High Levels Research Articles

Ritlecitinib, a JAK3/TEC family kinase inhibitor, stabilizes active lesions and repigments stable lesions in vitiligo.

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50mg (with or without 4-week 100-mg or 200-mg loading dose), 30mg, or 10mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

Enriching the formulation of low-fat mozzarella cheese using micro-coated vitamin D3

Purpose The use of polysaccharides increases solubility and consistency and causes functions such as viscosity? Moisture and food emulsifier stabilizer. This study aims to enrich the formulation of low-fat mozzarella cheese using microcoated vitamin D3 (VD3). Design/methodology/approach This study investigates the addition of hydrocolloids to low-fat mozzarella cheese to enhance its properties and nutritional value. Tests were conducted on cheese samples with 0.05% and 0.25% hydrocolloid concentrations at various stages: before production and at three and six months’ postproduction. The samples were evaluated for elasticity, pH and solubility to select the best one, which was then fortified with VD3. The vitamin was microencapsulated using alginate and whey protein to shield it from light and oxygen, optimizing the formula using the response surface method. The fortified cheese was tested for VD3 content over its shelf life. Findings Results indicated that all hydrocolloids tested improved moisture and meltability of the cheese while higher protein levels increased stretchability two to threefold. Rice starch hydrocolloid at 0.05% concentration was chosen due to superior sensory scores and minimal oil separation. This study concluded that VD3 levels remained stable during the cheese’s shelf life, suggesting that this approach could enhance the nutritional value of low-fat cheese without compromising its quality. Therefore, after examining the obtained results and comparing the regression models, the results indicated that the Quadratic model was chosen to investigate the effect of independent variables on the response rate, which had a statistically significant difference with other models (p = 0.0019). Also the results of the area under the curve and using the encapsulation efficiency equation, the percentage of microencapsulated vitamin was obtained, and according to the simulation results, the encapsulation efficiency was reported as 89.02%. Originality/value Developing innovative functional dairy products fortified with VD3 could improve the vitamin D status in deficient populations. Therefore, these designs can be applied at industrial scales for functional cheese production.

Pancreatic Stone Protein in the Diagnosis of Sepsis in Children Admitted to High-Dependency Care: A Single-Center Prospective Cohort Study.

Blood level of pancreatic stone protein (PSP) is a promising biomarker of sepsis both in adults and children. The aim of our study was to investigate the diagnostic accuracy of PSP in children with suspected sepsis and to compare diagnostic performance with other sepsis biomarkers approved for clinical use, that is, procalcitonin (PCT) and C-reactive protein (CRP). Prospective study. PICU and pediatric emergency department. Blood levels of PSP were measured using a nanofluidic point-of-care immunoassay (abioSCOPE, Abionic SA, Switzerland) within 24 hours of admission. We studied 99 children aged between older than 1 month and younger than 18 years with signs and symptoms of systemic inflammatory response syndrome (irrespective of associated organ dysfunction). The prevalence of sepsis was 35 of 99 (35.4%). Patients with sepsis had higher PSP levels (p < 0.001) than patients with systemic inflammation of noninfectious cause. In this analysis, the optimal cutoff for the diagnosis of sepsis using PSP was 123 ng/mL, which resulted in a sensitivity of 0.63 (95% CI, 0.43-0.80), specificity of 0.89 (95% CI, 0.77-0.95). The PSP test area under the receiver operating characteristic curve (AUROC) was 0.82 (95% CI, 0.73-0.91) and, by comparison, procalcitonin and CRP AUROC were 0.70 (95% CI, 0.58-0.82) and 0.72 (95% CI, 0.60-0.84), respectively. Overall, the pretest to posttest probability of sepsis with a positive test changed from 0.35 to 0.73. In this single-center prospective pediatric cohort, admitted to the high intensive care and to the PICU, our findings suggested the potential use of PSP as a sepsis biomarker. However, because of the clinical diagnostic uncertainty with a positive result, further investigation is needed particularly in combination with other biomarkers.

Exploring the diagnostic potential of immunoglobulin A-microbiota interplay in liver cirrhosis and spontaneous bacterial peritonitis.

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.

