Quantitative relationship between grip strength and quality of life in the older adult based on a restricted cubic spline model.

Background: Grip strength have been showed diverse associations with quality of life for the older adult population in the literature, still there is lack of evidence of the threshold value of grip strength for maintaining good quality of life in older adults. The purpose of this study was to study the dose-effect relationship between grip strength and quality of life in the older adult, and to explore the factors affecting quality of life in the older adult, so as to provide effective theoretical basis for realizing healthy aging. Methods: A total of 105 older adult people over 60 years old were selected from 3 communities in Beijing. Grip strength was measured by hand dynamometer apparatus and quality of life was assessed by 36-item Short-Form (SF-36). On the basis of controlling confounding factors, the dose-effect relationship between grip strength and quality of life was analyzed with the restricted cubic spline model. Results: The results showed that there was a dose-effect relationship between grip strength and physical component summary (PCS) (p < 0.01). However, grip strength was not significantly associated with mental component summary (MCS) (p > 0.05). The threshold value of grip strength for male and female is 34.75 and 23.2 kg, for normal weight group and overweight and obesity group is 24.82 and 29.00 kg, for 60-69, 70-79, 80+ years group is 24.88, 23.37, and 22.97 kg, respectively. When the grip strength value is lower than the threshold value, the increase of grip strength was related to significant improvement of quality of life of the older adult, and when the grip strength value is higher than the threshold value, the quality of life can be maintained in good condition. Conclusion: A dose-effect relationship was found between grip strength and physical health in quality of life. Results of our study indicated that the grip strength of the older adults needed to be greater than certain threshold values to maintain good quality of life.

Utilizing Bladder Diaries to Prevent Unnecessary Treatment in Patients With Storage Dysfunction: A Retrospective Study.

Introduction A frequency volume chart (FVC) or bladder diary (BD) is used to diagnose lower urinary tract symptoms and to determine the effectiveness of treatment. In outpatient practice, patients who use an FVC or BD may experience improvement in storage symptoms and not desire further treatment. The aim of this study was to determine the characteristics of patients who did not desire treatment after BD recording and to assess the changes in storage symptoms after BD recording. Methods This was a retrospective study. Patients who completed a three-day BD record were included. The patients were divided into two groups: those whose symptoms improved after using a BD and no longer desired treatment, and those who desired treatment. We compared endpoints including patient background, BD, Overactive Bladder Symptom Score (OABSS), and International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) score. Results We recruited 79 patients. Four patients were excluded (two were minors and two due to cognitive impairment). Thus, 75 patients were included in the analysis. Of these, 27 (36.0%) did not desire treatment for storage symptoms after BD recording. Compared with the group of patients who desired treatment, those who did not desire treatment had significantly lower daytime and nighttime frequency and number of leaks recorded in their BD, and there were fewer patients with nocturia and habitual caffeine consumption. Baseline OABSS and ICIQ-UI SF scores were lower and there were no significant changes in storage symptoms after BD recording. The cut-off value for the baseline total score of OABSS that did not desire treatment for storage symptoms after BD recording was 6 points. Conclusion In this study, 36.0% of patients no longer desired treatment for storage symptoms after using a BD. These patients initially exhibited a normal daily urinary frequency and mild storage symptoms. These findings suggest that among patients presenting to the outpatient clinic with storage symptoms, those with mild symptom severity and a total OABSS of 6 points or less may be able to avoid unnecessary treatment through BD recording.

The relationship between static and dynamic postural deformities with pain and quality of life in non-athletic women.

