Inflammatory and immune variables as predictors of survival in dogs with myxomatous mitral valve disease.

BACKGROUND: We aimed to investigate the association between selected inflammatory and immune variables and survival of dogs with myxomatous mitral valve disease (MMVD). We evaluated data of 62 client-owned dogs with MMVD, grouped into preclinical, stable congestive heart failure (CHF) and unstable CHF. Univariate Cox proportional hazards regression analysis was used to quantify the association of white blood cell count, concentrations and percentages of T lymphocytes and their subtypes (T helper lymphocytes, cytotoxic T lymphocytes, double positive T lymphocytes, double negative T lymphocytes) and B lymphocytes with survival. P values < 0.1 in individual groups and P values < 0.05 in the group of all patients were considered significant. Spearman correlation coefficients between significant covariates were calculated to assess the relationships among variables and with survival. RESULTS: In the preclinical group, percentage of double positive T lymphocytes was negatively associated with survival (hazard ratio (HR) = 2.328; P = 0.051). In the unstable CHF, T lymphocyte (HR = 1.613; P = 0.085), cytotoxic T lymphocyte (HR = 1.562; P = 0.048), double positive (HR = 1.751; P = 0.042), and double negative T lymphocyte (HR = 1.613; P = 0.096) concentrations were negatively associated with survival, as well as cytotoxic T lymphocyte (HR = 1.502; P = 0.007) concentration in the group of all patients. The percentage of T helper lymphocytes was positively associated with survival in the unstable CHF (HR = 0.604; P = 0.053) and in the group of all patients (HR = 0.733; P = 0.044). The concentration of cytotoxic T lymphocytes positively correlated with left atrial to aortic ratio (LA/Ao) (rho = 0.259, P = 0.037), and peak velocity of early diastolic mitral flow (rho = 0.259, P = 0.039), whereas the percentage of T helper lymphocytes negatively correlated with left atrial to aortic ratio (LA/Ao) (rho = -0.212, P = 0.090) and early to late mitral flow ratio (rho = -0.232, P = 0.072). CONCLUSIONS: Cytotoxic T lymphocytes, T helper lymphocytes, double positive and double negative T lymphocytes as well as biomarkers cardiac troponin I, N-terminal pro-B-type natriuretic peptide, C-reactive protein are implicated in the progression of MMVD.

Toward sleep health as a focus of physical therapy practice: one lecture can positively impact sleep knowledge and beliefs in entry-level students.

BACKGROUND: Challenges to integrating health promotion including sleep health into entry-level physical therapist curricula include lack of faculty expertise, time, and support. A lecture provided by a content expert may mitigate such challenges. The purpose of this study was to determine if a sleep education session impacts Doctor of Physical Therapy students' knowledge and beliefs about sleep. METHODS: Faculty shared the opportunity to participate in the study 1-3 days prior to the remotely-provided lecture including sleep health assessment and interventions. The survey included demographics, a sleep health knowledge question, 11 questions on "What I think about sleep as a professional", and the 20-item Sleep Beliefs Scale. McNemar's and paired sample t-tests determined change in knowledge and beliefs. RESULTS: 209 individuals (70% female, 86% Caucasian, 25.5 ± 3.4 years old) completed the pre-lecture survey, and 137 individuals completed the post-lecture survey. There was an increase in knowledge about sleep health (p < .001) and change in Sleep Beliefs Scales score (p < .001). CONCLUSIONS: A single remotely provided sleep education session increased DPT students' knowledge and changed their beliefs about sleep. Future studies should determine if these positive beliefs about sleep translate into clinical practice and enhance patient outcomes.

Clinical trial to assess tolerability and subrogate efficacy effects of an abbreviated schedule with house dust mites mixture subcutaneous immunotherapy.

Summary: Objective. To evaluate the tolerability and efficacy of Dermatophagoides pteronyssinus/Dermatophagoides farinae mixture subcutaneous immunotherapy (SCIT). Methods. Patients received an abbreviated build-up schedule. The aims were: number, percentage, and severity of adverse reactions. Secondary outcomes included: changes in immunoglobulin titers and changes in dose-response skin prick tests. Results. Out of 289 administrations, 17% elicited any clinically relevant adverse reaction. Most of them were local reactions (LR) (9.4%) and the rest (7.6%) were systemic. Significant increases in sIgG and sIgG4 were detected in serum samples. Cutaneous reactivity decreased significantly. Conclusions. SCIT with house dust mites mixture of ROXALL Medicina España S.A. seems to have an acceptable tolerability profile, induces blocking IgG and decreases skin reactivity.

