valuable opportunities for exploration.

Nationwide trends in the use of ADHD medications in the period 2006–2022: a study from the Norwegian prescription database

BackgroundThe use of medication for Attention-Deficit/Hyperactivity Disorder (ADHD) increased globally throughout the early 2000s. This study examine trends in prevalences and incidences of medication use in Norway from 2006 to 2022.MethodsData from the Norwegian Prescription Database were used to present one-year-prevalence and incidence rates of ADHD medication (ATC-group N06BA and C02AC02) for the overall population (ages 6–64) and within sex and age subgroups of children (ages 6–17) and adults (ages 18–64). Incident use was defined as the dispensing of medication, with no recorded use in the previous two calendar years.ResultsThe overall prevalence of ADHD medication use in 6- to 64-year-olds increased from 5.2 to 19.4 per 1000 in the period, most pronounced from 2020 and onwards. While males experienced a nearly threefold increase in use (from 7.3 to 20.6 per 1000), the use among females increased almost sixfold during the study period (from 3.0 to 18.1 per 1000). Consequently, the male-to-female prevalence-ratio decreased from 2.4 to 1. Children exhibited a higher prevalence of use compared to adults throughout the period, although the largest relative increase was observed in adults, particularly in female adults. In children the male-to-female ratio decreased from 3.2 to 2.0, primarily due to an increasing use in 13–17-year-old females. Among adults, prevalences were similar across most age groups, with the highest rates observed among those aged 18–24, where female use exceeded male use by the end of the period. The male-to-female prevalence-ratio in adults decreased from 1.6 to 0.9 during the period. Parallel to prevalent use, overall incident use increased from 1.4 to 5.0 per 1000 during the period, with the most pronounced increase occurring from 2020 and onwards. From this point, incident use among females aged 13–17, 18–24, and 25–34, exceeded that of males. The male-to-female incidence-ratio decreased from 1.8 to 0.9. The overall incidence to prevalence ratio remained similar throughout the period, being 0.27 in 2006 and 0.25 in 2022.ConclusionA sustained increase in the prevalence of ADHD medication use was observed, with the most pronounced rise occurring among females and adults from 2020 and onwards. By 2022, the overall gender disparity in ADHD medication use had diminished, which should be considered in the context of a steep increase in incident use among adolescent and young adult females starting from 2020.

Development and Evaluation of a Novel Resuscitation Teamwork Model for Out-of-Hospital Cardiac Arrest in the Emergency Department

Cardiopulmonary resuscitation (CPR) is critical for out-of-hospital cardiac arrest patients but is prone to rapid changes and errors. Effective teamwork and leadership are essential for high-quality CPR. We aimed to introduce the Airway-Circulation-Leadership-Support (A-C-L-S) teamwork model in the emergency department (ED) to address these challenges. The study comprised 2 phases. The development phase involved reviewing CPR videos, categorizing problems, and formulating strategies using the Systems Engineering Initiative for Patient Safety model. Resuscitation tasks were organized into A-C-L-S domains using hierarchical task analysis. Equipment and environmental deficits were optimized ergonomically with a pit-crew style arrangement. Mnemonics enhanced teamwork and leadership. The evaluation phase assessed postimplementation ED resuscitation team performance, focusing on adherence, timeliness, and quality of A-C-L-S tasks. The development phase produced a structured teamwork model, assigning tasks, tools, mnemonics, and positions based on A-C-L-S domains. The A-team manages the airway and optimizes end-tidal CO2 levels; the C-team focuses on high-quality chest compressions and defibrillation. Leadership coordinates resuscitation efforts using goal-directed mnemonics (DABCD2E3), whereas the S-team handles medications, timekeeping, and recording. The evaluation phase showed improvements in adherence and timeliness of A-C-L-S tasks, with sustained increases in chest compression fraction before mechanical CPR, from 67.2% preimplementation to 83.0% postimplementation, 89.1% after 1 year, and 86.1% after 2 years. Overall, chest compression fraction also improved from 81.7% to 88.6%, peaking at 92.2% after 1 year and maintaining 90.8% after 2 years. The A-C-L-S teamwork model is feasible, applicable, and effective. Further research is needed to assess its influence on patient outcomes.

