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Melanin, particularly eumelanin, is commonly viewed as an efficient antioxidant and photoprotective pigment. Nonetheless, the ability of melanin to photogenerate reactive oxygen species and sensitize the formation of cyclobutane pyrimidine dimers may contribute to melanin‐dependent phototoxicity. The phototoxic potential of melanin depends on a variety of factors, including molecular composition, redox state, and degree of aggregation. Using complementary spectroscopic and analytical methods we analyzed the physicochemical properties of Dopa‐melanin, a synthetic model of eumelanin, subjected to oxidative degradation induced by aerobic photolysis or exposure to 0.1 M hydrogen peroxide. Both modes of oxidative degradation were accompanied by dose‐dependent bleaching of melanin and irreversible modifications of its paramagnetic, ion‐ and electron‐exchange and antioxidant properties. Bleached melanin exhibited enhanced efficiency to photogenerate singlet oxygen in both UVA and short‐wavelength visible light. Although chemical changes of melanin subunits, including a relative increase of DHICA content and disruption of melanin polymer induced by oxidative degradation were considered, these two mechanisms may not be sufficient for a satisfactory explanation of the elevated photosensitizing ability of the bleached eumelanin. This study points out possible adverse changes in the photoprotective and antioxidant properties of eumelanin that could occur in pigmented tissues after exposure to high doses of intense solar radiation. [ABSTRACT FROM AUTHOR]

AIM To assess the association of Lactate, Lactate Albumin Ratio, Procalcitonin and Immature Platelet Fraction in comparison to SOFA Score on admission as marker of severity in sepsis patients OBJECTIVES • To assess Lactate / Albumin Ratio (LAR) in patients with sepsis. • To assess Lactate value in patients with sepsis . • To assess Procalcitonin (PCT) value in patients with sepsis. • To assess Immature Platelet Function (IPF) value in patients with sepsis. • To compare Lactate, LAR, PCT and IPF with SOFA score on admission in patients with sepsis for prognostication MATERIAL AND METHODS • Hospital based Observational Cross-Sectional Study was conducted at Mahatma Gandhi Hospital, Jaipur between September 2022 to December 2023. Data of 180 patients was collected according to inclusion criteria. Sepsis biomarkers that is Lactate, LAR, IPF, PCT were calculated and were compared to SOFA score at the time of admission for the purpose of prognostication. RESULT These intra-group analyses underscore the nuanced interactions between biomarkers and organ dysfunction severity as assessed by SOFA scores in sepsis. While Procalcitonin demonstrated significant associations, highlighting their clinical relevance in stratifying disease severity, Lactate, Lacto-albumin ratio and IPF showed more variable associations. CONCLUSION In this study all four markers positively correlated with SOFA score, that is the level of markers increased along with severity of sepsis. But our study particularly identifies significant associations: SOFA scores correlate significantly with procalcitonin. The biomarkers of sepsis used in our study that is Lactate, Lactate Albumin Ratio (LAR), Immature Platelet Fraction (IPF), Procalcitonin (PCT) can be used to enhance early risk stratification and guide more tailored therapeutic interventions for septic patients. [ABSTRACT FROM AUTHOR]

Background:- Stroke is a leading cause of morbidity and disability in Asian population. Changes in the HbA1c and Uric acid levels have been suggested as a risk factor for developing ischemic stroke. The present study was designed to evaluate the HbA1c and Uric acid levels in a patient diagnosed with ischemic stroke and correlating it’s severity with the National Institute of Health Stroke Scale (NIHSS) and prediction of outcome based on Modified Rankin Scale (mRS) scoring system after 28 days from day of admission. Material methods:- A Hospital based Prospective Observational study included 150 Patients of Acute ischemic stroke visiting OPD and IPD of Medicine department of MGMC&H Jaipur. We estimated HbA1c and uric acid levels of these patient’s and compared them with severity of stroke according to NIHSS scale and correlated the outcome based on Modified Rankin Scale (mRS) scoring system after 28 days from day of admission. Results:- Increased HbA1c and Uric acid levels positively and significantly (p <0.001) correlated with NIHSS scale. Increased HbA1c and Uric acid levels positively and significantly (p <0.001) correlated with mRS scale. Conclusion:- It could be concluded that higher HbA1c and uric acid levels can be considered as a risk factor for ischemic cerebral events and higher level is associated with the more severe stroke and poor outcome. [ABSTRACT FROM AUTHOR]

Background- Sepsis is a severe, life-threatening condition resulting from an abnormal and uncontrolled immune response to infection, posing a significant global health challenge. Blood coagulation disorders are significant complications in sepsis, often exacerbating the severity of the condition. The APACHE II (Acute Physiology and Chronic Health Evaluation II) score is a widely used severity-of-disease classification system that provides valuable prognostic information in critically ill patients. This study aims to investigate the relationship between various blood coagulation parameters and the severity of sepsis as assessed by the APACHE II score. Materials And Methods- A descriptive cross-sectional hospital-based study was conducted in the Department of General Medicine at Mahatma Gandhi Medical College & Hospital, Jaipur, on patients admitted to the ICU diagnosed with sepsis according to Sepsis-3 criteria. Blood coagulation parameters, including platelet count, PT, aPTT, D-dimer, and fibrinogen levels, were monitored and compared to assess the severity of sepsis using the APACHE II score. Results- The study included 168 sepsis patients aged 18 to 65 years. The mean APACHE II score was 29.08, with a significant correlation between age and APACHE II scores (p<0.001). The study found 68.5% of patients in a hypo-coagulation state and 31.5% in a hyper-coagulation state. Significant correlations were observed between APACHE II scores and PT, aPTT, D-dimer, and platelet count. Conclusions- The study highlights the critical role of blood coagulation disorders in the pathophysiology of sepsis and their correlation with disease severity as assessed by the APACHE II score. Routine monitoring of coagulation parameters in sepsis patients is essential, and incorporating these parameters into the APACHE II scoring system could provide a more comprehensive assessment of sepsis severity, aiding in better prognostication and treatment planning. [ABSTRACT FROM AUTHOR]

Background: Social media (SM) has received considerable attention as a potential risk factor for adolescent suicide. Few empirical studies, however, have examined adolescents' daily negative and positive experiences on SM and its proximal impacts on suicidal ideation (SI), particularly using intensive monitoring designs. Method: Adolescents (N = 60; 14–17 years; 49% girls; 62% LGBTQ+) recruited using SM across the United States and participated in an 8‐week intensive monitoring protocol. Ecological momentary assessment (three brief surveys per day) asked about negative and positive SM experiences and SI (passive and active). Multilevel modelling was used to evaluate the within‐person relationships between daily SM experiences (e.g. individual fluctuations compared to a person's average) and SI, controlling for average levels of SM experiences, SM use screen time, and lifetime SI. Results: Significant within‐person effects of negative and positive SM experiences were associated with days when adolescents had SI. Specifically, on days when teens endorsed more frequent negative SM experiences than usual, they were more likely to report SI. However, more positive SM experiences than usual were associated with a lower likelihood of having SI. There were no significant effects of SM use ('screen time') on SI or on the reverse associations of SI on next‐day SM experiences. Conclusions: Results indicate that SM experiences may be dynamic and modifiable risk and protective factors for SI in adolescents, whereas there is no effect of SM screen time on SI. Our results highlight that targeting negative SM experiences and augmenting the positive experiences on SM may be critical targets to improve teens' mental health and prevent suicide, rather than focusing on limiting SM screen time. [ABSTRACT FROM AUTHOR]

Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary. [ABSTRACT FROM AUTHOR]

This paper presents a multifaceted assessment of inhibitors of anti-apoptotic proteins (IAPs) in the context of head and neck squamous cell carcinoma (HNSCC). The article discusses the results of in vitro, in vivo, and clinical studies, highlighting the significance of IAPs in the resistance of cancer cells to apoptosis, which is a key factor hindering effective treatment. The main apoptosis pathways, including the intrinsic and extrinsic pathways, and the role of IAPs in their regulation, are presented. The study's findings suggest that targeting IAPs with novel therapies may offer clinical benefits in the treatment of advanced HNSCC, especially in cases resistant to conventional treatment methods. These conclusions underscore the need for further research to develop more effective and safer therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Despite calls for regionalizing pancreatic cancer (PC) care to high-volume centers (HVCs), many patients with PC elect to receive therapy closer to their home or at multiple institutions. In the context of cross-institutional PC care, the challenges associated with coordinating care are poorly understood. Methods: In this qualitative study we conducted semi-structured interviews with oncology clinicians from a HVC (n = 9) and community-based hospitals (n = 11) to assess their perspectives related to coordinating the care of and treating PC patients across their respective institutions. Interviews were transcribed, coded, and analyzed using deductive and inductive approaches to identify themes related to cross-institutional coordination challenges and to note improvement opportunities. Results: Clinicians identified challenges associated with closed-loop communication due, in part, to not having access to a shared electronic health record. Challenges with patient co-management were attributed to patients receiving inconsistent recommendations from different clinicians. To address these challenges, participants suggested several improvement opportunities such as building rapport with clinicians across institutions and updating tumor board processes. The opportunity to update tumor board processes was reportedly multi-dimensional and could involve: (1) designating a tumor board coordinator; (2) documenting and disseminating tumor board recommendations; and (3) using teleconferencing to facilitate community-based clinician engagement during tumor board meetings. Conclusions: In light of communication barriers and challenges associated with patient co-management, enabling the development of relationships among PC clinicians and improving the practices of multidisciplinary tumor boards could potentially foster cross-institutional coordination. Research examining how multidisciplinary tumor board coordinators and teleconferencing platforms could enhance cross-institutional communication and thereby improve patient outcomes is warranted. [ABSTRACT FROM AUTHOR]

Background: An understanding of viral testing rates is crucial to accurately estimate the pathogen‐specific hospitalisation burden. We aimed to estimate the patterns of testing for respiratory syncytial virus (RSV), influenza virus, parainfluenza virus (PIV) and human metapneumovirus (hMPV) by geographical location, age and time in children <5 years old in Western Australia. Methods: We conducted a population‐based cohort study of children born between 1 January 2010 and 31 December 2021, utilising linked administrative data incorporating birth and death records, hospitalisations and respiratory viral surveillance testing records from state‐wide public pathology data. We examined within‐hospital testing rates using survival analysis techniques and identified independent predictors of testing using binary logistic regression. Results: Our dataset included 46,553 laboratory tests for RSV, influenza, PIV, or hMPV from 355,021 children (52.5% male). Testing rates declined in the metropolitan region over the study period (RSV testing in infants: from 242.11/1000 child‐years in 2012 to 155.47/1000 child‐years in 2018) and increased thereafter. Conversely, rates increased in non‐metropolitan areas (e.g., RSV in Goldfields: from 364.92 in 2012 to 504.37/1000 child‐years in 2021). The strongest predictors of testing were age <12 months (adjusted odds ratio [aOR] = 2.25, 95% CI 2.20–2.31), preterm birth (<32 weeks: aOR = 2.90, 95% CI 2.76–3.05) and remote residence (aOR = 0.77, 95% CI 0.73–0.81). Conclusion: These current testing rates highlight the potential underestimation of respiratory virus hospitalisations by routine surveillance and the need for estimation of the true burden of respiratory virus admissions. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising alternative treatment for localized lesions and infections, utilizing reactive oxygen species (ROS) generated by photosensitizers (PS) upon light activation. Singlet oxygen (1O2) is a key ROS responsible for photodynamic damage. However, the effectiveness of PS in biological systems may not correlate with the efficiency of singlet oxygen generation in homogeneous solutions. This study investigated singlet oxygen generation and its decay in various cellular microenvironments using liposome and ARPE-19 cell models. Rose Bengal (RB), methylene blue (MB), and protoporphyrin IX (PpIX) were employed as selected PS. Lifetimes of singlet oxygen generated by the selected photosensitizers in different cellular compartments varied, indicating different quenching rates with singlet oxygen. RB, located near cell membranes, exhibited the highest phototoxicity and lipid/protein peroxidation, followed by PpIX, while MB showed minimal cytotoxicity in similar conditions. Singlet oxygen decay lifetimes provide insights into PS localization and potential phototoxicity, highlighting the importance of the lipid microenvironment in PDT efficacy, providing useful screening method prior to in vivo applications. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO) is an enzyme that converts hypoxanthine into xanthine and xanthine into uric acid, which is then eliminated by the kidneys. Serum XO has been linked to diabetes, hypertension, liver dysfunction, and cardiovascular diseases. However, limited information exists on the relationship between serum XO activity and MetS. This study aimed to analyze the relationship between XO activity and metabolic syndrome (MetS) and its components in an adult population group in Bangladesh A total of 601 participants aged ≥18 years were included in the study. MetS was defined based on the criteria set by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Serum XO activity was measured using the enzyme-linked immunosorbent assay (ELISA), while other biochemical parameters were measured using colorimetric methods. The relationship between serum XO and MetS levels was determined through multivariate logistic regression analysis. Serum XO activity was found to be significantly higher in females (6.17 ± 3.77 U/L) as compared to males (4.00 ± 2.77 U/L) (p < 0.001). Furthermore, participants with MetS had significantly higher mean levels of serum XO (5.34 ± 3.39 U/L) than those without MetS (3.86 ± 2.90 U/L) (p < 0.001). The prevalence of MetS and its components, such as blood pressure and blood glucose increased across the XO quartiles (p < 0.001). Regression analysis indicated that XO activity was significantly and independently associated with the prevalence of MetS (at least p < 0.05 for all cases) and its components, including elevated blood pressure, high blood glucose, and low HDL-C (at least p < 0.05 for all cases). In conclusion, individuals with MetS had significantly higher XO levels than those without MetS. Serum XO activity showed an independent association with MetS and some of its components. Therefore, XO might serve as a useful marker of MetS. Prospective studies are needed to determine the underlying mechanisms linking XO and MetS. [ABSTRACT FROM AUTHOR]

