N-acetylcysteine during critical neurodevelopmental periods prevents behavioral and neurochemical deficits in the Poly I:C rat model of schizophrenia.

Schizophrenia is a chronic neurodevelopmental disorder with an inflammatory/prooxidant component. N-acetylcysteine (NAC) has been evaluated in schizophrenia as an adjuvant to antipsychotics, but its role as a preventive strategy has not been sufficiently explored. We aimed to evaluate the potential of NAC administration in two-time windows before the onset of symptoms in a schizophrenia-like maternal immune stimulation (MIS) rat model. Pregnant Wistar rats were injected with Poly I:C or Saline on gestational day (GD) 15. Three different preventive approaches were evaluated: 1) NAC treatment during periadolescence in the offspring (from postnatal day [PND] 35 to 49); 2) NAC treatment during pregnancy after MIS challenge until delivery (GD15-21); and 3) NAC treatment throughout all pregnancy (GD1-21). At postnatal day (PND) 70, prepulse inhibition (PPI) and anxiety levels were evaluated. In vivo magnetic resonance (MR) imaging was acquired on PND100 to assess structural changes in gray and white matter, and brain metabolite concentrations. Additionally, inflammation and oxidative stress (IOS) markers were measured ex vivo in selected brain regions. MIS offspring showed behavioral, neuroanatomical, and biochemical alterations. Interestingly, NAC treatment during periadolescence prevented PPI deficits and partially counteracted some biochemical imbalances. Moreover, NAC treatments during pregnancy not only replicated the beneficial outcomes reported by the treatment in periadolescence, but also prevented some neuroanatomical deficits, including reductions in hippocampal and corpus callosum volumes. This study suggests that early reduction of inflammation and prooxidation could help prevent the onset of schizophrenia-like symptoms, supporting the importance of anti-IOS compounds in ameliorating this disorder.

Effect of sitagliptin on down-regulation of KAT7 and SIRT1 gene expression in breast cancer cell line MCF7.

BACKGROUND: To date, the main clinical interest in DPP4 is focused on its inhibition in diabetic patients to prolong the half-life of incretins. Epigenetic alterations resulting from DPP4 inhibition have been poorly explored. OBJECTIVE: The objective of this study was to determine, whether sitagliptin, a DPP4 inhibitor, has effects on the expression of KAT7 and SIRT1 (genes encoding a histone acetyltransferase and a histone deacetylase, respectively) in MCF7 breast cancer cells, which play an essential role in modulating the epigenetic landscape of chromatin. MATERIAL AND METHODS: MCF7 cells were incubated for 20 h with sitagliptin at concentrations of 0.5, 1.0 and 2.0 µM. Total RNA was isolated and the relative mRNA expression of KAT7 and SIRT1 was determined by RT-qPCR. RESULTS: There was downregulation in the relative expression of both genes; for KAT7, downregulation reached up to 0.49 (p = 0.027) and for SIRT1, it reached up to 0.55 (p = 0.037). CONCLUSIONS: These results suggest that sitagliptin has effects on the histone epigenetic landscape. This topic deserves further study due to the current sample use of DPP4 inhibitors in diabetic patients.

ANTECEDENTES: Hasta la fecha, el principal interés clínico de la DPP4 se centra en su inhibición en pacientes diabéticos para prolongar la vida media de las incretinas. Las alteraciones epigenéticas resultantes de la inhibición de DPP4 han sido poco exploradas. OBJETIVO: Determinar si la sitagliptina, un inhibidor de DPP4, tiene efectos sobre la expresión de KAT7 y SIRT1 (genes que codifican una histona acetiltransferasa y una histona desacetilasa, respectivamente) en células de cáncer de mama MCF7, que desempeñan un papel esencial en la modulación del paisaje epigenético de la cromatina. MÉTODO: Las células MCF7 se incubaron durante 20 h con sitagliptina a concentraciones de 0.5, 1.0 y 2.0 µM. Se aisló el ARN total y se determinó la expresión relativa de ARNm de KAT7 y SIRT1 mediante RT-qPCR. RESULTADOS: Hubo una regulación a la baja en la expresión relativa de ambos genes; para KAT7, la regulación negativa alcanzó hasta 0.49 (p = 0.027) y para SIRT1 alcanzó hasta 0.55 (p = 0.037). CONCLUSIONES: Estos resultados sugieren que la sitagliptina tiene efectos sobre el paisaje epigenético de las histonas. Este tema merece más estudios debido al uso actual de inhibidores de DPP4 en pacientes diabéticos.