Taxonomic identification and bioactive compounds characterization of Psilocybe cubensis DPT1 to probe its antibacterial and mosquito larvicidal competency.

Mushrooms have an important role in sustainability since they have long been used as valuable food source and traditional medicine around the world. Regrettably, they are among the most rigorously affected populations, along with several plants and animals, due to the destructive activities of mankind. Thus the authentication and conservation of mushroom species are constantly needed to exploit the remarkable potential in them. In this perspective, an attempt has been made to identify and assess the biological attributes of psychedelic mushrooms collected from Kodaikanal, Tamil Nadu, India. The macromorphological features of the psychedelic mushroom DPT1 helped its presumptive identification and the molecular characters depicted by DNA marker revealed its close relationship with the genus Psilocybe. Accordingly, the psychedelic mushroom was identified as Psilocybe cubensis DPT1 and its crude ethyl acetate extract on analysis revealed the occurrence of phytoconstituents like alkaloids, flavonoids, tannins, saponins and carbohydrates. Moreover, it exhibited 80% larvicidal activity against Culex quinquefasciatus mosquito at 800 ppm concentration and an array of antibacterial effects with utmost susceptibility of Proteus vulgaris, and the identification of bioactive compounds by different analytical techniques substantiate that the bioactivities might be due to the presence of phytochemicals. The results of the study indicated that the extract of P. cubensis DPT1 having notable antibacterial and mosquito larvicidal efficacies which could be probed further for the isolation of medicinally important as well as bio-control compounds.

Maternal education and childhood immunization in Turkey.

We study the causal effect of maternal education on childhood immunization rates. We use the Compulsory Education Law of 1997, and the differentiation in its implementation across regions, as instruments for schooling of young mothers in Turkey. The Compulsory Education Law increased the compulsory years of schooling of those born after 1986 from 5 to 8 years. We find that education of mothers increases the probability of completing the full course of diphtheria, pertussis, and tetanus and Hepatitis B vaccinations for their children. The results are robust to variations in regression specification and including various individual and community variables.

Impact evaluation of a community engagement intervention in improving childhood immunization coverage: a cluster randomized controlled trial in Assam, India.

BACKGROUND: To improve immunization coverage, most interventions that are part of the national immunization program in India address supply-side challenges. But, there is growing evidence that addressing demand-side factors can potentially contribute to improvement in childhood vaccination coverage in low- and middle-income countries. Participatory engagement of communities can address demand-side barriers while also mobilizing the community to advocate for better service delivery. The objective of this study is to evaluate the impact of a novel community engagement approach in improving immunization coverage. In our proposed intervention, we go a step beyond merely engaging the community and strive towards increasing 'ownership' by the communities. METHODS/DESIGN: We adopt a cluster randomized design with two groups to evaluate the intervention in Assam, a state in the northeast region of India. To recruit villages and participants at baseline, we used a two-stage stratified random sampling method. We stratified villages; our unit of randomization, based on census data and randomly selected villages from each of the four strata. At the second-stage, we selected random sub-sample of eligible households (having children in the age group of 6-23 months) from each selected village. The study uses a repeated cross sectional design where we track the same sampled villages but draw independent random samples of households at baseline and endline. Total number of villages required for the study is 180 with 15 eligible HHs from each village. Post-baseline survey, we adopt a stratified randomization strategy to achieve better balance in intervention and control groups, leveraging information from the extensive baseline survey. DISCUSSION: The proposed intervention can help identify barriers to vaccination at the local level and potentially lead to more sustainable solutions over the long term. Our sampling design, sample size calculation, and randomization strategy address internal validity of our evaluation design. We believe that it would allow us to causally relate any observed changes in immunization coverage to the intervention. TRIAL REGISTRATION: The trial has been registered on 7th February, 2017 under the Clinical Trials Registry- India (CTRI), hosted at the ICMR's National Institute of Medical Statistics, having registration number CTRI/2017/02/007792 . This is the original study protocol.

Antitumor effect of Deoxypodophyllotoxin on human breast cancer xenograft transplanted in BALB/c nude mice model.

Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, was found to be a potent antitumor and antiproliferative agent, in several tumor cells, in vitro. However, DPT has not been used clinically yet because of the lack of in vivo studies. This study is the first report demonstrating the antitumor effect of DPT on MDA-MB-231 human breast cancer xenografts in nude mice. DPT, significantly, inhibited the growth of MDA-MB-231 xenograft in BALB/c nude mice. The T/C value (the value of the relative tumor volume of treatment group compared to the control group) of groups treated with 5, 10, and 20 mg/kg of intravenous DPT-HP-ß-CD was 42.87%, 34.04% and 9.63%, respectively, suggesting the positive antitumor activity of DPT. In addition, the antitumor effect of DPT-HP-ß-CD (20 mg/kg) in human breast cancer MDA-MB-231 xenograft was more effective than etoposide (VP-16) (20 mg/kg) and docetaxel (20 mg/kg). These findings suggest that this drug is a promising chemotherapy candidate against human breast carcinoma.

Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy.

N-myc down-regulated gene 1 (NDRG1) is a known metastasis suppressor in multiple cancers, being also involved in embryogenesis and development, cell growth and differentiation, lipid biosynthesis and myelination, stress responses and immunity. In addition to its primary role as a metastasis suppressor, NDRG1 can also influence other stages of carcinogenesis, namely angiogenesis and primary tumour growth. NDRG1 is regulated by multiple effectors in normal and neoplastic cells, including N-myc, histone acetylation, hypoxia, cellular iron levels and intracellular calcium. Further, studies have found that NDRG1 is up-regulated in neoplastic cells after treatment with novel iron chelators, which are a promising therapy for effective cancer management. Although the pathways by which NDRG1 exerts its functions in cancers have been documented, the relationship between the molecular structure of this protein and its functions remains unclear. In fact, recent studies suggest that, in certain cancers, NDRG1 is post-translationally modified, possibly by the activity of endogenous trypsins, leading to a subsequent alteration in its metastasis suppressor activity. This review describes the role of this important metastasis suppressor and discusses interesting unresolved issues regarding this protein.

Exposure-response modeling of non-cancer effects in humans exposed to Libby Amphibole Asbestos; update.

The United States Environmental Protection Agency (EPA) developed a quantitative exposure-response model for the non-cancer effects of Libby Amphibole Asbestos (LAA) (EPA, 2014). The model is based on the prevalence of localized pleural thickening (LPT) in workers exposed to LAA at a workplace in Marysville, Ohio (Lockey et al., 1984; Rohs et al., 2008). Recently, Lockey et al. (2015a) published a follow-up study of surviving Marysville workers. The data from this study increases the number of cases of LPT and extends the observation period for a number of workers, thereby providing a strengthened data set to define and constrain the optimal exposure-response model for non-cancer effects from inhalation exposure to LAA. The new data were combined with the previous data to update the exposure-response modeling for LPT. The results indicate that a bivariate model using cumulative exposure and time since first exposure is appropriate, and the benchmark concentration is similar to the findings previously reported by EPA (2014). In addition, the data were also used to develop initial exposure-response models for diffuse pleural thickening (DPT) and small interstitial opacities (SIO).

ISAR Imaging of Maneuvering Targets Based on the Modified Discrete Polynomial-Phase Transform.

Inverse synthetic aperture radar (ISAR) imaging of a maneuvering target is a challenging task in the field of radar signal processing. The azimuth echo can be characterized as a multi-component polynomial phase signal (PPS) after the translational compensation, and the high quality ISAR images can be obtained by the parameters estimation of it combined with the Range-Instantaneous-Doppler (RID) technique. In this paper, a novel parameters estimation algorithm of the multi-component PPS with order three (cubic phase signal-CPS) based on the modified discrete polynomial-phase transform (MDPT) is proposed, and the corresponding new ISAR imaging algorithm is presented consequently. This algorithm is efficient and accurate to generate a focused ISAR image, and the results of real data demonstrate the effectiveness of it.

The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs.

Pancreatic angiotensin-converting enzyme 2 (ACE2) has previously been shown to be critical for maintaining glycemia and ß-cell function. Efforts to maintain or increase ACE2 expression in pancreatic ß-cells might therefore have therapeutic potential for treating diabetes. In our study, we investigated the transcriptional role of hepatocyte nuclear factor 1α (HNF1α) and hepatocyte nuclear factor 1ß (HNF1ß) in induction of ACE2 expression in insulin-secreting cells. A deficient allele of HNF1α or HNF1ß causes maturity-onset diabetes of the young (MODY) types 3 and 5, respectively, in humans. We found that ACE2 is primarily transcribed from the proximal part of the ACE2 promoter in the pancreas. In the proximal part of the human ACE2 promoter, we further identified three functional HNF1 binding sites, as they have binding affinity for HNF1α and HNF1ß and are required for induction of promoter activity by HNF1ß in insulinoma cells. These three sites are well-conserved among mammalian species. Both HNF1α and HNF1ß induce expression of ACE2 mRNA and lead to elevated levels of ACE2 protein and ACE2 enzymatic activity in insulinoma cells. Furthermore, HNF1α dose-dependently increases ACE2 expression in primary pancreatic islet cells. We conclude that HNF1α can induce the expression of ACE2 in pancreatic islet cells via evolutionarily conserved HNF1 binding sites in the ACE2 promoter. Potential therapeutics aimed at counteracting functional HNF1α depletion in diabetes and MODY3 will thus have ACE2 induction in pancreatic islets as a likely beneficial effect.