Aims and objectives: A study was conducted at Department of General Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, India, to see prevalence of thyroid disorder in CKD patients. Material and methods: An Observational Cross-Sectional Study was conducted at Department of General Medicine, Mahatma Gandhi Medical College and Hospital form August 2022 to October 2023. Patients who were on conservative management fulfilling the criteria for chronic kidney disease admitted in Department of Medicine, Mahatma Gandhi Hospital, Jaipur Results: Euthyroid was present in 63% patients, Primary hypothyroidism was present in 11% patients and Subclinical hypothyroidism was present in 26% patients. CKD stage IV showed higher mean T3 value (0.94) as compared to CKD stage V (0.608). CKD stage V showed higher mean TSH value (6.69) as compared to CKD stage IV (4.21). CKD stage IV showed higher mean GFR value (18.17) as compared to CKD stage V (8.16). Mean eGFR value of euthyroid (9.76) was significantly higher than subclinical hypothyroidism (7.11) and primary hypothyroidism (6.25) among eGFR level. Primary hypothyroidism was present 87.5% in CKD stage V patients and Subclinical hypothyroidism was present 84.2%% in CKD stage V patients. Conclusion: The mean TSH value was greater in CKD stage V (6.69) than in CKD stage IV (4.21). The mean GFR value for CKD stage IV was greater than that of CKD stage V (8.16), at 18.17. Therefore, it is crucial to check for thyroid disorders in all patients with chronic renal disease, since they may negatively impact the prognosis of the illness as a whole. [ABSTRACT FROM AUTHOR]

Moving from an era of dam building to dam removal brings additional perspectives to indigenous water governance and hydrosocial relations in the Klamath River Basin (US). This collaborative research initiative with the Karuk Tribe builds greater understanding of the sociocultural impacts of Klamath dam removal and river restoration through Karuk knowledge. Addressing a knowledge gap around the social dimensions of dam removal, we held focus groups and interviews with Karuk cultural practitioners, tribal leaders, and tribal youth in the six-month period leading up to demolition. Extending beyond a focus on infrastructure removal or single-species restoration, we consider how Indigenous environmental relations and cosmologies are embedded in dam removal and river restoration. Specifically, Karuk knowledge shifts the significance of dam removal by elucidating deeply interconnected ecological, cultural, and ceremonial relations that are co-constituted with the Klamath watershed, thereby recasting dam removal as a holistic eco-cultural revitalization initiative. This reconfigures dam removal goals to include improving community health and well-being, enhancing spiritual elements of river restoration, responding to colonial legacies, and engaging tribal youth. In the Klamath case, restorative justice becomes possible through Karuk participation in river restoration to facilitate the revitalization of reciprocal relations held between Karuk people and the Klamath River—including Karuk eco-cultural and ceremonial practices for restoring balance in the world. [ABSTRACT FROM AUTHOR]

Purpose: Patients with Breast Cancer (BC) with Brain Metastasis (BCBM) have poor survival outcomes. We aimed to explore the clinico–pathologic and therapeutic factors predicting the survival in patients with de novo BCBM using the National Cancer Database (NCDB). Patients and methods: The NCDB was queried for patients with BC between 2010 and 2020. Survival analysis with Kaplan–Meier curves and log rank tests were used to find median overall survival (OS) in months (95% CI) across the different variables. A multivariate cox regression model was computed to identify significant predictors of survival. Results: Out of n = 2,610,598 patients, n = 9005 (0.34%) had de novo BCBM. A trend of decreasing OS was observed with increasing age, Charlson–Deyo score (CDS), and number of extracranial metastatic sites. The highest median OS was observed in the Triple Positive and the lowest OS in the Triple Negative subgroup. Based on treatment regimen, combination of systemic therapy and local therapy achieved the highest OS. A positive trend in OS was observed in the BC subgroup analysis with targeted therapy demonstrating a survival benefit when added to systemic therapy. The multivariate cox regression model showed that age, race, ethnicity, insurance, median income, facility type, CDS, BC subtype, metastatic location sites, and treatment combinations received were significantly associated with risk of death. Receiving only local treatment for BM without systemic therapy more than doubled the risk of death compared to combining it with systemic therapy. Conclusions: This analysis suggests that treatment of systemic disease is the major factor influencing survival in patients with BCBM. Moreover, targeted therapy with anti–HER2 increased survival when added to systemic therapy explaining the highest median OS noted in the Triple Positive subgroup. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes distress (DD) and diabetes burnout (DB) are recognized psychological phenomena in patients with T1DM (type 1 diabetes mellitus). Still, there is an urgent need to create professional psychological intervention procedures to provide patients with adequate care. Aim: The aim of the study was to assess the level of DD and DB in T1DM patients at baseline and after 5 of sessions psychological intervention in the group of participants who applied for help. Methods: 34 T1DM patients who requested psychological support (22 females, 12 males) and 30 patients in a control group (14 females, 16 males) participated in the study. At baseline clinical test results between groups were compared. Next, in the studied group measurements were repeated after a set of five psychological face-to-face individual interventions which lasted 30–60 min each. They were support sessions with elements of cognitive-behavioral interventions done by clinical psychologists. Session 1: introduction, interview and collection of test results; session 2–4: work on the indicated by the patient and test results most problematic aspect of diabetes, session 5: a summary and plan for further treatment if needed. The control group results were obtained only at baseline. Research tools: DDS; PAID, Diabetes Burnout test by Polonsky. Results: At the baseline, significant differences were observed between the studied group and control group: in DB/DD levels: DB (3.9 ± 1.7 vs 2.4 ± 1.6; p < 0.001); DDS (3.2 ± 1.0 vs 2.7 ± 1.0; p = 0.064); PAID (62.3 ± 14.1vs 34.4 ± 21.0; p < 0.001). There were also group differences in HbA1c levels (8.7 ± 2.4 vs 7.3 ± 1.5; p = 0.028). After psychological interventions, there was a significant improvement in DB (3.9 ± 1.7vs 2.9 ± 1.2; p < 0.001; DDS (3.2 ± 1 vs 3.0 ± 0.7; p = 0.03); PAID (62.3 ± 14.1 vs 51.8 ± 12.5; p < 0.001). Conclusions: DD and DB constitute a significant problem in the group of T1DM patients, but providing appropriate specialist care may help them accept diabetes and improve life satisfaction, as well as regain control over their diabetes management. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) affects a significant proportion of the global population, with many having moderate or severe forms of the disease. Home Sleep Apnea Testing (HSAT) has become the most common method of diagnosing OSA, replacing in-lab polysomnography. Polysmith software Version 11 by Nihon Kohden allows for the automatic scoring of respiratory events. This study aimed to assess the validity of this technology. Study Objectives: The objective was to assess the accuracy of the Polysmith Software Automatic Scoring Algorithm of HSATs in comparison to that of sleep technicians. Methods: One hundred twenty HSATs were scored by both sleep technicians and Polysmith software. The measured values were the respiratory event index (REI), apneic events, and hypopneic events. Agreement between the two methods was reached by utilizing the Kruskal–Wallis test, Pearson correlation coefficient, and Bland–Altman plot, as well as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: The correlation between the REI calculated by the software and technicians proved to be strong overall (r = 0.96, p < 0.0001). The mild OSA group had a moderate correlation (r = 0.45, p = 0.0129). The primary snoring, moderate OSA, and severe OSA groups showed stronger correlations (r = 0.69, p < 0.0001; r = 0.56, p = 0.012; r = 0.71, p < 0.0001). The analysis conducted across all groups demonstrated an average sensitivity of 81%, specificity of 94%, PPV of 82%, and NPV of 94%, with an overall accuracy of 81%. When combining the moderate and severe OSA groups into a single category, the sensitivity was 90%, specificity was 100%, PPV was 100%, and NPV was 91%. Conclusions: OSA can be reliably diagnosed from HSATs with the automated Polysmith software across all OSA disease severity groups, with higher levels of accuracy in moderate/severe OSA and lower levels of accuracy in mild OSA. [ABSTRACT FROM AUTHOR]