Riesgo de desarrollar diabetes mellitus tipo 2 según escala Finnish Diabetes Risk Score en atención primaria / Risk of Developing Type 2 Diabetes Mellitus According to the Finnish Diabetes Risk Score in Primary care

Introducción: La diabetes mellitus tipo 2, representa 90-95 por ciento de todas las diabetes, es una enfermedad crónica potencialmente prevenible, la escala Finnish Diabetes Risk Score es uno de los instrumentos más utilizados a nivel mundial para evaluar el riesgo de presentar diabetes en 10 años con enfoque fácil y económico. Objetivo: Determinar el riesgo de desarrollar diabetes en los próximos 10 años según escala Finnish Diabetes Risk Score en pacientes en una Unidad Médica Familiar de México. Métodos: Estudio transversal analítico, se aplicó la escala Finnish Diabetes Risk Score a 383 pacientes y se analizaron las variables implicadas en dicha escala, las variables edad e índice de masa corporal se describieron con medidas de tendencia central, las variables sexo, escolaridad, así como aquellas dicotómicas y de intervalo, mediante razones y proporciones. Se midió asociación mediante Odds Ratio para dicotómicas y coeficiente de Spearman para numéricas. Resultados: La mediana de edad fue de 47 años, predominó el sexo femenino, el 71,5 por ciento reportó sedentarismo, el 51,9 por ciento refirió un familiar de primer grado con diabetes, se determinó probabilidad del 67 por ciento de tener peso normal al realizar actividad física diaria; se determinó una probabilidad del 65 por ciento de presentar prediabetes si se tiene sobrepeso u obesidad, se determinó asociación lineal entre índice de masa corporal y edad, el riesgo predominante para desarrollar diabetes mellitus tipo 2 en 10 años fue alto. Conclusiones: El riesgo de desarrollar diabetes en 10 años en la población estudiada fue elevado y se relacionó con falta de actividad física, antecedentes familiares y sobrepeso(AU)

Introduction: Type 2 diabetes mellitus, accounts for 90-95 percent of all diabetes. It is a potentially preventable chronic disease. The Finnish Diabetes Risk Score is one of the most widely used instruments worldwide to assess the risk of developing diabetes in 10 years with an easy and inexpensive approach. Objective: To determine the risk of developing diabetes in the next 10 years according to the Finnish Diabetes Risk Score in patients in a Family Medical Unit in Mexico. Methods: Analytical cross-sectional study. The Finnish Diabetes Risk Score was applied to 383 patients and the variables involved in this scale were analyzed. The variables age and body mass index were described with measures of central tendency, while the variables gender, schooling, as well as dichotomous and interval variables, were described by ratios and proportions. Association was measured by Odds Ratio for dichotomous variables and Spearman's coefficient for numerical variables. Results: The average age was 47 years and female gender predominated. Sedentary lifestyle was reported by 71.5 percent and 51.9 percent reported a first-degree relative with diabetes. A 67percent probability of having a normal weight was determined when performing daily physical activity. In addition, a 65percent probability of having prediabetes was established if overweight or obese, and a linear association was found between body mass index and age. The predominant risk for developing type 2 diabetes mellitus in 10 years was high. Conclusions: The risk of developing diabetes in 10 years in the studied population was high and was related to lack of physical activity, family history and overweight(AU)

Targeting M2 Macrophages with a Novel NADPH Oxidase Inhibitor.

