Surge in Imported Cutaneous Leishmaniasis Cases from Mexico in 2023: A Case Series.

In Europe, American cutaneous leishmaniasis caused by Leishmania mexicana is a rare imported disease. A series of six cases in 2023 is a noteworthy escalation at our institutions compared to the past two decades. This surge is likely linked to an increase of cases and environmental changes in South-Eastern Mexico.

The nucleoid protein HU positively regulates the expression of type VI secretion systems in Enterobacter cloacae.

Enterobacter cloacae is an emerging pathogen isolated in healthcare-associated infections. A major virulence factor of this bacterium is the type VI secretion system (T6SS). The genome of E. cloacae harbors two T6SS gene clusters (T6SS-1 and T6SS-2), and the functional characterization of both systems showed that these two T6SSs are not expressed under the same conditions. Here, we report that the major histone-like protein HU positively regulates the expression of both T6SSs and, therefore, the function that each T6SS exerts in E. cloacae. Single deletions of the genes encoding the HU subunits (hupA and hupB) decreased mRNA levels of both T6SS. In contrast, the hupA hupB double mutant dramatically affected the T6SS expression, diminishing its transcription. The direct binding of HU to the promoter regions of T6SS-1 and T6SS-2 was confirmed by electrophoretic mobility shift assay. In addition, single and double mutations in the hup genes affected the ability of inter-bacterial killing, biofilm formation, adherence to epithelial cells, and intestinal colonization, but these phenotypes were restored when such mutants were trans-complemented. Our data broaden our understanding of the regulation of HU-mediated T6SS in these pathogenic bacteria. IMPORTANCE: T6SS is a nanomachine that functions as a weapon of bacterial destruction crucial for successful colonization in a specific niche. Enterobacter cloacae expresses two T6SSs required for bacterial competition, adherence, biofilm formation, and intestinal colonization. Expression of T6SS genes in pathogenic bacteria is controlled by multiple regulatory systems, including two-component systems, global regulators, and nucleoid proteins. Here, we reported that the HU nucleoid protein directly activates both T6SSs in E. cloacae, affecting the T6SS-related phenotypes. Our data describe HU as a new regulator involved in the transcriptional regulation of T6SS and its impact on E. cloacae pathogenesis.

Akkermansia muciniphila modifies the association between metal exposure during pregnancy and depressive symptoms in late childhood.

Emerging research suggests that exposures to metals during pregnancy and gut microbiome (GM) disruptions are associated with depressive disorders in childhood. Akkermansia muciniphila, a GM bacteria, has been studied for its potential antidepressant effects. However, its role in the influence of prenatal metal exposures on depressive symptoms during childhood is unknown. Leveraging a well-characterized pediatric longitudinal birth cohort and its microbiome substudy (n=112) and using a state-of-the-art machine-learning model, we investigated whether the presence of A.muciniphila in GM of 9-11-year-olds modifies the associations between exposure to a specific group of metals (or metal-clique) during pregnancy and concurrent childhood depressive symptoms. Among children with no A.muciniphila, a metal-clique of Zinc-Chromium-Cobalt was strongly associated with increased depression score (P<0.0001), whereas, for children with A.muciniphila, this same metal-clique was weakly associated with decreased depression score(P<0.4). Our analysis provides the first exploratory evidence hypothesizing A. muciniphila as a probiotic intervention attenuating the effect of prenatal metal-exposures-associated depressive disorders in late childhood.

Personal care products: an emerging threat to the marine bivalve Ruditapes philippinarum.

