Porous and Meltable Metal-Organic Polyhedra for the Generation and Shaping of Porous Mixed-Matrix Composites.

Here, we report the synthesis of BCN-93, a meltable, functionalized, and permanently porous metal-organic polyhedron (MOP) and its subsequent transformation into amorphous or crystalline, shaped, self-standing, transparent porous films via melting and subsequent cooling. The synthesis entails the outer functionalization of a MOP with meltable polymer chains: in our model case, we functionalized a Rh(II)-based cuboctahedral MOP with poly(ethylene glycol). Finally, we demonstrate that once melted, BCN-93 can serve as a porous matrix into which other materials or molecules can be dispersed to form mixed-matrix composites. To illustrate this, we combined BCN-93 with one of various additives (either two MOF crystals, a porous cage, or a linear polymer) to generate a series of mixed-matrix films, each of which exhibited greater CO2 uptake relative to the parent film.

Barreras para una alimentación saludable: un análisis cualitativo de las semánticas emergentes en las comunidades escolares de Ciudad Sur

La literatura ha hecho hincapié en la centralidad que cumplen los entornos alimentarios en las elecciones alimentarias y en el estado nutricional de la población. Objetivo: identificar las percepciones de padres, madres y apoderados, profesionales de establecimientos educacionales, funcionarios municipales, y feriantes pertenecientes a la zona sur de Santiago de Chile, respecto a las barreras y limitaciones de la puesta en práctica de una alimentación saludable en el ambiente alimentario escolar. Método: se realizaron seis grupos focales agrupando a 50 actores claves vinculados a los establecimientos educacionales de Ciudad Sur utilizando una muestra no probabilística. Se aplicó un análisis de contenido mediante la técnica de codificación temática buscando relevar los universos semánticos emergentes. Resultados: se identificaron nueve barreras, o semánticas, que caracterizan limitantes a la realización de la alimentación saludable en los entornos escolares desde la perspectiva de los participantes: la familia, kioscos escolares, la salida de los establecimientos escolares, gusto, determinantes socioeconómicos, política pública, falta de conocimiento, publicidad y disponibilidad de productos sin sellos. Conclusiones: las limitaciones asociadas al ambiente alimentario doméstico tienen una representación significativamente alta (47,9%) y contienen un carácter de responsabilización individual en su enunciación. Esta cultura explicativa es opuesta a la evidencia científica y académica respecto al funcionamiento de la conducta alimentaria, y a la centralidad de los ambientes alimentarios respecto a la facilitación u obstaculización del consumo de alimentos saludables o adecuados.

Literature has emphasized on food environments centrality in food choices and nutritional status. Objective: identify social perceptions of fathers, mothers and guardians, professionals from educational establishments, municipal officials, and stallholders belonging to the southern area of Santiago de Chile, regarding limitations of healthy diet implementation on school environments. Method: six focus groups were carried out grouping 50 key actors linked to educational establishments using a non-probabilistic sample. A content analysis was applied through thematic coding technique seeking to reveal emerging semantic universes. Results: Nine barriers, or semantics, were identified characterizing limitations to healthy eating habits in school environments: family, school kiosks, leaving school establishments, taste, socioeconomic determinants, public policy, lack of knowledge, publicity, and availability of products without seals. Conclusions: limitations associated with domestic food environment have a significantly high representation (47,9%) and contain an individualized responsibility feature. This explanatory culture is opposed to scientific and academic evidence regarding the functioning of eating behavior, and the centrality of food environments facilitating or hindering healthy food consumption.

A novel treatment to enhance survival for end stage triple negative breast cancer using repurposed veterinary anthelmintics combined with gut­supporting/immune enhancing molecules.

