HLA-E and NKG2A Mediate Resistance to M. bovis BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC. IFN-γ enhances HLA-E and PD-L1 expression in recurrent tumors, with an enrichment of intra-tumoral NKG2A-expressing NK and CD8 T cells. CXCL9+ macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7+ HLA-EHIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

The effects of incremental maxillomandibular advancement surgery on airway morphology: a cadaveric study.

Evidence demonstrates efficacy of maxillomandibular advancement (MMA) treatment of obstructive sleep apnea (OSA) and airway expansion. Patient studies are limited to pre/post-surgery comparisons. This cadaveric study evaluated intra-individual relationships between magnitudes of MMA advancement and airway changes. MMA with distraction osteogenesis devices and incremental advancement of the maxillomandibular complex, was performed on cadavers (n = 5). Computed tomography at each 2-mm advancement was used to measure volume and dimension of the oropharyngeal airway. Three-dimensional shape analysis visualized magnitudes and locations of changes. Incremental advancements caused volume, anteroposterior, and lateral dimensions to increase progressively, while length decreased. Changes were significant at lower advancements. Comparisons of MMA indicate alterations in airway volume from 4 to 6 mm and 6 to 8 mm were relatively greater than the changes from 8 to 10 mm (P = 0.044, P = 0.028, respectively), 10 to 12 mm (P = 0.024, P = 0.023), and 12 to 14 mm (P = 0.021, P = 0.019). These results may expand MMA application suggesting 6-8 mm advancements provide substantial increases in airway volume. MMA may be an OSA treatment option when large advancements are not possible. Lower magnitudes of advancement decrease risks of unfavorable facial esthetics from excess protrusion.

Breast/chest imaging findings and clinical considerations in transgender patients.

The transgender population, a historically marginalized group, is growing in size, visibility, and cultural acceptance. However, lack of provider knowledge contributes to the disparities and discrimination that this group continues to face in the healthcare setting. Special considerations for transgender individuals undergoing imaging for breast/chest care can improve health equity, including appropriate evidence-based screening, tailored protocols, and inclusive radiology facilities. This article will focus on the imaging findings that can be seen in transgender patients during the course of gender-affirming care, which may involve hormone therapy and/or surgery. Relevant examples of benign and malignant pathologies that can be seen in transgender patients will be highlighted, and their imaging on mammogram, ultrasound, and magnetic resonance imaging (MRI) will be reviewed.

Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase I multicenter study of BMS-986365 in patients with progressive mCRPC. PATIENTS AND METHODS: Patients who progressed on androgen deprivation therapy, one or more ARPIs, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (part A) and expansion (part B) of BMS-986365 up to 900 mg twice daily. Primary objectives were safety and tolerability, and to define maximum tolerated dose and/or recommended phase II dose. Key secondary endpoints included decline in prostate-specific antigen ≥50% (PSA50) and radiographic progression-free survival (rPFS). RESULTS: Parts A and B enrolled 27 and 68 patients, respectively. In part B, the median number of prior therapies was 4 (range 2-11). The most common treatment-related adverse events were asymptomatic prolonged corrected QT interval (47%) and bradycardia (34%). Part A maximum tolerated dose was not reached and recommended phase II dose selection is ongoing. Across part B three highest doses (400-900 mg twice daily, n = 60), PSA50 was 32% (n = 19), including 50% (n = 10/20) at 900 mg; median rPFS (95% confidence interval) was 6.3 months (5.3-12.6 months), including 8.3 months (3.8-16.6 months) at 900 mg; and rPFS was longer in patients without versus with prior chemotherapy: 16.5 months (5.5 months-not evaluable) versus 5.5 months (2.7-8.3 months), respectively. Efficacy was observed in patients with mCRPC with AR ligand binding domain (LBD) WT or with AR LBD mutations. CONCLUSIONS: BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with mCRPC with potentially higher benefit in chemotherapy-naive patients. These data show the potential of BMS-986365 to overcome resistance to current ARPIs, regardless of AR LBD mutation status.

The evolution of democratic peace in animal societies.

A major goal in evolutionary biology is to elucidate common principles that drive human and other animal societies to adopt either a warlike or peaceful nature. One proposed explanation for the variation in aggression between human societies is the democratic peace hypothesis. According to this theory, autocracies are more warlike than democracies because autocratic leaders can pursue fights for private gain. However, autocratic and democratic decision-making processes are not unique to humans and are widely observed across a diverse range of non-human animal societies. We use evolutionary game theory to evaluate whether the logic of democratic peace may apply across taxa; specifically adapting the classic Hawk-Dove model to consider conflict decisions made by groups rather than individuals. We find support for the democratic peace hypothesis without mechanisms involving complex human institutions and discuss how these findings might be relevant to non-human animal societies. We suggest that the degree to which collective decisions are shared may explain variation in the intensity of intergroup conflict in nature.