BACKGROUND: The assessment of the postural condition with functional tests are used with the least facilities in the shortest time, for a wide the range of movements for different parts of the body. Both static and dynamic posture measurements are predictive of injury. These two assessments provide different information regarding posture control. Also, with the advancement of this technology, the speed of posture assessment and deformity diagnosis can be increased and done with the minimum facilities. This can signal a new method for the quick diagnosis of abnormalities and ultimately prevent or correct psychological effects and musculoskeletal pain in the future. Because as seen according to the citations, abnormalities cause musculoskeletal pains, movement restrictions and ultimately affect the quality of life. METHODS: The current research is of the applied and semi-experimental type, and in terms of the results it is of the relational and correlational type. In this research, 148 non-Athletic women from Fardis City participated, in which the results obtained from the static evaluation was analyzed by the Posture Screen application after taking photos from four directions using a smartphone, and also the dynamic evaluation was identified and analyzed by the researcher using the overhead squat test of compensatory movements, with the data that from Cornell pain and quality of life SF-36 questionnaires was. Data description and correlation between variables were done with the η coefficient method. RESULTS: According to the findings there is a positive and significant correlation between the prevalence of uneven pelvic deformity and the amount of pain in non-athletic women (P = 0.036, η (148) = 0.17). In other words, pain increased significantly when the pelvis was changed from a normal position to a lateral deviation position. Also, there is a negative and significant relationship between the prevalence of deformity of knee movement, back arch, straight back, heel lift and the quality of life in non-athletic women (P = 0.020, η (148) = 0.19). CONCLUSIONS: According to the results, deformities have an effect on pain and the frequency of pain, on the other hand, in the present study, dynamic evaluations showed deformities more accurately than static evaluations.

An exploration into self-reported inactivity behaviours of adults with an intellectual disability using physical activity questionnaires.

BACKGROUND: Inactivity is a correlate of adverse health. Adults with an intellectual disability (ID) are more inactive than the general population and often present with more complex health issues. Self-reported activity questionnaires such as the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and Rapid Assessment of Physical Activity (RAPA) questionnaire are the predominant source of activity information because of their low cost, non-invasive nature, ease of administration and interpretation of results. METHODS: Correlates of inactivity among the general and ID populations were identified through a literature scoping review. Inactivity was measured using the RAPA and the IPAQ-SF. A multiple-imputation chained equation was used to impute missing data. Using Pearson chi-squared analyses, relationships between these correlates as well as covariates of age, sex, level of ID, body mass index (BMI) and aetiology, and RAPA and IPAQ-SF categories were explored. Logistic regression provided more detailed analyses. Results were summarised using the Systems of Sedentary Behaviour framework. Spearman correlations examined the IPAQ-SF and RAPA relationships. RESULTS: Three correlates for inactivity emerged from the IPAQ-SF and RAPA questionnaire. Up after 07:00 h was a correlate for both. Difficulty walking 100 yards and epilepsy were additional correlates of inactivity. Weak but significant correlations were seen between IPAQ-SF and RAPA scores. CONCLUSIONS: High inactivity levels are present in adults with an ID. The IPAQ-SF and RAPA questionnaires are weakly correlated.

The association of the comorbidity status of metabolic syndrome and cognitive dysfunction with health-related quality of life.

PURPOSE: Both metabolic syndrome (MetS) and cognitive dysfunction impair health-related quality of life (HRQOL). This study aims to determine whether individuals experiencing both MetS and cognitive dysfunction have lower HRQOL. METHODS: This cross-sectional study enrolled 567 participants who attended outpatient clinics at a medical center in northern Taiwan. MetS was diagnosed according to the modified criteria for the Asian population. Cognitive function was categorized as normal, mild cognitive dysfunction, and advanced cognitive dysfunction according to the score of the Montreal Cognitive Assessment, Taiwanese version. HRQOL was assessed using the SF-36v2® Health Survey (SF-36v2). The associations of the comorbidity status of MetS and cognitive dysfunction with HRQOL were analyzed using linear regression models, adjusting for age, sex, marital status, education level, income groups, and activities of daily living. RESULTS: Out of 567 participants, 33 (5.8%) had MetS with mild cognitive dysfunction, and 34 (6.0%) had MetS with advanced cognitive dysfunction. Participants with both MetS and advanced cognitive dysfunction exhibited the lowest scores in the physical component summary and almost all scales of HRQOL. MetS exacerbated the inverse association between mild cognitive dysfunction and the mental component summary. For those with MetS, the scores on scales of role physical, bodily pain, vitality, and social functioning worsened as cognitive function deteriorated (all Ptrend<0.05). CONCLUSION: As the severity of comorbidity between MetS and cognitive dysfunction varies, patients exhibited poorer performance in different aspects of HRQOL. Future research is needed to find solutions to improve HRQOL for patients with both MetS and cognitive dysfunction.