Long-Term Impact of Carotid Endarterectomy on Choroidal and Choriocapillaris Perfusion: The INFLATE Study

PurposeWhen performed for clinically significant carotid artery stenosis (CAS), the long-term impact of carotid endarterectomy (CEA) on choroidal and choriocapillaris (CC) circulation was studied using swept-source optical coherence tomography angiography (SS-OCTA). DesignProspective observational study. ParticipantsPatients with clinically significant CAS undergoing unilateral CEA. MethodsSS-OCTA scans were performed on both eyes at baseline (before CEA), within one week post-CEA (short-term follow-up [FU]), and at least 30 days post-CEA (long-term FU). Using validated algorithms, we measured mean choroidal thickness (MCT), choroidal vascularity index (CVI), choroidal vessel volume (CVV), CC flow deficit percentage (CC FD%), and CC thickness within the 5mm circle centered on the fovea for both the eye ipsilateral to CEA (surgical side) and the contralateral eye (nonsurgical side). Multivariable regression analysis was conducted to evaluate the impact of baseline demographic and clinical factors on the changes in choroidal and CC parameters. Main Outcome MeasuresBoth the short- and long-term changes in MCT, CVI, CVV, CC FD%, and CC thickness. ResultsThe study included 58 eyes from 29 patients. Significant short-term improvements in MCT (P<0.001) and CC thickness (P=0.006) were observed post-CEA on the surgical side. Long-term FU showed sustained increases in MCT compared with baseline (P=0.02), while CC thickness was not significantly different from baseline (P=0.10). The CVI did not change significantly from baseline at either short-term (P=0.45) or long-term (P=0.22) FU on the surgical side. While CVV demonstrated a short-term rise immediately post-CEA (P<0.001), the difference was not statistically significant at the long-term evaluation (P=0.06). No significant improvement in CC FD% from baseline was observed at any visit post-CEA (short-term P=0.81, long-term P=0.91). The nonsurgical side only showed a significant reduction in CVI at the long-term FU visit compared with before CEA (P=0.01). Clinical variables such as age, degree of stenosis, diabetes, hypertension, and smoking status did not greatly impact the outcomes. ConclusionsUnilateral CEA demonstrated a sustained increase in MCT suggesting persistent improvements in choroidal perfusion in the ipsilateral eye.

Decomposition characteristics of woody peat and its mixtures with liable organic materials in a newly reclaimed saline-alkali soil: A one-year incubation experiment

The combined application of woody peat with labile organic materials has been shown to be an effective strategy for rapidly improving soil organic matter (SOM) and soil fertility in newly reclaimed lands. However, their decomposition dynamics, which can be greatly influenced by the residue-mixing effect, are not well understood. Therefore, this study investigated the decomposition characteristics and residue-mixing effect of woody peat, corn straw, organic manure and their binary mixtures in a newly reclaimed saline-sodic soil through a 360-day incubation experiment. The results revealed that both straw and organic manure contained large amount of O-alkyl C, leading to rapid degradation in mass and organic C (OC). In contrast, woody peat is rich in alkyl C and aromatic C, exhibiting the highest alkyl C/O-alkyl C (A/O-A) ratio and aromaticity. As a result, woody peat only lost less than 6.4% OC and showed minimal changes in mass and nitrogen content within a year, indicating strong degradation resistance in the saline-sodic soil. The combination of woody peat with straw or organic manure induced significant non-additive synergistic effects on mass and OC loss, aromatic C, carbonyl C, A/O-A ratio and aromaticity. This suggests that the addition of woody peat significantly slowed down the degradation of the mixtures and prolonged the retention of OC in soil. On the contrary, the mixing of straw and organic manure led to significant non-additive antagonistic effects on mass and OC loss, indicating that their combination accelerated the decomposition of the mixture. Consequently, this study suggests that, in contrast to the applicated of various labile organic materials, the combined application of recalcitrant woody peat with labile organic materials can extend the presence of organic matter in the soil, thereby promoting a sustained increase in active and passive SOM content and soil fertility.