Oral Candida albicans strain diversity and maintenance in HIV positive women in South Africa.

OBJECTIVE: This study investigated C. albicans strain diversity and maintenance in the oral cavity of HIV positive women over a 6 month period. STUDY DESIGN: C. albicans strains were isolated from 17 HIV positive women at Charlotte Maxeke Academic Hospital, Johannesburg at 3 intervals over a 6 month period. Strains were genotyped using ABC and Multilocus Sequence Typing (MLST) techniques. In the MLST technique, for each strain, a Diploid Sequence Type (DST) number was obtained. Using cluster analysis, an Unweighted Pair Group Method with Arithmetic Mean (UPGMA) dendrogram and a matrix of strain similarities were generated. Strains were also compared to the previous South African isolates documented in the MLST database. RESULTS: Ninety four percent of women carried the same ABC genotype for 6 months. MLST technique, showed that ten women (58.8%) carried the same DST at 2 visits, while seven (41.2%) carried different DST at all visits. Further analysis showed that 64.7% of women were recolonised with different strains and 35.3% carried the same strains of C. albicans with heterozygosity. A total of 40 diploid sequence types were identified of which 27 DSTs were unique to this study group that were added to the MLST database. Most of the strains were closely related to previously isolated strains from South Africa. CONCLUSION: Recolonization of the oral cavity with different strains and microevolution of the original strains of C. albicans can occur, which can be a potential problem for HIV patients, in whom highly virulent and drug resistant strains can emerge.

A phase I dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results.

BACKGROUND: SERENA-1 (NCT03616587) is a phase I, multi-part, open-label study of camizestrant in pre- and post-menopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Parts A and B aim to determine the safety and tolerability of camizestrant monotherapy and define doses for clinical evaluation. PATIENTS AND METHODS: Women aged ≥18 years with metastatic or recurrent ER+, HER2- breast cancer, refractory (or intolerant) to therapy, were assigned 25 mg up to 450 mg once daily (QD; escalation) or 75, 150, or 300 mg QD (expansion). Safety and tolerability, antitumor efficacy, pharmacokinetics, and impact on mutations in the estrogen receptor gene (ESR1m) circulating tumor (ct)DNA levels were assessed. RESULTS: By 9 March 2021, 108 patients received camizestrant monotherapy at 25-450 mg doses. Of these, 93 (86.1%) experienced treatment-related adverse events (TRAEs), 82.4% of which were grade 1 or 2. The most common TRAEs were visual effects (56%), (sinus) bradycardia (44%), fatigue (26%), and nausea (15%). There were no TRAEs grade 3 or higher, or treatment-related serious adverse events at doses ≤150 mg. Median tmax was achieved ∼2-4 h post-dose at all doses investigated, with an estimated half-life of 20-23 h. Efficacy was observed at all doses investigated, including in patients with prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and/or fulvestrant treatment, with and without baseline ESR1 mutations, and with visceral disease, including liver metastases. CONCLUSIONS: Camizestrant is a next-generation oral selective ER antagonist and degrader (SERD) and pure ER antagonist with a tolerable safety profile. The pharmacokinetics profile supports once-daily dosing, with evidence of pharmacodynamic and clinical efficacy in heavily pre-treated patients, regardless of ESR1m. This study established 75-, 150-, and 300-mg QD doses for phase II testing (SERENA-2, NCT04214288 and SERENA-3, NCT04588298).

Stability Analysis and Identification of Superior Hybrids in Pearl Millet [Pennisetum glaucum (L.) R. Br.] Using the Multi Trait Stability Index.