Patients with end­stage metastatic disease have limited treatment options and those diagnosed with triple negative breast cancer (Her2, Estrogen receptor, Progesterone receptor) have a poor prognosis. Using a triple negative mammary tumor model selected for brain metastasis (4T1Br4) in the mouse, treatment options that may increase survival when therapeutics are applied at post­metastasis were assessed. Anti­parasitic benzimidazoles (BZs) destabilize microtubules, inhibit metabolic pathways, reduce cell proliferation, and induce apoptosis in tumor cells. Co­administration of two BZs was selected, oxfendazole (OFZ) and parbendazole (PBZ), shown to overcome resistance development in anthelmintic effects by imposing metabolic delay to assess if multiple BZ approach is also suitable to enhance anticancer effects. It has been previously reported that treatment of mammary tumor­bearing mice at an early stage with chitin microparticles (CMPs) decreased tumor growth and metastases by enhancing both innate M1 macrophage and TH1 adaptive immune response. Oral administration of CMPs was previously revealed to affect the gut in intestinal inflammation. A combination BZ (OFZ/PBZ) and CMP treatment was tested to target tumor development and metastasis and effects were compared in response to monotherapies of the same compounds or to untreated mice. The results demonstrated increased survival, decreased tumor cell proliferation, decreased metastasis in lungs and brain, increased levels of fecal SCFAs butyric, acetic, propionic and valeric acids with increased butyric and propionic acid levels in brain biopsies in combination treated compared with untreated mice. At the primary tumor, SCFA receptor FFAR2 expression was increased in combination treatment compared with untreated mice, suggestive of a non­invasive cancer phenotype. The superior cytotoxic effects of OFZ/PBZ were confirmed as opposed to single treatment with OFZ or PBZ using 3D spheroids generated from a human breast cancer cell line, MDA­MB­468. These data are compelling for treatment option possibility even at late stages of metastasized breast cancer.

Oxidative damage associated with exposure to heavy metals present in topsoils in central Chile.

Exposure to heavy metals may cause the overproduction of reactive oxygen species, generating oxidative stress and consequently, various harms to human health. The soil surrounding the Ventanas Industrial Complex, in Puchuncaví and Quintero municipal districts on the central Chilean coast, contains heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed the maximum permissible levels established by Italian soil standards (used as a reference). This study aimed to investigate the potential association between heavy metal exposure in humans and the levels of oxidative stress biomarkers in inhabitants of these locations. We took blood samples from 140 adults living in sites with high concentrations of heavy metals in the soil and compared them with blood samples from 140 adults living in areas with normal heavy metal concentrations. We assessed lipid peroxidation, damage to genetic material, and Total Antioxidant Capacity in these blood samples. Our results indicate an association between oxidative damage and heavy metal exposure, where the inhabitants living in exposed areas have a higher level of DNA damage compared with those living in control areas. Given that DNA damage is one of the main factors in carcinogenesis, these results are of interest, both for public health and for public policies aimed at limiting human exposure to environmental pollution.

Antiperistaltic Transverse Coloplasty: A Salvage Procedure in Extensive Bowel and Colorectal Resections to Avoid Intestinal Failure.

INTRODUCTION: After extensive small and colon resections, quality of life can be affected. We propose the antiperistaltic transverse coloplasty as a solution that allows for preservation of the transverse colon after both right and left colectomies while achieving a tension-free colorectal anastomosis slowing the transit and increasing the absorption time, resulting in better stool consistency and quality of life compared with an ileorectal anastomosis. METHODS: This technique was performed in a 41-year-old woman with Goblet cell adenocarcinoma of the appendix with peritoneal metastasis. The transverse colon is rotated anticlockwise over the axis of the middle colic vessels toward the left parietocolic flank and relocated to the usual position of the descending colon. RESULTS: After 1 year of follow-up, the patient led a normal life without parenteral nutrition with five bowel movements per day and a weight gain of 15%. CONCLUSIONS: The use of an antiperistaltic transverse coloplasty may be worthwhile to perform in cases of extensive bowel resections during cytoreductive surgery leading to short-bowel syndrome to avoid a permanent stoma or intestinal failure and improve patient outcomes.

Simultaneous Surgical Approach with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Concurrent Peritoneal and Liver Metastases of Colon Cancer Origin.

Background: Simultaneous liver resection and peritoneal cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial today. The aim of the study was to analyze the postoperative outcomes and survival of patients with advanced metastatic colon cancer (peritoneal and/or liver metastases). Methods: Retrospective observational study from a prospective maintained data base. Patients who underwent a simultaneous peritoneal cytoreduction and liver resection plus HIPEC were studied. Postoperative outcomes and overall and disease free survival were analyzed. Univariate and multivariate analyses were performed. Results: From January 2010 to October 2022, 22 patients operated with peritoneal and liver metastasis (LR+) were compared with 87 patients operated with peritoneal metastasis alone (LR-). LR+ group presented higher serious morbidity (36.4 vs. 14.9%; p: 0.034). Postoperative mortality did not reach statistical difference. Median overall and disease free survival was similar. Peritoneal carcinomatosis index was the only predictive factor of survival. Conclusions: Simultaneous peritoneal and liver resection is associated with increased postoperative morbidity and hospital stay, but with similar postoperative mortality and OS and disease free survival. These results reflect the evolution of these patients, considered inoperable until recently, and justify the trend to incorporate this surgical strategy within a multimodal therapeutic plan in highly selected patients.