Background: Stem cell-derived extracellular vesicles (EVs) are an emerging class of therapeutics with excellent biocompatibility, bioactivity and pro-regenerative capacity. One of the potential targets for EV-based medicines are cardiovascular diseases (CVD). In this work we used EVs derived from human induced pluripotent stem cells (hiPSCs; hiPS-EVs) cultured under different oxygen concentrations (21, 5 and 3% O2) to dissect the molecular mechanisms responsible for cardioprotection. Methods: EVs were isolated by ultrafiltration combined with size exclusion chromatography (UF + SEC), followed by characterization by nanoparticle tracking analysis, atomic force microscopy (AFM) and Western blot methods. Liquid chromatography and tandem mass spectrometry coupled with bioinformatic analyses were used to identify differentially enriched proteins in various oxygen conditions. We directly compared the cardioprotective effects of these EVs in an oxygen-glucose deprivation/reoxygenation (OGD/R) model of cardiomyocyte (CM) injury. Using advanced molecular biology, fluorescence microscopy, atomic force spectroscopy and bioinformatics techniques, we investigated intracellular signaling pathways involved in the regulation of cell survival, apoptosis and antioxidant response. The direct effect of EVs on NRF2-regulated signaling was evaluated in CMs following NRF2 inhibition with ML385. Results: We demonstrate that hiPS-EVs derived from physiological hypoxia at 5% O2 (EV-H5) exert enhanced cytoprotective function towards damaged CMs compared to EVs derived from other tested oxygen conditions (normoxia; EV-N and hypoxia 3% O2; EV-H3). This resulted from higher phosphorylation rates of Akt kinase in the recipient cells after transfer, modulation of AMPK activity and reduced apoptosis. Furthermore, we provide direct evidence for improved calcium signaling and sustained contractility in CMs treated with EV-H5 using AFM measurements. Mechanistically, our mass spectrometry and bioinformatics analyses revealed differentially enriched proteins in EV-H5 associated with the antioxidant pathway regulated by NRF2. In this regard, EV-H5 increased the nuclear translocation of NRF2 protein and enhanced its transcription in CMs upon OGD/R. In contrast, inhibition of NRF2 with ML385 abolished the protective effect of EVs on CMs. Conclusions: In this work, we demonstrate a superior cardioprotective function of EV-H5 compared to EV-N and EV-H3. Such EVs were most effective in restoring redox balance in stressed CMs, preserving their contractile function and preventing cell death. Our data support the potential use of hiPS-EVs derived from physiological hypoxia, as cell-free therapeutics with regenerative properties for the treatment of cardiac diseases. [ABSTRACT FROM AUTHOR]

The ventriculoperitoneal shunt (VP shunt) is one of the most common neurosurgical procedures performed in daily practice. Various complications following a VP shunt are as follows: post-procedure shunt-related infections, shunt block, shunt displacement or exteriorisation and haemorrhage associated with it. Delayed intraventricular haemorrhage is a relatively uncommon complication following the aforementioned procedure. Here we present an atypical case of a 72-year-old male who presented with subarachnoid haemorrhage with hydrocephalus and underwent a VP shunt, following which the patient had early intraventricular haemorrhage (eIVH) with an unfortunate outcome. Here, we propose pathophysiology and risk factors for eIVH. [ABSTRACT FROM AUTHOR]

Continuous exposure of human skin to air pollution can result in a range of undesirable skin conditions. In our recent study, UV and visible light were found to increase cytotoxicity of fine particulate matter (PM2.5) against human keratinocytes. Since it is impossible to avoid exposure of human skin to PM2.5, effective strategies are needed to reduce their damaging effects. l‐ascorbic acid and resveratrol were tested as potential topical agents against pollution‐related skin impairment. Although these agents were previously found to ameliorate PM‐dependent damage, the effect of light and seasonal variation of particles were not previously studied. EPR spin‐trapping, DPPH assay, and singlet oxygen phosphorescence were used to determine the scavenging activities of the antioxidants. MTT, JC‐10 and iodometric assays were used to analyze the effect on PM2.5‐induced cytotoxicity, mitochondrial damage and oxidation of lipids. Live‐cell imaging was employed to examine wound‐healing properties of cells. Light‐induced, PM2.5‐mediated oxidative damage was examined by immunofluorescent staining. Both antioxidants effectively scavenged free radicals and singlet oxygen produced by PM2.5, reduced cell death and prevented oxidative damage to HaCaT cells. l‐ascorbic acid and resveratrol, especially when applied in combination, can protect HaCaT cells against the dark and light induced toxicity of PM2.5. [ABSTRACT FROM AUTHOR]

Purpose: Effective cancer care coordination (CCC) is an integral component of health care delivery and critical to achieving optimal oncologic outcomes. Neoadjuvant therapy (NT), the delivery of multimodality therapy prior to surgery, is inherently complex and multidisciplinary, but CCC during NT is poorly understood. The objective of this study was to characterize patient perceptions of CCC during NT using a mixed methods approach. Methods: This study is a cross-sectional analysis of patients with gastrointestinal cancers receiving NT who participated in a prospective longitudinal cohort study evaluating their real-time experience using a customized smartphone application. Patients completed the Cancer Care Coordination Questionnaire for Patients (CCCQ-P), a 20-item validated measure of care coordination quality, six weeks after initiating NT. Items were scored on a 5-point Likert scale, and subsections on communication (13 questions) and navigation (7 questions) were calculated with higher scores signifying better CCC. Univariate linear regression was used to calculate the impact of fragmented care and other factors on perceived CCC. Semi-structured interviews were conducted among a convenience sample of patients (n = 5); transcribed interviews were then coded using an inductive approach. Results: Among 82 participants, mean age was 61 years old, 68% were male, and mean number of comorbidities was 1.68. Overall (mean 76.6 out of 100), communication subsection (48.6 out of 65), and navigation subsection (28.0 out of 35) CCCQ-P scores suggested overall positive perceptions of care coordination. Qualitative analysis of patient interviews highlighted the need for coordination among physicians before communicating the plan to patients as well as the importance of providers communicating plans in verbal and written form. Conclusions: Successful completion of NT requires significant care coordination between patients and healthcare professionals. Yet, in this cross-sectional analysis of patients on a prospective cohort study, patient perceptions of CCC during NT were overall positive. Future research should focus on optimizing other aspects of care delivery in order to improve outcomes of NT. [ABSTRACT FROM AUTHOR]