Healthcare workers’ knowledge, attitude and practices on infection prevention and control in the context of the COVID-19 pandemic at the Faranah regional hospital and associated healthcare centers, Guinea

BackgroundIn response to the COVID-19 pandemic, WHO launched a strategic preparedness and response plan, outlining public health measures to support countries worldwide. Healthcare workers have an increased risk of becoming infected and their behaviour regarding infection prevention and control (IPC) influences infection dynamics. IPC strategies are important across the globe, but even more in low-resource settings where capacities for testing and treatment are limited. Our study aimed to assess and implement COVID-19 pandemic preparedness and response measures in Faranah, Guinea, primarily focusing on healthcare workers’ IPC knowledge, attitude and practice (KAP).MethodsThe study was conducted between April 2020 and April 2021 assessing IPC pandemic preparedness and response measures such as healthcare workers’ KAP, alcohol-based handrub (ABHR) consumption and COVID-19 triaging in the Faranah Regional Hospital and two associated healthcare centres. The assessment was accompanied by IPC training and visual workplace reminders and done in pre- and post- phases to evaluate possible impact of these IPC activities.ResultsThe overall knowledge score in the Faranah Regional Hospital was 32.0 out of 44 at baseline, and did not change in the first, but increased significantly by 3.0 points in the second follow-up. The healthcare workers felt closer proximity to SARS-CoV-2 overtime in addition to higher stress levels in all study sites. There was significant improvement across the observed triaging practices. Hand hygiene compliance showed a significant increase across study sites leading to 80% in Faranah Regional Hospital and 63% in healthcare centers. The average consumption of ABHR per consultation was 3.29 mL with a peak in February 2020 of 23 mL.ConclusionDespite increased stress levels among HCWs, the ongoing IPC partnership well prepared the FRH in terms of triaging processes with a stronger impact on IPC practice than on theoretical knowledge. Throughout the pandemic, global shortages and surges in consumption did not affect the continuous ABHR provision of the FRH. This highlights local ABHR production as a key pandemic preparedness strategy.

Discrete Element Method Simulation of Vibratory Filling of Convoluted Hot Isostatic Pressing Canisters Using Idaho Calcine Waste Simulant

This research presents a discrete element method (DEM) model for simulating the vibratory filling of the Idaho calcine waste simulant into various convoluted hot isostatic pressing canisters. The simulation closely emulates the experimental vibratory powder-filling processes, achieving accurate representations of surface profiles and powder bed heights. Notably, the model underestimates lower fill levels but demonstrates improved accuracy at higher levels due to diminished air influence. Executed on a consumer-grade desktop PC, the DEM model replicates tapped powder bed heights to within millimeters, proving its capability to efficiently simulate commercial-scale bulk material handling processes using standard computing hardware.

Trauma reminders and disgust: The roles of posttraumatic stress disorder symptom severity, trauma type, and reminder type.

Disgust is a common emotional response to trauma but is studied less frequently than fear or other negative emotions. In laboratory settings, individuals with a history of sexual assault report more disgust following exposure to trauma reminders than those exposed to other trauma types, and people with more severe posttraumatic stress disorder (PTSD) symptoms typically report more disgust than those with lower symptom levels. It remains unknown whether this association is also present in ecological contexts and if these associations vary by trauma reminder type. The present sample included 80 trauma-exposed community members (PTSD: n = 39, no PTSD: n = 41) who completed up to 17 prompts per day for 3 days (2,158 total completed surveys). Multilevel models indicated that trauma reminders were associated with increased feelings of disgust, B = 0.16, SE = 0.06, p <.001, which was consistent across trauma reminder types, p <.001-p =.001. PTSD symptom severity moderated the association between trauma reminders and disgust such that it was stronger for participants with higher CAPS-5 scores, B = 0.02, SE = 0.01, p =.011. All trauma reminder types demonstrated the same pattern of moderation, ps =.003-.022, except flashbacks, p =.070. Trauma type was not a significant moderator of any trauma reminder type, ps =.193-.929. These findings suggest that trauma reminders encountered in daily life are associated with feelings of disgust. The results underscore the importance of exploring disgust as a trauma-related emotional experience among trauma survivors.

