An international multicentre study of SwiTching from Intravenous to subcutaneous inflixiMab and vEdolizumab in inflammatory bowel diseases: The TIME study.

BACKGROUND AND AIMS: Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. METHODS: This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. RESULTS: Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10-10) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months. CONCLUSION: SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.

Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells.

Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer.

Quality Studies on Cynometra iripa Leaf and Bark as Herbal Medicines.

Cynometra iripa Kostel. is a Fabaceae species of mangrove used in traditional Ayurvedic medicine for treating inflammatory conditions. The present study aims to establish monographic botanical and chemical quality criteria for C. iripa leaf and bark as herbal substances and to evaluate their in vitro antioxidant potential. Macroscopic and microscopic qualitative and quantitative analyses, chemical LC-UV/DAD-ESI/MS profiling, and the quantification of key chemical classes were performed. Antioxidant activity was evaluated by DPPH and FRAP assays. Macroscopically, the leaf is asymmetrical with an emarginated apex and cuneate base. Microscopically, it shows features such as two-layered adaxial palisade parenchyma, vascular bundles surrounded by 3-6 layers of sclerenchyma, prismatic calcium oxalate crystals (5.89 ± 1.32 µm) along the fibers, paracytic stomata only on the abaxial epidermis (stomatal index-20.15), and non-glandular trichomes only on petiolules. The microscopic features of the bark include a broad cortex with large lignified sclereids, prismatic calcium oxalate crystals (8.24 ± 1.57 µm), and secondary phloem with distinct 2-5 seriated medullary rays without crystals. Chemical profile analysis revealed that phenolic derivatives, mainly condensed tannins and flavonoids, are the main classes identified. A total of 22 marker compounds were tentatively identified in both plant parts. The major compounds identified in the leaf were quercetin-3-O-glucoside and taxifolin pentoside and in the bark were B-type dimeric proanthocyanidins and taxifolin 3-O-rhamnoside. The total phenolics content was higher in the leaf (1521 ± 4.71 mg GAE/g dry weight), while the total flavonoids and condensed tannins content were higher in the bark (82 ± 0.58 mg CE/g and 1021 ± 5.51 mg CCE/g dry weight, respectively). A total of 70% of the hydroethanolic extracts of leaf and bark showed higher antioxidant activity than the ascorbic acid and concentration-dependent scavenging activity in the DPPH assay (IC50 23.95 ± 0.93 and 23.63 ± 1.37 µg/mL, respectively). A positive and statistically significant (p < 0.05) correlation between the phenol content and antioxidant activity was found. The results obtained will provide important clues for the quality control criteria of C. iripa leaf and bark, as well as for the knowledge of their pharmacological potential as possible anti-inflammatory agents with antioxidant activity.

Breast cancer in women by HIV status: A report from the South African National Cancer Registry.

BACKGROUND: Breast cancer (BC) is the leading cause of cancer-related morbidity and mortality in women living in South Africa, a country with a high HIV burden. However, characteristics of the double burden of HIV and BC in South Africa have not been properly investigated. We described characteristics of BC cases by HIV status in South Africa. METHODS: In this nationwide South African study, we obtained BC records for women aged ≥15 years diagnosed in the public health sector between January 2004 and December 2014. We included records from the National Cancer Registry that had been linked to HIV-related laboratory records from the National Health Laboratory Service. We assessed the odds of being HIV positive versus HIV negative in relation to patient-, cancer-, and municipality-related characteristics. RESULTS: From 2004-2014, 40 520 BC cases were diagnosed in women aged ≥15 years. Of these, 73.5% had unknown HIV status, 18.7% were HIV negative, and 7.7% were HIV positive. The median age at BC diagnosis was 43 years (interquartile range [IQR]: 37-52) in HIV positive and 57 years (IQR: 46-68) in HIV negative women, respectively. The odds of being HIV positive was higher for women who were aged 30-34 years compared to women aged 35-39 years at cancer diagnosis (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.10-1.71), Black versus non-Black (OR 6.41, 95% CI 5.68-7.23), diagnosed with cancer in rural versus urban areas (OR 1.59, 95% CI 1.40-1.82) and diagnosed in municipalities with low and middle (OR 3.46, 95% CI 2.48-4.82) versus high socioeconomic position (OR 2.69, 95% CI 2.11-3.42). CONCLUSION: HIV status was unknown for the majority of BC patients. Among those with known HIV status, being HIV positive was associated with a younger age at cancer diagnosis, being Black and receiving care in municipalities of poor socioeconomic position. Future studies should examine opportunities to integrate HIV and BC control programs.

