Six months of physical inactivity is insufficient to cause chronic kidney disease in C57BL/6J mice.

Chronic kidney disease (CKD) is a progressive disorder marked by a decline in kidney function. Obesity and sedentary behavior contribute to the development of CKD, though mechanisms by which this occurs are poorly understood. This knowledge gap is worsened by the lack of a reliable murine CKD model that does not rely on injury, toxin, or gene deletion to induce a reduction in kidney function. High-fat diet (HFD) feeding alone is insufficient to cause reduced kidney function until later in life. Here, we employed a small mouse cage (SMC), a recently developed mouse model of sedentariness, to study its effect on kidney function. Wildtype C57BL/6J male mice were housed in sham or SMC housing for six months with HFD in room (22°C) or thermoneutral (30°C) conditions. Despite hyperinsulinemia induced by the SMC+HFD intervention, kidneys from these mice displayed normal glomerular filtration rate (GFR). However, the kidneys showed early signs of kidney injury, including increases in Col1a1 and NGAL transcripts, as well as fibrosis by histology, primarily in the inner medullary/papilla region. High-resolution respirometry and fluorometry experiments showed no statistically significant changes in the capacities for respiration, ATP synthesis, or electron leak. These data confirm the technical challenge in modeling human CKD. They further support the notion that obesity and a sedentary lifestyle make the kidneys more vulnerable, but additional insults are likely required for the pathogenesis of CKD.

Effects of Different Eccentric Cycling Intensities on Brachial Artery Endothelial Shear Stress and Blood Flow Patterns.

Eccentric exercise has gained attention as a novel exercise modality that increases muscle performance at a lower metabolic demand. However, vascular responses to eccentric cycling (ECC) are unknown, thus gaining knowledge regarding endothelial shear stress (ESS) during ECC may be crucial for its application in patients. The purpose of this study was to explore ECC-induced blood flow patterns and ESS across three different intensities in ECC. Eighteen young, apparently healthy subjects were recruited for two laboratory visits. Maximum oxygen consumption, power output, and blood lactate (BLa) threshold were measured to determine workload intensities. Blood flow patterns in the brachial artery were measured via ultrasound imaging and Doppler on an eccentric ergometer during a 5 min workload steady exercise test at low (BLa of 0-2 mmol/L), moderate (BLa 2-4 mmol/L), and high intensity (BLa levels > 4 mmol/L). There was a significant increase in the antegrade ESS in an intensity-dependent manner (baseline: 44.2 ± 8.97; low: 55.6 ± 15.2; moderate: 56.0 ± 10.5; high: 70.7 ± 14.9, all dynes/cm2, all p values < 0.0002) with the exception between low and moderate and Re (AU) showed turbulent flow at all intensities. Regarding retrograde flow, ESS also increased in an intensity-dependent manner (baseline 9.72 ± 4.38; low: 12.5 ± 3.93; moderate: 15.8 ± 5.45; high: 15.7 ± 6.55, all dynes/cm2, all p values < 0.015) with the exception between high and moderate and Re (AU) showed laminar flow in all intensities. ECC produced exercise-induced blood flow patterns that are intensity-dependent. This suggests that ECC could be beneficial as a modulator of endothelial homeostasis.

Colombian surgical outcomes study insights on perioperative mortality rate, a main indicator of the lancet commission on global surgery - a prospective cohort study.