ROS in cancer cells play a key role in pathways regulating cell death, stemness maintenance, and metabolic reprogramming, all of which have been implicated in resistance to chemo/ immunotherapy. Adjusting ROS levels to reverse the resistance of cancer cells without impairing normal cell functions is a new therapeutic avenue. In this paper, we describe new inhibitors of NADPH oxidase (NOX), a key enzyme in many cells of the tumor microenvironment. The first inhibitor, called Nanoshutter-1, NS1, decreased the level of tumor-promoting "M2" macrophages differentiated from human blood monocytes. NS1 disrupted the active NADPH oxidase-2 (NOX2) complex at the membrane and in the mitochondria of the macrophages, as shown by confocal microscopy. As one of the characteristics of tumor invasion is hypoxia, we tested whether NS1 would affect vascular reactivity by reducing ROS or NO levels in wire and pressure myograph experiments on isolated blood vessels. The results show that NS1 vasodilated blood vessels and would likely reduce hypoxia. Finally, as both NOX2 and NOX4 are key proteins in tumors and their microenvironment, we investigated whether NS1 would probe these proteins differently. Models of NOX2 and NOX4 were generated by homology modeling, showing structural differences at their C-terminal NADPH site, in particular in their last Phe. Thus, the NADPH site presents an unexploited chemical space for addressing ligand specificity, which we exploited to design a novel NOX2-specific inhibitor targeting variable NOX2 residues. With the proper smart vehicle to target specific cells of the microenvironment as TAMs, NOX2-specific inhibitors could open the way to new precision therapies.

Partial Two-Stage Exchange for Infected Total Hip Arthroplasty: A Treatment to Take into Account.

INTRODUCTION: Two-stage revision is the gold standard for chronic periprosthetic joint infection (PJI). The removal of well-fixed implants, especially the femoral component, can be extremely difficult and additional osteotomies may be needed, which is time-consuming and results in bone stock loss. When the femoral stem is osseointegrated, there is no clear indication for the use of partial two-stage revision. The primary objective was to assess infection eradication after surgery. METHODS: Retrospective study of specific case series. A total of eight patients with a chronic uncemented PJI, in the setting of complex revision surgeries, were treated with partial two-stage revision, which included selective retention of the well-fixed femoral component and complete acetabular removal. Stem retention was carried out regardless of the bacteria or associated comorbidities. RESULTS: All patients were re-revision cases with at least two previous surgeries (range, 2-4). Complex revisions were performed in five cases (non-articulated spacer) and simple revisions in three cases (articulated spacer). The minimum follow-up time was 24 months (range, 24-132 months). The infection eradication rate at final follow-up was 100%. CONCLUSION: Partial two-stage reconstruction is a promising technique for the treatment of chronic PJI in patients with a well-fixed stem and complex re-revision acetabular procedures. Further prospective studies and prolonged follow-ups are required to confirm our results.

De la salud colectiva a la medicina "personalizada": desafíos bioéticos de la evaluación genética preimplantatoria desde la perspectiva norte-sur / From collective health to "personalized" medicine: bioethical challenges in preimplantation genetic testing from a North-South perspective

RESUMEN El artículo se interroga por los alcances y los límites del paradigma de la medicina de precisión y su relación con el enfoque de la salud colectiva. Para ello, se toma la evaluación genética preimplantatoria o PGT (preimplantation genetic testing) dado que constituye un ejemplo paradigmático de tecnologías que apuntan a la "individualización" de los procesos de salud. En esta dirección, se revisan las características y los fundamentos científico-normativos acerca de las tecnologías PGT en Argentina, y el camino que queda por recorrer para su análisis bioético. De manera más específica, se visibilizan algunas de las condiciones de posibilidad para su implementación desde la perspectiva norte-sur. Como síntesis del análisis, proponemos tres ejes o nudos problemáticos relacionados con los sesgos en la producción de conocimiento, los valores e intereses subyacentes a sus usos y los presupuestos epistemológicos que operan en la base de estas tecnologías. A lo largo de este trabajo, presentamos estos dilemas y sugerimos algunas recomendaciones para ser tenidas en cuenta en futuras investigaciones.

ABSTRACT This article examines the scope and limitations of the precision medicine paradigm and its relationship with the collective health approach. To that end, it takes preimplantation genetic testing (PGT) as a paradigmatic example of technologies aimed at the "individualization" of health processes. In this regard, we review the characteristics and scientific and regulatory foundations of PGT technologies in Argentina, and discuss the next steps for their bioethical analysis. More specifically, we shed light on some of the conditions for their implementation from a north-south perspective. We propose three themes or problematic aspects as a synthesis of our analysis, related to biases in the production of knowledge, the values and interests underlying its uses, and the underlying epistemological assumptions of these technologies. Throughout the article, we review these dilemmas and suggest some issues that should be taken into account in future research.