A 49-year-old female patient presented at the hospital with a history of herpetic blisters, frequent episodes of vomiting and loose stools, bilateral upper and lower limb weakness, and diminishing sensorium. She was diagnosed with hyponatraemia and respiratory failure and later became unconscious with absent brainstem reflexes. The patient was initially treated for herpetic encephalitis, a chronic obstructive pulmonary disease with acute exacerbation, hyponatraemia and neuroparalytic snake bite. Further evaluation, however, identified the uncommon Guillain Barre syndrome presentation with overlap of Bickerstaff brainstem encephalitis. This is an uncommon disorder characterised by the involvement of higher mental functions, fixed dilated pupils, absent brainstem reflexes and quadriplegia that resembles a neuroparalytic snake bite and brain death. After receiving intravenous immunoglobulins for treatment, the patient completely recovered. [ABSTRACT FROM AUTHOR]

Digit ratio (2D:4D), as endocrine fingerprint, can indicate prenatal androgen exposure. It serves as an anatomical marker for various systemic diseases and a few studies relating it to oral health. The present study aims to evaluate the association between digit ratio and susceptibility to dental plaque formation. The study was conducted on young adults aged between 18 and 25 years. Digit ratio and reproductive hormones were measured; dental plaque score and gingival index (GI) were recorded. Data were analysed using the MedCalc. v.20. Male and female participants were categorized into two groups based on their digit ratios being either above or below the calculated average (0.99 for females, 0.98 for males). Those with a digit ratio below the average had a significantly higher mean dental plaque score (p < 0.0001) than those with ratios at or above the average. However, there was no significant difference in the GI between the two groups. Reproductive hormone profiles varied significantly between the higher and lower digit ratio groups for both sexes. Digit ratio may find potential to be used as an anatomical marker to identify the susceptibility to dental plaque build-up. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control. Methods: We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000–2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection. Results: The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants. Conclusions: The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV. [ABSTRACT FROM AUTHOR]

Background Providing efficient mechanical ventilation using artificial manual breathing unit is a tiring and laborious task for healthcare providers. The current pilot study was planned to assess the efficacy of an automated artificial mechanical breathing unit (respiration control [RC] device) in patients requiring mechanical ventilation in a tertiary care hospital in North India. RC device is an automated bag valve mask ventilator developed in collaboration with Gyrodrive Machineries (P) Ltd. India and Postgraduate Institute of Medical Education and Research, Chandigarh. Materials and Methods Ten adult patients from the emergency and trauma section requiring mechanical ventilation who were unable to obtain ventilators in the intensive care unit were enrolled in the study. The vital parameters of the patients and the respiratory parameters from arterial blood gas were recorded at given time periods. Results All 10 patients recruited in the study were ventilated using the RC device for at least 24 hours. The mean age of the patients was 32.3 ± 4.3 years. The mean Glasgow coma scale was 7.2 ± 2.0 (range: 3–10). The heart rate, systolic blood pressure, and diastolic blood pressure remained within normal limits. There were no episodes of desaturation in any of the patients. The patients' care provider rated their satisfaction with the device as excellent in two patients and good in eight patients. Conclusion RC device has shown a promising result in providing satisfactory care among trauma patients and may be used in providing routine mechanical ventilation among these patients. [ABSTRACT FROM AUTHOR]

Herbal supplements containing several types of plant sterols, vitamins, and minerals, are marketed for prostate health. In the majority of these supplements, the most abundant plant sterol is saw palmetto extract or its' principal component, beta-sitosterol. In terms of prostate health, previous work almost exclusively focused on the effects of beta-sitosterol on prostatic epithelium, with little attention paid to the effects on prostatic stroma. This omission is a concern, as the abnormal accumulation of collagen, or fibrosis, of the prostatic stroma has been identified as a factor contributing to lower urinary tract symptoms and dysfunction in aging men. To address whether beta-sitosterol may be promoting prostatic fibrosis, immortalized and primary prostate stromal fibroblasts were subjected to immunoblotting, immunofluorescence, qRT-PCR, ELISA, and image quantitation and analysis techniques to elucidate the effects of beta-sitosterol on cell viability and collagen expression and cellular localization. The results of these studies show that beta-sitosterol is nontoxic to prostatic fibroblasts and does not stimulate collagen production by these cells. However, beta-sitosterol alters collagen distribution and sequesters collagen within prostatic fibroblasts, likely in an age-dependent manner. This is a significant finding as prostate health supplements are used predominantly by middle aged and older men who may, then, be affected disproportionately by these effects. [ABSTRACT FROM AUTHOR]

Cleft lip and palate deformities substantially burden individuals and families, particularly in low‐income communities. However, a comprehensive understanding of the patterns and distribution of these deformities in Kenya remains limited. This retrospective cross‐sectional study analyzed 647 clinical records from the BelaRisu Foundation registry in Kenya, spanning 2018–2022. After meticulous record verification and data extraction, cleft pattern modeling was used to analyze each case. Data were imported to SPSS version 29.0 and descriptive statistics were calculated, which included means, ranges, frequencies, percentages, and standard deviations. Additionally, a comparative analysis between genders was conducted. The findings revealed a higher average age of presentation compared with previous studies in Kenya, along with a greater susceptibility of males to cleft lip and palate defects overall. Noteworthy disparities in case distribution across provinces were observed. Cleft lip emerged as the most observed primary defect, while palatal fistulae constituted the most frequent secondary defect. Interestingly, while some results aligned with global trends, others diverged significantly from the existing literature, warranting further exploration and investigation. These findings shed light on the unique patterns and distribution of cleft lip and palate deformities in Kenya, highlighting the need for targeted interventions and support systems. [ABSTRACT FROM AUTHOR]

Purpose: This review aimed to assess the measurement and reporting of time toxicity (i.e., time spent receiving care) within prospective oncologic studies. Methods: On July 23, 2023, PubMed, Scopus, and Embase were queried for prospective or randomized controlled trials (RCT) from 1984 to 2023 that reported time toxicity as a primary or secondary outcome for oncologic treatments or interventions. Secondary analyses of RCTs were included if they reported time toxicity. The included studies were then evaluated for how they reported and defined time toxicity. Results: The initial query identified 883 records, with 10 studies (3 RCTs, 2 prospective cohort studies, and 5 secondary analyses of RCTs) meeting the final inclusion criteria. Treatment interventions included surgery (n = 5), systemic therapies (n = 4), and specialized palliative care (n = 1). The metric “days alive and out of the hospital” was used by 80% (n = 4) of the surgical studies. Three of the surgical studies did not include time spent receiving ambulatory care within the calculation of time toxicity. “Time spent at home” was assessed by three studies (30%), each using different definitions. The five secondary analyses from RCTs used more comprehensive metrics that included time spent receiving both inpatient and ambulatory care. Conclusions: Time toxicity is infrequently reported within oncologic clinical trials, with no standardized definition, metric, or methodology. Further research is needed to identify best practices in the measurement and reporting of time toxicity to develop strategies that can be implemented to reduce its burden on patients seeking cancer care. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated changes in selected spatiotemporal and kinematic gait parameters and balance in girls with Adolescent idiopathic scoliosis (AIS) with and without the Chêneau brace. Methods: 15 subjects with scoliosis wearing the Chêneau brace and an equal comparative control group underwent objective gait analysis with the 3D BTS motion caption system. Balance assessment was done with the Kistler platform. The analysis was performed at comparison of gait and balance parameters in patients with scoliosis in two conditions: with and without the Chêneau brace during the study. Results: Statistically significant differences occurred in many spatiotemporal and kinematic parameters both for the AIS group with and without the Chêneau brace and in the AIS group with and without the Chêneau brace as compared to the control group. When comparing adolescents with AIS with and without the Chêneau brace, statistically significant differences were noted in the COP-X amplitude and in the path length in trials with closed eyes. Compared to the control group the following differences were statistically significant: the value of the COP-Y amplitude during the trial with closed eyes, both with and without the Chêneau brace, and the Equivalent area of the COP during the trial with closed eyes with the Chêneau brace. Conclusions: The Chêneau brace in patients with juvenile idiopathic scoliosis affects the level of selected balance and gait parameters. [ABSTRACT FROM AUTHOR]