In the last few decades, there has been a growing interest in understanding the behavior of personal care products (PCPs) in the aquatic environment. In this regard, the aim of this study is to estimate the accumulation and effects of four PCPs within the clam Ruditapes philippinarum. The PCPs selected were triclosan, OTNE, benzophenone-3, and octocrylene. A progressive uptake was observed and maximum concentrations in tissues were reached at the end of the exposure phase, up to levels of 0.68 µg g-1, 24 µg g-1, 0.81 µg g-1, and 1.52 µg g-1 for OTNE, BP-3, OC, and TCS, respectively. After the PCP post-exposure period, the removal percentages were higher than 65%. The estimated logarithm bioconcentration factor ranged from 3.34 to 2.93, in concordance with the lipophobicity of each substance. No lethal effects were found although significant changes were observed for ethoxyresorufin O-demethylase activity, glutathione S-transferase activity, lipid peroxidation, and DNA damage.

Sociodemographic characteristics and their association with survival in women with cervical cancer.

BACKGROUND: In 2020, the highest incidence and mortality from cervical cancer (CC) were detected in low and middle-income countries. CC remains a health problem for women living in them. In Mexico, CC ranks second in cancer incidence and mortality in women. The main characteristics of this population are low income, low educational level, and inadequate medical coverage. The present study characterized the Mexican population by CC, and the sociodemographic variables that impacted overall survival (OS) were identified. METHODS: A retrospective study that included a cohort of patients with a confirmed diagnosis of CC at the Instituto Nacional de Cancerologia between 2003 and 2016. Information was collected on sociodemographic variables related to the disease and OS. RESULTS: Four thousand six hundred thirty-one patients were included. The median age was 51 years, 78.5% were unemployed, 44.4% lived in a rural/suburban area, 50.8% had a partner when collecting this information, and 74.3% were classified as having low socioeconomic status. Age, living in a rural/suburban area, more advanced stages of the disease, and not receiving cancer treatment were associated with lower OS. CONCLUSION: CC continues to affect mainly women with minimal resources, low educational levels, and living in marginalized areas. These characteristics influence the OS. Prevention and timely detection programs, education, and training focused on this population and with broader coverage are required to identify patients with CC at earlier stages.

EACVI survey on the evaluation of mitral regurgitation.

AIMS: To evaluate the diagnosis and imaging of patients with mitral regurgitation and the management in routine clinical practice across Europe, the EACVI Scientific Initiatives Committee performed a survey across European centres. In particular, the routine use of echocardiography, advanced imaging modalities, heart valve clinics and heart valve teams was explored. METHODS AND RESULTS: A total of 61 responders, mainly tertiary centres or university hospitals, from 26 different countries responded to the survey, which consisted of 22 questions. For most questions related to echocardiography and advanced imaging, the answers were relatively homogeneous and demonstrated good adherence to current recommendations. In particular, the centres used a multiparametric echocardiographic approach, and selected the effective regurgitant orifice and vena contracta width as their preferred assessments. Two-dimensional (2D) measurements are still the most widely used parameters to assess left ventricular structure, however the majority use three-dimensional (3D) trans-oesophageal echocardiography (TOE) to evaluate valve morphology in severe MR. The majority of centres reported the onsite availability and clinical use of ergometric stress echocardiography, cardiac computed tomography (CCT) and cardiac magnetic resonance imaging (CMR). Heart valve clinics and heart valve teams were also widely prevalent. CONCLUSION: Consistent with current guidelines echocardiography (TTE and TOE) remains the first line and central imaging modality for the assessment of mitral regurgitation although the complementary use of 3D TOE, CT and CMR appears to be growing. Heart valve clinics and heart valve teams are now widely prevalent.

Supplementation of vitamin E or a botanical extract as antioxidants to improve growth performance and health of growing pigs housed under thermoneutral or heat-stressed conditions.