Protective Impact of Influenza Vaccination on Healthcare Workers

Background: Influenza vaccine uptake among healthcare workers is crucial for preventing influenza infections, yet its effectiveness needs further investigation. Objectives: This prospective observational study aimed to assess the protective effect of influenza vaccination among healthcare workers in Shenzhen. Methods: We enrolled 100 participants, with 50 receiving the 2023–2024 quadrivalent influenza vaccine (QIV) and 50 serving as unvaccinated controls. Epidemiological data were collected when the participants presented influenza-like illness. Serum samples were collected at three time points (pre-vaccination and 28 and 180 days after vaccination). Hemagglutination inhibition (HI) assay was performed against the strains included in the 2023–2024 QIV (H1N1, H3N2, BV and BY strains) to assess antibody protection levels. Demographics comparisons revealed no significant differences between the vaccinated and control groups (p &gt; 0.05), ensuring group comparability. Results: The incidence of influenza-like illness was significantly lower in the vaccinated (18%) compared to the control group (36%; p = 0.046; OR = 0.39; 95% CI: 0.15 to 0.98). The vaccinated group also exhibited a higher rate of consecutive two-year vaccinations (48% vs. 24% in the control group, p &lt; 0.05). Additionally, the vaccinated healthcare workers were more inclined to recommend vaccination to their families (80% vs. 48%, p &lt; 0.05). HI titers against H1N1 (p &lt; 0.01), H3N2 (p &lt; 0.01), BV (p &lt; 0.001) and BY (p &lt; 0.01) significantly increased in the vaccinated group at 28 days post-vaccination. Moreover, a marked and sustained increase in HI titers against the H3N2 strain (p &lt; 0.001) was observed at 180 days post-vaccination, highlighting the vaccine’s enduring impact on the immune response. The fold change in the HI titers, indicative of the magnitude of the immune response, was significantly higher for H1N1 (p &lt; 0.01), H3N2 (p &lt; 0.001), BV (p &lt; 0.01) and BY (p &lt; 0.05) among the vaccinated individuals compared to the control group, underscoring the vaccine’s efficacy in eliciting a robust and sustained antibody response. Conclusion: Influenza vaccination significantly reduces the incidence of influenza-like illness among healthcare workers and promotes a sustained immune response. The study supports the importance of annual vaccination for this group to enhance personal and public health.

Differences in resting sympathetic nervous activity between orthostatic hypertension, conventional hypertension, and healthy individuals

Abstract Introduction Standing places a significant hemodynamic burden on the cardiovascular system. In healthy individuals, neurohumoral reflex mechanisms, particularly the arterial baroreflex, maintain blood pressure during standing. However, in some cases, the counterregulatory response can be excessive, resulting in a condition known as orthostatic hypertension (OHT), which appears to be linked to an increased cardiovascular risk. In recent years, OHT has been recognized as an indicator for assessing the effectiveness of renal denervation. It is suggested that abnormalities in sympathetic nervous system regulation, particularly related to the renal sympathetic nerves, may play a role in influencing RDN outcomes, however, the relationship between OHT and sympathetic nerve activity remains poorly understood. This study aims to assess the differences in sympathetic nerve activity between OHT patients, conventional hypertensive(cHT) patients and healthy individuals using muscle sympathetic nerve activity (MSNA) measurements. Methods We conducted an examination of hypertensive patients undergoing drug treatment at our clinic between April 1, 2023, and June 30, 2023, to identify cases of OHT. OHT was defined as a sustained increase in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg within 3 minutes of standing. We measured MSNA in the cases for which consent was obtained. Results Among the 138 cases, 31 were diagnosed with OHT, and 7 of them consented to MSNA measurement. Of the 11 cases of cHT patients who consented, two groups were well age-matched. And it was also compared with 11 cases of healthy individuals who underwent MSNA measurement during the same period. Both of the MSNA burst frequency and burst incidence in OHT (38.4 +/- 12.2 bursts/min, 61.1 +/- 21.3 bursts/100 heartbeats) was significantly greater (p&amp;lt;0.05) than that in cHT (28.3 +/- 5.7 bursts/min, 44.6 +/- 11.1 bursts/100 heartbeats), and all these were significantly greater (p&amp;lt;0.05) than in healthy individuals (21.8 ± 7.3 bursts/min, 35.8 +/- 11.3 bursts/100 heartbeats) at rest. Conclusions OHT is associated with sympathetic hyperactivity compared to normal hypertensive patients, contributing to an increased cardiovascular risk. These results indicate that therapy for OHT in hypertensive patients would be required to prevent sympathetic augmentation.