Associations between day and night-shifts, work-related musculoskeletal symptoms and absenteeism in the manufacturing industry.

Objectives. Associations between shift-work, musculoskeletal symptoms and absenteeism are poorly investigated in the manufacturing industry. This study aimed to investigate associations between working schedule, musculoskeletal symptoms and days of absenteeism among pulp and paper industry workers. Methods. Musculoskeletal symptoms of 904 workers were assessed through the Nordic Musculoskeletal Questionnaire. χ2 tests assessed associations between being a day-worker or shift-worker, the prevalence of musculoskeletal symptoms and days of absenteeism. Results. A significant association was found between working schedule and symptoms in the lower back in the last 12 months, with shift-workers presenting higher prevalence than day-workers (p = 0.022). Significant associations were also found between days of absenteeism and symptoms in the shoulders (p = 0.002), which mostly led to absenteeism of 100-365 days; elbows (p < 0.001), wrists/hands (p = 0.045) and ankles/feet (p = 0.042), which produced absenteeism mostly of 25-99 days; and dorsal region (p = 0.001), which mainly led to absenteeism of 10-24 days. No associations were found between working schedule and days of absenteeism (p = 0.265). Conclusion. Shift-work is associated with increased prevalence of lower back symptoms, but seems not to influence days of absenteeism. Shoulders seem to be the region leading to higher days of absenteeism, followed by elbows, wrists/hands, ankles/feet and the dorsal region.

Motivational strategies used by health care professionals in stroke survivors in rehabilitation: a scoping review of experimental studies.

Introduction: Cognitive and motor impairments are common among stroke survivors. Physical therapy is often used to improve the functional capacity of stroke survivors. However, limited adherence to rehabilitation programs is a challenge. Motivation plays a crucial role in the success of rehabilitation programs as it influences individual adherence to treatment and overall health outcomes. This review aims to identify current trends in motivational strategies used by healthcare professionals for stroke survivor rehabilitation. Methods: Following the framework developed by Arksey and O'Malley, a scoping review was conducted. We performed a literature search using MEDLINE, CINAHL, the Cochrane Central Register of Controlled Trials, Nursing & Allied Health, and MedicLatina databases. Results: A total of 906 papers were identified. After selecting and analyzing the articles, 17 papers were included in this review. Health professionals use various strategies to motivate stroke survivors. These approaches include establishing a therapeutic alliance, improving patients' health literacy, defining realistic goals, fostering problem-solving skills, personalizing the rehabilitation program, showcasing success stories, utilizing persuasive techniques, offering encouragement and compliments, providing emotional support, and effectively managing symptoms. Conclusion: The knowledge gathered in this review can guide healthcare professionals in helping patients overcome barriers to rehabilitation, improve their motivation, and ultimately enhance their recovery outcomes.

Do social protection programmes affect the burden of breast and cervical cancer? A systematic review.

