Intestinal inflammation marker calprotectin regulates epithelial intestinal zinc metabolism and proliferation in mouse jejunal organoids.

Calprotectin (CP), a heterodimer of S100A8 and S100A9, is expressed by neutrophils and a number of innate immune cells and is used widely as a marker of inflammation, particularly intestinal inflammation. CP is a ligand for toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, CP can act as a microbial modulatory agent via a mechanism termed nutritional immunity, depending on metal binding, most notably Zn2+. The effects on the intestinal epithelium are largely unknown. In this study we aimed to characterize the effect of calprotectin on mouse jejunal organoids as a model epithelium, focusing on Zn2+ metabolism and cell proliferation. CP addition upregulated the expression of the Zn2+ absorptive transporter Slc39a4 and of methallothionein Mt1 in a Zn2+-sensitive manner, while downregulating the expression of the Zn2+ exporter Slc30a2 and of methallothionein 2 (Mt2). These effects were greatly attenuated with a CP variant lacking the metal binding capacity. Globally, these observations indicate adaptation to low Zn2+ levels. CP had antiproliferative effects and reduced the expression of proliferative and stemness genes in jejunal organoids, effects that were largely independent of Zn2+ chelation. In addition, CP induced apoptosis modestly and modulated antimicrobial gene expression. CP had no effect on epithelial differentiation. Overall, CP exerts modulatory effects in murine jejunal organoids that are in part related to Zn2+ sequestration and partially reproduced in vivo, supporting the validity of mouse jejunal organoids as a model for mouse epithelium.

Adaptive laboratory evolution of Clostridium autoethanogenum to metabolize CO2 and H2 enhances growth rates in chemostat and unravels proteome and metabolome alterations.

Gas fermentation of CO2 and H2 is an attractive means to sustainably produce fuels and chemicals. Clostridium autoethanogenum is a model organism for industrial CO to ethanol and presents an opportunity for CO2-to-ethanol processes. As we have previously characterized its CO2/H2 chemostat growth, here we use adaptive laboratory evolution (ALE) with the aim of improving growth with CO2/H2. Seven ALE lineages were generated, all with improved specific growth rates. ALE conducted in the presence of 2% CO along with CO2/H2 generated Evolved lineage D, which showed the highest ethanol titres amongst all the ALE lineages during the fermentation of CO2/H2. Chemostat comparison against the parental strain shows no change in acetate or ethanol production, while Evolved D could achieve a higher maximum dilution rate. Multi-omics analyses at steady state revealed that Evolved D has widespread proteome and intracellular metabolome changes. However, the uptake and production rates and titres remain unaltered until investigating their maximum dilution rate. Yet, we provide numerous insights into CO2/H2 metabolism via these multi-omics data and link these results to mutations, suggesting novel targets for metabolic engineering in this bacterium.

Ion uptake in naturally acidic water.

The first studies on ion regulation in fish exposed to low pH, which were inspired by the Acid Rain environmental crisis, seemed to indicate that ion transport at the gills was completely and irreversibly inhibited at pH 4.0-4.5 and below. However, work on characid fish native to the Rio Negro, a naturally acidic, blackwater tributary of the Amazon River, found that they possess ion transport mechanisms that are completely insensitive to pHs as low as 3.25. As more species were examined it appeared that pH-insensitive transport was a trait shared by many, if not most, species in the Order Characiformes. Subsequently, a few other species of fish have been shown to be able to transport ions at low pH, in particular zebrafish (Danio rerio), which show rapid recovery of Na+ uptake at pH 4.0 after initial inhibition. Measurements of rates of Na+ transport during exposure to pharmacological agents that inhibit various transport proteins suggested that characiform fish do not utilize the generally accepted mechanisms for Na+ transport that rely on some form of H+ extrusion. Examination of zebrafish transport at low pH suggest the rapid recovery may be due to a novel Na+/K+ exchanger, but after longer term exposure they may rely on a coupling of Na+/H+ exchangers and NH3 excretion. Further work is needed to clarify these mechanisms of transport and to find other acid-tolerant species to fully gain an appreciation of the diversity of physiological mechansisms involved.

The influence of age, period, and cohort factors on the incidence of kidney cancer in Spain 1990-2019: Evidence from the global burden of disease study.