A mesoporous Zr-based metal-organic framework driven by the assembly of an octatopic linker.

Metal-organic frameworks (MOFs) based on high-connected nets are generally very attractive due to their combined robustness and porosity. Here, we describe the synthesis of BCN-348, a new high-connected Zr-MOF built from an 8-connected (8-c) cubic Zr-oxocluster and an 8-c organic linker. BCN-348 contains a minimal edge-transitive 3,4,8-c eps net, and combines mesoporosity with thermal and hydrolytic stability. Encouraging results from preliminary studies on its use as a catalyst for hydrolysis of a nerve-agent simulant suggest its potential as an agent for detoxification of chemical weapons and other pernicious compounds.

Study of the biological activity of photoactive bipyridyl-Ru(II) complexes containing 1,3,5-triaza-7-phosphaadamantane (PTA).

The water-soluble ruthenium complex cis-[Ru(dcbpyH)2(PTAH)2]Cl2·3H2O (1) (dcbpy = 4,4'-dicarboxy-2,2'-bipyridine; PTA = 1,3,5-triaza-7-phosphaadamantane) has been synthesized and characterised by NMR, IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. The optical properties of 1 were studied, including photoactivation under visible light, as well as its biological properties, together with those of the previously published Ru complexes cis-[Ru(bpy)2(PTA)2]Cl2 (2), trans-[Ru(bpy)2(PTA)2](CF3SO3)2 (3) and cis-[Ru(bpy)2(H2O)(PTA)](CF3SO3)2 (4) (bpy = 2,2'-bipyridine). Anticancer activities of the complexes against human lung (A549), cervical (HeLa) and prostate (PC3) carcinoma cells were evaluated under dark conditions and upon photoactivation with visible light. None of the complexes exhibited cytotoxic activity in the absence of light irradiation (IC50 > 100 µM). However, after photoactivation, the cytotoxicity of complexes 1, 2 and 3 against the three cell lines markedly increased, resulting in IC50 values between 25.3 µM and 9.3 µM. Notably, these complexes did not show toxicity against red blood cells. These findings show the potential of complexes 1, 2 and, particularly, 3 for selective and controlled cancer photochemotherapy. The reactivity of the Ru complexes against DNA under UV-Vis irradiation was studied by analysing plasmid mobility. Experimental data shows that 4 unfolds supercoiled DNA (SC DNA) both in the dark and under visible irradiation, while 1 and 3 are only active under light, being 2 inactive in either case. The unfolding activities of complexes 3 and 4 were dependent on the air present in the reaction. The measured intracellular levels of reactive oxygen species (ROS) upon irradiation with complexes 1, 2 and 3 suggest that their mechanism of action is related to oxidative stress.

Monolithic Zirconium-Based Metal-Organic Frameworks for Energy-Efficient Water Adsorption Applications.

Space cooling and heating, ventilation, and air conditioning (HVAC) accounts for roughly 10% of global electricity use and are responsible for ca. 1.13 gigatonnes of CO2 emissions annually. Adsorbent-based HVAC technologies have long been touted as an energy-efficient alternative to traditional refrigeration systems. However, thus far, no suitable adsorbents have been developed which overcome the drawbacks associated with traditional sorbent materials such as silica gels and zeolites. Metal-organic frameworks (MOFs) offer order-of-magnitude improvements in water adsorption and regeneration energy requirements. However, the deployment of MOFs in HVAC applications has been hampered by issues related to MOF powder processing. Herein, three high-density, shaped, monolithic MOFs (UiO-66, UiO-66-NH2 , and Zr-fumarate) with exceptional volumetric gas/vapor uptake are developed-solving previous issues in MOF-HVAC deployment. The monolithic structures across the mesoporous range are visualized using small-angle X-ray scattering and lattice-gas models, giving accurate predictions of adsorption characteristics of the monolithic materials. It is also demonstrated that a fragile MOF such as Zr-fumarate can be synthesized in monolithic form with a bulk density of 0.76 gcm-3 without losing any adsorption performance, having a coefficient of performance (COP) of 0.71 with a low regeneration temperature (≤ 100 °C).