A qualitative, multi-centre approach to the current state of digitalisation and automation of surveillance in infection prevention and control in German hospitals

BackgroundHealthcare associated infections (HAI) pose a major threat to healthcare systems resulting in an increased burden of disease. Surveillance plays a key role in rapidly identifying these infections and preventing further transmissions. Alas, in German hospitals, the majority of surveillance efforts have been heavily relying on labour intensive processes like manual chart review. In order to be able to identify further starting points for future digital tools and interventions to aid the surveillance of HAI we aimed to gain an understanding of the current state of digitalisation in the context of the general surveillance organisation in German clinics across all care-levels. The end user perspective of infection prevention and control (IPC) professionals was chosen to identify digital interventions that have the biggest impact on the daily surveillance work routines of IPC professionals. Perceived impediments in the advancement of surveillance digitalisation should be explored.MethodsFollowing the development of an interview guideline, eight IPC professionals from seven German hospitals of different care levels were questioned in semi- structured interviews between December 2022 and January 2023. These included questions about general surveillance organisation, access to digital data sources, software to aid the surveillance process as well as current issues in the surveillance process and implementation of software systems. Subsequently, after full transcription, the interview sections were categorized in code categories (first deductive then inductive coding) and analysed qualitatively.ResultsResults were characterised by high heterogeneity in terms of general surveillance organisation and access to digital data sources. Software configuration of hospital and laboratory information systems (HIS/LIS) as well as patient data management systems (PDMS) varied not only between hospitals of different care levels but also between hospitals of the same care level. Outside research projects, neither fully automatic software nor solutions utilising artificial intelligence have currently been implemented in clinical routine in any of the hospitals.ConclusionsAccess to digital data sources and software is increasingly available to aid surveillance of HAI. Nevertheless, surveillance processes in hospitals analysed in this study still heavily rely on manual processes. In the analysed hospitals, there is an implementation and funding gap of (semi-) automatic surveillance solutions in clinical practice, especially in healthcare facilities of lower care levels.

Myelin basic protein mRNA levels affect myelin sheath dimensions, architecture, plasticity, and density of resident glial cells.

Myelin basic protein (Mbp) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyelination. How different Mbp mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer-edited mouse lines that accumulate Mbp mRNA levels ranging from 8% to 160% of wild type. In young mice, reduced Mbp mRNA levels resulted in corresponding decreases in Mbp protein accumulation and myelin sheath thickness, confirming the previously demonstrated rate-limiting role of Mbp transcription in the control of initial myelin synthesis. However, despite maintaining lower line specific Mbp mRNA levels into old age, both Mbp protein levels and myelin thickness improved or fully normalized at rates defined by the relative Mbp mRNA level. Sheath length, in contrast, was affected only when mRNA levels were very low, demonstrating that sheath thickness and length are not equally coupled to Mbp mRNA level. Striking abnormalities in sheath structure also emerged with reduced mRNA levels. Unexpectedly, an increase in the density of all glial cell types arose in response to reduced Mbp mRNA levels. This investigation extends understanding of the role Mbp plays in myelin sheath elaboration, architecture, and plasticity across the mouse lifespan and illuminates a novel axis of glial cell crosstalk.

Comparing pragmatic abilities across multiple languages in adults with ADHD: Insights from a self-report questionnaire

ABSTRACT Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with pragmatic language impairments in children, but less is known about the communicative abilities of adults with ADHD, especially when using a second or third language. In this study, we developed a questionnaire to collect self-report measures of a set of pragmatic skills in a person’s first, second and third language, comparing adults with and without an ADHD diagnosis. One hundred seventy-nine multilingual adults with (N = 91) and without ADHD (N = 88) completed the survey. As predicted, adults with ADHD reported more pragmatic difficulties than the control group. More specifically, people with ADHD showed pronounced impairments in regulating their behaviour in spoken interactions in the form of excessive talking, frequently interrupting others, and speaking without thinking first. Notably, these types of hyperactive and impulsive behaviours were significantly reduced when people with ADHD communicated in a second or third language. For pragmatic difficulties related to inattention such as concentrating on a conversation, both groups tended to be more inattentive in their third language compared to their first and second language. The understanding of non-literal language was only affected by ADHD in the first language and was generally more taxing in a language with lower proficiency levels. Our study contributes to a more nuanced understanding of how ADHD affects different kinds of communicative abilities in multilingual adults. It also has implications for clinical practice, highlighting the importance of assessing symptoms of inattention, hyperactivity, and impulsivity in a person’s dominant language.

Reviewing the science on 50years of conservation: Knowledge production biases and lessons for practice.

Drawing on 662 studies from 102 countries, we present a systematic review of published empirical studies about site-level biodiversity conservation initiated between 1970 and 2019. Within this sample, we find that knowledge production about the Global South is largely produced by researchers in the Global North, implying a neocolonial power dynamic. We also find evidence of bias in reported ecological outcomes linked to lack of independence in scientific studies, serving to uphold narratives about who should lead conservation. We explore relationships in the sample studies between conservation initiative types, the extent of Indigenous Peoples' and local communities' influence in governance, and reported social and ecological outcomes. Findings reveal positive ecological and social outcomes are strongly associated with higher levels of influence of Indigenous Peoples and local communities and their institutions, implying equity in conservation practice should be advanced not only for moral reasons, but because it can enhance conservation effectiveness.