Psychometric analysis and validation of the SF-34 PREG: An adaptation of the SF-36 for assessing quality of life in pregnant women.

OBJECTIVE: This study aims to perform a psychometric analysis of the 36-item short form health survey (SF-36) in a population of pregnant women and validate an adapted version of the instrument to measure health-related quality of life specific to pregnancy. METHODS: A cross-sectional study design was carried out with data collection between 7 and 36 weeks of gestation, with a total sample of 547 pregnant women divided into two randomized subsamples. Data were collected between September 2021 and April 2023. An exploratory factor analysis was initially performed on one subsample, followed by a confirmatory factor analysis on the other. Internal consistency was assessed using Cronbach's alpha and McDonald's omega, and correlations between factors were analyzed. RESULTS: Results from the exploratory factor analysis proposed a seven-factor model explaining 56% of the variance. All proposed dimensions achieved Cronbach's alpha scores above 0.75, with a total test score of 0.92. Furthermore, all dimensions exhibited positive and statistically significant correlations. Bartlett's test of sphericity and the Kaiser-Meyer-Olkin test yielded values of 5599 (P < 0.001) and 0.871, respectively. The confirmatory factor analysis reaffirmed this model with good fit indices: χ2 792 (P < 0.001), comparative fit index (CFI) and Tucker-Lewis index (TLI) >0.90, and standardized root mean square residual (SRMR) and root mean square error of approximation (RMSEA) <0.06. CONCLUSION: This study developed and validated the "SF-34 PREG," an adapted version of the SF-36, specifically designed for pregnant women. The SF-34 PREG demonstrated high reliability and a robust factorial structure, making it a more precise and relevant tool for assessing health-related quality of life during pregnancy. Although it does not include the social functioning dimension of the original SF-36, the SF-34 PREG offers improved relevance and accuracy for this specific population. Further research and clinical use of the SF-34 PREG are recommended.

Cancer-associated SF3B1 Mutations Inhibit mRNA Nuclear Export by Disrupting SF3B1-THOC5 Interactions.

Mutations in SF3B1 are common in many types of cancer, which promotes cancer progression through aberrant RNA splicing. Recently, mRNA nuclear export has been reported to be defective in cells with SF3B1 K700E mutation. However, the mechanism remains unclear. Our study reveals that the K700E mutation in SF3B1 attenuates its interaction with THOC5, an essential component of mRNA nuclear export complex THO. Furthermore, SF3B1 mutation caused reduced binding of THOC5 with some mRNA and inhibited the nuclear export of these mRNA. Interestingly, THOC5 overexpression restores the nuclear export of these mRNA in cells with SF3B1 K700E mutation. Importantly, other types of cancer-associated SF3B1 mutations also inhibited mRNA nuclear export similarly, suggesting that it is common for cancer-associated SF3B1 mutation to inhibit mRNA nuclear export. Our research highlights the critical role of the THOC5-SF3B1 interaction in the regulation of mRNA nuclear export and provides valuable insights into the impact of SF3B1 mutations on mRNA nuclear export.

Killing of xenogenous and virally infected homogenous target cells by shrimp lymphocyte-like haemocytes.

