医学最新文献

Background: Malignant hypertension (mHTN) is a severe hypertensive emergency, often associated with renal deterioration. Kidney length may be of useful to identify patients with renal dysfunction. Whether kidney length in mHTN patients is associated with renal prognosis is unclear.

Methods: The study enrolled 280 mHTN patients with renal thrombotic microangiopathy (TMA) who underwent renal biopsy between 2008 and 2023. Linear regression was used to explore patient characteristics of kidney length. The association between kidney length and ≥15% increase in estimated glomerular filtration rate (eGFR), and end-stage renal disease (ESRD) was analyzed using Cox regression and logistic regression, respectively. Kidney length was analyzed in tertiles, using the first tertile as reference.

Results: Patients with larger kidney length had higher levels of body mass index (BMI) and eGFR, but lower levels of urea nitrogen, serum creatinine, uric acid, global sclerosis ratio, and tubular atrophy/interstitial fibrosis ratio. Kidney length was strongly positively correlated with BMI, and negatively related to tubular atrophy/interstitial fibrosis ratio. During the follow-up, 72 patients experienced a ≥15% increase in eGFR and 172 patients progressed to ESRD. Patients in the third tertile of kidney length had a better renal recovery outcome of ≥15% increase in eGFR and lower odds of ESRD.

Conclusions: In mHTN patients with renal TMA, large kidney length is associated with better renal function improvement of ≥15% increase in eGFR, and lower risk of ESRD. In clinical practice, the measurement of kidney length may serve as a non-invasive indicator to assess renal prognosis and inform timely treatment interventions in mHTN patients.

Anecdotal reports highlight increased methamphetamine, cocaine, and codeine-cough syrup use in Zimbabwe, with no clear empirical basis. Therefore, the scoping review aimed to identify primary evidence of patterns, harms and responses to substance use (SU) within Zimbabwe. Arksey and O'Malley's (2005) framework and the PRISMA Extension for Scoping Reviews (Tricco et al., 2018) were followed. Medline (Pub Med), Scopus, Academic Search Premier, Cumulative Index to Nursing and Allied Health Literature (CINAHL Plus), African Index Medicus, Africa-Wide Information, Web of Science, PsycInfo, PsycArticles, and Web of Science conference proceedings were searched. 27 studies published between 2012, and February 2025 met the inclusion criteria and were synthesized using combined inductive-deductive thematic analysis. Patterns of SU included a wide range of drugs (e.g. alcohol, tobacco, cannabis, inhalants, codeine-cough syrups), with emergent literature on methamphetamine, cocaine and heroin. Socio-demographic patterns elucidated vulnerable groups (e.g. children living on the streets), and concentration of SU in high density urban areas. SU harms predominantly centered on the link to the HIV epidemic, whilst clinical and health responses to SU were significantly limited. SU should therefore be treated as a public health priority in Zimbabwe, and research capacity building is urgently required to address significant literature gaps.

Heterologous boosting with aerosolized or intramuscular Ad5-nCoV following a two-dose CoronaVac prime has been shown to induce higher antibody levels than a homologous CoronaVac booster. However, no specific modeling has been reported to characterize the kinetics of antibody waning for these heterologous regimens. By integrating longitudinal serological data from three randomized trials conducted in Jiangsu, China (NCT04892459, NCT04952727, NCT05043259), we applied linear mixed-effects models to establish both exponential and power-law decay models for neutralizing antibodies, including live-virus neutralizing antibodies against the prototype, Delta, and Omicron BA.1 variants, and pseudovirus neutralizing antibodies against Omicron BA.4/5 variant, respectively. The findings showed that the power-law model exhibited a superior fit over the exponential model across all antibody types (all ΔAICc < 0). According to the power-law model (at day 90), the half-lives of live-virus neutralizing antibodies against the wild-type SRAS-CoV-2 strain was 195 d (95% CI: 185-210) in the aerosolized Ad5-nCoV group, 226 d (220-252) in the intramuscular Ad5-nCoV group, versus 230 d (95% CI: 222-257) in the three-dose CoronaVac group. For the Omicron BA.1 variant, the half-life was 314 d (248-453) in the aerosolized Ad5-nCoV group, 168 d (159-180) in the intramuscular Ad5-nCoV group, compared to 196 d (174-230) in the three-dose CoronaVac group. Our model indicated that the heterologous booster with Ad5-nCoV after two-dose CoronaVac, particularly the aerosolized Ad5-nCoV, induces longer-lasting neutralizing antibodies than three-dose CoronaVac, preferably characterized by power-law decay models.

Perfluorooctane sulfonate (PFOS), a persistent environmental pollutant, is associated with cognitive dysfunction through mechanisms involving neuroinflammation, oxidative stress, and metabolic disruption. Icaritin, a bioactive flavonoid with antioxidant and anti-inflammatory properties, exhibits therapeutic potential, though its efficacy against PFOS-induced cognitive impairment remains unexplored. Herein, a mouse model of PFOS-induced cognitive dysfunction was established and treated with oral ICT. Integrated 16S rRNA sequencing and untargeted metabolomics revealed that ICT restored gut microbial homeostasis by enriching beneficial genera (e.g. Akkermansia, Lactobacillus) and reducing ammonia-producing bacteria (e.g. Proteus, Helicobacter, Escherichia), thereby improving gut barrier integrity. Metabolomic profiling identified significant perturbations in ammonia-related pathways, particularly arginine and proline metabolism, underscoring ammonia dysmetabolism as a pivotal mediator of PFOS neurotoxicity. These modifications attenuated systemic and cerebral ammonia accumulation, mitigated neuroinflammation and oxidative stress, and ultimately improved cognitive function. Our findings elucidate ammonia dysmetabolism as a central mechanism in PFOS-induced cognitive decline and highlight the microbiota-gut-brain axis as a promising therapeutic target. This study provides a mechanistic foundation for targeting microbial and metabolic pathways in environmental neurotoxicity.