Deoxypodophyllotoxin Mediates Autophagy Death through Inhibition of GRP78 in Human Osteosarcoma.

BACKGROUND: Glucose-regulated protein 78 (GRP78), as a chaperone protein, can protect the endoplasmic reticulum of cells and is expressed to influence chemoresistance and prognosis in cancer. Deoxypodophyllotoxin (DPT) is a compound with antitumor effects on cancers. DPT inhibits the proliferation of osteosarcoma by inducing apoptosis, necrosis, or cell cycle arrest. OBJECT: This study was performed to demonstrate the molecular mechanism by which DPT attenuates osteosarcoma progression through GRP78. METHODS: Natural compound libraries and western blot (WB) were used to screen the inhibitors of osteosarcoma GRP78. The expression of mitochondria-related genes in cancer cells of the treatment group was detected by quantitative real-time PCR (qPCR) and WB. 3-(4,5)- Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-ethynyl-2'- deoxyuridine (EDU) were used to discover the activity and proliferation of osteosarcoma cells treated with DPT. We constructed an in vivo mouse model of DPT drug therapy and carried out immunohistochemical detection of xenografts. The treated osteosarcoma cells were analyzed using bioinformatics and electron microscopy. The data were analyzed finally. RESULTS: DPT inhibited osteosarcoma cell survival and the growth of tumor xenografts. It promoted up-regulation of BCL2-associated X protein (Bax) and B-cell CLL/lymphoma 2 (Bcl-2), which serves to mediate and attenuate, respectively, the killing activities of DPT through mitochondria dysfunction. The effect of DPT against cancer cells could be attenuated by the overexpression of GRP78, characterized by the inactivation of the caspase cascade. The loss of GRP78 in osteosarcoma cells negatively mediated the basal level of autophagyassociated genes. DPT stimulated autophagy via the phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog (AKT), a mechanistic target of rapamycin (mTOR) axis. The autophagy caused by DPT played an active role in the osteosarcoma of humans and blocked the apoptotic cascade. CONCLUSION: Combination treatment with the GRP78 inhibitor DPT and pharmacological autophagy inhibitors will be a meaningful method of obviating osteosarcoma cells.

Exploring alternatives for detecting microplastics in the human body: questionnaire survey.

Microplastics (MPs) can enter the body via plastic products. Given modern plastic exposure, we seek to assess MP exposure in large populations through epidemiological tools. In this quasi-experimental study, every participant filled out a questionnaire, and those who satisfied any of the following requirements were not allowed to continue in the study: Diabetes, ulcerative colitis, Crohn's disease, infectious diseases. Participants in the exposure and control groups were provided three hot meals in disposable plastic tableware (DPT) (n = 30) or non-DPT (n = 30), respectively. After a month of observation, individuals in the exposure group discontinued the three meals provided in DPT (n = 27) for 1 month as the post-exposure group. Each Participant in the three groups received a questionnaire survey and fecal sample collection. We compared the differences in MP levels between different groups and used the Bland-Altman analysis method to evaluate the consistency of the results obtained by different measurement methods. Statistically significant differences in the total quantity (P (0.80 matching degree) = 0.020; P (0.65 matching degree) < 0.001) and types (Polyethylene Terephthalate (EVA) (P = 0.039), Polyethylene Terephthalate (PET) (P = 0.022), Polyvinyl Butyral (PVB) (P = 0.013), Chlorinated Polyethylene (CPE) (P = 0.039), phenolic epoxy resin (P = 0.012)) of MPs were observed between the exposure and post-exposure groups. The Bland-Altman analysis results indicate that the two methods exhibit good consistency in the three groups (control group: mean difference = 0.54, agreement limits (95% CI) = - 0.44 ~ 1.54; exposure group: mean difference = 0.41, agreement limits (95% CI) = - 0.19 ~ 1.01; post-exposure group: mean difference = 0.19, agreement limits (95% CI) = - 0.63 ~ 1.02). The method based on questionnaire surveys can substitute the method of fecal sample detection to evaluate the exposure of MP particles.