OBJECTIVE: This study aimed to assess the influence of age, period, and cohort (A-P-C) factors on kidney cancer (KC) incidence trends in Spain from 1990 to 2019. METHODS: Employing data from the Global Burden of Disease Study 2019, we employed joinpoint analysis to determine long-term patterns and A-P-C modelling to quantify net drift, local drift, longitudinal age curves, and rate ratios (RRs) of period and cohort effects. RESULTS: Over the period 1990-2019, an estimated 142,811 cases of KC were diagnosed in Spain. A consistent upward trend in KC incidence was observed for both men and women, with the male-to-female ratio remaining stable at 2.6. Joinpoint analysis identified three distinct periods for men: An initial period (1990-1995) characterised by a significant increase in rates, a subsequent period (1995-2016) characterised by a slowdown in the rate of increase, and a final period (2016-2019) in which rates have plateaued. In women, 2 time periods were observed: an initial period (1990-2007) in which rates increased significantly, followed by a period of stabilization (2007-2019). Men born in the early-mid 20th century had a rising KC risk, peaking in the 1960s. Women's risk rose steadily, peaking in the late 1990s. CONCLUSION: A-P-C analysis reveals steady KC incidence increase in both genders over three decades. This highlights the need for targeted public health policies and effective prevention strategies.

[Translated article] Prurigiform Angiomatosis: A New Term for Describing the Prominent Dermal Angiomatoid Proliferation Underlying Epidermal Changes in Prurigo Nodularis/Lichen Simplex Chronicus.

Vascular hyperplasia is a common finding in prurigo nodularis/lichen simplex chronicus (LSC). The term prurigiform angiomatosis was recently proposed to describe a histologic pattern characterized by prominent vascular hyperplasia in patients with LSC. The aim of this study was to identify cases of LSC with this pattern and analyze associations with clinical and pathologic features and disease course. We reviewed 54 cases of histologically confirmed LSC and detected findings consistent with prurigiform angiomatosis in 10 (18.5%). The patients (7 men, 3 women) had a mean age of 59.7 years. The lesions were pruritic and predominantly located on the extremities and trunk. The most notable histologic finding was vascular proliferation in the superficial dermis associated with a lymphocytic inflammatory infiltrate. Recognition of prurigiform angiomatosis is important as it helps not only to distinguish LSC from other entities (mainly vascular tumors) but also to detect lesions that need to be surgically excised due to poor response to topical treatment.

Electroporación irreversible: ampliando las fronteras de la ablación / Irreversible electroporation: Beyond the limits of tumor ablation

La electroporación irreversible o IRE (irreversible electroporation) es una técnica de ablación tumoral no térmica basada en la aplicación de pulsos eléctricos de alto voltaje entre pares de agujas insertadas alrededor de un tumor. La corriente generada favorece la creación de nanoporos en la membrana plasmática, desencadenando la apoptosis. Por ello, la IRE puede utilizarse de manera segura en localizaciones cercanas a estructuras vasculares delicadas, contraindicadas para el resto de técnicas termoablativas. Actualmente la IRE se emplea con éxito para la ablación de tumores en páncreas, riñón e hígado y, de manera muy extendida, como opción terapéutica focal para el cáncer de próstata. La necesidad de un manejo anestésico específico y la colocación precisa y en paralelo de múltiples agujas implican un alto nivel de complejidad, siendo necesaria una gran experiencia del equipo intervencionista. No obstante, se trata de una técnica muy prometedora con una gran capacidad inmunológica sistémica que puede provocar un efecto a distancia del tumor tratado (efecto abscopal).(AU)

Irreversible electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated. Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer. The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).(AU)

Irreversible electroporation: Beyond the limits of tumor ablation.

Irreversible Electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated. Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer. The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).

Effect of water calcium, copper, and silver on branchial Na+ permeability in a characid and cichlid fish.