Background: Socioeconomic conditions are strongly associated with breast and cervical cancer incidence and mortality patterns; therefore, social protection programmes (SPPs) might impact these cancers. This study aimed to evaluate the effect of SPPs on breast and cervical cancer outcomes and their risk/protective factors. Methods: Five databases were searched for articles that assessed participation in PPS and the incidence, survival, mortality (primary outcomes), screening, staging at diagnosis and risk/protective factors (secondary outcomes) for these cancers. Only peer-reviewed quantitative studies of women receiving SPPs compared to eligible women not receiving benefits were included. Independent reviewers selected articles, assessed eligibility, extracted data, and assessed the risk of bias. A harvest plot represents the included studies and shows the direction of effect, sample size and risk of bias. Findings: Of 17,080 documents retrieved, 43 studies were included in the review. No studies evaluated the primary outcomes. They all examined the relationship between SPPs and screening, as well as risk and protective factors. The harvest plot showed that in lower risk of bias studies, participants of SPPs had lower weight and fertility, were older at sexual debut, and breastfed their infants for longer. Interpretation: No studies have yet assessed the effect of SPPs on breast and cervical cancer incidence, survival, or mortality; nevertheless, the existing evidence suggests positive impacts on risk and protective factors.

The Effect of Muscle Fatigue on the Knee Proprioception: A Systematic Review.

This study aimed to systematically review and summarise the evidence about the effect of muscle fatigue on the knee proprioception of trained and non-trained individuals. A search in PubMed, Scopus, Web of Science and EBSCO databases and Google Scholar was conducted using the expression: "fatigue" AND ("proprioception" OR "position sense" OR "repositioning" OR "kinesthesia" OR "detection of passive motion" OR "force sense" OR "sense of resistance") AND "knee". Forty-two studies were included. Regarding joint-position sense, higher repositioning errors were reported after local and general protocols. Kinesthesia seems to be more affected when fatigue is induced locally, and force sense when assessed at higher target forces and after eccentric protocols. Muscle fatigue, both induced locally or generally, has a negative impact on the knee proprioception.

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study.

BACKGROUND: There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. METHODS: In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. FINDINGS: 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). INTERPRETATION: Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. FUNDING: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

Potential Environmental Reservoirs of Candida auris: A Systematic Review.

Candida auris, a multidrug-resistant yeast, poses significant challenges in healthcare settings worldwide. Understanding its environmental reservoirs is crucial for effective control strategies. This systematic review aimed to review the literature regarding the natural and environmental reservoirs of C. auris. Following the PRISMA guidelines, published studies until October 2023 were searched in three databases: PubMed, Web of Science, and Scopus. Information regarding the origin, sampling procedure, methods for laboratory identification, and antifungal susceptibility was collected and analyzed. Thirty-three studies published between 2016 and 2023 in 15 countries were included and analyzed. C. auris was detected in various environments, including wastewater treatment plants, hospital patient care surfaces, and natural environments such as salt marshes, sand, seawater, estuaries, apples, and dogs. Detection methods varied, with molecular techniques often used alongside culture. Susceptibility profiles revealed resistance patterns. Phylogenetic studies highlight the potential of environmental strains to influence clinical infections. Despite methodological heterogeneity, this review provides valuable information for future research and highlights the need for standardized sampling and detection protocols to mitigate C. auris transmission.

Timing of TORC1 inhibition dictates Pol III involvement in Caenorhabditis elegans longevity.

Organismal growth and lifespan are inextricably linked. Target of Rapamycin (TOR) signalling regulates protein production for growth and development, but if reduced, extends lifespan across species. Reduction in the enzyme RNA polymerase III, which transcribes tRNAs and 5S rRNA, also extends longevity. Here, we identify a temporal genetic relationship between TOR and Pol III in Caenorhabditis elegans, showing that they collaborate to regulate progeny production and lifespan. Interestingly, the lifespan interaction between Pol III and TOR is only revealed when TOR signaling is reduced, specifically in adulthood, demonstrating the importance of timing to control TOR regulated developmental versus adult programs. In addition, we show that Pol III acts in C. elegans muscle to promote both longevity and healthspan and that reducing Pol III even in late adulthood is sufficient to extend lifespan. This demonstrates the importance of Pol III for lifespan and age-related health in adult C. elegans.