Background: While surgery is generally necessary for most solid-organ cancers, curative-intent resection is occasionally aborted due to unanticipated unresectability or occult metastases. Following aborted cancer surgery (ACS), patients have unique and complex care needs and yet little is known about the optimal approach to their management. Objective: The aim of this study was to define the practice patterns and perspectives of an international cohort of cancer surgeons on the management of ACS. Methods: A validated survey assessing surgeon perspectives on patient care needs and management following ACS was developed. The survey was distributed electronically to members of the Society of Surgical Oncology (SSO). Results: Among 190 participating surgeons, mean age was 49 ± 11 years, 69% were male, 61% worked at an academic institution, and most had a clinical practice focused on liver/pancreas (30%), breast (23%), or melanoma/sarcoma cancers (20%). Participants estimated that ACS occurred in 7 ± 6% of their cancer operations, most often due to occult metastases (67%) or local unresectability (30%). Most surgeons felt (very) comfortable addressing their patients' surgical needs (92%) and cancer treatment-related questions (90%), but fewer expressed comfort addressing psychosocial needs (83%) or symptom-control needs (69%). While they perceived discussing next available therapies as the patients' most important priority after ACS, surgeons reported avoiding postoperative complications as their most important priority (p < 0.001). While 61% and 27% reported utilizing palliative care and psychosocial oncology, respectively, in these situations, 46% noted care coordination as a barrier to addressing patient care needs. Conclusions: Results from this SSO member survey suggest that ACS is relatively common and associated with unique patient care needs. Surgeons may feel less comfortable assessing psychosocial and symptom-control needs, highlighting the need for novel patient-centered approaches. [ABSTRACT FROM AUTHOR]

Background: Hospital based prospective cross sectional study conducted at a tertiary care center on Estimation of Serial QT on day of admission, day 3rd, day 5th and day 7th in ECG of patients admitted in critical care at tertiary care centre. Materials and Methods: An observational, cross-sectional with prospectively collected data, From January 2021-April 2022 in adult patients admitted to medical (M), surgical (S), and emergency (E) ICUs, and HDU in a Mahatma Gandhi Medical Hospital, Jaipur. All study patients signed an Informed Consent Form. During the study period, all patients of both genders, over 18 years-old, admitted to the ICU were invited to the study. Result: In current study, the mean QTc value more than 500ms were found in patients with CAD with ischemic disease, CKD, Pneumonia with Sepsis, HF, TB with ATT, Seizure with metabolic abnormality, and patients taking Trimethoprim-Sulfamethoxazole drug on day of admission, 3rd day, 5th day and 7th day. Conclusion: The prevalence of prolonged QTc interval is high in Indian emergency medical patients. There was no difference in hospital mortality though on subgroup analysis, patients with markedly prolonged QTc interval had significantly more episodes of in-hospital ventricular tachycardia and hospital mortality. A variety of factors including certain comorbidities, biochemical abnormalities and drugs were associated with QTc prolongation. Based on findings of index study, it would be prudent to closely monitor QTc interval, especially in patients with certain comorbidities and biochemical abnormalities, avoid medications associated with QTc prolongation. [ABSTRACT FROM AUTHOR]

Dengue infection is a mosquito borne arboviral disease of the tropics. It has a wide spectrum of presentation from flu-like illness to lethal hemorrhagic fever. Neurological manifestations are rare in dengue and can be due to neurotropic effect, immune mediated, or due to systemic complication. We hereby present a case report of a 21-year-old male presenting to us with acute pure motor quadriparesis due to hypokalemia caused by dengue fever. [ABSTRACT FROM AUTHOR]

Carbon interlayers have been shown to improve the uniformity and reversibility of lithium (Li) plating in anode-free solid-state batteries (SSBs). However, there remains a lack of fundamental understanding of the dynamic mechanisms that control Li transport and nucleation at these interfaces. In this study, we utilize a combination of electrochemical analysis and operando microscopy to examine the lithiation of carbon interlayers and the subsequent transition to Li plating. The current density during charging was varied to examine the corresponding changes in carbon lithiation, lithium nucleation, and the subsequent relaxation dynamics. A combination of electrochemical impedance spectroscopy, current-interrupt measurements, operando video microscopy, and post-mortem microscopy were performed. The results demonstrate that a transition in reaction pathways from lithiation of carbon to Li plating occurs, which is dependent on the applied current density during charging. As a result, a gradient in the state of charge of the carbon interlayer is observed, which subsequently relaxes during open-circuit rest periods. Finally, the influence of concentration gradients in the carbon interlayer on Li metal nucleation and subsequent solid-state lithiation is shown, which illustrates the importance of the charging protocol on the establishment of a stable Li metal anode interface. These fundamental electrochemical studies will further our understanding of the design requirements for interlayers that can enable Li metal anodes in SSB systems. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effectiveness of maternal pertussis vaccination for preventing pertussis infections in Aboriginal and Torres Strait Islander infants under seven months of age. Study design: Retrospective cohort study; analysis of linked administrative health data. Setting, participants: Mother–infant cohort (Links2HealthierBubs) including all pregnant women who gave birth to live infants (gestational age ≥ 20 weeks, birthweight ≥ 400 g) in the Northern Territory, Queensland, and Western Australia during 1 January 2012 – 31 December 2017. Main outcome measures: Proportions of women vaccinated against pertussis during pregnancy, rates of pertussis infections among infants under seven months of age, and estimated effectiveness of maternal vaccination for protecting infants against pertussis infection, each by Indigenous status. Results: Of the 19 892 Aboriginal and Torres Strait Islander women who gave birth to live infants during 2012–2017, 7398 (37.2%) received pertussis vaccine doses during their pregnancy, as had 137 034 of 259 526 non‐Indigenous women (52.8%; Indigenous v non‐Indigenous: adjusted odds ratio, 0.66; 95% confidence interval [CI], 0.62–0.70). The annual incidence of notified pertussis infections in non‐Indigenous infants declined from 16.8 (95% CI, 9.9–29) in 2012 to 1.4 (95% CI, 0.3–8.0) cases per 10 000 births in 2017; among Aboriginal and Torres Strait Islander infants, it declined from 47.6 (95% CI, 16.2–139) to 38.6 (95% CI, 10.6–140) cases per 10 000 births. The effectiveness of maternal vaccination for protecting non‐Indigenous infants under seven months of age against pertussis infection during 2014–17 was 68.2% (95% CI, 51.8–79.0%); protection of Aboriginal and Torres Strait Islander infants was not statistically significant (36.1%; 95% CI, –41.3% to 71.1%). Conclusions: During 2015–17, maternal pertussis vaccination did not protect Aboriginal and Torres Strait Islander infants in the NT, Queensland, and WA against infection. Increasing the pertussis vaccination rate among pregnant Aboriginal and Torres Strait Islander women requires culturally appropriate, innovative strategies co‐designed in partnership with Indigenous organisations and communities. [ABSTRACT FROM AUTHOR]