Haemocytes play a crucial role in the invertebrate's immune system. In our lab, five subpopulations of shrimp haemocytes were identified in the past: hyalinocytes, granulocytes, semi-granulocytes and two subpopulations of non-phagocytic cells. In the latter two subpopulations, their characteristics such as having small cytoplasmic rims and not adhering to plastic cell-culture plates are very similar to those of mammalian lymphocytes. Therefore, they were designated lymphocyte-like haemocytes. Although little is known about their function, we hypothesize, based on their morphology, that they may have a cytotoxic activity like natural killer cells, with the ability to recognize and kill target cells. In our study, K562 cells and Sf9 cells were used as xenogenous target cells to detect the cytotoxic activity of the shrimp non-adherent lymphocyte-like haemocytes. Non-adherent haemocytes were collected and mixed with K562 cells and Sf9 cells at a 5:1 ratio and the binding activity was examined under a microscope. The binding rate of non-adherent haemocytes to K562 cells and Sf9 cells reached 6.6 % and 2.4 % after 240 min of culture, respectively. Then, the killing activity of non-adherent haemocytes was detected by an EMA staining (fluorescence microscopy), which showed 3.75 % dead K562 cells and 1.025 % dead Sf9 cells, and by Sytox® blue staining (flow cytometry), which showed 4.97 % of dead K562 cells. Next, a killing assay was developed to visualize the killing activity of shrimp non-adherent haemocytes. Non-adherent haemocytes were pre-labeled in blue (CellTracker blue) and K562/Sf9 cells in green (CFSE); dead cells were differentially stained red with ethidium bromide. The cytotoxic activity increased and reached a level of 2.59 % in K562 cells and 0.925 % in Sf9 cells at 120 min after co-culture. Furthermore, in the co-cultures of non-adherent haemocytes with K562 cells and Sf9 cells, upregulation of the gene and protein expression of the cytotoxic molecules torso-like protein and granzyme B was observed by RT-qPCR at 240 min and western blotting at 180 min. Additionally, non-adherent haemocytes were co-cultured with WSSV-inoculated shrimp ovary and lymphoid organ cells to detect the cytotoxicity to homogenous target cells. The binding activity started at 60 min in both the ovary and lymphoid organ cultures and reached at 240 min 50.62 % and 40.7 %, respectively. The killing activity was detected by EMA staining and the percentage of dead ovary and lymphoid organ cells increased respectively from 10.84 % to 6.89 % at 0 min to 13.09 % and 8.37 % at 240 min. In conclusion, we demonstrated the existence of cytotoxic activity of shrimp lymphocyte-like haemocytes against xenogenous cells from mammals and insects and against WSSV-infected homogenous shrimp cells.

Research and Analysis on Enhancement of Surface Flashover Performance of Epoxy Resin Based on Dielectric Barrier Discharge Plasma Fluorination Modification.

To conquer the challenges of charge accumulation and surface flashover in epoxy resin under direct current (DC) electric fields, numerous efforts have been made to research dielectric barrier discharge (DBD) plasma treatments using CF4/Ar as the medium gas, which has proven effective in improving surface flashover voltage. However, despite being an efficient plasma etching medium, SF6/Ar has remained largely unexplored. In this work, we constructed a DBD plasma device with an SF6/Ar gas medium and explored the influence of processing times and gas flow rates on the morphology and surface flashover voltage of epoxy resin. The surface morphology observed by SEM indicates that the degree of plasma etching intensifies with processing time and gas flow rate, and the quantitative characterization of AFM indicates a maximum roughness of 144 nm after 3 min of treatment. Flashover test results show that at 2 min of processing time, the surface flashover voltage reached a maximum of 19.02 kV/mm, which is 25.49% higher than that of the untreated sample and previously reported works. In addition to the effect of surface roughness, charge trap distribution shows that fluorinated groups help to deepen the trap energy levels and density. The optimal modification was achieved at a gas flow rate of 3.5 slm coupled with 2 min of processing time. Furthermore, density functional theory (DFT) calculations reveal that fluorination introduces additional electron traps (0.29 eV) and hole traps (0.38 eV), enhancing the capture of charge carriers and suppressing surface flashover.

The Correlation Between Body Mass Index and Health-Related Quality of Life: Data from Two Weight Loss Intervention Studies.

INTRODUCTION: The correlation between body mass index (BMI) and utility in participants with obesity was assessed using health-related quality-of-life data collected in two weight loss intervention studies, SCALE and STEP 1. METHODS: Short Form Health Survey 36-Item (SF-36) scores from SCALE and STEP 1 were mapped to EuroQoL-5 dimensions-3 levels (EQ-5D-3L) using an established algorithm to derive utilities for the UK. SF-36 scores from STEP 1 were converted into Short Form 6 dimension (SF-6D) utilities for Portugal using the tool developed by the University of Sheffield. The correlation between baseline BMI and utility was assessed by multiple linear regression analyses, controlling for demographic and clinical parameters. RESULTS: A higher baseline BMI correlated with lower EQ-5D-3L and SF-6D utilities, although the trend was non-significant. Assuming linearity between BMI ranges 30-40 kg/m2, an additional unit of BMI correlated with 0.0041 and 0.0031 lower EQ-5D-3L scores in SCALE and 0.0039 and 0.0047 lower EQ-5D-3L and 0.0027 and 0.0020 lower SF-6D scores in STEP 1 for men and women, respectively. CONCLUSION: In individuals with comparable demographic characteristics and weight-related comorbidities, a 1 unit change in BMI leads to a difference of up to 0.005 in utility indices. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: SCALE (NCT01272219) and STEP 1 (NCT03548935).