Comparative analysis of muscle sympathetic nerve activity in patients afflicted with orthostatic hypertension versus conventional hypertension

Abstract Introduction Standing places a significant hemodynamic burden on the cardiovascular system. In healthy individuals, neurohumoral reflex mechanisms, particularly the arterial baroreflex, maintain blood pressure during standing. However, in some cases, the counterregulatory response can be excessive, resulting in a condition known as orthostatic hypertension (OrthoHT), which appears to be linked to an increased cardiovascular risk. Epidemiologically, orthostatic hypertension has been reported in 5-30% of hypertensive patients. Furthermore, in recent years, it has garnered attention as a responder group in renal denervation therapy. Purpose In hypertensive patients, sympathetic hyperactivity is expected to exacerbate cardiovascular risk. However, the relationship between OrthoHT and sympathetic nerve activity remains poorly understood. This study aims to assess the differences in sympathetic nerve activity between OrthoHT and conventional hypertensive patients using muscle sympathetic nerve activity (MSNA) measurements. Methods We conducted an examination of hypertensive patients undergoing drug treatment at our clinic between April 1, 2023, and June 30, 2023, to identify cases of OrthoHT. Only patients with essential HT were included in the HT group; patients diagnosed with secondary HT were excluded. HT patients with other active CV diseases (i.e., symptomatic cerebral/coronary artery diseases or heart failure) and/or severe renal dysfunction (estimated glomerular filtration rate &amp;lt;30 mL/min/1.73 m2) were also excluded. OrthoHT was defined as a sustained increase in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg within 3 minutes of standing. MSNA was recorded from the left peroneal nerve using a tungsten microelectrode at supine position. We measured MSNA in the cases for which consent was obtained. Statistical analyses were performed using SPSS software. Results Among the 183 cases, 31 were diagnosed with OrthoHT, and 7 of them consented to MSNA measurement. Of the 11 cases of hypertensive patients who consented, two groups were well age-matched. We assessed body mass index, resting systolic blood pressure, diastolic blood pressure, heart rate, blood glucose level, creatinine, cholesterol, brain natriuretic hormone, and ejection fraction measured by echocardiography, but found no significant differences between the two groups. OrthoHT patients exhibited elevated MSNA burst frequency (28.3 +/- 5.7 vs. 38.4 +/- 12.2 bursts/min, P &amp;lt; 0.05) and burst incidence (44.6 +/- 11.1 vs. 61.1 +/- 21.3 bursts/100 heartbeats, P &amp;lt; 0.05) at rest. Conclusions OrthoHT is associated with sympathetic hyperactivity compared to normal hypertensive patients, contributing to an increased cardiovascular risk.

Impact of retirement on physical activity in older adults: a longitudinal analysis from SHARE