CD20+ T cells in monoclonal B cell lymphocytosis and chronic lymphocytic leukemia: frequency, phenotype and association with disease progression.

Introduction: In monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), the expansion of malignant B cells disrupts the normal homeostasis and interactions between B cells and T cells, leading to immune dysregulation. CD20+ T cells are a subpopulation of T cells that appear to be involved in autoimmune diseases and cancer. Methods: Here, we quantified and phenotypically characterized CD20+ T cells from MBL subjects and CLL patients using flow cytometry and correlated our findings with the B-cell receptor mutational status and other features of the disease. Results and discussion: CD20+ T cells were more represented within the CD8+ T cell compartment and they showed a predominant memory Tc1 phenotype. CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vß 5.1 in CD4+ CD20+ T cells in CLL.

Advancing Precision Medicine: A Review of Innovative In Silico Approaches for Drug Development, Clinical Pharmacology and Personalized Healthcare.

The landscape of medical treatments is undergoing a transformative shift. Precision medicine has ushered in a revolutionary era in healthcare by individualizing diagnostics and treatments according to each patient's uniquely evolving health status. This groundbreaking method of tailoring disease prevention and treatment considers individual variations in genes, environments, and lifestyles. The goal of precision medicine is to target the "five rights": the right patient, the right drug, the right time, the right dose, and the right route. In this pursuit, in silico techniques have emerged as an anchor, driving precision medicine forward and making this a realistic and promising avenue for personalized therapies. With the advancements in high-throughput DNA sequencing technologies, genomic data, including genetic variants and their interactions with each other and the environment, can be incorporated into clinical decision-making. Pharmacometrics, gathering pharmacokinetic (PK) and pharmacodynamic (PD) data, and mathematical models further contribute to drug optimization, drug behavior prediction, and drug-drug interaction identification. Digital health, wearables, and computational tools offer continuous monitoring and real-time data collection, enabling treatment adjustments. Furthermore, the incorporation of extensive datasets in computational tools, such as electronic health records (EHRs) and omics data, is also another pathway to acquire meaningful information in this field. Although they are fairly new, machine learning (ML) algorithms and artificial intelligence (AI) techniques are also resources researchers use to analyze big data and develop predictive models. This review explores the interplay of these multiple in silico approaches in advancing precision medicine and fostering individual healthcare. Despite intrinsic challenges, such as ethical considerations, data protection, and the need for more comprehensive research, this marks a new era of patient-centered healthcare. Innovative in silico techniques hold the potential to reshape the future of medicine for generations to come.

Ethnomedicinal, Chemical, and Biological Aspects of Lannea Species-A Review.

Lannea L. genus belongs to the Anacardiaceae botanical family and has long been used in traditional medicinal systems of many countries to manage several health conditions, but no studies have been conducted regarding its usefulness as a source of herbal medicine for human use. A literature review was conducted on scientific papers indexed on B-On, Pubmed, and Web of Science databases. Our results showed that medicinal plants from this botanical genus, mostly constituted by bark and leaf, are often used to approach a wide variety of disease symptoms, like fever, inflammatory states, pain, and gastrointestinal disorders. Phytochemical profiles of Lannea species revealed that phenolic acid derivatives including hydroquinones, phenolic acids, flavonoids, condensed tannins, and triterpenoids are the main classes of secondary metabolites present. Among the total of 165 identified compounds, 57 (34.5%) are flavonoids, mostly quercetin- and myricetin-derived flavonols and catechin and epicatechin flavan-3-ol derivatives also containing a galloyl group. In vitro and in vivo studies allowed the identification of 12 different biological activities, amongst which antimicrobial, antioxidant, anti-inflammatory, and cytotoxic activities were the most frequently cited and observed in in vitro essays. Our review contributes useful information for the scientifical validation of the use of Lannea species in traditional medicinal systems and shows that more research needs to be conducted to better understand the concrete utility of these as herbal medicines.