Background: Surgical care holds significant importance in healthcare, especially in low and middle-income countries, as at least 50% of the 4.2 million deaths within the initial 30 days following surgery take place in these countries. The Lancet Commission on Global Surgery proposed six indicators to enhance surgical care. In Colombia, studies have been made using secondary data. However, strategies to reduce perioperative mortality have not been implemented. This study aims to describe the fourth indicator, perioperative mortality rate (POMR), with primary data in Colombia. Methods: A multicentre prospective cohort study was conducted across 54 centres (hospitals) in Colombia. Each centre selected a 7-day recruitment period between 05/2022 and 01/2023. Inclusion criteria involved patients over 18 years of age undergoing surgical procedures in operating rooms. Data quality was ensured through a verification guideline and statistical analysis using mixed-effects multilevel modelling with a case mix analysis of mortality by procedure-related, patient-related, and hospital-related conditions. Findings: 3807 patients were included with a median age of 48 (IQR 32-64), 80.3% were classified as ASA I or II, and 27% of the procedures had a low-surgical complexity. Leading procedures were Orthopedics (19.2%) and Gynaecology/Obstetrics (17.7%). According to the Clavien-Dindo scale, postoperative complications were distributed in major complications (11.7%, 10.68-12.76) and any complication (31.6%, 30.09-33.07). POMR stood at 1.9% (1.48-2.37), with elective and emergency surgery mortalities at 0.7% (0.40-1.23) and 3% (2.3-3.89) respectively. Interpretation: The POMR was higher than the ratio reported in previous national studies, even when patients had a low-risk profile and low-complexity procedures. The present research represents significant public health progress with valuable insights for national decision-makers to improve the quality of surgical care. Funding: This work was supported by Universidad del Rosario and Fundación Cardioinfantil-Instituto de Cardiología grant number CTO-057-2021, project-ID IV-FGV017.

Outdoor artificial light-at-night and cardiometabolic disease risk: an urban perspective from the Catalan GCAT cohort study.

We investigated the association between outdoor artificial light-at-night (ALAN) exposure and cardiometabolic risk in the GCAT study. We included 9,752 participants from Barcelona (59% women). We used satellite images (30m resolution) and estimated photopic illuminance and the circadian-regulation relevant melanopic illuminance (melanopic EDI). We explored the association between ALAN exposure and prevalent obesity, hypertension, and diabetes with logistic regressions. We assessed the relationship with incident cardiometabolic diseases ascertained through electronic health records (mean follow-up 6.5 years) with Cox proportional hazards regressions. We observed an association between photopic illuminance and melanopic EDI and prevalent hypertension, Odds ratio (OR) = 1.09 (95% CI, 1.01-1.16) and 1.08 (1.01-1.14) per interquartile range increase (0.59 and 0.16 lux, respectively). Both ALAN indicators were linked to incident obesity (hazard ratio [HR] = 1.29, 1.11-1.48 and 1.19, 1.05-1.34) and haemorrhagic stroke (HR = 1.73, 1.00-3.02 and 1.51, 0.99-2.29). Photopic illuminance was associated with incident hypercholesterolemia in all participants (HR = 1.17, 1.05-1.31) and with angina pectoris only in women (HR = 1.55, 1.03-2.33). Further research in this area and increased awareness on the health impacts of light pollution are needed. Results should be interpreted carefully since satellite-based ALAN data do not estimate total individual exposure.

Outcomes of Radiotherapy in Oligoprogressive Breast Cancer.

INTRODUCTION: Radiotherapy (RT) shows potential for improving local control in cases of oligoprogressive metastatic breast cancer (mBC). This retrospective analysis aims to evaluate the advantages of RT in such a clinical scenario. METHODS: We conducted a retrospective analysis including patients with mBC who received radiation therapy (RT) for up to three sites of oligoprogression while continuing systemic therapy. The study took place between January 2014 and December 2021. Our endpoints were progression-free survival after radiotherapy (PFS-AR), the rate of discontinuation of systemic therapy (RDT) at three months post-RT, and overall survival (OS). We used Cox regression analysis to perform multivariate analysis for PFS-AR. RESULTS: Fifty-nine patients met the inclusion criteria. The PFS-AR was 13 months (95% CI 8.5-18.8 months). At three months, the RDT was 3% (two patients). A significant difference in median PFS-AR was observed between patients in the first + second-line group and those in the subsequent line group (p = 0.03). In the multivariate analysis conducted for PFS-AR, the biologically effective dose (BED) with α/ß = 4 > 100 Gy emerged as the sole significant variable (p = 0.0017). The median overall survival (OS) was 24.4 months (95% CI 17-24.4 months). CONCLUSIONS: This study is the first report on the outcomes of radiotherapy in a cohort of over 50 patients with oligoprogressive metastatic breast cancer (mBC). Our findings emphasize the significant relationship between PFS-AR, the number of ongoing lines of systemic therapy, and the BED of radiotherapy.