Cost-effectiveness analyses compare health benefits and costs between treatments to inform decisions on healthcare resource allocation. Health benefits are typically quantified as quality-adjusted life-years (QALYs) gained. The calculation of QALYs relies on health-related quality-of-life (HRQoL) data, which are collected from participants. However, to allow comparisons across multiple interventions and diseases, HRQoL needs to be converted into a standardized, generic measure, i.e., a utility index ranging from 0 (equivalent to death) to 1 (perfect health). In this study, HRQoL data from the SCALE and STEP 1 clinical trials were converted into utility indexes and analyzed against participants' weight at study start, expressed as body mass index (BMI, kg/m²). Our study indicates that there is a negative correlation between BMI and health utility at a population level whereby an additional unit of BMI, within the range of 30­40 kg/m², was consistently correlated with an up to 0.005 worsening in the utility index across men and women. The estimated effect size was small, indicating that BMI alone may not explain the differences in participants' HRQoL and general population evaluation of these.

Assessment of radiological and functional outcomes of complex acetabulum fracture managed with combined anterior and posterior approach in a single anaesthetic setting: a retrospective study.

BACKGROUND: Appropriate selection of surgical approach for associated fractures of the acetabulum that involves both columns is still elusive. Therefore, present study aimed to assess the quality of life of complex acetabulum fracture managed with combined anterior and posterior approach (dual approach) as well as the association of postoperative reduction and patient reported outcomes. MATERIAL AND METHODS: This retrospective study was performed on 42 associated acetabular fracture patients with involvement of both columns, who were treated with a dual approach including combined anterior modified ilio-inguinal approach in combination with posterior Kocher-Langenbeck (K-L) approach in a single anaesthetic session having minimum two years follow-up. Postoperative reduction and radiological outcomes were assessed using Matta criteria. Functional outcome was assessed by a score system developed by Merle d'Aubigné-Postel. Patient-reported outcomes were assessed using the 36-Item Short Form Survey (SF-36). RESULTS: The mean age of participants was 47.9 ± 11.95 years and mean follow-up period was 2.8 ± 0.49 years. Anatomical reduction was achieved in 32 (76.19%) cases in postoperative period. 8 (19.04%) cases had congruent and 2 (4.76%) had incongruent reduction. Radiological and functional outcome was excellent/good n = 35 (83.33%) cases. Patient-reported outcome on domains physical function and role physical showed a significant improvement between 6 to 24 months period (p < 0.001). CONCLUSIONS: The dual approach for complex acetabulum fracture with mid-term follow-up showed good to excellent radiological and functional outcomes. A significant improvement in patient-reported outcomes on Physical function and Role physical domains of SF-36 was also seen over the follow-up period.

Quality of Life Assessment in Romanian Patients with Spinal Muscular Atrophy Undergoing Nusinersen Treatment.

Spinal muscular atrophy (SMA), identified over a century ago, is characterized by severe muscle wasting and early mortality. Despite its rarity, the high carrier frequency of the responsible genetic mutations and the variability in its manifestations make it a significant research focus. This prospective cross-sectional descriptive study evaluated health-related quality of life (HRQoL) across eight health domains in 43 Romanian SMA patients treated with nusinersen, using the SF-36 questionnaire to analyze influencing factors. The survey was conducted online with informed consent, and the data were analyzed using MedCalc software, employing both parametric and non-parametric statistical tests for accurate interpretation. The results revealed significant variations in HRQoL. Most patients were non-ambulatory (74.4%), reflecting SMA's impact on mobility. Urban residents reported better outcomes, particularly in physical functioning (p = 0.014), which may be attributed to improved access to healthcare services. Younger participants (under 14), represented by proxy responses, noted better general health (p = 0.0072) and emotional well-being (p = 0.0217) compared to older participants. These findings suggest that younger patients or their proxies perceive a better health status, highlighting the need for age-specific approaches in SMA management and the potential optimistic bias associated with proxy reporting on perceived health outcomes.