Pearl millet stands as an important staple food and feed for arid and semi-arid regions of India and South Africa. It is also a quick supplier of important micronutrients like Fe and Zn via grain to combat micronutrient deficiencies among people in developing countries. India has notably spearheaded advancements in pearl millet production and productivity through the All India Coordinated Pearl Millet Improvement Project. There were 21 hybrids evaluated over arid and semi-arid ecologies of the western and southern regions of India. AMMI and GGE biplot models were adopted to recommend a specific hybrid for the particular locality. A joint analysis of variation indicated a significant genotype-environment interaction for most of the agronomical and grain micronutrient parameters. Pearson's correlation values dissected the significant and positive correlation among agronomic traits and the negative correlation with grain micronutrient traits. GGE biplot analysis recommended the SHT 106 as a dual-purpose hybrid and SHT 115 as a biofortified hybrid for the grain's Fe and Zn content. SHT 110 and SHT 108 were selected as stable and high grain yield-producing hybrids across all environments and specifically for E1, E2, and E4 as per the Which-Won-Where and What biplot. SHT 109 and SHT 103 hybrids were stable and high dry fodder yield-producing hybrids across all environments. In this study, the Multi-Trait Stability Index (MTSI) was employed to select the most stable and high-performing hybrids for all traits. It selected SHT 120, SHT 106, and SHT 104 for stability and great performance across all environments. These findings underscored the significance of tailored hybrid recommendations and the potential of pearl millet in addressing both food security and malnutrition challenges in various agro-ecological regions.

Improved patient safety with a simplified operating room to pediatric intensive care unit handover tool (PATHQS).

Introduction: Patient handover is a crucial transition requiring a high level of coordination and communication. In the BC Children's Hospital (BCCH) pediatric intensive care unit (PICU), 10 adverse events stemming from issues that should have been addressed at the operating room (OR) to PICU handover were reported into the patient safety learning system (PSLS) within 1 year. We aimed to undertake a quality improvement project to increase adherence to a standardized OR to PICU handover process to 100% within a 6-month time frame. In doing so, the secondary aim was to reduce adverse events by 50% within the same 6-month period. Methods: The model for improvement and a Plan, Do, Study, Act method of quality improvement was used in this project. The adverse events were reviewed to identify root causes. The findings were reviewed by a multidisciplinary inter-departmental group comprised of members from surgery, anesthesia, and intensive care. Issues were batched into themes to address the most problematic parts of handover that were contributing to risk. Intervention: A bedside education campaign was initiated to familiarize the team with an existing handover standard. The project team then formulated a new simplified visual handover tool with the mnemonic "PATHQS" where each letter denoted a step addressing a theme that had been noted in the pre-intervention work as contributing to adverse events. Results: Adherence to standardized handover at 6 months improved from 69% to 92%. This improvement was sustained at 12 months and 3 years after the introduction of PATHQS. In addition, there were zero PSLS events relating to handover at 6 and 12 months, with only one filed by 36 months. Notably, staff self-reporting of safety concerns during handover reduced from 69% to 13% at 6 months and 0% at 3 years. The PATHQS tool created in this work also spread to six other units within the hospital as well as to one adult teaching hospital. Conclusion: A simplified handover tool built collaboratively between departments can improve the quality and adherence of OR to PICU handover and improve patient safety. Simplification makes it adaptable and applicable in many different healthcare settings.

Development and validation of a novel craniofacial statistical shape model for the virtual reconstruction of bilateral maxillary defects.

Bilateral maxillary defects are a challenge for fibula free flap reconstruction (FFFR) surgery due to limitations in virtual surgical planning (VSP) workflows. While meshes of unilateral defects can be mirrored to virtually reconstruct missing anatomy, Brown class c and d defects lack a contralateral reference and associated anatomical landmarks. This often results in poor placement of osteotomized fibula segments. This study was performed to improve the VSP workflow for FFFR using statistical shape modeling (SSM) - a form of unsupervised machine learning - to virtually reconstruct premorbid anatomy in an automated, reproducible, and patient-specific manner. A training set of 112 computed tomography scans was sourced from an imaging database by stratified random sampling. The craniofacial skeletons were segmented, aligned, and processed via principal component analysis. Reconstruction performance was validated on a set of 45 unseen skulls containing various digitally generated defects (Brown class IIa-d). Validation metrics demonstrated promising accuracy: mean 95th percentile Hausdorff distance of 5.47 ± 2.39 mm, mean volumetric Dice coefficient of 48.8 ± 14.5%, compactness of 7.28 × 105 mm2, specificity of 1.18 mm, and generality of 8.12 × 10-6 mm. SSM-guided VSP will allow surgeons to create patient-centric treatment plans, increasing FFFR accuracy, reducing complications, and improving postoperative outcomes.

Emergence and control of an outbreak of PVL-positive MRSA in a UK-based maternity setting.