Modulation of Postprandial Plasma Concentrations of Digestive Hormones and Gut Microbiota by Foods Containing Oat ß-Glucans in Healthy Volunteers.

Cereal ß-glucans are beneficial health ingredients that reduce cholesterolemia and postprandial glycaemia. However, their impact on digestive hormones and gut microbiota is not yet fully established. Two randomized, double-blind, controlled studies were conducted. In the first study, 14 subjects ingested a breakfast with or without ß-glucan from oats (5.2 g). Compared to the control, ß-glucan increased orocecal transit time (p = 0.028) and decreased mean appetite score (p = 0.014) and postprandial plasma ghrelin (p = 0.030), C-peptide (p = 0.001), insulin (p = 0.06), and glucose (p = 0.0006). ß-glucan increased plasma GIP (p = 0.035) and PP (p = 0.018) without affecting leptin, GLP-1, PYY, glucagon, amylin, or 7α-hydroxy-4-cholesten-3-one, a biomarker of bile acid synthesis. In the second study, 32 subjects were distributed into 2 groups to ingest daily foods with (3 g/day) or without ß-glucan for 3 weeks; stools were collected before/after treatment. No changes in fecal microbiota composition/diversity (deep sequencing) were detected with ß-glucans. These results indicate that acute intake of 5 g ß-glucan slows transit time and decreases hunger sensation and postprandial glycaemia without affecting bile-acid synthesis, these changes being associated with decreased plasma insulin, C-peptide, and ghrelin, and increased plasma GIP and PP. However, regular daily intake of 3 g ß-glucan is not sufficient to have an effect on fecal microbiota composition.

Consultas nutricionales en menores de 9 años en la región del Maule, Chile, entre 2017-2021, efecto de estallido social y pandemia COVID-19

Introducción: La consulta nutricional es la primera línea de atención en niñas y niños en salud pública que presentan condiciones de malnutrición por déficit o exceso. Sin embargo, la atención a estos niños y niñas fue afectada por las movilizaciones sociales y la pandemia por COVID-19. Objetivo: Evaluar la tendencia de las consultas realizadas a menores de 9 años por profesional nutricionista en la región del Maule, Chile, desde el año 2017 a 2021. Métodos: Estudio descriptivo de corte longitudinal histórico basado en los datos de los Registros Estadísticos Mensuales (REM) del Servicio de Salud del Maule, las tendencias fueron analizadas con coeficiente de determinación (R2) mediante la regresión de Prais-Winsten. Resultados: Se analizaron 274.377 consultas nutricionales de niños/as menores de 9 años. 53,8% en clasificación de malnutrición por exceso y 12,1% en déficit. Se registró una disminución de 56,8% en las consultas nutricionales durante las movilizaciones sociales y un 92% al inicio de pandemia. Se observó una tendencia al aumento de las consultas por déficit nutricional, especialmente en menores de 12 meses (R2 0,633, β=4,45, p<0,001). Conclusión: La situación social y epidemiológica afectaron significativamente las atenciones nutricionales en salud pública. Es necesario dar una mayor visibilidad de los profesionales nutricionistas y promover el desarrollo de estrategias innovadoras para afrontar este escenario epidemiológico.

Background: The nutritional appointments is the first line of care for children with malnutrition or overweight in public primary health, but its normal functioning was affected by social mobilizations and the COVID-19 pandemic. Objective: To evaluate trends in consultations among children under 9 years of age in the Maule region, Chile, between 2017 and 2021. Methods: Descriptive longitudinal study based on data from the Monthly Statistical Records (REM) of the Maule Health Service, the trends were analyzed with coefficient of determination (R2) using Prais-Winsten regression. Results: 274,377 nutritional consultations were analyzed, of which 53.8% were overweight and 12.1% with malnutrition. A 56.8% decrease in nutritional consultations was recorded during social mobilizations and 92% at the beginning of the pandemic. A tendency to increase consultations due to malnutrition was observed, especially in children under 12 months of age (R2 0.633, β=4.45, p<0.001). Conclusion: The social and epidemiological situations significantly affected nutritional care in public health. It is necessary to give nutrition professionals greater visibility and promote the development of innovative strategies to deal with this epidemiological scenario.