Efficacy of Shugan Hewei formula combined with rabeprazole in refractory gastroesophageal reflux disease: randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To assess the efficacy of the Chinese herbal medication Shugan Hewei formula (SHF) combined with rabeprazole in patients with refractory gastroesophageal reflux disease (rGERD). METHOD: A total of 264 participants were randomly assigned to the treatment group (n = 132) receiving SHF granules (20 mg) combined with rabeprazole (10 mg) and the control group (n = 132) receiving placebo SHF granules (20 mg) combined with rabeprazole (20 mg). Both groups undergo 8 weeks of treatment and 2 weeks of follow-up. RESULTS: The treatment group showed higher total clinical symptom efficacy and lower total symptom scores compared to the control group. The treatment group was superior to the control group in reducing rGERD major symptom scores, including heartburn, retrosternal pain, regurgitation and belching, and acid regurgitation. Additionally, treatment group (Z = 8.169, P < 0.001) and control group (Z = 9.800, P < 0.001) treatments were all significantly attenuated esophageal inflammation, demonstrating comparable efficacy. Patients with esophagitis grade A decreased from 40.34% to 17.23%, and those with grade B decreased from 11.76% to 3.78% in the treatment group. The results of the SF-36 scale showed that combination therapy was more effective in improving role limitations due to physical health, vitality, general health, total somato-physical health, and psychiatric mental health. CONCLUSION: Our study reveals that the combined treatment of SHF with rabeprazole is more efficacious in managing patients with rGERD when contrasted with sole rabeprazole treatment.

EQ-5D-5L and SF-6Dv2 health utilities scores of diffuse large B-cell lymphoma patients in China.

BACKGROUND: This study evaluates the health-related quality of life (HRQoL) of persons with diffuse large B-cell lymphoma (DLBCL) by using EQ-5D-5L and SF-6Dv2 and compares the measurement properties of the two instruments. METHOD: DLBCL patients were identified via a patient group and were surveyed using web-based questionnaires. Demographic information, socioeconomic status (SES), clinical characteristics, and EQ-5D-5L and SF-6Dv2 responses were collected and statistically described. The association between the EQ-5D-5L and SF-6Dv2 dimensions were analyzed using the Spearman's correlation coefficient, whereas the correlation of the utility scores was evaluated using Pearson's correlation coefficient. The agreement between the responses of the two instruments were examined using a Bland-Altman (B-A) plot. A one-way analysis of variance (ANOVA) was performed to compare the utility scores across subgroups in different clinical states (a t-test was used if there were two subgroups). In addition, the graded response model (GRM) was used to describe the discrimination ability and difficulty characteristics of the dimensions in the two instruments. RESULTS: In total, 582 valid responses were collected, among which 477 respondents were associated with initial-treatment and 105 respondents were relapsed/refractory (RR) patients. The mean (standard deviation [SD]) EQ-5D-5L and SF-6Dv2 utility scores of the DLBCL patients were 0.828 (0.222) and 0.641 (0.220), respectively. The correlation between the EQ-5D-5L and SF-6Dv2 dimensions ranged from 0.299 to 0.680, and the correlation between their utility scores was 0.787. The B-A plot demonstrated an acceptable but not strong agreement between EQ-5D-5L and SF-6Dv2 utility scores. The GRM model results indicated that all dimensions of each instrument were highly discriminating overall, but EQ-5D-5L had suboptimal discriminative power among patients with good health. CONCLUSION: Both the EQ-5D-5L and SF-6Dv2 showed valid properties to assess the HRQoL of DLBCL patients. However, utility scores derived from the two instruments had substantial difference, thereby prohibiting the interchangeable use of utilities from the two instruments.

SF3B2 Haploinsufficiency Associated With Hirschprung Disease and Complex Cardiac Defect Without Craniofacial Microsomia.