Liposome-siderophore conjugates loaded with moxifloxacin serve as a model for drug delivery against Mycobacterium tuberculosis.

Tuberculosis (TB) is an infectious disease that annually affects millions of people, and resistance to available antibiotics has exacerbated this situation. Another notable characteristic of Mycobacterium tuberculosis, the primary causative agent of TB, is its ability to survive inside macrophages, a key component of the immune system. In our quest for an effective and safe treatment that facilitates the targeted delivery of antibiotics to the site of infection, we have proposed a nanotechnology approach based on an iron chelator. Iron chelators are the primary mechanism by which bacteria acquire iron, a metal essential for their metabolism. Four liposomes were synthesized and characterized using the dynamic light scattering technique (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). All of these methods revealed the presence of spherical particles, approximately 200 nm in size. NTA indicated a concentration of around 1011 particles/mL. We also developed and validated a high-performance liquid chromatography method for quantifying Moxifloxacin to determine encapsulation efficiency (EE) and release profiles (RF). The EE was 51.31 % for LipMox and 45.76 % for LipIchMox. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the phagocytosis of liposomal vesicles by macrophages. Functionalizing liposomes with iron chelators can offer significant benefits for TB treatment, such as targeted drug delivery to intracellular bacilli through the phagocytosis of liposomal particles by cells like macrophages.

Hidden threats in the plastisphere: Carbapenemase-producing Enterobacterales colonizing microplastics in river water.

Carbapenem resistance poses a significant burden on healthcare systems worldwide. Microplastics (MPs) have emerged as potential contributors to antibiotic resistance spread in the environment. However, the link between MPs and carbapenem resistance remains unexplored. We investigated the prevalence of carbapenem-resistant bacteria colonizing MPs placed in a river. Three replicates of a mixture of polypropylene (PP), polyethylene (PE) and polyethylene terephthalate (PET) and of PET alone were placed both upstream and downstream a wastewater treatment plant (WWTP) discharge. Carbapenem-resistant Enterobacterales (CRE) were further characterized by phenotypic tests and whole-genome sequencing. The abundance of carbapenem-resistant bacteria on MPs increased significantly downstream the WWTP. Their prevalence was higher in the MPs mixture compared to PET alone. CRE strains colonizing MPs included Klebsiella pneumoniae (n = 3), Klebsiella quasipneumoniae (n = 3), Raoultella ornithinolytica (n = 2), Enterobacter kobei (n = 1) and Citrobacter freundii (n = 1), most (n = 8) recovered after the WWTP discharge. All strains exhibited at least one of the tested virulence traits (biofilm formation at 37 °C, haemolytic activity and siderophore production), were multi-drug resistant and carried carbapenemase-encoding genes [blaKPC-3 (n = 5), blaGES-5 (n = 2) or blaKPC-3 + blaGES-5 (n = 3)]. Uncommon phenotypes of resistance to imipenem/relebactam (n = 3) and ceftazidime/avibactam (n = 2) were observed. Two blaKPC-3-positive K. pneumoniae successfully transfer this gene trough conjugation. Genome analysis predicted all strains as human pathogens. The blaKPC-3 was associated with the Tn4401d transposon on a pBK30683-like plasmid in most of the isolates (n = 7). The blaGES-5 was mostly linked to class 3 integrons. A K. pneumoniae strain belonging to the outbreak-causing high-risk clone ST15 carried both blaKPC-3 and blaCTX-M-15. Two K. quasipneumoniae isolates carried the plasmid-mediated colistin resistance gene mcr-9. Our results underscore the role of MPs as vectors for CRE dissemination, particularly following WWTPs discharges. MPs may act as carriers, facilitating the dissemination of carbapenemase-encoding genes and potentially contributing to increased CRE incidence in the environment.

Evaluation of rapid optimized flow cytometry crossmatch (Halifaster) in living donor kidney transplantation.