Betel quid: New insights into an ancient addiction.

The use of areca nuts (areca) in the form of betel quids constitutes the fourth most common addiction in the world, associated with high risk for oral disease and cancer. Areca is a complex natural product, making it difficult to identify specific components associated with the addictive and carcinogenic properties. It is commonly believed that the muscarinic agonist arecoline is at the core of the addiction. However, muscarinic receptor activation is not generally believed to support drug-taking behaviour. Subjective accounts of areca use include descriptions of both sedative and stimulatory effects, consistent with the presence of multiple psychoactive agents. We have previously reported partial agonism of α4-containing nicotinic acetylcholine receptors by arecoline and subsequent inhibition of those receptors by whole areca broth. In the present study, we report the inhibition of nicotinic acetylcholine receptors and other types of neurotransmitter receptors with compounds of high molecular weight in areca and the ability of low molecular weight areca extract to activate GABA and glutamate receptors. We confirm the presence of a high concentration of GABA and glutamate in areca. Additionally, data also indicate the presence of a dopamine and serotonin transporter blocking activity in areca that could account for the reported stimulant and antidepressant activity. Our data suggest that toxic elements of high molecular weight may contribute to the oral health liability of betel quid use, while two distinct low molecular weight components may provide elements of reward, and the nicotinic activity of arecoline contributes to the physical dependence of addiction.

Cross-cultural adaptation and validation of a questionnaire on eating habits and physical activity of university students in confinement due to coronavirus disease.

OBJECTIVE: The purpose of the current study was to cross-culturally adapt and validate an online questionnaire to assess eating habits and physical activity of university students under confinement due to coronavirus disease (COVID-19). DESIGN: Generation of a cross-sectional online survey to university students conducted during confinement due to COVID-19. The study was divided into two phases. SETTINGS: Students, Chile. PARTICIPANTS: Phase 1 considered the process of translation and back translation, expert panel, cultural adaptation and the generation of a pilot to validate a preliminary format of the questionnaire. In Phase 2, information from the instrument was collected from two hundred and sixty-eight university students, ages 16 to 30 years old, with a mean age of 21·6 (3·3) The major proportion of participants were female (82 %). RESULTS: The adapted questionnaire was statistically validated in three dimensions: (A) eating habits and behaviours during quarantine, (B) perception of risk and (C) physical activity changes during the quarantine. The reliability of Cronbach's α for dimensions A, B and C was 0·59, 0·85 and 0·97, respectively. The complete questionnaire obtained 0·61 in internal consistency and 0·61 (0·58-0·67) ICC reliability. A statistically significant positive correlation matrix was observed. CONCLUSIONS: This questionnaire is a practical tool to obtain accurate information about the relation of COVID-19 confinement on people's eating habits and physical activity. Therefore, it could contribute to establishing appropriate strategies to prevent negative effects on people's health.

Cephalic pancreaticoduodenectomy for ductal adenocarcinoma in the elderly. Can we do it safely?

INTRODUCTION: Surgery and chemotherapy have increased the survival of pancreatic cancer. The decrease in postoperative morbidity and mortality and increase in life expectancy, has expanded the indications por cephalic pancreaticoduodenectomy (PDC), although it remains controversial in the geriatric population. METHODS: Retrospective study on a prospective database of patients with ductal adenocarcinoma of pancreas who underwent PDC between 2007-2018. The main objective was to analyse the morbidity-mortality and survival associated with PDC in patients ≥75 years (elderly). RESULTS: 79 patients were included, 21 of them older than 75 years (27%); within this group, 23'9% were over 80 years old. The ASA of both groups was similar. Patients ≥75 years required more transfusions. No differences in operating time were observed, although more vascular resection were performed in the elderly (26 vs. 8.7%; P = .037). Morbidity was higher in the elderly (61.9% vs. 46.6%), although without differences. Patients aged ≥75 years had more non-surgical complications (33.3%, P = .050), being pneumonia the most frequent. Postoperative mortality was higher in the ≥75 years (9 vs. 0%; P = .017). The overall survival and disease-free survival did not show significant differences in both groups. CONCLUSIONS: Elderly patients had higher postoperative mortality and more non-surgical complications. Survival did not show differences, so with an adequate selection of patients, age should not be considered itself as a contraindication for PDC.