Haploinsufficiency of SF3B2 is associated with craniofacial microsomia, characterized by mandibular hypoplasia and microtia, often with preauricular tags or pits, epibulbar dermoids, and cleft palate. In addition, extracraniofacial anomalies may be present, such as skeletal, cardiac renal, and abnormalities of the central nervous system. Variants have been either de novo or inherited, and both inter- and intrafamilial variability has been observed. Here we describe a patient referred for exome sequencing for a complex congenital heart defect and Hirschsprung disease found by exome sequencing to be heterozygous for a loss of function variant, c.945dup (p.Val316SerfsTer5), in SF3B2. This variant was inherited from a parent with an isolated cardiac defect. Interestingly, neither have the defining craniofacial features or other dysmorphisms. This report further illustrates the degree of phenotypic variability seen in SF3B2-related disease and expands the spectrum to include Hirschsprung disease.

Analyzing the role of TM4SF1 expression in pancreatic adenocarcinoma: understanding prognostic implications and therapeutic opportunities.

Background: Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy characterized by aggressive growth and poor prognosis. Understanding the molecular mechanisms underlying PAAD is crucial for developing effective therapies. This study aimed to explore the role of TM4SF1 and other key genes in PAAD progression, their prognostic implications, and therapeutic opportunities. Methods: Differential gene expression analysis was performed using PAAD and normal tissue samples to identify upregulated genes, with TM4SF1 emerging as significantly elevated in PAAD. Functional enrichment analysis elucidated associated signaling pathways. A prognostic model comprising BPIFB4, PLEKHN1, CPTP, DVL1, and DDR1 was developed using least absolute shrinkage and selection operator (LASSO) regression and validated in an independent cohort. Genetic mutation analysis provided insights into the functional significance of identified genes. Pharmacogenomic analysis examined associations between gene expression and drug sensitivity. Experimental validation included quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses to confirm gene expression patterns and protein levels. Results: Lower TM4SF1 expression correlated with enhanced anti-tumor immune activity in PAAD, suggesting a complex interplay between genetic expression and immune response. The prognostic model showed robust associations with patient survival outcomes, validated across diverse patient cohorts. Genetic mutation analysis highlighted potential therapeutic targets. Pharmacogenomic analysis revealed correlations between gene expression profiles and drug responsiveness, suggesting personalized treatment strategies. Experimental validation confirmed elevated TM4SF1 levels in tumor tissues and demonstrated its role in promoting cancer cell proliferation and colony formation. Conclusions: This study advances understanding of the molecular landscape of PAAD, emphasizing TM4SF1 as a key regulator and potential therapeutic target. The integration of genetic expression, immune response dynamics, and pharmacogenomics offers a multifaceted approach to personalized treatment strategies for PAAD, paving the way for improved patient outcomes and novel therapeutic interventions. Further research is warranted to elucidate the clinical utility of targeting TM4SF1 and other identified genes in PAAD management.

Prognostic impact of DTA mutation and co-occurring mutations in patients with myelodysplastic syndrome.