An increasing amount of molecular imaging studies are ordered each year for an oncologic population that continues to expand and increase in age. The importance of these studies in dictating further care for oncologic patients underscores the necessity of differentiating benign from malignant findings, particularly for a population in whom incidental findings are common. The aim of this review is to provide pictorial examples of benign musculoskeletal pathologies which may be found on molecular imaging and which may be mistaken for malignant processes. Imaging examples are provided in the form of radiographs, bone scintigraphy, computed tomography, and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans. Special attention is paid to specific features that help narrow the differential diagnosis and distinguish benign from malignant processes, with the goal of avoiding unnecessary invasive procedures. [ABSTRACT FROM AUTHOR]

The model plant Arabidopsis thaliana was exposed to combined stress factors, i.e., titanium dioxide nanoparticles (TiNPs) and high light. The concentrations of TiNPs used for irrigation were 250, 500, and 1000 μg/mL. This study shows that TiNPs alter the morphology and nanomechanical properties of chloroplasts in A. thaliana, which leads to a decrease in membrane elasticity. We found that TiNPs contributed to a delay in the thermal response of A. thaliana under dynamic light conditions, as revealed by non-invasive thermal imaging. The thermal time constants of TiNP-treated plants under excessive light are determined, showing a shortening in comparison to control plants. The results indicate that TiNPs may contribute to an alleviation of temperature stress experienced by plants under exposure to high light. In this research, we observed a decline in photosystem II photochemical efficiency accompanied by an increase in energy dissipation upon exposure to TiNPs. Interestingly, concentrations exceeding 250 µg/mL TiNPs appeared to mitigate the effects of high light, as shown by reduced differences in the values of specific OJIP parameters (FV/FM, ABS/RC, DI0/RC, and Pi_Abs) before and after light exposure. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restoration of blood flow. However, the mechanisms underlying such MSC-EV activity still remain poorly understood. The present study analyzes biological effects of bone marrow (BM) MSC-EVs on endothelial cells (ECs) in ischemic tissues both in in vitro and in vivo conditions and elucidates the molecular mechanisms underlying the tissue repair. MSC-EVs were isolated from murine BM-derived MSCs and their morphological, antigenic and molecular composition regarding protein and microRNA levels were evaluated to examine their properties. Global proteomic analysis demonstrated the presence in MSC-EVs of proteins regulating pro-regenerative pathways, including integrin α5 (Itgα5) and neuropilin-1 (NRP1) involved in lymphangiogenesis. MSC-EVs were also enriched in microRNAs regulating angiogenesis, TGF-β signaling and processes guiding cellular adhesion and interactions with extracellular matrix. The functional effects of MSC-EVs on capillary ECs in vitro included the increase of capillary-like tube formation and cytoprotection under normal and inflammatory conditions by inhibiting apoptosis. Notably, MSC-EVs enhanced also capillary-like tube formation of lymphatic ECs, which may be regulated by Itgα5 and NRP1. Moreover, in a mouse model of critical hind limb ischemia, MSC-EVs increased the recovery of blood flow in ischemic muscle tissue, which was accompanied with increased vascular density in vivo. This pro-angiogenic effect was associated with an increase in nitric oxide (NO) production via endothelial NO-synthase activation in ischemic muscles. Interestingly, MSC-EVs enhanced lymphangiogenesis, which has never been reported before. The study provides evidence on pro-angiogenic and novel pro-lymphangiogenic role of MSC-EVs on ECs in ischemic tissue mediated by their protein and miRNA molecular cargos. The results highlight Itgα5 and NRP1 carried by MSC-EVs as potential therapeutic targets to boost lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Objects: Studies of older age bipolar disorder (OABD) have mostly focused on "younger old" individuals. Little is known about the oldest OABD (OOABD) individuals aged ≥70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE‐BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups. Methods: We conducted cross‐sectional analyses of the GAGE‐BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50–69 (OABD, n = 881), and ≥70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies. Results: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59). Conclusions: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD. Key points: Limited knowledge of older and oldest older age bipolar disorder derived from limited sample sizes.The Global Aging and Geriatric Experiments in Bipolar Disorder consortium provided international data to compare younger age, older age, and oldest older age people with BDInternational sites (n = 14) provided data on patients aged <50 (n = 184 YABD), 50–69 (n = 881 OABD), and ≥70 (n = 304 OOABD) to assess differences among three groupsOABD and OOABD represent distinct cohorts within BD and differ in sociodemographic and clinical characteristics from YABD in general. OOABD individuals may be easier to manage psychiatrically but require more attention to their comorbid physical conditions. OOABD likely is a survivor cohort associated with resilience despite high medical burden, warranting future study using both qualitative and quantitative methods to better understand what makes OOABD resilient, how to advance clinical care and age successfully with BD. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of CoolSense and EMLA cream on pain reduction during intravenous cannulation in the pediatric population. Methods: A total of 140 American Society of Anesthesiologist I/II children of 6–12 y requiring intravenous cannulation before induction of anesthesia were randomized into two groups of 70 each. Before intravenous cannulation, group I received CoolSense pretreatment while group II received EMLA cream pretreatment. The primary outcome was to assess the efficacy of CoolSense and EMLA cream on pain reduction during intravenous cannulation. The secondary outcomes included the anxiety level of children, successful first attempt at cannulation, technical difficulties faced, adverse reactions, and parents' satisfaction score. Results: There was a significant reduction in pain scores during intravenous cannulation in the CoolSense group compared to the EMLA cream group (mean pain score 7.14 ± 4.322 versus 29.32 ± 8.95, p value 0.001). Comparison of pre- and postprocedural anxiety levels showed a decrease in the anxiety level in the CoolSense group (p value = 0.003) as compared to the EMLA group. The duration of application of CoolSense was significantly less than EMLA cream. Conclusion: CoolSense was more efficacious in reducing the pain of intravenous cannulation than the EMLA cream. In the pediatric population, CoolSense appears to be a simple and rapid means of providing adequate analgesia for venous cannulation. [ABSTRACT FROM AUTHOR]

The murder of the mayor of Gdańsk Paweł Adamowicz in 2019 and its circumstances formed the topic of many media reports. These events released strong emotions and reactions. The image of Adamowicz constructed by the media immediately following his death was virtually irreproachable, these positive reports being connected with the so-called taboo of death. Over the following years, one of the main topics of the discourse became the question of the moral responsibility for the mayor's death. The authors of this article concentrate on rhetorical strategies of portraying the protagonists in the media coverage, utilising concepts including those of Robert Rowland. The daily press ("Gazeta Wyborcza", "Rzeczpospolita" and "Dziennik Zachodni") and socio-political weekly publications ("Wprost", "Newsweek", "Polityka", "Sieci" and "Do Rzeczy") are analysed. [ABSTRACT FROM AUTHOR]