Infertility: A common target of antivaccine misinformation campaigns.

Misinformation, disinformation, and conspiracy theories about vaccines are key drivers of vaccine hesitancy. A repeated false claim about COVID-19 vaccines is that the vaccines cause female infertility. Dating back decades, various conspiracy theories have linked vaccination programs with infertility and thus harmed vaccination programs in Africa, Asia, and Central America, particularly against polio and tetanus. In the United States, Europe, and Australia, human papilloma virus (HPV) vaccines have been falsely blamed for infertility and primary ovarian insufficiency (POI). After distribution of COVID-19 vaccines began in December 2020, almost immediately there arose conspiracy theories claiming that these vaccines cause menstrual irregularities, miscarriages, and infertility, promoted by noted antivaccine activists Robert F. Kennedy, Jr. and Andrew Wakefield among others. Here we will explore the history of this antivaccine narrative, how it has been promulgated in the past and repurposed to COVID-19 vaccines, and strategies to counter it.

Downregulation of dermatopontin in cholangiocarcinoma cells suppresses CCL19 secretion of macrophages and immune infiltration.

OBJECTIVE: The tumor microenvironment (TME) in cholangiocarcinoma (CHOL) is typically characterized by a low level of immune infiltration, which accounts for the dismal prognosis of this patient population. This study sought to investigate the mechanisms underlying the reduced infiltration of immune cells into the CHOL TME. METHODS: We constructed a Least Absolute Shrinkage and Selection Operator (LASSO) regression model to identify prognosis-related differentially expressed genes (DEGs). The 'Corrplot' package was employed to analyze the correlation between dermatopontin (DPT) and immune infiltration in CHOL. The Tumor and Immune System Interaction Database (TISIDB) was used to evaluate the association between DPT and immunology. Single-cell analysis was conducted to localize CCL19 secretions. Western blot and qPCR were utilized to detect DPT expression, while immunofluorescence was performed to investigate the cellular localization of DPT. Additionally, ELISA analysis was employed to assess the alteration in CCL19 secretion in cancer-associated fibroblasts (CAFs) and macrophages. RESULTS: Our findings revealed that CHOL patients with low DPT expression had a poorer prognosis. Enrichment analysis demonstrated a positive correlation between DPT levels and the infiltration of immunomodulators and immune cells. Moreover, high DPT levels were associated with enhanced anti-PD-1/PD-L1 immunotherapeutic responses. Furthermore, DPT expression impacted the landscape of gene mutations, showing a negative association with tumor grade, stage, and lymph node metastasis. Based on the results of protein peptides analysis and cell experiments, it was inferred that the downregulation of DPT in CHOL cells effectively suppressed the secretion of CCL19 in macrophages. CONCLUSIONS: DPT is a novel prognosis-related biomarker for CHOL patients, and this study provides preliminary insights into the mechanism by which DPT promotes the infiltration of immune cells into the CHOL TME.

Immunogenicity and safety of adsorbed diphtheria-purified pertussis-tetanus-inactivated polio (Sabin strain)-Haemophilus type b conjugate combined vaccine (DPT-IPV-Hib) in healthy Japanese Infants ≥ 2 and < 43 months of Age: A phase III, multicenter, active controlled, assessor-blinded, randomized, parallel-group study.

OBJECTIVE: This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator. METHODS: This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 µg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization. RESULTS: In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 µg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified. CONCLUSION: A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik).

Normative values for tests of central auditory processing disorder in children aged from 6 to 12 years old.