We tested the hypothesis that water Ca2+ is involved in control of branchial Na+ permeability in low pH tolerant convict cichlids and black neon tetras. We measured Na+ efflux in water with different Ca2+ concentrations during exposure to low pH, silver, and copper, at levels which are known to stimulate Na+ efflux. For convict cichlids at pH 7.5 exposure to 0 µmol L-1 Ca2+caused Na+ efflux to rise 2.5 times above controls at 100 µmol L-1 Ca2+. However, raising [Ca2+] to 500 µmol L-1 had no effect. Upon exposure to pH 3.5 (control [Ca2+]) Na+ efflux rose almost 5× and increasing the [Ca2+] 5-fold did not reduce the magnitude of stimulation. Exposure to 1 µmol L-1 silver and 25 µmol L-1 copper stimulated Na+ efflux 7×, and 2×, respectively. Raising [Ca2+] concentration during metal exposure halved the stimulation of Na+ efflux caused by silver, and eliminated the stimulation elicited by copper. For black neon tetras raising or lowering water [Ca2+] had no effect on Na+ efflux at pH 7.5. Exposure to pH 3.5 caused Na+ efflux to rise 2.5× but changing [Ca2+] had no effect. Exposure to 1 µmol L-1 silver, or 25 µmol L-1 copper caused Na+ efflux of tetras to rise 4-fold and 3-fold, respectively. Raising [Ca2+] during silver exposure reduced the stimulation of Na+ efflux by about 50%, but during copper exposure increased [Ca2+] had no effect on stimulation of Na+ efflux. These results suggest water Ca2+ plays a role in control of branchial Na+ permeability in cichlids, but perhaps not tetras. In addition, the silver and copper concentrations required to inhibit Na+ uptake and stimulate Na+ efflux were higher than the concentrations used on non-characids and non-cichlids, which indicates that our fish are much more tolerant of these metals.

Psychosocial Determinants of Mental Healthcare Use Among Mexican-origin Women from Farmworker Families in Southern California.

Little is known about the contribution of psychosocial factors related to mental healthcare use among Mexican-origin women from farmworker families. Therefore, this study assessed relationships between acculturative stress, depressive symptoms, mental healthcare service use, and preferences for seeking care. Linear and logistic regression models and chi-square tests were performed to analyze survey data from 78 Mexican-origin women from farmworker families. Women were recruited in collaboration with promotoras and completed measures of acculturative stress, depressive symptoms, and mental healthcare use and preferences. Overall, 29.5% of the sample reported clinically significant depressive symptomatology. Acculturative stress was positively associated with depressive symptoms (b = 0.43, 95%CI = 0.27,0.59) after controlling for years in the U.S., primary language, and demographic characteristics. In addition, acculturative stress was associated with lower odds of mental healthcare use (OR = 0.96) after controlling for years in the U.S. and depressive symptoms. However, this association was no longer statistically significant when controlling for health insurance status and access to transportation. Mexican-origin women with high levels of acculturative stress were significantly more likely to seek care from a psychiatrist/psychologist than their peers (54.3% vs. 45.7%); however, this preference was not indicative of their use of mental healthcare services. Results suggest that acculturative stress is a risk factor for depressive symptoms and might contribute to a delay in seeking mental healthcare services in Mexican-origin women from farmworker families. Thus, interventions for this group should address aspects of acculturative stress as a strategy to increase mental health services use.

Effect of a dairy farmworker stewardship training program on antimicrobial drug usage in dairy cows.

Antimicrobial use (AMU) is critical to preserving animal health and welfare. However, the development of antimicrobial resistance (AMR) represents a public health threat. Although most antimicrobials used on the farm require a veterinarian prescription, farmworkers make daily on-farm treatment decisions. Therefore, farmworker training is vital to promote responsible AMU. This research project aimed to evaluate the impact of farmworker antimicrobial stewardship (AMS) training on the quantity of AMU on dairy farms in Ohio and California. We hypothesized that farms receiving AMS training would have reduced AMU in dairy cattle compared with farms where training wasn't administered. We designed a quasi-experimental study with 18 conventional dairy farms enrolled in Ohio and California. Twelve farms received AMS training and 6 farms did not. AMS program included a 12-week training focused on accurate identification of cows requiring antimicrobial treatment. We quantified AMU by collecting used drug containers, manually counted by researchers during farm visits. Treatment incidence (TI) was calculated using animal daily-doses (ADD), and Poisson regression models were used to analyze the TI data. Disease incidence rate (DIR) in lactating cows was 2.2, 1.5, 1.0, 0.4, 0.3, 0.2, and 0.03/1,000 cow-days for mastitis, lameness, metritis, pneumonia, retained placenta, diarrheas, and other diseases (e.g., conjunctivitis, injuries), respectively. The highest TI by antimicrobial class was cephalosporin (5.9), penicillin (5.2), tetracyclines (0.4), lincosamides (0.2), and sulfonamides (0.1 ADD/1,000 cow-days). Among the trained farms using a within-treatment group analysis, no significant differences were observed in TI pre-intervention (10.9) compared with TI post-intervention (10.3) ADD/1,000 cow-days. Treatment incidence from the training group was (10.8) and although numerically lower, it was not significantly different compared with TI in the control groups at (13.9) ADD/1,000 cow-days (rate ratio = 0.77, CIs = 0.25-2.38). Future research on AMS should incorporate farmworker training with social science approaches to overcome barriers and promote on-farm responsible use.