In the retina, retinoids involved in vision are under constant threat of oxidation, and their oxidation products exhibit deleterious properties. Using pulse radiolysis, this study determined that the bimolecular rate constants of scavenging cation radicals of retinoids by taurine are smaller than 2 × 107 M−1s−1 whereas lutein scavenges cation radicals of all three retinoids with the bimolecular rate constants approach the diffusion-controlled limits, while zeaxanthin is only 1.4–1.6-fold less effective. Despite that lutein exhibits greater scavenging rate constants of retinoid cation radicals than other antioxidants, the greater concentrations of ascorbate in the retina suggest that ascorbate may be the main protectant of all visual cycle retinoids from oxidative degradation, while α-tocopherol may play a substantial role in the protection of retinaldehyde but is relatively inefficient in the protection of retinol or retinyl palmitate. While the protection of retinoids by lutein and zeaxanthin appears inefficient in the retinal periphery, it can be quite substantial in the macula. Although the determined rate constants of scavenging the cation radicals of retinol and retinaldehyde by dopa-melanin are relatively small, the high concentration of melanin in the RPE melanosomes suggests they can be scavenged if they are in proximity to melanin-containing pigment granules. [ABSTRACT FROM AUTHOR]

Bladder cancer is a common malignancy associated with high recurrence rates and potential progression to invasive forms. Sorafenib, a multi-targeted tyrosine kinase inhibitor, has shown promise in anti-cancer therapy, but its cytotoxicity to normal cells and aggregation in solution limits its clinical application. To address these challenges, we investigated the formation of supramolecular aggregates of sorafenib with Congo red (CR), a bis-azo dye known for its supramolecular interaction. We analyzed different mole ratios of CR-sorafenib aggregates and evaluated their effects on bladder cancer cells of varying levels of malignancy. In addition, we also evaluated the effect of the test compounds on normal uroepithelial cells. Our results demonstrated that sorafenib inhibits the proliferation of bladder cancer cells and induces apoptosis in a dose-dependent manner. However, high concentrations of sorafenib also showed cytotoxicity to normal uroepithelial cells. In contrast, the CR-BAY aggregates exhibited reduced cytotoxicity to normal cells while maintaining anti-cancer activity. The aggregates inhibited cancer cell migration and invasion, suggesting their potential for metastasis prevention. Dynamic light scattering and UV-VIS measurements confirmed the formation of stable co-aggregates with distinctive spectral properties. These CR-sorafenib aggregates may provide a promising approach to targeted therapy with reduced cytotoxicity and improved stability for drug delivery in bladder cancer treatment. This work shows that the drug-excipient aggregates proposed and described so far, as Congo red—sorafenib, can be a real step forward in anti-cancer therapies. [ABSTRACT FROM AUTHOR]

This review is intended to contribute to the evidence of the effects of static magnetic field on cells and tissue, as well as to present research results that will elucidate the complex matters involved in the formation and remodeling of cells. The cell characteristics studied in the papers that are reviewed include cell viability and proliferation, aggregation and their differentiation, structure and membrane potential. A moderate static magnetic field in the most commonly used range of 2-80 mT has potential application in the formation and remodeling of plant and human cells. However, in the case of cancer cells, the range of fields commonly used was 0.2-9 T. Magnetism promotes changes in plant cell growth, which prompts the cell to proliferate, thereby ensuring an increased rate of biomass production. Some researches presented the enhancement of the differentiation of plant cells and skeletal muscle tissue by over 30% at 80 mT static magnetic field. Changes in the cell cycle and growth reflect directly on the cell number and viability and provide useful information to detect modifications in the cell machinery. Static magnetic field, depending on its intensity, enhances cell proliferation and thus may improve, among other processes, tissue regeneration, wound healing and the inhibition of cancer cell proliferation. Researchers showed, among other things, that cells under the influence of static magnetic field changed their shape, had a larger chloroplast, stiffer cell wall, density of the cytoskeleton and cytoplasm contained several mitochondria. Numerous studies also discussed the behavior of the cell membrane of plant and animal organisms, including humans, under the influence of an static magnetic field. The effects of static magnetic field on the cell membrane of plant and human cells were similar. The research results indicate that static magnetic fields can significantly change membrane depolarization and its potential that regulates ion movement and thus can have a significant impact on the properties and biological functionality of the cell. Studies have shown that continuous application of static magnetic field caused deformation and damage of cell membrane. Based on the theoretical analyses presented also in this review, it can be concluded that static magnetic field affects cells and tissue, giving them changes in properties and behaviors and modulates, e.g. in the activity of ion channels. Thus it may produce effects leading to changes in the functioning of the cell. It is possible to formulate directions for further research aimed at using static magnetic fields for the non-invasive remodeling and formation of plant and human cells. [ABSTRACT FROM AUTHOR]

In the era of miniaturization of electronic equipment and the need to connect sensors with textile materials, including clothing, the processing of signals received from the implemented sensors becomes an important issue. Information obtained by measuring the electrical properties of the sensors must be sent, processed, and visualized. For this purpose, the authors of this article have developed a prototype of a data collector obtained from textronic sensors created on composite textile substrates. The device operates in a system consisting of an electronic module based on the nRF52 platform, which supports wireless communication with sensors using Bluetooth technology and transmits the obtained data to a database hosted on the Microsoft Azure platform. A mobile application based on React Native technology was created to control the data stream. The application enables automatic connection to the selected collector, data download and their presentation in the form of selected charts. Initial verification tests of the system showed the correctness and reliability of its operation, and the presented graphs created from the obtained data indicate the usefulness of the device in applications where measurements and recording of impedance, resistance, and temperature are necessary. The presented prototype of a data collector can be used for resistance, impedance, and temperature measurements in the case of textronic structures but also in other wearable electronic systems. [ABSTRACT FROM AUTHOR]

Objective: The current literature on employment in older adults with bipolar disorder (OABD) is limited. Using the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE‐BD), we examined the relationship of occupational status in OABD to other demographic and clinical characteristics. Methods: Seven hundred and thirty‐eight participants from 11 international samples with data on educational level and occupational status were included. Employment status was dichotomized as employed versus unemployed. Generalized linear mixed models with random intercepts for the study cohort were used to examine the relationship between baseline characteristics and employment. Predictors in the models included baseline demographics, education, psychiatric symptom severity, psychiatric comorbidity, somatic comorbidity, and prior psychiatric hospitalizations. Results: In the sample, 23.6% (n = 174) were employed, while 76.4% were unemployed (n = 564). In multivariable logistic regression models, less education, older age, a history of both anxiety and substance/alcohol use disorders, more prior psychiatric hospitalizations, and higher levels of BD depression severity were associated with greater odds of unemployment. In the subsample of individuals less than 65 years of age, findings were similar. No significant association between manic symptoms, gender, age of onset, or employment status was observed. Conclusion: Results suggest an association between educational level, age, psychiatric severity and comorbidity in relation to employment in OABD. Implications include the need for management of psychiatric symptoms and comorbidity across the lifespan, as well as improving educational access for people with BD and skills training or other support for those with work‐life breaks to re‐enter employment and optimize the overall outcome. [ABSTRACT FROM AUTHOR]