[Knowledge, beliefs, and attitudes about obesity and overweight in a sample of dietitians-nutritionists in Spain]. / Conocimientos, creencias y actitudes sobre la obesidad y el sobrepeso en una muestra de dietistas-nutricionistas de España.

INTRODUCTION: Introduction: overweight and obesity make up one of the greatest public health challenges worldwide. Dietitians-nutritionists promote the acquisition of healthy habits to adjust weight. There are interesting contributions by psychology to be considered. Objectives: a) to study the link between the variables included in the study and the therapeutic intervention of dietitians in overweight and obesity; b) to collect the opinions of dietitians on the psychological aspects involved; c) to analyze the predictors of therapeutic success. Methods: a descriptive cross-sectional study that, through a survey to dietitians-nutritionists in Spain (n = 266), analyzes demographic, training, and occupational data, as well as knowledge, beliefs, and interventions on obesity and overweight, with emphasis on psychological aspects. Chi-squared analyses were performed for qualitative variables, and a regression analysis was performed to estimate the perception of therapeutic success. Results: specialization in overweight and obesity was linked to nutrition education interventions. The consideration of psychological aspects was associated with addressing emotional and social problems. Nutritional education, number of sessions, and average time per session predicted the perception of therapeutic success, all of these explaining 46.5 % of the variance. Conclusions: the findings documented a highly specific training in obesity, and a limited use of clinical practice guidelines; the cause of obesity is mostly attributable to environmental factors, and teamwork is preferred by most. Psychological factors were considered very necessary in the approach to this problem, with nutritional education being most efficient. The professionals' self-perception of therapeutic success is remarkable.

INTRODUCCIÓN: Introducción: el sobrepeso y la obesidad (SP/OB) conforman uno de los mayores retos de salud pública a escala mundial. Los profesionales de Dietética y Nutrición promueven la adquisición de hábitos saludables para adecuar el peso. Desde la psicología, existen aportaciones interesantes a ser consideradas. Objetivos: a) estudiar el vínculo entre las variables del estudio y la intervención terapéutica de los nutricionistas en el SP/OB; b) recabar las opiniones de los nutricionistas sobre los aspectos psicológicos implicados; c) analizar los factores predictores del éxito terapéutico. Métodos: estudio de corte transversal, descriptivo que, a través de una encuesta a dietistas-nutricionistas de España (n = 266), analiza los datos sociodemográficos, formativos y laborales, así como los conocimientos, las creencias y las intervenciones para el SP/OB, haciendo énfasis en los aspectos psicológicos. Se realizaron análisis del chi cuadrado para las variables cualitativas y análisis de regresión para estimar la percepción del éxito terapéutico. Resultados: la especialización en SP/OB se vinculó a las intervenciones de educación nutricional. La consideración de los aspectos psicológicos se asoció al abordaje de los problemas emocionales y sociales. La educación nutricional, el número de sesiones y el tiempo de atención por sesión predijeron la percepción del éxito terapéutico, explicando en conjunto el 46,5 % de la varianza. Conclusiones: los hallazgos informan de una alta formación específica, un uso limitado de las guías de práctica clínica, la atribución mayoritaria del SP/OB a factores ambientales y la preferencia por el trabajo en equipo. Los factores psicológicos se estiman muy necesarios en el abordaje de mayor preferencia, considerando la educación nutricional como el más eficiente. Es destacada la autopercepción del éxito terapéutico entre los profesionales.

Diabetes/Dementia in Sub-Saharian Africa and Nigerian Women in the Eye of Storm.