Transthyretin cardiac amyloid: Broad heart failure phenotypic spectrum and implications for diagnosis.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) is most often associated with heart failure with preserved ejection fraction (HFpEF). However, patients may present with impaired systolic function at the time of diagnosis, which has not been widely investigated. We sought to explore the prevalence of various heart failure (HF) phenotypes and their associated clinical characteristics at the time of ATTR-CA diagnosis. METHODS: We performed a single-centre retrospective cohort study of consecutive patients with ATTR-CA evaluated between February 2016 and December 2022. Data on patient demographics, comorbidities, imaging and laboratory findings were compared across HF phenotypes (age: 78.1 ± 8.6 years, with 91.1% male). A total of 21.6% (n = 46) presented with heart failure with reduced ejection fraction (HFrEF), 17.8% (n = 38) with heart failure with mildly reduced ejection fraction (HFmrEF) and 60.6% (n = 129) with HFpEF at the time of diagnosis with ATTR-CA. Those presenting with HFrEF or HFmrEF were more likely to be African American and had significantly worse New York Heart Association (NYHA) functional class, higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and higher serum creatinine levels as compared with those with HFpEF. CONCLUSIONS: Although ATTR-CA is traditionally thought to be seen primarily among patients with HFpEF, our data suggest that ATTR-CA has a higher prevalence among patients with HFrEF, which underscores the importance of heightened clinical suspicion regardless of ejection fraction when considering ATTR-CA. Furthermore, although comorbidities are similar, patients with HFmrEF and HFrEF had a worse symptom burden.

Radiodensities of skeletal muscle and visceral adipose tissues are prognostic factors in clear cell renal cell carcinoma.

BACKGROUND: Body composition may be related to survival in clear cell renal cell carcinoma (ccRCC) patients but studies have not simultaneously considered adipose and muscle tissue quantity and radiodensity. METHODS: We analyzed data from 1,022 ccRCC patients who underwent nephrectomy between 2000 -2020 at Memorial Sloan Kettering Cancer Center. Skeletal muscle, visceral adipose, and subcutaneous adipose tissue index (SMI, VATI, SATI respectively; cm2/m2) and radiodensity (SMD, VATD, SATD respectively; Hounsfield Units [HU]) were assessed from non-contrast pre-surgical computed tomography scans; clinical and demographic characteristics were available from the time of surgery. Hazard ratios (HR) and confidence intervals (CI) were estimated for overall (OS) and disease-free survival (DFS) through March 2023 in multivariable models that simultaneously accounted for all body composition measures. RESULTS: Median age was 58 years, 69% were male, and 90% White. There were 169 OS events over 8,392 person-years, and 253 DFS events over 7,753 person-years of follow-up. In adjusted analyses, poor OS was associated with lower SMD (-10 HU, HR (95% CI): 1.37 [1.05, 1.77]), and greater VATD (+10 HU: 1.66 [1.06, 2.59]), with similar findings for DFS. Poor survival was also associated with greater VATI (+40 cm2/m2, OS: 1.32 [0.97, 1.79]; DFS: 1.33 [1.04, 1.71]). Associations with SMD were limited to patients with stage 1/2 disease. CONCLUSIONS: Radiodensities of skeletal muscle and visceral adipose tissue may be novel pre-surgical prognostic factors for ccRCC patients. IMPACT: Findings underscore the importance of evaluating the full range of body composition features simultaneously in multivariable models.

Analyzing the European institutional response to ethical and regulatory challenges of artificial intelligence in addressing discriminatory bias.