BACKGROUND: Heat stress has severe negative consequences on performance and health of pigs, leading to significant economic losses. The objective of this study was to investigate the effects of supplemental vitamin E and a botanical extract in feed or drinking water on growth performance, intestinal health, and oxidative and immune status in growing pigs housed under heat stress conditions. METHODS: Duplicate experiments were conducted, each using 64 crossbred pigs with an initial body weight of 50.7 ± 3.8 and 43.9 ± 3.6 kg and age of 13-week and 12-week, respectively. Pigs (n = 128) were housed individually and assigned within weight blocks and sex to a 2 × 4 factorial arrangement consisting of 2 environments (thermo-neutral (21.2 °C) or heat-stressed (30.9 °C)) and 4 supplementation treatments (control diet; control + 100 IU/L of D-α-tocopherol in water; control + 200 IU/kg of DL-α-tocopheryl-acetate in feed; or control + 400 mg/kg of a botanical extract in feed). RESULTS: Heat stress for 28 d reduced (P ≤ 0.001) final body weight, average daily gain, and average daily feed intake (-7.4 kg, -26.7%, and -25.4%, respectively) but no effects of supplementation were detected (P > 0.05). Serum vitamin E increased (P < 0.001) with vitamin E supplementation in water and in feed (1.64 vs. 3.59 and 1.64 vs. 3.24), but not for the botanical extract (1.64 vs. 1.67 mg/kg) and was greater when supplemented in water vs. feed (P = 0.002). Liver vitamin E increased (P < 0.001) with vitamin E supplementations in water (3.9 vs. 31.8) and feed (3.9 vs. 18.0), but not with the botanical extract (3.9 vs. 4.9 mg/kg). Serum malondialdehyde was reduced with heat stress on d 2, but increased on d 28 (interaction, P < 0.001), and was greater (P < 0.05) for antioxidant supplementation compared to control. Cellular proliferation was reduced (P = 0.037) in the jejunum under heat stress, but increased in the ileum when vitamin E was supplemented in feed and water under heat stress (interaction, P = 0.04). Tumor necrosis factor-α in jejunum and ileum mucosa decreased by heat stress (P < 0.05) and was reduced by vitamin E supplementations under heat stress (interaction, P < 0.001). CONCLUSIONS: The addition of the antioxidants in feed or in drinking water did not alleviate the negative impact of heat stress on feed intake and growth rate of growing pigs.

The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?

Physiological concentrations of reactive oxygen species (ROS) play vital roles in various normal cellular processes, whereas excessive ROS generation is central to disease pathogenesis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor that regulates the cellular antioxidant systems in response to oxidative stress by governing the expression of genes encoding antioxidant enzymes that shield cells from diverse oxidative alterations. NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) have been the focus of numerous investigations in elucidating whether NRF2 suppresses tumor promotion or conversely exerts pro-oncogenic effects. NRF2 has been found to participate in various pathological processes, including dysregulated cell proliferation, metabolic remodeling, and resistance to apoptosis. Herein, this review article will examine the intriguing role of phase separation in activating the NRF2 transcriptional activity and explore the NRF2 dual impacts on tumor immunology, cancer stem cells, metastasis, and long non-coding RNAs (LncRNAs). Taken together, this review aims to discuss the NRF2 multifaceted roles in both cancer prevention and promotion while also addressing the advantages, disadvantages, and limitations associated with modulating NRF2 therapeutically in cancer treatment.

Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury.

OBJECTIVE: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. METHODS: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. RESULTS: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. CONCLUSIONS: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.

Urinary biomarkers associated with acute kidney injury in pediatric mechanical circulatory support patients.

BACKGROUND: In patients requiring mechanical circulatory support (MCS), the incidence of acute kidney injury (AKI) is between 37 and 63%. In this study, we performed an exploratory analysis evaluating the relationship of multiple urine biomarkers with AKI development in pediatric MCS patients. METHODS: This is a single center retrospective study in a pediatric cohort receiving MCS from August 2014 to November 2020. We measured 14 urine biomarkers of kidney injury on day 1 following MCS initiation and analyzed their association with development of AKI in the first 7 days of MCS initiation. RESULTS: Sixty patients met inclusion criteria. Patients with AKI were more likely to be supported by venoarterial extracorporeal membrane oxygenation (65% vs. 8.3%, p < 0.001), compared to the no AKI group and less likely to have ventricular assist devices (10% vs. 50%, p < 0.001). There was a significant increase in the median urine albumin and urine osteoactivin in the AKI group, compared to the no AKI group (p = 0.020 and p = 0.018, respectively). When normalized to urine creatinine (UCr), an increased log osteoactivin/UCr was associated with higher odds of AKI development (OR: 2.05; 95% CI: 1.07, 4.44; p = 0.028), and higher log epidermal growth factor (EGF)/UCr (OR: 0.41; 95% CI: 0.15, 0.96) was associated with decreased odds of AKI. CONCLUSIONS: Early increase in urine osteoactivin is associated with AKI development within 7 days of MCS initiation in pediatric patients. Contrary, an increased urine EGF is associated with kidney protection. A higher resolution version of the Graphical abstract is available as Supplementary information.