Association between developmental patterns of single and concurrent externalizing behaviors and internalizing problems over the preschool years.

The present study investigated whether distinct developmental patterns of externalizing behaviors (EBs: hyperactivity-impulsivity, noncompliance, physical aggression) based on parent reports were repeatedly and differentially associated with separate dimensions of internalizing problems such as general anxiety, separation anxiety, and depressive symptoms across the early, middle, and late preschool years in a population birth cohort (N = 2,057, 50.7% boys). Six high trajectory classes obtained by latent growth modeling were used as longitudinal indicators of single EB and co-occurrent EBs. Children following low or moderate trajectories for all EBs served as the reference class. Results revealed that children in trajectory classes reflecting high levels of co-occurring EBs showed higher levels of general anxiety, separation anxiety, and depressive symptoms across the preschool years. In contrast, children in trajectory classes reflecting single EB manifested higher levels of some, but not all, dimensions of internalizing problems. In addition, their scores varied from one period to another. No sex differences were observed in the above associations. These results underline the need for comprehensive assessments across distinct types of EBs and internalizing problems to better reflect the characteristics that distinguish individual children. Finally, results suggest that children showing early co-occurrent EBs and internalizing symptoms may be an important group to target for in-depth assessment and possibly preventive intervention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The fate of closed schools: Documenting the relationships between school property reuses and their beneficiaries in Ontario, Canada

ABSTRACT Public schools play a pivotal role in successful community development. Yet, with school closures on the rise across North America, there is limited knowledge on the outcomes of closed school properties. This study documents the afterlife of closed school properties in Ontario, Canada, identifying their potential beneficiaries, and assessing the prevalence of property vacancies. Using a dataset of over 400 schools closed between 2011 and 2021, we determined that the prevalence of certain school property reuses varied by degree of urbanicity. Fewer than one-fifth of reused properties were designed to benefit highly deprived populations, despite over half of the school closures occurring in neighborhoods with higher levels of deprivation. Furthermore, one-third of school properties remained vacant at the time of study, 36% of which closed over a decade ago. The findings reflect the need for additional consideration of the future uses of school properties prior to their closures.

Detection of Specific IgE against Molds Involved in Allergic Bronchopulmonary Mycoses in Patients with Cystic Fibrosis.

Allergic bronchopulmonary mycoses (ABPM) can be due to molds other than Aspergillus fumigatus in patients with cystic fibrosis (pwCF). We aimed to develop immunoassays for the detection of specific IgE (sIgE) directed against five fungal species involved in ABPM: Aspergillus terreus, Scedosporium apiospermum, Lomentospora prolificans, Rasamsonia argillacea, and Exophiala dermatitidis. Serum samples (n = 356) from 238 pwCF, collected in eight CF care centers in France, Germany, and Italy, were analyzed by dissociated enhanced lanthanide fluorescent immunoassay (DELFIA®) to assess levels of sIgE directed against antigenic extracts of each fungus. Clinical, biological, and radiological data were collected for each episode. One hundred serum samples from healthy blood donors were used as controls. Sera were classified into four groups depending on the level of sIgE according to the quartile repartition calculated for the pwCF population. A score of 4 for values above the 3rd quartile corresponds to an elevated level of sIgE. PwCF showed higher levels of sIgE than controls. Based on criteria from the ABPA-ISHAM working group, with an additional criterion of "a sIgE score of 4 for at least one non-A. fumigatus mold", we were able to diagnose six cases of ABPM. Using 417IU/mL as the threshold for total IgE and the same additional criterion, we identified seven additional pwCF with "putative ABPM". Detection of sIgE by DELFIA® showed good analytical performance and supports the role played by non-A. fumigatus molds in ABPM. However, commercially available kits usable in routine practice are needed to improve the diagnosis of ABPM.

Understanding Intensive Care Unit Family Caregivers' Vulnerability to Post-Traumatic Stress Disorder: The Impact of Neurotic Personality Traits, Emotional Suppression, and Perceptions of Unexpected Death.