Reconstruyendo 50 años del Colegio Colombiano de Terapia Ocupacional / Reconstructing 50 years of the Colegio Colombiano de Terapia Ocupacional / Reconstruindo 50 anos do Colegio Colombiano de Terapia Ocupacional

A través de una línea del tiempo se exponen hechos significativos en la historia del Colegio Colombiano de Terapia Ocupacional. Esta se elaboró como parte de un trabajo de grado en la Universidad Nacional de Colombia, el cual tuvo como objetivo revisar y reportar hallazgos en el archivo histórico del Colegio y de dicha Universidad. Se rastrearon y clasificaron documentos de archivo histórico y se recurrió a la validación con actores clave. La línea del tiempo expone una breve muestra de lo encontrado en ese proceso. Como reflexión del grupo de estudiantes, la agremiación es una herramienta social para la construcción colectiva y dinámica desde procesos democráticos y críticos.

Significant events are exposed through a timeline in the history of the Colegio Colombiano de Terapia Ocupacional. This was prepared as part of an undergraduate degree at the Universidad Nacional de Colombia, whose objective was reviewing and reporting findings in the historical archive of the College and of the university. Historical archival documents were tracked and classified, and validation was performed with key stakeholders. The timeline exposes a brief sample of what was found in this process. The reflection of the group of students is that professional organizations are a social tool for collective and dynamic construction from democratic and critical processes.

Através de uma linha do tempo, são expostos eventos significativos na história do Colegio Colombiano de Terapia Ocupacional. Este foi elaborado como parte de um projeto de graduação da Universidad Nacional de Colombia, cujo objetivo foi revisar e relatar descobertas no arquivo histórico do Colégio e da referida universidade. Documentos históricos de arquivo foram rastreados, bem como classificados, e a validação foi feita com atores chaves. A linha do tempo expõe um resumo do que foi encontrado nesse processo. Conforme refletido pelo grupo de estudantes, as associações profissionais são uma ferramenta social de construção coletiva e dinâmica, a partir de processos democráticos e críticos.

Association of ABC and RENAL Scoring Systems With Morbidity in Partial Nephrectomy.

BACKGROUND/AIM: Different nephrometry scoring systems (NSSs) are used to evaluate the surgical complexity and outcomes of partial nephrectomy (PN) in patients with small renal tumors. This study aimed to assess the validity of nephrometry scoring systems towards aiding the preoperative planning of laparoscopic partial nephrectomy (PN). PATIENTS AND METHODS: Data of 77 patients who underwent partial nephrectomy at the Puerto Real University Hospital between January 2011 and December 2017 were retrospectively analyzed. Statistical analyses were carried out to determine whether there was an association between the complexity of the surgical procedure and the assigned nephrometry scores. RESULTS: Operative complications (bleeding volume, conversion to open surgery, perioperative bleeding, and postoperative fistula) were significantly associated with independent variables (age, sex, body mass index, radiological tumor size, and operative ischemia time) and with the classification of patients using arterial-based complexity (ABC) and radius endophytic/exophytic nearness anterior-posterior location (RENAL) scores. There was also a strong correlation between the RENAL and ABC scores [Cramer's V coefficient (0.682) and Fisher's test (p<0.0001)]. CONCLUSION: The RENAL and ABC scores are associated with the risk of the complexity of partial nephrectomy for T1 renal tumors, even for ≥T1b tumors and/or with complex anatomical features.

Whole-genome DNA methylation patterns of Oryza sativa (L.) and Oryza glumaepatula (Steud) genotypes associated with aluminum response.

Epigenetic mechanisms in crops have emerged as a fundamental factor in plant adaptation and acclimation to biotic and abiotic stresses. Among described epigenetic mechanisms, DNA methylation has been defined as the most studied epigenetic modification involved in several developmental processes. It has been shown that contrasting methylation marks are associated with gene expression variations between cultivated and wild crop species. In this study, we analyzed single-base resolution methylome maps for Oryza sativa (a cultivated species) and Oryza glumaepatula (a wild species) genotypes grown under control conditions. Our results showed that overall, genome-wide methylation profiles are mainly conserved between both species, nevertheless, there are several differentially methylated regions with species-specific methylation patterns. In addition, we analyzed the association of identified DNA methylation marks in relation with Aluminum-tolerance levels of studied genotypes. We found several differentially methylated regions (DMRs) and DMR-associated genes (DAGs) that are linked with Al tolerance. Some of these DAGs have been previously reported as differentially expressed under Al exposure in O. sativa. Complementarily a Transposable Elements (TE) analysis revealed that specific aluminum related genes have associated-TEs potentially regulated by DNA methylation. Interestingly, the DMRs and DAGs between Al-tolerant and susceptible genotypes were different between O. sativa and O. glumaepatula, suggesting that methylation patterns related to Al responses are unique for each rice species. Our findings provide novel insights into DNA methylation patterns in wild and cultivated rice genotypes and their possible role in the regulation of plant stress responses.