[Incidence of pelvic and acetabular fractures in the elderly due to high energy trauma]. / Incidencia de fracturas de pelvis y acetábulo en el adulto mayor por trauma de alta energía.

INTRODUCTION: as the population pyramid gets inverted, more active and longer lives are lived, geriatric patients with high energy trauma (HET) become more frequent; requiring more resources, getting worse results with more perioperative complications, coupled with a fragile state of health and osteopenia, make these fractures difficult to manage. With the hypothesis that the incidence of pelvic and acetabular fractures in the elderly due to HET is higher than that reported in the world literature, the research question was generated: What is the incidence of pelvic and acetabular fractures in the elderly due to HET, in a 5-year period? MATERIAL AND METHODS: with the authorization of the Ethics Committee, an observational study of a retrospective cohort was carried out, using medical records, identifying the incidence of these fractures, surgically treated in our institution Clínica Las Vegas, Medellin, Colombia, a level III hospital, from July 1, 2016 to June 30, 2021. RESULTS: a cumulative incidence of 1.95 new cases per 100,000 person-years was calculated, a prevalence of 13.8%; resulting in a higher incidence and prevalence, confirming our hypothesis. CONCLUSION: treatment should be aimed at improving quality of life with stable fixation, identification and treatment of associated injuries, minimizing the risk of mechanical complications and prioritizing the reinforcement of preventive measures, also in the improvement of male role behavior, whom, as it seems, will keep carrying out risky activities despite their age.

INTRODUCCIÓN: a medida que se invierte la pirámide poblacional, se viven vidas más largas y activas, se vuelven más frecuentes los pacientes geriátricos con trauma de alta energía; requiriendo más recursos, obteniéndose peores resultados, con más complicaciones perioperatorias, hacen a estas fracturas difíciles de manejar. Establecida la hipótesis de que la incidencia de las fracturas de pelvis y acetábulo, en el adulto mayor por trauma de alta energía, es superior a la reportada en la literatura mundial, se generó la pregunta de investigación: ¿Cuál es la incidencia de fracturas de pelvis y acetábulo por trauma de alta energía en el adulto mayor en un período de cinco años? MATERIAL Y MÉTODOS: una vez obtenida la autorización del Comité de Ética, se realizó un estudio observacional de una cohorte retrospectiva, utilizando registros médicos, identificando la incidencia de estas fracturas, tratadas quirúrgicamente en nuestro hospital de III nivel, Clínica Las Vegas, Medellín, Colombia, del 1 de Julio de 2016 a 30 de Junio de 2021. RESULTADOS: se calculó una incidencia acumulada de 1.95 nuevos casos por cada 100,000 personas-año, una prevalencia de 13.8%; resultando en una mayor incidencia y prevalencia, confirmándose nuestra hipótesis. CONCLUSIÓN: el tratamiento debe orientarse a mejorar la calidad de vida con una fijación estable, identificación y tratamiento de lesiones asociadas, minimizando el riesgo de complicaciones mecánicas y priorizar el reforzamiento de medidas preventivas y a la mejora del comportamiento del rol masculino, que aparentemente, seguirán realizando actividades de riesgo a pesar de su edad.

Prurigiform Angiomatosis: A New Term for Describing the Prominent Dermal Angiomatoid Proliferation Underlying Epidermal Changes in Prurigo Nodularis/Lichen Simplex Chronicus. / Angiomatosis prurigiforme: una nueva entidad propuesta para la proliferación angiomatoide dérmica prominente subyacente a los cambios epidérmicos de prurigo nodularis/liquen simple crónico.

Vascular hyperplasia is a common finding in prurigo nodularis/lichen simplex chronicus (LSC). The term prurigiform angiomatosis was recently proposed to describe a histologic pattern characterized by prominent vascular hyperplasia in patients with LSC. The aim of this study was to identify cases of LSC with this pattern and analyze associations with clinical and pathologic features and disease course. We reviewed 54 cases of histologically confirmed LSC and detected findings consistent with prurigiform angiomatosis in 10 (18.5%). The patients (7 men, 3 women) had a mean age of 59.7 years. The lesions were pruritic and predominantly located on the extremities and trunk. The most notable histologic finding was vascular proliferation in the superficial dermis associated with a lymphocytic inflammatory infiltrate. Recognition of prurigiform angiomatosis is important as it helps not only to distinguish LSC from other entities (mainly vascular tumors) but also to detect lesions that need to be surgically excised due to poor response to topical treatment.