INTRODUCTION: Central auditory processing disorders (CAPD) can significantly affect the daily functioning of a child, and the first step in determining whether rehabilitation procedures are required is a proper diagnosis. Different guidelines for making diagnoses have been published in the literature, and in various centers normative values for psychoacoustic tests of CAPD have been used internally. The material presented in this paper is based on more than 1000 children and is the largest collection so far published. The aim of this study is to present normative values for tests assessing CAPD in children aged 6 to 12 years, divided by age at last birthday. METHOD: We tested 1037 children aged 6 to 12 years who were attending primary schools and kindergartens. The criteria for inclusion were a normal audiogram, intellectually normal, no developmental problems, and no difficulties in auditory processing. To evaluate auditory processing all children were given three tests on the Senses Examination Platform: the Frequency Pattern Test (FPT), Duration Pattern Test (DPT), and Dichotic Digit Test (DDT). RESULTS: The results from 1,037 children allowed us to determine normative values for FPT, DPT, and DDT in seven different age groups (6 through to 12 years). We developed a newapproach, based on quantile-based norms, to determine normative values in each group. Three categories - average, below-average, and above-average - allow for a broader but more realistic interpretation than those used previously. We compare our results with published standards. CONCLUSIONS: Our study is the largest normative database published to date for CAPD testing, setting a standard for each child by age in years. We used the Senses Examination Platform, a universal tool, to unify standards for the classification of CAPD. Our study can serve as a basis for the development of a Polish model for the diagnosis of CAPD.

Kidney double positive T cells have distinct characteristics in normal and diseased kidneys.

Multiple types of T cells have been described and assigned pathophysiologic functions in the kidneys. However, the existence and functions of TCR+CD4+CD8+ (double positive; DP) T cells are understudied in normal and diseased murine and human kidneys. We studied kidney DPT cells in mice at baseline and after ischemia reperfusion (IR) and cisplatin injury. Additionally, effects of viral infection and gut microbiota were studied. Human kidneys from patients with renal cell carcinoma were evaluated. Our results demonstrate that DPT cells expressing CD4 and CD8 co-receptors constitute a minor T cell population in mouse kidneys. DPT cells had significant Ki67 and PD1 expression, effector/central memory phenotype, proinflammatory cytokine (IFNγ, TNFα and IL-17) and metabolic marker (GLUT1, HKII, CPT1a and pS6) expression at baseline. IR, cisplatin and viral infection elevated DPT cell proportions, and induced distinct functional and metabolic changes. scRNA-seq analysis showed increased expression of Klf2 and Ccr7 and enrichment of TNFα and oxidative phosphorylation related genes in DPT cells. DPT cells constituted a minor population in both normal and cancer portion of human kidneys. In conclusion, DPT cells constitute a small population of mouse and human kidney T cells with distinct inflammatory and metabolic profile at baseline and following kidney injury.

Prevalence and Trends of Not Receiving a Dose of DPT-Containing Vaccine Among Children 12-35 Months: An Analysis of 81 Low- And Middle-Income Countries.

Not receiving a DPT-containing vaccine in early childhood indicates an absence of routine immunization, which puts children at an elevated risk of mortality, morbidity, and worse human development over the life course. We estimated the percentage of children 12-35 months who did not receive a dose of DPT-containing vaccine (termed zero-dose children) using household surveys from 81 low- and middle-income countries conducted between 2014 and 2023. For 68 countries with more than one survey (with the earlier survey conducted 2000-2013), we estimated the average annual percentage point change in prevalence of zero-dose children between the earliest and latest surveys. We also explored the association of zero-dose prevalence with postneonatal and child mortality, health expenditure, and Gavi-eligibility. Overall, 16% of children in our pooled sample had not received a dose of DPT-containing vaccine. There was a 0.8% point decline in zero-dose prevalence per year on average across the period studied. A single percentage point average annual decline in zero-dose prevalence was associated with an average annual decrease of 1.4 deaths in the postneonatal and childhood period per 1000 live births. Gavi-eligible countries had a much faster decline in zero-dose prevalence than other countries. Large gains have been made in reducing the percentage of children who did not receive a DPT-containing vaccine. Efforts to reduce the number of zero-dose children should focus on countries with high prevalence to achieve the Immunization Agenda 2030. Healthcare spending could be prioritized so that the prevalence of zero-dose children is reduced.

Wastewater from textile digital printing as a substrate for microalgal growth and valorization.

This study aims at evaluating an innovative biotechnological process for the concomitant bioremediation and valorization of wastewater from textile digital printing technology based on a microalgae/bacteria consortium. Nutrient and colour removal were assessed in lab-scale batch and continuous experiments and the produced algae/bacteria biomass was characterized for pigment content and biomethane potential. Microbial community analysis provided insight of the complex community structure responsible for the bioremediation action. Specifically, a community dominated by Scenedesmus spp. and xenobiotic and dye degrading bacteria was naturally selected in continuous photobioreactors. Data confirm the ability of the microalgae/bacteria consortium to grow in textile wastewater while reducing the nutrient content and colour. Improvement strategies were eventually identified to foster biomass growth and process performances. The experimental findings pose the basis of the integration of a microalgal-based process into the textile sector in a circular economy perspective.