The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia.

There is evidence that in schizophrenia, imbalances in inflammatory and oxidative processes occur during pregnancy and in the early postnatal period, generating interest in the potential therapeutic efficacy of anti-inflammatory and antioxidant compounds. Mangiferin is a polyphenolic compound abundant in the leaves of Mangifera indica L. that has robust antioxidant and anti-inflammatory properties, making it a potential candidate for preventive or co-adjuvant therapy in schizophrenia. Hence, this study set-out to evaluate the effect of mango leaf extract (MLE) in a model of schizophrenia based on maternal immune activation, in which Poly I:C (4 mg/kg) is administered intravenously to pregnant rats. Young adult (postnatal day 60-70) or adolescent (postnatal day 35-49) male offspring received MLE (50 mg/kg of mangiferin) daily, and the effects of MLE in adolescence were compared to those of risperidone, assessing behavior, brain magnetic resonance imaging (MRI), and oxidative/inflammatory and antioxidant mediators in the adult offspring. MLE treatment in adulthood reversed the deficit in prepulse inhibition (PPI) but it failed to attenuate the sensitivity to amphetamine and the deficit in novel object recognition (NOR) induced. By contrast, adolescent MLE treatment prevented the sensorimotor gating deficit in the PPI test, producing an effect similar to that of risperidone. This MLE treatment also produced a reduction in grooming behavior, but it had no effect on anxiety or novel object recognition memory. MRI studies revealed that adolescent MLE administration partially counteracted the cortical shrinkage, and cerebellum and ventricle enlargement. In addition, MLE administration in adolescence reduced iNOS mediated inflammatory activation and it promoted the expression of biomarkers of compensatory antioxidant activity in the prefrontal cortex and hippocampus, as witnessed through the reduction of Keap1 and the accumulation of NRF2 and HO1. Together, these findings suggest that MLE might be an alternative therapeutic or preventive add-on strategy to improve the clinical expression of schizophrenia in adulthood, while also modifying the time course of this disease at earlier stages in populations at high-risk.

In vivo Positron Emission Tomography to Reveal Activity Patterns Induced by Deep Brain Stimulation in Rats.

Deep brain stimulation (DBS) is an invasive neurosurgical technique based on the application of electrical pulses to brain structures involved in the patient's pathophysiology. Despite the long history of DBS, its mechanism of action and appropriate protocols remain unclear, highlighting the need for research aiming to solve these enigmas. In this sense, evaluating the in vivo effects of DBS using functional imaging techniques represents a powerful strategy to determine the impact of stimulation on brain dynamics. Here, an experimental protocol for preclinical models (Wistar rats), combined with a longitudinal study [18F]-fluorodeoxyclucose positron emission tomography (FDG-PET), to assess the acute consequences of DBS on brain metabolism is described. First, animals underwent stereotactic surgery for bilateral implantation of electrodes into the prefrontal cortex. A post-surgical computerized tomography (CT) scan of each animal was acquired to verify electrode placement. After one week of recovery, a first static FDG-PET of each operated animal without stimulation (D1) was acquired, and two days later (D2), a second FDG-PET was acquired while animals were stimulated. For that, the electrodes were connected to an isolated stimulator after administering FDG to the animals. Thus, animals were stimulated during the FDG uptake period (45 min), recording the acute effects of DBS on brain metabolism. Given the exploratory nature of this study, FDG-PET images were analyzed by a voxel-wise approach based on a paired T-test between D1 and D2 studies. Overall, the combination of DBS and imaging studies allows describing the neuromodulation consequences on neural networks, ultimately helping to unravel the conundrums surrounding DBS.

Metal-Mediated Organocatalysis in Water: Serendipitous Discovery of Aldol Reaction Catalyzed by the [Ru(bpy)2(nornicotine)2]2+ Complex.