Metabolic and immune development in neonates are shaped by the succession of the gut microbiome. Maternal obesity can perturb this process by altering interactions of human milk bioactive elements, including oligosaccharides (HMOs), microbial populations, and metabolites. We conducted a longitudinal study of Mexican mother-infant dyads to examine maternal BMI-associated variations in HMOs and infant fecal microbiota. Breastmilk samples from 97 mothers were collected at 48 h, one month, and three months postpartum. We used targeted and untargeted metabolomics to profile breastmilk samples, while shotgun metagenomics was used to analyze infant fecal microbiome composition in a subset of samples. Mothers with obesity showed decreased concentration of key HMOs shortly after birth, correlating with an altered succession of their infant's gut microbiota. This included reduced early colonizers (Enterobacteriaceae) and increased abundance of intermediate and late colonizers (Bifidobacterium and members of the Lachnospiraceae family), over subsequent months. These taxa negatively correlated with HMOs such as 6'SL, LNnT, and LNT. Additionally, functional profiling revealed alterations in metabolic pathways related to polyamine biosynthesis, suggesting changes in microbial metabolism linked to maternal BMI. Despite the cohort's size, our study offers unique insights into the relationship between maternal obesity, HMO composition, and early infant microbial colonization in Latin-American mothers. This exploratory research serves as proof of concept, underscoring the need for larger-scale studies to validate these findings and better understand their implications for infant health. More importantly, our results highlight the interplay between maternal BMI and human milk bioactives, underscoring the importance of correlating microbial succession with maternal metabolic health to better understand early immune development in neonates.

Glioblastoma (GBM) is the most common primary central nervous system tumor with a dismal prognosis and limited treatment options. Recent success utilizing immunotherapies for treating other solid tumors have been largely unsuccessful in GBM. One of the primary mechanisms of GBM immunotherapeutic resistance is because of excessive infiltration of myeloid cells that create an immunosuppressive tumor microenvironment (TME). Among these infiltrating myeloid cells, tumor-associated macrophages (TAMs), comprise a substantial portion of the TME and are associated with poor prognosis in GBM patients. Researchers have only recently begun to dissect the dynamics and complexity of TAMs. However, reliable and reproducible translational methods for generating GBM TAMs in vitro are lacking. Here, we have investigated an in vitro, reproducible murine-based model for bone marrow-derived, glioma-educated macrophages (gTAMs) and performed rigorous analysis to expand our understanding of gTAMs to provide a validated tool for investigating therapeutic response.

Globally, childhood immunization remains a major public health concern, with 19.4 million children not fully vaccinated in 2018, the majority from low- and middle-income countries. Ethiopia, in particular, reports alarmingly low immunization coverage, with nearly one million children unvaccinated and vaccine-preventable diseases accounting for approximately 16% of childhood mortality. This study aimed to examine the spatiotemporal distribution and associated factors of immunization among children aged 12-23 months in Ethiopia. Data were obtained from four rounds of the Ethiopia Demographic and Health Survey (EDHS) conducted between 2000 and 2016, comprising a sample of 6767 children. Spatial analysis was performed using ArcGIS, and statistical analysis was carried out using SAS software. The spatial partial proportional odds model was used due to the violation of the proportional odds assumption. Full immunization coverage showed a gradual increase from 14.6% in 2000 to 39.4% in 2016. Spatial clustering of immunization coverage was observed in all survey years, indicating nonrandom distribution across regions. Children born to mothers with primary education were significantly more likely to be fully vaccinated than those whose mothers had no education. The model identified several significant predictors of immunization status, including region, residence, maternal education, religion, household wealth, maternal employment, place of delivery, antenatal care, and health worker visits. A significant negative spatial auto-covariance suggested that areas with low coverage were often surrounded by higher-coverage zones. Targeted interventions, particularly in identified hotspot areas, and increased public health education are recommended, along with further research using recent data.

Very short answer questions (VSAQs) have gained attention for their superior psychometric properties compared to multiple-choice questions (MCQs). While VSAQs require knowledge recall, MCQs primarily involve knowledge recognition. This difference in cognitive processes may lead to varying cognitive workloads, defined as the amount of mental processing in working memory. Previous studies have not demonstrated consistent differences, likely due to reliance on self-reported measures. Eye tracking provides objective, process-level indicators of cognitive workload. This study investigated whether answering VSAQs requires a higher cognitive workload than answering MCQs. In a within-subject randomized crossover experiment, sixth-year medical students answered both VSAQs and MCQs. Cognitive workload was measured using screen-based eye tracking, focusing on the number of fixations and revisitations as objective indicators of mental effort. Data were analyzed using mixed-effects models. Thirty-four medical students participated, yielding 1,326 observations, which is the multiplication of the number of students by the number of questions (39 questions). Mixed-effects models showed a significant effect of question type on both workload indicators: VSAQs elicited more fixations and revisitations than MCQs (β_std = 0.30-0.39, p < .001). This effect remained after controlling for accuracy. Incorrect answers were associated with higher workload (β_std = -0.15--0.16, p < .01). Heatmaps confirmed these findings, showing denser fixations on key diagnostic features for VSAQs and on answer options for MCQs. Answering VSAQs imposed a higher cognitive workload than MCQs. The presence of answer options in MCQs may reduce workload by providing unintentional cues, while VSAQs require active retrieval. Eye tracking proved valuable for distinguishing cognitive workload across assessment formats.

Interleukin (IL)-1β is known to promote lung cancer growth in both humans and mice. However, in the context of the current standard of care, which includes chemotherapy and immune checkpoint inhibitors, IL-1β can overcome resistance.