Abstract Background With ageing populations experiencing longer post-retirement years, understanding the influence of major life transitions on health behaviours such as physical activity (PA) is crucial. This study assesses how retirement affects PA levels by analysing longitudinal data from the Survey of Health, Ageing and Retirement in Europe (SHARE). Methods This analysis utilised longitudinal data from 2004 to 2020, categorising PA according to WHO guidelines adapted to individual-level data from successive waves of SHARE. The study examined the relative risks (RR) of being physically active, using generalised estimating equation models to compare periods before and after retirement. Results The cohort consisted of 8,998 individuals aged 50 and older who were employed at baseline and retired during the study period. Initially, 83.6% of participants were categorised as physically active. A noticeable decline in PA was observed post-retirement, with RR decreasing from 1.08 (95%CI 1.07-1.10) more than 10 years before retirement to 0.90 (95%CI 0.88-0.93) more than 10 years after retirement, compared to the year of retirement. Previously inactive individuals often increased their PA levels, peaking 3 to 4 years post-retirement (RR increased from 0.79, 95%CI 0.70-0.88, to 1.49, 95%CI 1.36-1.63), suggesting a temporary boost in moderate-intensity PA during the so-called “honeymoon phase”. Conclusions Retirement can serve as a window of opportunity for enhancing leisure-time PA, particularly among those previously inactive. Sustained increases in PA are less common, highlighting the need for targeted interventions to support continued engagement in PA among retirees. The variations in PA trends suggest that interventions should be tailored to individual characteristics such as age at retirement, previous job type, and educational background to maximise public health impact. This study underscores the challenges of ensuring long-term health benefits through PA. Key messages • Retirement significantly alters physical activity patterns, highlighting an opportunity for targeted health interventions. • Longitudinal data reveals critical periods post-retirement that could benefit from public health strategies to maintain or increase physical activity among older adults.

Impact of Hypoxia and the Levels of Transcription Factor HIF-1α and JMJD1A on Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Cell Lines.

This study aimed to assess the impact of hypoxia on epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC), focusing on the involvement of transcription factors hypoxia inducible factor 1 (HIF-1α) and Jumonji Domain-Containing Protein 1A (JMJD1A). FaDu and Cal33 cell lines were subjected to hypoxic and normoxic conditions. Cell proliferation was quantified electronically, while PCR and western blot analyses were used to measure mRNA and protein levels of HIF-1α, JMJD1A, and EMT markers. EMT was further characterized through immunofluorescence, migration, and invasion assays. Hypoxic conditions significantly reduced cell proliferation after 48 hours in both cell lines. HIF-1α mRNA levels increased initially during short-term hypoxia but declined thereafter, while JMJD1A mRNA levels showed a sustained increase with prolonged hypoxia. Western blot analysis revealed contrasting trends in protein levels. EMT marker expression varied markedly over time at both the mRNA and protein levels, suggesting EMT induction in hypoxia within 24 hours. Immunofluorescence, migration, and invasion assays supported these findings. The study provides evidence of hypoxia-induced EMT in HNSCC, although conflicting results suggest a complex interplay among molecular regulators involved in this process.

Comparative Study of Olmesartan versus Telmisartan, in Patient with Stage I Hypertension

Background: Hypertension is one of the most common diseases in the world. It is defined as sustained increase in blood pressure ≥ 140/90 mmHg. The risk of both microvascular &amp; microvascular complications including stroke, coronary artery disease, peripheral vascular disease, retinopathy, nephropathy &amp; possibly neuropathy increases with hypertension. Olmesartan medoxomil is a non-peptide angiotensin II receptor antagonist. The drug acts by selectively blocking angiotensin II type 1 receptor. Telmisartan is angiotensin receptor blocker shows high affinity for the angiotensin II type 1 receptors. Objective of the study is to compare the efficacy of Olmesartan and Telmisartan in Patient with stage –I hypertension. Materials and methods: This was a randomized, open‑label, parallel‑group, comparative study conducted in 120 patients of Stage I hypertension carried out from January 2021to June 2022. Patients were recruited from the cardiology outpatient department (OPD) of Shaheed Suhrawardy Medical College hospital.Results: In olmesartan group there were 39 male and 21 female patients and in telmisartan group there were 36 male and 24 female patients. Both Olmesartan and Telmisartan are effective in lowering systolic &amp; diastolic BP at different intervals of 2nd, 4th, 8th and 12th week. There was a statistically significant decrease in mean blood glucose level after 12 weeks of treatment in telmisartan group when compared to baseline. Serum total cholesterol, triglycerides, and low‑density lipoproteins decreased significantly after 12‑week treatment with olmesartan and telmisartan. Conclusion: Olmesartan and telmisartan are equally efficacious in reducing DBP. Olmesartan, when compared to telmisartan is more efficacious in reducing SBP. Whereas Telmisartan shows the most favorable effects on FBG and lipid profile. J Shaheed Suhrawardy Med Coll 2023; 15(1): 8-12