Secular trends in blood lead concentrations of school-age children in Montevideo, Uruguay from 2009 to 2019.

Lead exposure continues to be a public health problem globally, yet very few countries perform systematic biomonitoring or surveillance of children's blood lead levels (BLLs). Secular trends in children's BLLs have not been well characterized outside North America and Europe. In 2009-19, we conducted a series of non-representative cross-sectional surveys in Montevideo, Uruguay, enrolling children living in areas of the city with known or suspected lead contamination. Lead was measured with atomic absorption spectrometry on fasting venous blood samples. Of the 856 children representing independent (non-sibling) observations, 759 had BLL measures. Other missing data were imputed. Using linear and logistic regression models, we estimated the covariate-adjusted year to year difference in mean BLL and the likelihood of having BLL ≥5 and BLL ≥3.5 µg/dL. At the start of the study, mean ± SD BLL was 4.8 ± 2.6 µg/dL, and at the end 1.4 ± 1.4 µg/dL. The prevalence of BLL ≥5 and BLL ≥3.5 µg/dL also differed markedly between 2009 and 2019 (30.8% vs. 2.7% and 53.8% vs. 5.8%). Similarly, where 80.8% of children had BLL ≥2 µg/dL in 2011, in 2019 that number was 19.3%. The estimated year to year difference in BLL was ∼0.3 µg/dL. Despite this progress, pediatric lead exposure remains a problem in Montevideo. In years 2015-19, between 19 and 48% of school children had BLL ≥2 µg/dL, a level at which adverse neurobehavioral outcomes continue to be reported in the literature. Continued prevention and risk-reduction efforts are needed in Montevideo, including systematic surveillance of BLLs in all children.

Pre-clinical evaluation of biomarkers for the early detection of nephrotoxicity following alpha-particle radioligand therapy.

PURPOSE: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as an additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLT nephrotoxicity. METHODS: A bifunctional cyclic peptide, melanocortin 1 ligand (MC1L), labeled with [203Pb]Pb-MC1L, was used for [212Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [212Pb]Pb-MC1L in a dose-escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. RESULTS: Biodistribution analysis identified [212Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [212Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [212Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. CONCLUSION: Urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.

[Pituitary cryptococcoma: a strange case of secondary granulomatous hypophysitis]. / Cryptococcoma hipofisiario: un extraño caso de hipofisitis granulomatosa secundaria.

Hypophysitis is a pathology with low incidence and prevalence. Likewise, deep fungal infections in immunocompetent patients also represent a rare phenomenon. Even rarer is the case described below, where these two mentioned elements are combined, namely: pituitary cryptococcoma or granulomatous hypophysitis caused by said pathogen in a host without altered immune response. After research in PubMed, there are limited cases in the medical literature of granulomatous hypophysitis caused by Cryptococcus spp., which simulated a pituitary macroadenoma by clinical and imaging manifestations. We did not find reports in which there is no evidence of involvement of the meningeal tissue. The fungal etiology is scarcely described in the reference guidelines for hypophysitis and we believe that Cryptococcus spp. it should be taken into account in the differential diagnosis of secondary granulomatous hypophysitis since it is a ubiquitous pathogen and the treatment is substantially different from other entities. It becomes more relevant given the current trend towards the use of high-dose systemic glucocorticoids for the treatment of hypophysitis, which could have generated greater damage if the correct diagnosis had not been made.