This paper aims to describe the investigation and control of an outbreak of USA300 ST8 Panton-Valentine leucocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA), confirmed by whole genome sequencing (WGS), within a maternity and neonatal setting in the UK. The identification of two linked PVL-MRSA cases led to an outbreak investigation. A lookback exercise conducted using the infection control surveillance database, typing of saved MRSA isolates, enhanced patient screening, and staff screening were used to identify further cases. Environmental screening was also performed. Genetic relatedness between isolates was assessed by WGS. During the outbreak, 18 cases were identified between 11th July 2021 and 22nd December 2022: 10 cases were infections and eight cases were colonizations. A healthcare worker (HCW) tested positive for colonization with the same strain, and environmental swabbing identified contaminated information technology equipment in the hospital. The outbreak was brought to an end by exclusion of the colonized HCW from work, and infection prevention and control measures. Since the end of the outbreak, cases of PVL-MRSA with similar molecular profiles have been found in the community. It is likely that the HCW played a role in the transmission of PVL-MRSA. Their exclusion from work and decolonization were key to preventing further cases. WGS was valuable in identifying and linking cases. The identification of community cases of PVL-MRSA with similar molecular profiles confirms transmission of the organism outside of healthcare settings.

Multiparametric MRI and T2/FLAIR mismatch complements the World Health Organization 2021 classification for the diagnosis of IDH-mutant 1p/19q non-co-deleted/ATRX-mutant astrocytoma.

AIM: To investigate whether T2-weighted imaging-fluid-attenuated inversion recovery (T2/FLAIR) mismatch, T2∗ dynamic susceptibility contrast (DSC) perfusion, and magnetic resonance spectroscopy (MRS) correlated with the histological diagnosis and grading of IDH (isocitrate dehydrogenase)-mutant, 1p/19q non-co-deleted/ATRX (alpha-thalassemia mental retardation X-linked)-mutant astrocytoma. MATERIALS: Imaging of 101 IDH-mutant diffuse glioma cases of histological grades 2-3 (2019-2021) were analysed retrospectively by two neuroradiologists blinded to the molecular diagnosis. T2/FLAIR mismatch sign is used for radio-phenotyping, and pre-biopsy multiparametric MRI images were assessed for grading purposes. Cut-off values pre-determined for radiologically high-grade lesions were relative cerebral blood volume (rCBV) ≥2, choline/creatine ratio (Cho/Cr) ≥1.5 (30 ms echo time [TE]), Cho/Cr ≥1.8 (135 ms TE). RESULTS: Sixteen of the 101 cases showed T2/FLAIR mismatch, all of which were histogenetically confirmed IDH-mutant 1p/19q non-co-deleted/ATRX mutant astrocytomas; 50% were grade 3 (8/16) and 50% grade 2 (8/16). None showed contrast enhancement. Nine of the 16 had adequate multiparametric MRI for analysis. Any positive value by combining rCBV ≥2 with Cho/Cr ≥1.5 (30 ms TE) or Cho/Cr ≥1.8 (135 ms TE) predicted grade 3 histology with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%. CONCLUSION: The T2/FLAIR mismatch sign detected diffuse astrocytomas with 100% specificity. When combined with high Cho/Cr and raised rCBV, this predicted histological grading with high accuracy. The future direction for imaging should explore a similar integrated layered approach of 2021 classification of central nervous system (CNS) tumours combining radio-phenotyping and grading from structural and multiparametric imaging.

Asteroid impact: the potential of astrocytes to modulate human neural networks within organoids.

Astrocytes are a vital cellular component of the central nervous system that impact neuronal function in both healthy and pathological states. This includes intercellular signals to neurons and non-neuronal cells during development, maturation, and aging that can modulate neural network formation, plasticity, and maintenance. Recently, human pluripotent stem cell-derived neural aggregate cultures, known as neurospheres or organoids, have emerged as improved experimental platforms for basic and pre-clinical neuroscience compared to traditional approaches. Here, we summarize the potential capability of using organoids to further understand the mechanistic role of astrocytes upon neural networks, including the production of extracellular matrix components and reactive signaling cues. Additionally, we discuss the application of organoid models to investigate the astrocyte-dependent aspects of neuropathological diseases and to test astrocyte-inspired technologies. We examine the shortcomings of organoid-based experimental platforms and plausible improvements made possible by cutting-edge neuroengineering technologies. These advancements are expected to enable the development of improved diagnostic strategies and high-throughput translational applications regarding neuroregeneration.

AN EVALUATION OF ANTIBIOTIC PRESCRIPTION PRACTICES: PERSPECTIVES OF VETERINARY TRAINEES AND PRACTICING VETERINARIANS.