Adaptations in hepatic glucose metabolism after chronic social defeat stress in mice

Chronic stress has been shown to induce hyperglycemia in both peripheral blood and the brain, yet the detailed mechanisms of glucose metabolism under stress remain unclear. Utilizing 13C6-labeled glucose to trace metabolic pathways, our study investigated the impact of stress by chronic social defeat (CSD) on glucose metabolites in the liver and brain one week post-stress. We observed a reduction in 13C6-enrichment of glucose metabolites in the liver, contrasting with unchanged levels in the brain. Notably, hepatic glycogen levels were reduced while lactate concentrations were elevated, suggesting lactate as an alternative energy source during stress. Long-term effects were also examined, revealing normalized blood glucose levels and restored glycogen stores in the liver three weeks post-CSD, despite sustained increases in food intake. This normalization is hypothesized to result from diminished glucagon levels leading to reduced glycogen phosphorylase activity. Our findings highlight a temporal shift in glucose metabolism, with hyperglycemia and glycogen depletion in the liver early after CSD, followed by a later phase of metabolic stabilization. These results underscore the liver’s critical role in adapting to CSD and provide insights into the metabolic adjustments that maintain glucose homeostasis under prolonged stress conditions.

The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials

Regulatory T cell (Treg) impairment is implicated in the pathogenesis of chronic inflammatory diseases, but relatively little is known about the therapeutic potential of Treg restoration. Here we present clinical evidence for the Treg-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). Key inclusion criteria for AD included an Eczema Area and Severity Index (EASI) score ≥ 16 and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and for PsO included a Psoriasis Area and Severity Index (PASI) score of ≥ 12 and a static Physician’s Global Assessment (sPGA) score of ≥ 3. REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 µg/kg or 24 µg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives, respectively. AD patients receiving the higher dose demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These exploratory clinical improvements are accompanied by sustained increases in CD25bright Tregs. REZPEG thus represents a homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control.

Elritercept, a modified activin receptor IIA ligand trap, increased erythropoiesis and thrombopoiesis in a phase 1 trial

AbstractThe transforming growth factor β (TGF-β) superfamily plays a crucial role in regulating biological processes of virtually every tissue and system in the body, including hemostasis and hematopoiesis. Elritercept (KER-050) is an investigational, modified activin receptor type IIA ligand trap designed to bind and inhibit activin A and other select TGF-β superfamily ligands, including activin B, growth differentiation factor 8 (GDF-8), and GDF-11. The objectives of this phase 1 randomized, placebo-controlled study of elritercept were to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic markers of activin inhibition and hematopoiesis in healthy postmenopausal women (N = 48). This study comprised 2 parts: single ascending doses ranging from 0.05 to 4.5 mg/kg; and multiple (up to 2 doses) ascending doses of 0.75 mg/kg administered subcutaneously (SC) every 4 weeks. Elritercept was generally well tolerated at all dose levels, with no dose-limiting toxicities observed. There were no severe or serious adverse events nor clinically significant changes in safety laboratory measures. Serum concentrations increased in dose-proportional manner after single SC doses, with peak concentrations achieved in 4.5 to 6 days and a mean elimination half-life of 12 days. These parameters were comparable after multiple doses. Elritercept elicited rapid, sustained, and dose-dependent increases in reticulocytes, red blood cells, hemoglobin, and platelets without eliciting detrimental changes in white blood cells such as neutrophils and lymphocytes. The time course and duration of changes in these cell populations supported a differentiated pharmacologic profile that is consistent with the stimulation of both early- and late-stage hematologic pathways. The trial was registered at www.anzctr.org.au/ as #ACTRN12619000318189.