The [Ru(bpy)2(Nor)2]2+ complex (Nor = nornicotine) is an efficient catalyst for the aldol reaction of acetone with activated benzaldehydes in a buffered aqueous solution. The metal plays the role of an activator for the nornicotine organocatalyst ligands. The resulting catalytic activity is potentiated by a factor of about 4.5 as compared to free nornicotine. Similar rate enhancements can be achieved by using Zn(II) cations as the activator. The observations are rationalized with the reduced basicity of the pyrrolidine N in nornicotine due to the enhanced electron withdrawal of the metal-complexed pyridyl moiety.

An Update on the Exploratory Use of Curcumin in Neuropsychiatric Disorders.

Curcumin is a polyphenol extracted from the rhizome of the turmeric plant. Beyond its common use as a culinary spice in Eastern Asia, curcumin has been proposed as a therapeutic compound due to its antioxidant, anti-inflammatory and neuroprotective properties. Thus, its efficacy has been evaluated in various inflammatory-based psychiatric disorders, such as schizophrenia, depression, or autism. Our aim is to review those preclinical and clinical studies carried out in psychiatric disorders whose therapeutic approach has involved the use of curcumin and, therefore, to discern the possible positive effect of curcumin in these disorders. Preclinical studies and completed clinical trials of curcumin for psychiatric disorders published from January 2005 to October 2021 were identified through searching relevant databases until 31st October 2021. Sixty-five preclinical studies and 15 clinical trials and open-label studies were selected. Results showed a bias toward studies in depression and, to a lesser extent, schizophrenia. In all disorders, the results were positive in reducing psychiatric deficits. Despite the considerable number of beneficial outcomes reported, the small number of trials and the heterogeneity of protocols make it difficult to draw solid conclusions about the real potency of curcumin in psychiatric disorders.

Dronabinol en manejo de apetito y pérdida de peso en pacientes con cáncer terminal, VIH, cuidados paliativos y vejez. Revisión de la literatura / Dronabinol in appetite management and weight loss in patients with terminal cancer, HIV, palliative care and old age. Literature review

Resumen: Introducción: La caquexia es un síndrome asociado al cáncer avanzado, VIH, pacientes en quimioterapia y quienes tienen seguimiento en cuidados paliativos. La prevalencia es de 25% de los pacientes con diagnóstico de cáncer, 26% en quienes reciben quimioterapia y de 14 a 38% de pacientes con VIH. Un pilar para el manejo es el cannabis debido al efecto del delta-9-tetrahidrocanabinol (THC), del cual se derivó el dronabinol, un fármaco desarrollado para estimular apetito y ganancia de peso. El objetivo de esta revisión bibliográfica es obtener la información sobre los cannabinoides y la evidencia más sólida existente con respecto al uso del dronabinol en pacientes que han presentado pérdida de peso y apetito. Material y métodos: Revisión de la bibliografía con buscador PubMed con las palabras clave Palliative care (cuidados paliativos), Cannabinoids (cannabinoides), cachexia (caquexia), Dronabinol (dronabinol), Appetite (apetito), de 1990 a 2018, limitado a humanos, obteniendo 259 artículos, eliminando 222 por repetirse o tener poca relevancia, dejando 37 artículos para análisis. Resultados: De 37 artículos revisados, nueve fueron estudios experimentales, 10 revisiones sistematizadas, un metaanálisis y 16 artículos de recomendaciones y sugerencias de manejo. Conclusión: El manejo del apetito y pérdida de peso en pacientes en cuidados paliativos, VIH, ancianos o en quimioterapia debe ser multidisciplinario, involucrando nutriólogos, psicólogos y médicos, ajustando el manejo a las características individuales que manifiesten. El dronabinol es un fármaco de primera elección para el manejo de dichos síntomas cuando la historia natural de la enfermedad se acompaña de náusea, vómito o dolor.