Kidney transplantation is often the preferred treatment for end-stage renal disease. However, the presence of preformed donor-specific antibodies (DSA), including those against HLA, can lead to antibody-mediated rejection and significantly impact transplant outcomes. The Flow Cytometry Crossmatch (FCXM) is a crucial tool in kidney transplantation, as it also enables the measurement of low levels of anti-HLA DSA antibodies. However, current methodologies for detecting these antibodies, however, are time-consuming and require extensive reagents. In this study, we analyzed the performance of the Halifaster FCXM protocol in 133 consecutive living kidney donor pairs, correlating these results with single antigen-based anti-HLA DSA results. Anti-HLA DSA was identified in 31 patients (23.3%). Both T and B lymphocyte FCXM assays demonstrated high sensitivity and specificity in detecting anti-HLA DSA. Furthermore, a Tree model to determine the levels of anti-HLA DSA to produce a flow crossmatch positivity, was developed offering an accuracy of 93% and 90% for T and B lymphocytes, respectively. Both approaches point to a thresh old of 1000-2000 MFI for T lymphocytes and 3000 MFI for B lymphocytes. Our findings indicate that the Halifaster protocol facilitates fast and efficient FCXM testing without compromising accuracy, marking a significant advancement in the field of kidney transplantation. The inclusion of HLA-specific antibody analysis underscores the protocol's comprehensive approach to improving transplant outcomes.

Income Segregation, Conditional Cash Transfers, and Breast Cancer Mortality Among Women in Brazil.

Importance: Women living in income-segregated areas are less likely to receive adequate breast cancer care and access community resources, which may heighten breast cancer mortality risk. Objective: To investigate the association between income segregation and breast cancer mortality and whether this association is attenuated by receipt of the Bolsa Família program (BFP), the world's largest conditional cash-transfer program. Design, Setting, and Participants: This cohort study was conducted using data from the 100 Million Brazilian Cohort, which were linked with nationwide mortality registries (2004-2015). Data were analyzed from December 2021 to June 2023. Study participants were women aged 18 to 100 years. Exposure: Women's income segregation (high, medium, or low) at the municipality level was obtained using income data from the 2010 Brazilian census and assessed using dissimilarity index values in tertiles (low [0.01-0.25], medium [0.26-0.32], and high [0.33-0.73]). Main Outcomes and Measures: The main outcome was breast cancer mortality. Mortality rate ratios (MRRs) for the association of segregation with breast cancer deaths were estimated using Poisson regression adjusted for age, race, education, municipality area size, population density, area of residence (rural or urban), and year of enrollment. Multiplicative interactions of segregation and BFP receipt (yes or no) in the association with mortality (2004-2015) were assessed. Results: Data on 21 680 930 women (mean [SD] age, 36.1 [15.3] years) were analyzed. Breast cancer mortality was greater among women living in municipalities with high (adjusted MRR [aMRR], 1.18; 95% CI, 1.13-1.24) and medium (aMRR, 1.08; 95% CI, 1.03-1.12) compared with low segregation. Women who did not receive BFP had higher breast cancer mortality than BFP recipients (aMRR, 1.17; 95% CI, 1.12-1.22). By BFP strata, women who did not receive BFP and lived in municipalities with high income segregation had a 24% greater risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.24: 95% CI, 1.14-1.34); women who received BFP and were living in areas with high income segregation had a 13% higher risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.13; 95% CI, 1.07-1.19; P for interaction = .008). Stratified by the amount of time receiving the benefit, segregation (high vs low) was associated with an increase in mortality risk for women receiving BFP for less time but not for those receiving it for more time (<4 years: aMRR, 1.16; 95% CI, 1.07-1.27; 4-11 years: aMRR, 1.09; 95% CI, 1.00-1.17; P for interaction <.001). Conclusions and Relevance: These findings suggest that place-based inequities in breast cancer mortality associated with income segregation may be mitigated with BFP receipt, possibly via improved income and access to preventive cancer care services among women, which may be associated with early detection and treatment and ultimately reduced mortality.