OBJECTIVE: To evaluate the frequency and prognostic significance of DTA (DNMT3A、TET2、ASXL1) gene mutation and co-occurring mutations in patients with myelodysplastic syndrome (MDS). METHODS: The clinical data of 102 newly diagnosed MDS patients who accepted Next Generation Sequencing (NGS) was retrospectively analyzed. According to whether the patients had DTA gene mutation, the patients were divided into DTA mutated (DTA-mut) group and wild type (DTA-wt) group, and the relationship between gene mutation and clinical characteristics and prognosis was analyzed. RESULTS: Among the 102 MDS patients, 96% (98/102) presented with mutation, while the mean number of mutations was 3.04 mutations/patient. DTA-mut was detected in 56.9% (58/102) patients. The most frequent co-mutated genes in DTA-mut group were SF3B1 (25.8%), RUNX1 (24.1%), U2AF1 (18.9%), SRSF2, EZH2, SETBP1 (17.2%), STAG2 (15.5%), IDH2 (12.1%) and BCOR, CBL (10.3%). The two groups showed no significant differences in ages, blood parameters, bone marrow blasts, WHO 2022 classification, IPSS-R risk category and rate of conversion to leukemia. Compared with the DTA-wt group, the mutation frequency of RUNX1 was higher (P = 0.02), while mutation frequency of TP53 was lower (P = 0.001) and the mutation frequency of ≥ 3 co-mutated genes was higher in DTA-mut group (P = 0.00). Survival analysis showed that the overall survivals (OS) of DTA-mut patients was significantly inferior to that of DTA-wt patients (P = 0.0332). According to IPSS-R classification, a statistically significant difference in OS was only observed in higher risk (IPSS-R > 3.5) group (P = 0.0058). In the context of DTA mutation, the OS of patients with RUNX1 mutation was shorter than that of patients without RUNX1 mutation significantly (P = 0.0074). The OS of patients with SF3B1 mutation was longer than that of patients without SF3B1 mutation, but there was no statistical difference (P = 0.0827). DTA mutations were not independent prognostic factors when DTA and co-mutated genes with frequency > 10% were considered in Cox regression model (P = 0.329). However, multivariate analysis confirmed an independently adverse prognosis of RUNX1 co-mutation (P = 0.042, HR = 2.426, 95% CI:1.031-5.711) in DTA-mut cohort. Moreover, our multivariable analysis suggests that SRSF2-mut was an independent poor prognostic factor for all MDS patients (P = 0.047), but lost significance (P = 0.103) for DTA-mut patients. CONCLUSIONS: DTA mutations are frequently observed in patients with MDS, often accompanied by genes involved in RNA splicing and transcription factors like SF3B1 and RUNX1. DTA and concomitant mutations affect prognosis in MDS patients and RUNX1 was identified as an independent poor prognostic factor in patients with DTA mutations.

Assessing Self-Rated Physical Health Scores Following Repeat Exposure to Anthropogenic and Natural Hazards in Houston, TX.

BACKGROUND: Research connects health outcomes to hazard exposures but often neglects the nature of the exposure or repeated events. METHODS: We undertook a cross-sectional study (N = 1,094) from a representative sample in the Houston Metropolitan Statistical Area (HMSA). Respondents were recruited using Qualtrics panels, targeting individuals reflecting the population of the HMSA. Physical composite scores (PCS) were calculated using the SF-12v2. RESULTS: Among the hazards (hurricanes, flooding, tornadoes, chemical spills, industrial fires), only chemical spills showed a dose-response: physical health scores declined significantly with repeated exposures. This decline persisted after multiple linear regression. Covariates including sex, race, age, education, and chemical exposure affected PCS, but chemical spill exposure remained the most significant, negatively affecting PCS even after adjusting for other factors (coef =-2.24, 95% CI, -3.33 to -1.15). CONCLUSION: Grasping the effects of hazards, especially repeated ones, can guide emergency management in mitigation, recovery, and preparedness efforts.

An Evaluation of the Quality of Life and Emotional Status of Patients With Implantable Cardioverter Defibrillators at the Vilnius University Hospital, Lithuania.

Background and objective An arrhythmia is a disorder of the heart rate or rhythm. An implantable cardioverter defibrillator (ICD) is a small electronic device connected to the heart to continuously keep track of and help control rapid and sometimes life-threatening electrical problems with the heart. However, it may result in psychological tension in patients' lives, eventually affecting their quality of life (QoL). In light of this, we aimed to assess the QoL of patients with ICD at the Vilnius University Hospital, Lithuania. Methods We employed the following three questionnaires in this study: an originally prepared questionnaire including sociodemographic and health factors; the 36-item Short Form Health Survey questionnaire (SF-36); and the Hospital Anxiety and Depression Scale (HADS) to assess depression and anxiety. Data analysis was performed using SPSS Statistics v. 13.00 (IBM Corp., Armonk, NY). Results Of the patients evaluated in all areas of QoL, males demonstrated higher scores compared to females. A statistically significant difference was found when assessing the domains of physical activity, social function, pain, and physical and mental health QoL. Conclusions Based on our findings, the majority of ICD patients can achieve their desired QoL and psychosocial outcomes. Our results show that patients with ICDs have the potential to return to a normal life. Depression and anxiety manifested more commonly in respondents with a disease duration of up to five years.

Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model.

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC0 - 24 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.