Abstract: Introduction: Cachexia is a syndrome associated with advanced cancer, HIV, patients on chemotherapy and those who are followed in palliative care. The prevalence is 25% of patients diagnosed with cancer, 26% in those receiving chemotherapy and 14 to 38% of patients with HIV. A mainstay for management is cannabis, due to the effect of delta-9-tetrahydrocannabinol (THC) from which dronabinol, a drug developed to stimulate appetite and weight gain, was derived. The aim of this literature review is to obtain information on cannabinoids and the strongest existing evidence regarding the use of dronabinol in patients who have presented weight and appetite loss. Material and methods: Literature review with PubMed search engine with the keywords Palliative care, Cannabinoids, cachexia, Dronabinol, Appetite, from 1990 to 2018, limited to humans, obtaining 259 articles, eliminating 222 for repetition or low relevance, leaving 37 articles for analysis. Results: Out of 37 articles reviewed 9 were experimental studies, 10 systematized reviews, 1 meta-analysis and 16 articles of recommendations and management suggestions. Conclusion: The management of appetite and weight loss in palliative care, HIV, elderly or chemotherapy patients should be multidisciplinary, involving nutritionists, psychologists and physicians, adjusting the management to the individual characteristics manifested. Dronabinol is a drug of first choice for the management of these symptoms when the natural history of the disease is accompanied by nausea, vomiting or pain.

Treatment of Metastatic Castration-resistant Prostate Cancer Patients With Abiraterone Acetate and Prednisone and Corresponding Survival Prognostic Factors.

BACKGROUND/AIM: The aim of the study was to evaluate the combined treatment with abiraterone acetate and prednisone (AA+P) in patients with castration-resistant prostate cancer (mCPRC), and to identify the survival prognostic factors. PATIENTS AND METHODS: Patients diagnosed with mCPRC not previously treated with chemotherapy and administered with AA+P were classified into two groups: those with lower and higher survival rates (at 30 months vs. 60 months). RESULTS: A total of 53 patients were studied at the time of mCRPC diagnosis. Patients with the highest survival rate had suffered prostate cancer for >45 months. At the time of initial prostate cancer diagnosis, they belonged to the risk groups 1-4, had pain intensity measured according to the brief pain inventory (BPI) scale of 0-2, were treated with AA+P>16 months, and had the following tumour marker serum levels: LDH baseline ≤163 U/l, alkaline phosphatase at 6 months ≤56 U/l and PSA at 6 months ≤0.95 ng/ml. CONCLUSION: Good response to treatment with AA+P for patients with mCRPC was demonstrated. Factors that contributed to the higher prognostic accuracy were time suffering from prostate cancer, the intensity of the pain measured by the BPI scale, the duration of AA+P treatment, and tumour marker levels.

The prevalence of intraarticular associated lesions after acute acromioclavicular joint injuries is 20%. A systematic review and meta-analysis.

PURPOSE: To synthesise the evidence on the prevalence of associated intraarticular lesions in subjects with acute acromioclavicular joint (ACJ) dislocations. METHODS: A search in two electronic databases (PUMBMED and EMBASE) was performed from 1985 to 2019. Two independent reviewers selected studies that complied with the following inclusion criteria: (1) the study included data on surgically treated ACJ dislocation grade III-V in the Rockwood classification, (2) the ACJ injuries were acute (the surgery was performed less than 6 weeks after injury), (3) an arthroscopic evaluation of the glenohumeral joint was performed during surgery. The quality of the studies included was assessed using the tool of the Joanna Briggs Institute. RESULTS: A total of 47 studies with acute ACJ injuries met the initial inclusion criteria. Of these, 21 studies (9 retrospective case series, 9 prospective case series and 3 retrospective cohort studies) presented data on associated intraarticular lesions amenable for use in the meta-analysis. The meta-analysed studies included a total of 860 subjects with acute ACJ dislocations with a male/female ratio of 6.5 and a mean age of 32 years. The meta-analysis showed a prevalence of associated intraarticular lesions in subjects with acute ACJ of 19.9% (95% confidence interval [CI] 14.0-26.4%; 21 studies, 860 analysed participants; P = 0.000; I2: 74.5% random-effects model; low risk of bias). CONCLUSION: One in five subjects with surgically treated acute ACJ dislocations will have an associated intraarticular lesion that requires further intervention. The case for a customary arthroscopic evaluation of the joint, even when an open procedure is performed to deal with the ACJ dislocation, is strong. Level of evidence IV Trial registry Systematic review registration number: PROSPERO CRD42018090609.

The Beneficial Effects of Lippia Citriodora Extract on Diet-Induced Obesity in Mice Are Associated with Modulation in the Gut Microbiota Composition.