Gaussian and Gaussian-pulsed-like Fermi velocity graphene structures.

Gaussian and Gaussian-related structures are quite attractive due to its versatility to modulate the electronic transport, including its possibility as electron filters. Here, we show that these non-conventional profiles are not the exception when dealing with Fermi velocity barriers in monolayer graphene. In particular, we show that Gaussian Fermi velocity graphene barriers (G-FVGBs) and Gaussian-pulsed-like Fermi velocity graphene superlattices (GPL-FVGSLs) can serve as electron band-pass filters and oscillating conductance structures. We reach this conclusion by theoretically studying the transmission and transport properties of the mentioned structures. The study is based on the continuum model, the transfer matrix method and the Landauer-Büttiker formalism. We find nearly flat transmission bands or pass bands for G-FVGBs modulable through the system parameters. The pass bands improve as the maximum ratio of Fermi velocities (ξmax) increases, however its omnidirectional range is reduced. These characteristics result in a decaying conductance (integrated transmission) withξmax. The integrated transmission remains practically unaltered with the size of the system due to the saturation of the electron pass band filtering. In the case of GPL-FVGSLs the GPL profile results in regions of high transmission probability that can merge as flat transmission minibands if the pulse fraction and the superlattice parameters are appropriately tuned. The GPL profile also results in conductance (integrated transmission) oscillations that can be multiplied or reduced in number by adjusting the pulse fraction as well as the superlattice parameters.

Association between depressive and anxious symptoms with cognitive function and quality of life in drug-resistant epilepsy.

•Depressive/anxious disorders and cognitive impairment are frequent comorbidities in epilepsy and have a more deleterious effect in DRE.•Studies concerning the relationship between anxiety and depression and cognitive performance in DRE are scarce.•Higher scores in HADS are associated with lower QOLIE-31 scores and might be considered as predictors of QOL in DRE.•A relationship between anxious and depressive symptoms -measured with HADS and SCL-90R- and cognition might not exist.•There remains an unexplored study area regarding this relationship which requires more attention to improve the assessment of DRE.

The Children, Caregivers, and Community (C3) study of together growing strong: A protocol for an observational, place-based initiative in Sunset Park, Brooklyn.

Reaching population-level impact for families in poverty requires moving beyond a sole focus on individuals, to a wider focus on interactions between individuals and their broader environmental contexts. Place-based initiatives have emerged as a policy response to promote community-level change around these broader interactions between individuals and their local communities through addressing long-standing disparities in housing, employment, education, and health. Together Growing Strong (TGS) is one such place-based initiative focused on transforming the health, wellbeing, and development of young children and their families in Sunset Park, Brooklyn. The Children, Caregivers, and Community (C3) Study is an outcomes-based study designed to assess the trajectories of children and families in Sunset Park along indicators such as family health and wellbeing and child development in relation to TGS program participation. The aims, scope, and protocol of the C3 Study are the subjects of this paper.

Development and validation of a clinical score for early diagnosis of constipation in critically ill children.

Constipation affects almost 50% of critically ill pediatric patients and is related to their morbidity and mortality. However, little attention is paid to it and it is diagnosed late and when there are already complications. The objective of this study is to develop and validate a score to identify critically ill children with high risk of constipation 48 h after admission. A single center two phase-study was carried out; the first one (retrospective observational study) to develop the score and the second one to validate it in another prospective observational study. Children between 15 days of life and 18 years old admitted to the PICU for more than 3 days were included. Demographic and clinical data during the first 48 h after PICU admission were collected. Univariate and multivariate analysis and ROC curves were used to develop and validate the score. Data from 145 patients (62.8% boys) with a mean age of 34.9 ± 7.3 months were used to develop the score. Independent factors identified to develop the score were: weight > 7 kg, admission to PICU after surgery, need of vasoconstrictors, doses of fentanyl ≥ 2 mcg/kg/h, and initiation of enteral nutrition later than 48 h after admission. Two cut-off values were identified to set low constipation risk (< 5.7 points) and high constipation risk (> 6.2 points). This score was validated in 124 patients showing a sensibility of 63.2%, specificity of 95.5% and a positive/negative predictive values (P/NPV) of 100% and 82.1% respectively to identify constipated patients. This is the first score to identify high constipation risk in critically ill children. This score is easy to apply, and internal validation has shown a PPV of 100%.