The European Union and some of its institutions have taken significant steps to address the challenges posed by the development and use of Artificial Intelligence (AI) in various contexts. The ubiquity of AI applications in everyday life, affecting both citizens and professionals, has made AI a common topic of discussion. However, as is evident from the documents analyzed here, concerns have been raised about the possible negative social consequences of AI, in particular discriminatory bias, making it a particularly relevant issue if people-centred, rights-based AI is to be implemented. This article aims to examine the challenges of defining, identifying and mitigating discriminatory bias in AI systems from two perspectives: (1) to conduct an ethical and normative review of European Commission documents from the last 8 years (from GDPR to AI Act regulation); and (2) to expose recommendations for key stakeholders, including designers, end-users and public authorities, to minimize/mitigate this risk. The document review was carried out on 21 EU regulatory and ethical guidelines in the field of AI, from which 152 measures were extracted, differentiated between design, governance and organizational measures. It has also been observed that there is no clear conceptual framework on the issue at the European level, showing a clear problem in providing definitions of algorithmic bias and discrimination, but not in assessing their potential negative impact on individuals. Secondly, these gaps may affect the concreteness and detail of the possible mitigation/minimization measures proposed and, subsequently, their application in different contexts. Finally, the last section of this paper presents a brief discussion and conclusions on possible issues related to the implementation of the measures extracted and certain limitations of the study.

Advancing Tau PET Quantification in Alzheimer Disease with Machine Learning: Introducing THETA, a Novel Tau Summary Measure.

Alzheimer disease (AD) exhibits spatially heterogeneous 3- or 4-repeat tau deposition across participants. Our overall goal was to develop an automated method to quantify the heterogeneous burden of tau deposition into a single number that would be clinically useful. Methods: We used tau PET scans from 3 independent cohorts: the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center (Mayo, n = 1,290), the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 831), and the Open Access Series of Imaging Studies (OASIS-3, n = 430). A machine learning binary classification model was trained on Mayo data and validated on ADNI and OASIS-3 with the goal of predicting visual tau positivity (as determined by 3 raters following Food and Drug Administration criteria for 18F-flortaucipir). The machine learning model used region-specific SUV ratios scaled to cerebellar crus uptake. We estimated feature contributions based on an artificial intelligence-explainable method (Shapley additive explanations) and formulated a global tau summary measure, Tau Heterogeneity Evaluation in Alzheimer's Disease (THETA) score, using SUV ratios and Shapley additive explanations for each participant. We compared the performance of THETA with that of commonly used meta-regions of interest (ROIs) using the Mini-Mental State Examination, the Clinical Dementia Rating-Sum of Boxes, clinical diagnosis, and histopathologic staging. Results: The model achieved a balanced accuracy of 95% on the Mayo test set and at least 87% on the validation sets. It classified tau-positive and -negative participants with an AUC of 1.00, 0.96, and 0.94 on the Mayo, ADNI, and OASIS-3 cohorts, respectively. Across all cohorts, THETA showed a better correlation with the Mini-Mental State Examination and the Clinical Dementia Rating-Sum of Boxes (ρ ≥ 0.45, P < 0.05) than did meta-ROIs (ρ < 0.44, P < 0.05) and discriminated between participants who were cognitively unimpaired and those who had mild cognitive impairment with an effect size of 10.09, compared with an effect size of 3.08 for meta-ROIs. Conclusion: Our proposed approach identifies positive tau PET scans and provides a quantitative summary measure, THETA, that effectively captures heterogeneous tau deposition observed in AD. The application of THETA for quantifying tau PET in AD exhibits great potential.

Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.

PURPOSE: This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV). METHODS: Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted. RESULTS: Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease (P = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without (P > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways. CONCLUSION: Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra.

Mexican Multicenter Experience of Metastatic Spinal Disease.

Background Spinal metastatic disease is a silent progressive cancer complication with an increasing prevalence worldwide. The spine is the third most common site where solid tumors metastasize. Complications involved in spinal metastasis include root or spinal cord compression, progressing to a declining quality of life as patient autonomy reduces and pain increases. The main objective of this study is to report the incidence of patients and typology of spinal metastases in three reference centers in Mexico. Methodology Retrospective cohorts of patients diagnosed with spinal metastases from January 2010 to February 2017 at the National Cancer Institute, National Rehabilitation Institute, and the Traumatology and Orthopedics Hospital "Lomas Verdes" in Mexico City were analyzed. Results A total of 326 patients (56% males) with spinal metastases were reported. The mean age was 58.06 ± 14.05 years. The main sources of spinal metastases were tumors of unknown origin in 53 (16.25%) cases, breast cancer in 67 (20.5%) cases, prostate cancer in 59 (18%) cases, myeloma in 24 (7.4%) cases, and lung cancer in 23 (7.1%) cases. Conclusions The data obtained in this analysis delivers an updated standpoint on Mexico, providing the opportunity to distinguish the current data from global references. Collecting more epidemiological information for better recording of cancer and its associated complications, as well as further studies on them, is necessary.