Structural and Functional Shifts in the Microbial Community of a Heavy Metal-Contaminated Soil Exposed to Short-Term Changes in Air Temperature, Soil Moisture and UV Radiation.

The interplay between metal contamination and climate change may exacerbate the negative impact on the soil microbiome and, consequently, on soil health and ecosystem services. We assessed the response of the microbial community of a heavy metal-contaminated soil when exposed to short-term (48 h) variations in air temperature, soil humidity or ultraviolet (UV) radiation in the absence and presence of Enchytraeus crypticus (soil invertebrate). Each of the climate scenarios simulated significantly altered at least one of the microbial parameters measured. Irrespective of the presence or absence of invertebrates, the effects were particularly marked upon exposure to increased air temperature and alterations in soil moisture levels (drought and flood scenarios). The observed effects can be partly explained by significant alterations in soil properties such as pH, dissolved organic carbon, and water-extractable heavy metals, which were observed for all scenarios in comparison to standard conditions. The occurrence of invertebrates mitigated some of the impacts observed on the soil microbial community, particularly in bacterial abundance, richness, diversity, and metabolic activity. Our findings emphasize the importance of considering the interplay between climate change, anthropogenic pressures, and soil biotic components to assess the impact of climate change on terrestrial ecosystems and to develop and implement effective management strategies.

The intersection of race/ethnicity and socioeconomic status: inequalities in breast and cervical cancer mortality in 20,665,005 adult women from the 100 Million Brazilian Cohort.

OBJECTIVES: There is limited evidence regarding the impact of race/racism and its intersection with socioeconomic status (SES) on breast and cervical cancer, the two most common female cancers globally. We investigated racial inequalities in breast and cervical cancer mortality and whether SES (education and household conditions) interacted with race/ethnicity. DESIGN: The 100 Million Brazilian Cohort data were linked to the Brazilian Mortality Database, 2004-2015 (n = 20,665,005 adult women). We analysed the association between self-reported race/ethnicity (White/'Parda'(Brown)/Black/Asian/Indigenous) and cancer mortality using Poisson regression, adjusting for age, calendar year, education, household conditions and area of residence. Additive and multiplicative interactions were assessed. RESULTS: Cervical cancer mortality rates were higher among Indigenous (adjusted Mortality rate ratio = 1.80, 95%CI 1.39-2.33), Asian (1.63, 1.20-2.22), 'Parda'(Brown) (1.27, 1.21-1.33) and Black (1.18, 1.09-1.28) women vs White women. Breast cancer mortality rates were higher among Black (1.10, 1.04-1.17) vs White women. Racial inequalities in cervical cancer mortality were larger among women of poor household conditions, and low education (P for multiplicative interaction <0.001, and 0.02, respectively). Compared to White women living in completely adequate (3-4) household conditions, the risk of cervical cancer mortality in Black women with 3-4, 1-2, and none adequate conditions was 1.10 (1.01-1.21), 1.48 (1.28-1.71), and 2.03 (1.56-2.63), respectively (Relative excess risk due to interaction-RERI = 0.78, 0.18-1.38). Among 'Parda'(Brown) women the risk was 1.18 (1.11-1.25), 1.68 (1.56-1.81), and 1.84 (1.63-2.08), respectively (RERI = 0.52, 0.16-0.87). Compared to high-educated White women, the risk in high-, middle- and low-educated Black women was 1.14 (0.83-1.55), 1.93 (1.57-2.38) and 2.75 (2.33-3.25), respectively (RERI = 0.36, -0.05-0.77). Among 'Parda'(Brown) women the risk was 1.09 (0.91-1.31), 1.99 (1.70-2.33) and 3.03 (2.61-3.52), respectively (RERI = 0.68, 0.48-0.88). No interactions were found for breast cancer. CONCLUSION: Low SES magnified racial inequalities in cervical cancer mortality. The intersection between race/ethnicity, SES and gender needs to be addressed to reduce racial health inequalities.