In the next few years, the prevalence of diabetes mellitus (DM) is projected to dramatically increase globally, but most of the cases will occur in low-to-middle-income countries. Some of the major risk factors for diabetes accelerate the development of dementia in African-Americans, thus leading to a higher prevalence of dementia than Caucasians. Sub-Saharian Africa women have a disproportionately two-to-eight fold increased prevalence of dementia. In the eye of this storm, Nigeria holds the highest number of diabetics on the African continent, and its prevalence is rising in parallel to obesity, hypertension, and the population's aging. The socio-economic impact of the rising prevalence of DM and dementia will be huge and unsustainable for the healthcare system in Nigeria, as has been recognized in developed economies. Here, we analyze the current situation of women's health in Nigeria and explore future perspectives and directions. The complex interplay of factors involved in diabetes and dementia in Nigerian women include key biological agents (metabolic syndrome, vascular damage, inflammation, oxidative stress, insulin resistance), nutritional habits, lifestyle, and anemia, that worsen with comorbidities. In addition, restricted resources, lack of visibility, and poor management result in a painful chain that increases the risk and burden of disease in Nigerian women from youth to old ages. Heath policies to increase the ratio of mental health professionals per number of patients, mostly in rural areas, foment of proactive primary care centers, and interventions targeting adolescents and adult women and other specific mothers-children pairs are strongly required for a sustainable development goal.

A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices.

Monoamine neurotransmitters are associated with numerous neurologic and psychiatric ailments. Animal models of such conditions have shown alterations in monoamine neurotransmitter release and uptake dynamics. Technically complex methods such as electrophysiology, Fast Scan Cyclic Voltammetry (FSCV), imaging, in vivo microdialysis, optogenetics, or use of radioactivity are required to study monoamine function. The method presented here is an optimized two-step approach for detecting monoamine release in acute brain slices using a 48-well plate containing tissue holders for examining monoamine release, and high-performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) for monoamine release measurement. Briefly, rat brain sections containing regions of interest, including prefrontal cortex, hippocampus, and dorsal striatum were obtained using a tissue slicer or vibratome. These regions of interest were dissected from the whole brain and incubated in an oxygenated physiological buffer. Viability was examined throughout the experimental time course, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The acutely dissected brain regions were incubated in varying drug conditions that are known to induce monoamine release through the transporter (amphetamine) or through the activation of exocytotic vesicular release (KCl). After incubation, the released products in the supernatant were collected and analyzed through an HPLC-ECD system. Here, basal monoamine release is detected by HPLC from acute brain slices. This data supports previous in vivo and in vitro results showing that AMPH and KCl induce monoamine release. This method is particularly useful for studying mechanisms associated with monoamine transporter-dependent release and provides an opportunity to screen compounds affecting monoamine release in a rapid and low-cost manner.

Abdominal metastatic melanoma invading the transverse colon and stomach.

Gastrointestinal melanoma metastases are not uncommon, with the jejunum and ileum being the most common locations (58 %), followed by the stomach (26 %), colon (22 %), duodenum (12 %), and rectum (5 %).

Identification of Critical Residues in the Carboxy Terminus of the Dopamine Transporter Involved in the G Protein ßγ-Induced Dopamine Efflux.

The dopamine transporter (DAT) plays a crucial role in the regulation of brain dopamine (DA) homeostasis through the re-uptake of DA back into the presynaptic terminal. In addition to re-uptake, DAT is also able to release DA through a process referred to as DAT-mediated DA efflux. This is the mechanism by which potent and highly addictive psychostimulants, such as amphetamine (AMPH) and its analogues, increase extracellular DA levels in motivational and reward areas of the brain. Recently, we discovered that G protein ßγ subunits (Gßγ) binds to the DAT, and that activation of Gßγ results in DAT-mediated efflux - a similar mechanism as AMPH. Previously, we have shown that Gßγ binds directly to a stretch of 15 residues within the intracellular carboxy terminus of DAT (residues 582-596). Additionally, a TAT peptide containing residues 582 to 596 of DAT was able to block the Gßγ-induced DA efflux through DAT. Here, we use a combination of computational biology, mutagenesis, biochemical, and functional assays to identify the amino acid residues within the 582-596 sequence of the DAT carboxy terminus involved in the DAT-Gßγ interaction and Gßγ-induced DA efflux. Our in-silico protein-protein docking analysis predicted the importance of F587 and R588 residues in a network of interactions with residues in Gßγ. In addition, we observed that mutating R588 to alanine residue resulted in a mutant DAT which exhibited attenuated DA efflux induced by Gßγ activation. We demonstrate that R588, and to a lesser extent F5837, located within the carboxy terminus of DAT play a critical role in the DAT-Gßγ physical interaction and promotion of DA efflux. These results identify a potential new pharmacological target for the treatment of neuropsychiatric conditions in which DAT functionality is implicated including ADHD and substance use disorder.