New variants expand the neurological phenotype of COQ7 deficiency.

The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.

Potential impact of nirsevimab and bivalent maternal vaccine against RSV bronchiolitis in infants: A population-based modelling study.

BACKGROUND: A new monoclonal antibody (nirsevimab; Beyfortus®) and a bivalent prefusion RSV vaccine (Abrysvo®) for maternal immunization have been approved recently. This is a modelling study to estimate the potential impact of different immunization programs with these products on RSV-bronchiolitis. METHODS: Population-based real-world data from primary care and hospitalizations were considered. RSV bronchiolitis dynamics in absence of these immunization scenarios were explained by a multivariate age-structured Bayesian model. Then, the potential impact was simulated under different assumptions including the most recent clinical trial data. Differences in endpoints, populations, and timeframes between trials make the two products' efficacy difficult to compare. RESULTS: A seasonal with catch-up program, assuming a constant effectiveness of 79.5 % during the first 5 months followed by a linear decay to 0 by month 10 with nirsevimab, would prevent between 5121 and 8846 RSV bronchiolitis per 100,000 infants-years. Assuming 77.3 % effectiveness with the same decay, between 976 and 1686 RSV-hospitalizations per 100,000 infants-years could be prevented depending on the uptake. A year-round maternal immunization program, with 51 % of effectiveness during the first 6 months followed by a linear decay to 0 by month 10 would prevent between 3246 and 5606 RSV bronchiolitis cases per 100,000 infants-years. Assuming 56.9 % effectiveness with the same decay, between 713 and 1231 RSV-hospitalizations per 100,000 infants-years could be prevented. CONCLUSIONS: Our results suggest that each strategy would effectively reduce RSV-bronchiolitis.

Long-Term Safety of Level II Oncoplastic Surgery after Neoadjuvant Treatment for Locally Advanced Breast Cancer: A 20-Year Experience.

Background: Oncoplastic surgery (OPS) reliability in the post-neoadjuvant chemotherapy (NACT) setting is still debated due to weak scientific evidences in such scenarios. Methods: Our analysis aims to report results obtained in a retrospective series of 111 patients consecutively treated with level II OPS after NACT at the Multidisciplinary Breast Center of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS between 1998 and 2018. The surgical endpoints were the mean specimen volume, rates of positive margins (PMR), re-excision (RR), conversion to mastectomy (CMR), and complications (CR). The oncological endpoints were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). To evaluate the impact of NACT on surgical and oncological outcomes at 302 months, we conducted a propensity score matching, pairing patients in post-NACT and upfront surgery groups. Results: The mean sample volume was 390,796 mm3. We registered a 3.6% of PMR, 1.8% RR, 0.9% CMR, 5% CR. The 10-year OS and 10-year DFS with a median follow-up of 88 months (6-302) were 79% and 76%, respectively, with an LR recurrence rate of 5%. The post-NACT group received significantly larger excised volumes and lower PMR. NACT did not affect surgical and oncological outcomes. Conclusions: Level II OPS can be considered a reliable alternative to mastectomy even in the post-NACT setting.

Young Women with Early-Stage Breast Cancer Treated with Upfront Surgery: Overview of Oncological Outcomes.