La hipofisitis es una afección con baja incidencia y prevalencia. Asimismo, las infecciones profundas por hongos en pacientes inmunocompetentes también representan un fenómeno infrecuente. Más raro aún es el caso que se describe a continuación, en donde se conjugan estos dos elementos mencionados, a saber: cryptococcoma hipofisario o hipofisitis granulomatosa causado por dicho patógeno en un huésped sin alteración de la respuesta inmune. Luego de una búsqueda realizada en PubMed, existen limitados casos en la literatura médica de hipofisitis granulomatosa por Cryptococcus spp., que simuló por manifestaciones clínicas e imagenológicas un macroadenoma hipofisario. No encontramos informes en los que no haya evidencia de afectación del tejido meníngeo. La etiología micótica está escasamente descrita en las guías de referencia para hipofisitis y creemos que Cryptococcus spp. debe ser tenido en cuenta en el diagnóstico diferencial de las hipofisitis granulomatosas secundarias dado que es un patógeno ubicuo y el tratamiento es sustancialmente diferente a otras entidades. Cobra mayor relevancia ante la tendencia actual al uso de glucocorticoides sistémicos a altas dosis para el tratamiento de la hipofisitis, que podría haber generado mayor daño de no haberse hecho el diagnóstico correcto.

Aqueous Fraction from Cucumis sativus Aerial Parts Attenuates Angiotensin II-Induced Endothelial Dysfunction In Vivo by Activating Akt.

BACKGROUND: Endothelial dysfunction (ED) is a marker of vascular damage and a precursor of cardiovascular diseases such as hypertension, which involve inflammation and organ damage. Nitric oxide (NO), produced by eNOS, which is induced by pAKT, plays a crucial role in the function of a healthy endothelium. METHODS: A combination of subfractions SF1 and SF3 (C4) of the aqueous fraction from Cucumis sativus (Cs-Aq) was evaluated to control endothelial dysfunction in vivo and on HMEC-1 cells to assess the involvement of pAkt in vitro. C57BL/6J mice were injected daily with angiotensin II (Ang-II) for 10 weeks. Once hypertension was established, either Cs-AqC4 or losartan was orally administered along with Ang-II for a further 10 weeks. Blood pressure (BP) was measured at weeks 0, 5, 10, 15, and 20. In addition, serum creatinine, inflammatory status (in the kidney), tissue damage, and vascular remodeling (in the liver and aorta) were evaluated. Cs-AqC4 was also tested in vitro on HMEC-1 cells stimulated by Ang-II to assess the involvement of Akt phosphorylation. RESULTS: Cs-AqC4 decreased systolic and diastolic BP, reversed vascular remodeling, decreased IL-1ß and TGF-ß, increased IL-10, and decreased kidney and liver damage. In HMEC-1 cells, AKT phosphorylation and NO production were increased. CONCLUSIONS: Cs-AqC4 controlled inflammation and vascular remodeling, alleviating hypertension; it also improved tissue damage associated with ED, probably via Akt activation.

Catecholaminergic Polymorphic Ventricular Tachycardia and Gene Therapy: A Comprehensive Review of the Literature.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited channelopathy. In this review, we summarize the epidemiology, pathophysiology, clinical characteristics, diagnostics, genetic mutations, standard treatment, and the emergence of potential gene therapy. This inherited cardiac arrhythmia presents in a bimodal distribution with no association between sex or ethnicity. Six different CPVT genes have been identified, however, most of the cases are related to a heterozygous, gain-of-function mutation on the ryanodine receptor-2 gene (RyR2) and calsequestrin-2 gene (CASQ2) that causes delayed after-depolarization. The diagnosis is clinically based, seen in patients presenting with syncope after exercise or stress-related emotions, as well as cardiac arrest with full recovery or even sudden cardiac death. Standard treatment relies on beta-blockers, with add-on therapy, flecainide, and cardiac sympathetic denervation as second-line treatments. An implantable cardioverter-defibrillator is indicated for patients who have suffered a cardiac arrest. Potential gene therapy has emerged in the last 20 years and accelerated because of associated viral vector application in increasing the efficiency of prolonged cardiac gene expression. Nevertheless, human trials for gene therapy for CPVT have been limited as the population is rare, and an excessive amount of funding is required.