Rationale: Family members of patients who die in an intensive care unit (ICU) are at heightened risk of post-traumatic stress disorder (PTSD) symptoms. Not all surrogates develop these symptoms and heterogeneity exists in PTSD symptom clusters. Objectives: The study tested a personality model of PTSD symptoms in bereaved family caregivers of ICU patients. It was hypothesized that family members endorsing higher levels of neurotic personality traits would report higher levels of PTSD symptom clusters and that these associations would be explained by tendencies to view the patient's death as unexpected and to cope by suppressing their emotions. Methods: Participants were family members of ICU patients at an urban, academic medical center who either died or were discharged to an inpatient hospice unit. Participants were contacted for participation at least six months after the patient's death. Participants completed measures of personality, emotion regulation, and PTSD symptoms. Data were analyzed using path analysis. Results: Approximately one-third (35%) of the sample of 162 caregivers endorsed at-risk levels of PTSD. Individuals reporting higher levels of neurotic personality traits reported more PTSD symptoms (r = 0.53, p < 0.001). Perceptions that the patient death was unexpected partially explained the association of neuroticism with the intrusive re-experiencing PTSD symptoms (B = 0.45, p = 0.031). In contrast, emotional suppression partially explained the association of neuroticism with avoidance (B = 0.70, p = 0.010) and hyperarousal symptom clusters (B = 0.37, p = 0.041). Conclusions: Family vulnerability to PTSD after an ICU death can be conceptualized based on neurotic personality traits. Tendencies to view the patient's death as unexpected may contribute to intrusive thoughts and memories of the ICU experience. Individuals may avoid reminders and remain at heightened levels of arousal when they suppress their emotional experiences. Key Message: Family members who experience the death of a loved one following ICU treatment are vulnerable to PTSD symptoms. These reactions to ICU-related losses may be shaped by family members' personalities, expectations, and emotion regulation styles. Understanding these characteristics could inform family screening and intervention efforts in the ICU.

Burnout, racial trauma, and protective experiences of Black psychologists and counselors.

The present study explored rates of burnout and racial trauma among 182 Black mental health professionals (BMHPs) and utilized racial-cultural theory to explore potential protective factors against burnout and racial trauma. We collected data from 182 Black psychologists and counselors who were active mental health professionals during 2020. Descriptive statistics, multivariate analyses of variance, follow-up univariate analyses of variance, bivariate correlations, and multiple regression analyses were used. Both burnout and racial trauma were considerably higher among BMHPs than has been reported across general samples of helping professionals and across a sample of Black participants across the United States. Differences among rates of burnout and racial trauma existed across genders and specialties (i.e., counseling and psychology). Higher levels of social support and an external locus of control significantly predicted lower levels of burnout and racial trauma. In addition, higher levels of resilient coping predicted lower levels of burnout. Last, more frequent meetings with a mentor significantly predicted lower levels of racial trauma. Results from this study suggest that BMHPs may be more susceptible to burnout and race-based traumatic stress as a result of their work. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Influence of acupuncture and moxibustion on gastrointestinal function and adverse events in gastric cancer patients after surgery and chemotherapy: a meta-analysis.

The impact of acupuncture and moxibustion on postoperative complications and adverse events (AEs) of chemotherapy in patients with gastric cancer (GC) has been investigated. Through a meta-analysis of existing randomized controlled trials (RCTs), this study sought to strengthen the evidentiary basis to help investigators further understand the effects of moxibustion and acupuncture on postoperative complications and AEs of chemotherapy among GC patients. Embase, Web of Science, PubMed, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database for Chinese Technical Periodicals were searched to collect RCTs on effects of acupuncture and moxibustion on gastrointestinal function and AEs among GC patients undergoing surgery and chemotherapy. Outcome measures included postoperative gastrointestinal recovery (bowel sound recovery time, time to first flatus/defecation/feeding), the incidence of AEs (nausea and vomiting, abdominal distension, and diarrhea), myelosuppression (white blood cells, hemoglobin, and platelet), and immune function indicators (CD3+ and CD4+). To assess quality, the Cochrane Risk of Bias Tool was utilized. Review Manager 5.4 was implemented to do the meta-analysis. Fifteen eligible RCTs involved 1259 patients. Meta-analysis results showed that the experimental group had a significantly shorter bowel sound recovery time (MD = - 14.57, 95% CI = [- 18.97, - 10.18], P < 0.00001), time to first flatus (MD = - 17.56, 95% CI = [- 22.23, - 12.88], P < 0.00001), time to first defecation (MD = - 17.05, 95% CI = [- 21.02, - 13.09], P < 0.00001), and time to first feeding (MD = - 23.49, 95% CI = [- 28.81, - 18.17], P < 0.00001) than the control group. There were significant decreases in the incidence of nausea and vomiting (RR = 0.46, 95% CI = [0.21, 1.02], P = 0.05) and abdominal distension (RR = 0.45, 95% CI = [0.27, 0.75], P = 0.002) observed in the experimental group in comparison with the control group. The experimental group demonstrated a significant increase in white blood cell counts in comparison with to the control group (MD = 0.89, 95% CI = [0.23, 1.55], P = 0.008). The experimental group showed significantly higher levels of CD3+ (MD = 7.30, 95% CI = [1.86, 12.74], P = 0.009) and CD4+ (MD = 2.75, 95% CI = [1.61, 3.90], P < 0.00001) than the control group. Among GC patients, acupuncture and moxibustion can aid in gastrointestinal function recovery, reduce the incidence of AEs of surgery and chemotherapy, and improve immune function.