Antibiotic resistance is a major worldwide problem that has an impact on the well-being of humans as well as animals. Antibiotic resistance is caused by the misuse and excessive use of antibiotics. The key to reducing this issue lies in educating veterinary medical learners on the proper and accountable utilization of antibiotics for the care of animals. Objective - using awareness-raising and instruction as the foundation, this research of Indian veterinary learners can help resolve the issue of antibiotic resistance throughout the care of animals. The questionnaire survey was taken between June and July 2022 and it was aimed at learners registered in veterinary medical studies at academic and research institutions in India. The study included 500 pupils overall. The purpose of the survey was to gather information about students' knowledge of antibiotics, including antibiotic resistance, as well as their feelings on the consequences of antibiotic resistance on the globe at large and their acquaintance with the one health ideology. According to this study's findings, 83.3 percent of respondents thought antibiotic resistance was a serious problem. 57.92 percent of respondents understood the issue's worldwide consequences and its one health ideology. The study emphasizes the significance of expanding the veterinary educational program to include thorough instruction on prudent antibiotic usage and the concepts of one health.

UNDERSTANDING THE VITAL DETERMINANTS SHAPING LEARNERS' PHYSICAL ACTIVITYAND PSYCHOEMOTIONAL WELLBEING IN THE COVID-19 PERIOD.

The Corona Virus (COV-19) epidemic significantly affected the educational environment, requiring a quick transition to distance and blended learning methods. This extraordinary disruption had an incredible impact on pupil's levels of physical activity (PA), psycho-emotional health (PEH) and engagement with academic material. The research aims to examine the vital determinants that influenced various areas of learners' lives during CoV-19. The purpose of this 600-person study was to collect data on the subjects' overall health and PA levels for the CoV-19 pandemic. The SPSS application was used to process the questionnaire's collected data. The information given reveals the respondents' degree of PA throughout the quarantine. According to the breakdown, 15% indicated low levels of PA, 39% reported medium levels and 46% reported high levels. The data show that, despite the respondents' different levels of PA, little PA predominated for most of them. The limitations of distance learning throughout quarantine and the prevalent recommendation of leaving residence for necessary reasons were blamed for this tendency. There were fewer prospects for higher-intensity PA due to these circumstances.

COVID-19 SAFETY MEASURES AND THEIR EFFECTS ON GAMBLING HABITS: AN INVESTIGATIVE STUDY.

This study looked at the way COVID-19 was starting to affect gambling during first six weeks of emergency actions. The following factors were evaluated: the economic effect of COVID-19 on internet gambling, according to COVID-19, psychological issues, addiction to drugs, and risky gambling habits and intentions. Online survey with cross-sectional data of 2015 gamblers was conducted, with a subsample of 1048 people who gambled online (age 18 and older). Numerous metrics of correlation and probability ratio analyses were performed. The Issue of Gambling Intensity Index's extremely dangerous gamblers and those who have gambled online are more likely to engage in gambling online, according to the outcomes, even though there was an obvious transition toward physical gaming. The most predicted indicators for high-risk gamblers on the internet were moderate to severe depression and anxiety, reduced work weeks, convincing themselves to gamble by COVID-19, gambling under the effects of alcohol or cannabis, and dangerous gambling motivations related to psychological disorders, such as gambling to relieve anxiety and depressive disorders, chasing gambling damages, and trying to make money from gambling. This research has validated numerous risk connections associated with gambling risk, psychological issues, and substance use reported in previous studies on the worldwide recession and upcoming COVID-19-related investigations. In contrast to many other inquiries, the current research considers each component comprehensively. It offers more information on the risk factors associated with online gambling throughout the epidemic.

AN INCREASED RISK OF HORMONAL DISORDERS, PRIMARILY DIABETES, IN INDIVIDUALS WITH Β -THALASSEMIA MAJOR: A RETROSPECTIVE ANALYSIS.