Effects of Five Coumarins and Standardized Extracts from Tagetes lucida Cav. on Motor Impairment and Neuroinflammation Induced with Cuprizone.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with no curative treatment, and the available therapies aim to modify the course of the disease. It has been demonstrated that extracts of Tagetes lucida have immunomodulatory and neuroprotective effects. This work induced motor damage and neuroinflammation in male BALB/c mice by oral administration of cuprizone (CPZ) (40 mg/kg) for five weeks. In addition, the extracts and coumarins of Tagetes lucida (25 mg/kg) were used to control these damage variables; during the experiment, animals were subject to behavioral tests, and at the end of 5 weeks, mice from each group were used to measure the integrity of biological barriers (brain, kidneys, and spleen) through the extravasation test with blue Evans dye. In another group of animals, the ELISA method measured the brain concentrations of IL-1ß, IL-4, IL-10, and TNF-α. The results presented here allow us to conclude that the extracts and coumarins IC, HN, PE, DF, and SC of Tagetes lucida exert a neuroprotective effect by controlling the motor damage and neuroinflammation by increasing the expression of IL-4 and IL-10 and decreasing IL-1ß and TNF-α; notably, these treatments also protect organs from vascular permeability increase, mainly the BBB, in mice with CPZ-induced experimental encephalomyelitis (VEH * p < 0.05). However, more studies must be carried out to elucidate the molecular mechanisms of the pharmacological effects of this Mexican medicinal plant.

Short-term effects and safety of a natural oral supplement containing glucosinolates, phytosterols, and citrus flavonoids compared with hormone treatment for the management of postmenopausal symptomatic women: a pilot single-center randomized phase 2 clinical trial.

OBJECTIVE: This study aimed to evaluate the short-term efficacy and safety of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids for menopausal symptoms in comparison with estrogen plus progestogen therapy (EPT) among postmenopausal women. METHODS: This was a pilot single-blinded, three-armed phase II randomized clinical trial, controlled with EPT. Sixty participants were randomly assigned to receive treatment for 3 months: (1) an oral herbal supplement of 1,500 mg/d (G1, n = 20), (2) an oral herbal supplement of 3,000 mg/d (G2, n = 20), or (3) conjugated equine estrogens 0.625 mg/d plus medroxyprogesterone acetate of 5 mg/d (EPT group, n = 20). The primary endpoint was the intensity of menopausal symptoms as measured using the Menopause-Specific Quality of Life Questionnaire (global and domain scores). The Menopause-Specific Quality of Life Questionnaire uses a 7-point scale to rate the symptom intensity, with higher scores indicating severity. The secondary endpoints were hormonal, lipid, and safety profiles. RESULTS: Fifty-four participants (n = 54) completed the study. The mean, model-estimated, and global menopausal symptom scores at 3 months were 85.8 in the EPT group, 61.3 in G1, and 62.5 in G2. Participants treated with the herbal compound had lower global (13.7 [6.9-20.4], P < 0.001) and physical symptom scores (6.6 [1.6-11.5], P = 0.002) on the second month and lower psychosocial symptom scores (3.8 [1.3 to 6.3], P < 0.001) on the third month of follow-up, compared with EPT. Conversely, participants receiving EPT showed better outcomes on vasomotor symptoms since the first month of treatment (-6.1 [-8.3 to -4.0], P < 0.001). The EPT group exhibited higher values of estradiol and lower follicle-stimulating hormone and luteinizing hormone since the first month of follow-up. Also, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significantly higher in this group than in G2. CONCLUSIONS: In this small single-blind exploratory trial, the oral herbal supplement was more efficacious in reducing global, physical, and psychosocial menopausal symptoms in the short term than EPT. However, further studies are needed to adequately assess the efficacy and safety of this herbal supplement in the treatment of menopausal symptoms.