AlgU mediates hyperosmotic tolerance in Pseudomonas protegens SN15-2 by regulating membrane stability, ROS scavenging, and osmolyte synthesis.

Pseudomonas protegens can serve as an agricultural biocontrol agent. P. protegens often encounters hyperosmotic stress during industrial production and field application. The ability of P. protegens to withstand hyperosmotic stress is important for its application as a biocontrol agent. AlgU is a global regulator responsible for stress response and biocontrol ability. However, the specific regulatory role of AlgU in the hyperosmotic adaptation of P. protegens is poorly understood. In this study, we found that the AlgU mutation disrupted the hyperosmotic tolerance of P. protegens. Many genes and metabolites related to cell envelope formation were significantly downregulated in ΔalgU compared with that in the wild-type (WT) strain under hyperosmotic conditions, and we found that the algU mutation caused membrane integrity to be compromised and increased membrane permeability. Further experiments revealed that the cell envelope integrity protein TolA, which is regulated by AlgU, contributes to cell membrane stability and osmotic tolerance in P. protegens. In addition, several genes related to oxidative stress response were significantly downregulated in ΔalgU, and higher levels of intracellular reactive oxygen species were found in ΔalgU. Furthermore, we found that the synthesis of N-acetyl glutaminyl glutamine amide is directly regulated by AlgU and contributes to the hyperosmotic adaptation of P. protegens. This study revealed the mechanisms of AlgU's participation in osmotic tolerance in P. protegens, and it provides potential molecular targets for research on the hyperosmotic adaptation of P. protegens.IMPORTANCEIn this study, we found that the extracytoplasmic function sigma factor AlgU is essential for the survival of P. protegens under hyperosmotic conditions. We provided evidence supporting the roles of AlgU in influencing cell membrane stability, intracellular reactive oxygen species (ROS) accumulation, and dipeptide N-acetylglutaminylglutamine amide (NAGGN) synthesis in P. protegens under hyperosmotic conditions. Our findings revealed the mechanisms of AlgU's participation in hyperosmotic stress tolerance in P. protegens, and they provide potential molecular targets for research on the hyperosmotic adaptation of P. protegens, which is of value in improving the biocontrol ability of P. protegens.

Peripheral blood MR1 tetramer-positive mucosal-associated invariant T-cell function is modulated by mammalian target of rapamycin complex 1 in patients with active tuberculosis.

Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.

The effect of the level of data presentation on visual analysts' decisions.

Single-case design (SCD) is frequently utilized in research and applied settings to evaluate the effect of an intervention over time. Once collected, single-case data are typically graphed and analyzed visually in both research and practice contexts. Despite the ubiquity of visual analysis in SCD, this analytic framework has often been critiqued due to findings of limited reliability across visual analysts. Recent research has identified that the way a graph is constructed may contribute to the limitations of visual analysis. The present study sought to evaluate the effect of visually representing multiple measurement occasions as a single data point (e.g., combining measurements taken daily into a weekly composite data point) on visual analysts' decisions regarding the magnitude of an intervention effect. Eleven participants viewed identical data sets, plotted to show different numbers of measurement occasions combined as a single data point, and provided ratings regarding the magnitude of intervention effect depicted within the graph. Results indicated a significant main effect, with data sets with higher levels of data combination being rated as demonstrating significantly larger intervention effects. The results of the study provide additional support for standardization of data presentation and graph construction within SCD in both research and practice contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).