ß-Thalassemia major is an inherited blood condition marked by a serious anemia and a lifetime need for blood transfusions. The effects of ß-thalassemia major on endocrine health, notably the risk of diabetes, remain largely unstudied, despite the fact that its haematological components are established. The purpose of this systematic analysis was to examine the incidence of reduced metabolism of glucose in ß--thalassemia major. The articles were under the inclusion requirements, after which the data was retrieved. The main outcome was determined to be every prevalence (P) of DM (diabetes mellitus) in ß-thalassemia major. In order to examine the percentage of aberrant glucose metabolism (GM) with individuals among ß-thalassemia major, the P with the 95% CI (Confidence Interval) was utilized. In this retrospective investigation, we looked at a cohort of people with ß-thalassemia major diagnoses to determine the incidence and risk of hormonal diseases, particularly diabetes. A specialist thalassemia facility treated 315 individuals with ß-thalassemia major, and their medical records were examined. Age, gender, age at which a main diagnosis of ß-thalassemia was made, the length of transfusion treatment, and concomitant diseases were gathered as part of the demographic and clinical data. Our research, which included 17 studies and 1500 cases altogether, showed that with ß -thalassemia major had a considerably greater frequency of diabetes than people in general. With a mean beginning age of 30 years, diabetes was identified in 28% of the research cohort's participants. The combined meta-analysis showed that each year had a rather stable level of DM P in ß-thalassemia major. In people with major ß-thalassemia, the P of impaired fasting glucose (IFG), DM, and impaired glucose tolerance (IGT) was 17.22% (95% CI: 8.44%-26.02%), (6.57 (95% CI: 5.31%- 7.79%) and 12.47 % (95% CI: 5.97%-18.95%), respectively. Our research suggests that people with ß-thalassemia major have a high chance of acquiring diabetes, particularly if they get extended transfusion treatment. For prompt diagnosis and care, early detection of diabetes and other hormonal problems in this group is crucial. In ß-thalassemia major, there is a high frequency of endocrine problems, including improper GM. To stop growth and endocrine issues, treatment and preventative measures can be required.

Prevalence of chronic non-cancer pain among military veterans: a systematic review and meta-analysis of observational studies.

INTRODUCTION: Chronic non-cancer pain is common among military veterans; however, the prevalence is uncertain. This information gap complicates policy decisions and resource planning to ensure veterans have access to healthcare services that align with their needs. METHODS: Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, we searched MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science from inception to 9 February 2023 for observational studies reporting the prevalence of chronic non-cancer pain among military veterans. We performed random-effects meta-analysis to pool pain prevalence data across studies and used the Grading of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence. RESULTS: Forty-two studies that included 14 305 129 veterans were eligible for review, of which 28 studies (n=5 011 634) contributed to our meta-analysis. Most studies (90%; 38 of 42) enrolled US veterans, the median of the mean age among study participants was 55 years (IQR 45-62) and 85% were male. The pooled prevalence of chronic non-cancer pain was 45%; however, we found evidence of a credible subgroup effect based on representativeness of the study population. Moderate certainty evidence found the prevalence of chronic pain among studies enrolling military veterans from the general population was 30% (95% CI 23% to 37%) compared with 51% (95% CI 38% to 64%) among military veterans sampled from populations with high rates of conditions associated with chronic pain (p=0.005). CONCLUSION: We found moderate certainty evidence that 3 in every 10 military veterans from the general population live with chronic non-cancer pain. These findings underscore the importance of ensuring access to evidence-based care for chronic pain for veterans, and the need for prevention and early management to reduce transition from acute to chronic pain. Further research, employing a standardised assessment of chronic pain, is needed to disaggregate meaningful subgroups; for example, the proportion of veterans living with moderate to severe pain compared with mild pain.

UNDERSTANDING THE LONG-TERM INTERPLAY BETWEEN GLUCOCORTICOIDS, PARATHYROID HORMONE LEVELS, AND OSTEOPOROSIS IN PATIENTS.

Drugs called glucocorticoids (GC) are often prescribed for both inpatient and outpatient settings. They are often used to treat a number of disorders due to their anti-inflammatory activity. Long-term use of GCs, especially long-term high-dose administrations, may result in a variety of negative effects. In Hilla City, Babylon Governorate of Iraq, Merjan Teaching Hospital, Al-Hilla Teaching Hospital's Joint Enology Clinic, and Al-Imam Al-Sadiq Hospital, were the sites of this case-control research, which was carried out. There were 100 total participants in this trial, of whom 50 were patients with osteoporosis (OP). The ages of the patients and the control collection were. They were chosen since their gender and ages matched. The findings show extensively senior level of parathyroid hormone (PTH) in OP patients when compared to the control group, whereas calcium (Ca) level into the patient group significantly lowered during association toward the manage set. In summary, there is a positive correlation between PTH and the condition of bone mineralization. In those who use GCs for a long time, PTH may be used as a prognostic marker to predict when bone mineral abnormalities would develop.