Background: Breast cancer in young women aged < 40 years is rare and often aggressive with less favorable survival rates. The lack of systematic screening, later stage at diagnosis, and a more aggressive disease biology may all contribute to their poor prognosis. Data on the best management remain conflicting, especially those regarding surgical management, either breast-conserving or mastectomy. To our knowledge, there are limited studies surrounding the treatment of young women with early breast cancer, and this analysis evaluated the oncological outcomes for those patients who underwent surgery upfront. Methods: We conducted a retrospective study including 130 young women with early breast cancer from a total of 373 consecutive patients treated with upfront surgery between January 2016 and December 2021 at our institution. Local recurrence-free survival (LR-FS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated. Results: The median follow-up was 61.1 months (range, 25-95). A total of 92 (70.8%) patients underwent breast-conserving surgery, while 38 (29.2%) patients underwent conservative mastectomy with immediate implant breast reconstruction. In total, 8 of 130 patients (6.2%) developed a local recurrence in the treated breast, an7 (5.4%) patients presented distant metastasis. Overall, two (1.6%) patients died due to breast cancer recurrence. Conclusions: The results of our study interestingly support breast-conserving surgery in young patients with early-stage breast cancer. While appropriate breast-conserving surgery can achieve favorable oncological outcomes and can always be considered a valid alternative to conservative mastectomy in upfront surgery, a younger age at diagnosis should never be used alone to choose the type of surgery.

Exploring the Efficacy of Nonlinear Filters in CMOS for 2-D Signal Processing for Image Quality Enhancement.

This study rigorously investigates the effectiveness of nonlinear filters in CMOS for 2-D signal processing to enhance image quality. We comprehensively compare traditional linear filters' performance, which operate on the principle of linearity, with nonlinear filters, such as the median-median (Med-Med) approach, designed to handle nonlinear data. To ensure the validity of our findings, we use widely accepted metrics like normalized squared error (NSE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM) to quantify the differences. Our simulations and experiments, conducted under controlled conditions, demonstrate that nonlinear filters in CMOS outperform linear filters in removing impulse noise and enhancing images. We also address the challenges of implementing these algorithms at the hardware level, focusing on power consumption and chip area optimization. Additionally, we propose a new architecture for the Med-Med filter and validate its functionality through experiments using a 9-pixel image sensor array. Our findings highlight the potential of nonlinear filters in CMOS for real-time image quality enhancement and their applicability in various real-world imaging applications. This research contributes to visual technology by combining theoretical insights with practical implementations, paving the way for more efficient and adaptable imaging systems.

The European psychiatric association (EPA) - early career psychiatrists committee survey on trainees' and early-career psychiatrists' attitudes towards therapeutic drug monitoring (TDM) use and utility during antipsychotic treatment.

OBJECTIVES: This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics. METHODS: A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01/2022-31/12/2023. The frequency of using TDM for antipsychotics other than clozapine was the main outcome in a linear regression analysis, including sex, clinical setting, caseload, and factors generated by an exploratory factor analysis. Comparisons between residents and early-career psychiatrists, respondents working in in- and outpatient settings, and low-/middle- and high-income countries were performed. RESULTS: Altogether, 1,237 respondents completed the survey, with 37.9% having never used TDM for antipsychotics. Seven factors explained 41% of response variance; six of them were associated with frequency of TDM use (p < 0.05). Items with highest loadings for factors included clinical benefits of TDM (factors A and E: 0.7), negative expectations for beliefs of patients towards TDM (factor B: 0.6-0.7), weak TDM scientific evidence (factor C: 0.8), and TDM availability (factor D: -0.8). Respondents from low-/middle-income countries were less likely to frequently/almost always use TDM compared to high-income countries (9.4% vs. 21.5%, p < 0.001). DISCUSSION: TDM use for antipsychotics was poor and associated with limited knowledge and insufficient availability.

Enhanced Timeliness and Co-Administration of Meningitis B Vaccination in Children: Impact of Funding in Valencian Community, Spain.

Public funding of vaccines may enhance vaccination rates, co-administration, and timeliness. The impacts of including the serogroup B meningococcus vaccine (MenB) into the national immunisation schedule on vaccination rates, co-administration rates, and timeliness were assessed using a population-based pre-funding (2022) and post-funding (2023) study design. MenB vaccination rates improved after funding and were in line with previously funded vaccines. Co-administration rates also increased significantly. Timely administration increased, protecting children at an early age. Public funding has a positive impact on vaccine accessibility and early protection. Consistent population characteristics highlight the role of funding.

Predictors of developing renal dysfunction following diagnosis of transthyretin cardiac amyloidosis.

BACKGROUND: In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients. OBJECTIVES: This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA. METHODS: We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF. RESULTS: Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF. CONCLUSION: Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.