Associations between parent-adolescent health-related conversations and mealtime media use among Hispanic families.

INTRODUCTION: Whereas parents play an important role in shaping the home environment, it is unknown whether health-related parent-adolescent conversations may be associated with different health-promoting parenting practices, such as limiting adolescent mealtime media use in Hispanic families. METHOD: For this cross-sectional analysis, Hispanic parents (n = 344; 40.4 ± 6.6 years; 89.2% female) of sixth- to eighth-grade adolescents self-reported the frequency of having health- or weight-related conversations with their adolescent child, and the frequency of adolescent mealtime media device use. Spearman's rank correlations were used to assess whether parent-adolescent health-related conversations are associated with mealtime media device use by adolescents. RESULTS: Over 75% of parents reported having conversations about healthy eating and being physically active at least a few times per week. Fewer parents reported having frequent weight-related conversations. Frequency of mealtime media use was low, except for television/movie watching (only 30% of parents reported their child rarely/never watching television during family meals). Having conversations related to the adolescent weighing too much was correlated with the mealtime use of television (r = .207; p < .001), cellphones (r = .134; p = .018), and headphones for music listening (r = .145; p = .010). Conversations about exercising to lose weight were correlated with television/movie watching during mealtimes (r = .129; p = .035). DISCUSSION: Findings suggest the co-occurrence of less health-promoting parenting behaviors, such as focusing on weight-related conversations and allowing the use of media devices during mealtimes. Focusing on health- rather than weight-related parent-adolescent conversations and implementing mealtime media use rules may have the potential to shape a home food environment which ultimately could improve an adolescent's overall health outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pre-clinical Evaluation of Biomarkers for Early Detection of Nephrotoxicity Following Alpha-particle Radioligand Therapy.

Purpose: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLTs nephrotoxicity. Methods: A bifunctional cyclic peptide, melanocortin ligand-1(MC1L), labeled with [ 203 Pb]Pb-MC1L, was used for [ 212 Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [ 212 Pb]Pb-MC1L in a dose escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. Results: Biodistribution analysis identified [ 212 Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [ 212 Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary Neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [ 212 Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. Conclusion: urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.

Percutaneous drainage and combined praziquantel-albendazole therapy: a novel approach for the treatment of simple echinococcal liver cysts.

Cystic echinococcosis (CE) is a worldwide helminthic zoonosis causing serious disease in humans. The WHO Informal Working Group on Echinococcosis recommends a stage-specific treatment approach of hepatic CE that facilitates the decision on what therapy option is most appropriate. Percutaneous aspiration, instillation of a scolicide, e.g., ethanol or hypertonic saline, and subsequent re-aspiration (PAIR) have been advocated for treating medium-size unilocular WHO-stage CE1 cysts. PAIR can pose a risk of toxic cholangitis because of spillage of ethanol in the case of a cysto-biliary fistula or of life-threatening hypernatriaemia when hypertonic saline is used. The purpose of our study is to develop an alternative, safe, minimally invasive method to treat CE1 cysts, avoiding the use of toxic topic scolicides.We opt for percutaneous drainage (PD) in four patients: the intrahepatic drainage catheter is placed under CT-fluoroscopy, intracystic fluid is aspirated, and the viability of intracystic echinococcal protoscolices is assessed microscopically. Oral praziquantel (PZQ) is added to albendazole (ABZ) instead of using topical scolicidals.Protoscolices degenerate within 5 to 10 days after PZQ co-medication at a cumulative dosage of 250 to 335 mg/kg, and the cysts collapse. The cysts degenerate, and no sign of spillage nor relapse is observed in the follow-up time of up to 24 months post-intervention.In conclusion, PD combined with oral PZQ under ABZ coverage is preferable to PAIR in patients with unilocular echinococcal cysts.