SCOPE: Obesity is characterized by a dysfunction in the adipose tissue and an inflammatory subclinical state leading to insulin resistance and increased risk of cardiovascular diseases. It is also associated with intestinal dysbiosis that contributes to inflammation development. Lippia citriodora (LCE) contains high levels of polyphenolpropanoids and has shown promising results in obesity. The aim of this study is to investigate a well-characterized extract of LCE in a model of metabolic syndrome in mice, focusing on its effects on metabolic tissues, endothelial dysfunction, and microbiome. METHODS: Mice are fed a high fat diet (HFD) for six weeks and treated daily with LCE (1, 10, and 25 mg kg-1 ). Glucose and lipid metabolism is investigated. The inflammatory state in the metabolic tissues and the intestinal microbiota composition are characterized, as well as the endothelium-dependent vasodilator response to acetylcholine. RESULTS: LCE reduces fat accumulation and improves plasma glycemic and lipid profiles, as well as the inflammatory process and vascular dysfunction. Moreover, LCE lessens intestinal dysbiosis, as it reduces the Firmicutes/Bacteroidetes ratio and increases Akkermansia abundance in comparison with untreated HFD mice. CONCLUSION: The antiobesity therapeutic properties of LCE are most probably mediated by the synergic effects of its bioactive compounds.

Cardiometabolic risk factors associated with renal function in apparently healthy young students: a cross-sectional study

ABSTRACT Background: Cardiometabolic risk factors (CMRFs) appear decades before developing chronic kidney disease (CKD) in adulthood. Objective: The objective of the study was to identify the prevalence and association between CMRFs and kidney function in apparently healthy young adults (18-25 years old). Methods: We included 5531 freshman year students. Data collected on CMRFs included central obesity, high body mass index (hBMI >25), blood pressure, glycemia, lipids, uric acid (UA >6.8 mg/dL), and insulin. Glomerular filtration rate (GFR) was estimated by CKD-Epidemiology Collaboration formula. We used logistic regression and a log linear for odds ratio (OR) (95% confidence level) and probabilities. Results: The presence of any CMRF was observed in 78% (4312) of individuals; GFR ≥120/130 mL/min/1.73 m2sc was found in 33%, GFR <90 mL/min/1.73 m2sc in 3%, and proteinuria in 3%. Factors associated with high GFR were hBMI (OR 1.3 [1.14, 1.47]), UA (OR 0.2 [0.15, 0.26]), high-density lipoprotein (HDL) (OR 1.4 [1.2, 1.6]), and insulin resistance (OR 1.3 [1.05, 1.7]). CMRF associated with low GFR was UA (OR 1.8 [1.3, 2.6]), low-density lipoprotein cholesterol (OR 1.66 [1.05, 2.6]), and proteinuria (OR 3.4 [2.07, 5.7]). Proteinuria was associated with high UA (OR 1.59 [1.01, 2.5]) and hypercholesterolemia (OR 1.8 [1.03, 3.18]). The sole presence of hBMI+UA predicted low GFR with p = 0.6 and hBMI+UA+low HDL predicted proteinuria with p = 0.55. Conclusions: CMRFs were highly prevalent among this freshman student population and were associated with proteinuria and GFR abnormalities. Future studies should focus on public health programs to prevent or delay the development of CKD.

Predicting Glioblastoma Recurrence from Preoperative MR Scans Using Fractional-Anisotropy Maps with Free-Water Suppression.

Diffusion tensor imaging (DTI), and fractional-anisotropy (FA) maps in particular, have shown promise in predicting areas of tumor recurrence in glioblastoma. However, analysis of peritumoral edema, where most recurrences occur, is impeded by free-water contamination. In this study, we evaluated the benefits of a novel, deep-learning-based approach for the free-water correction (FWC) of DTI data for prediction of later recurrence. We investigated 35 glioblastoma cases from our prospective glioma cohort. A preoperative MR image and the first MR scan showing tumor recurrence were semiautomatically segmented into areas of contrast-enhancing tumor, edema, or recurrence of the tumor. The 10th, 50th and 90th percentiles and mean of FA and mean-diffusivity (MD) values (both for the original and FWC-DTI data) were collected for areas with and without recurrence in the peritumoral edema. We found significant differences in the FWC-FA maps between areas of recurrence-free edema and areas with later tumor recurrence, where differences in noncorrected FA maps were less pronounced. Consequently, a generalized mixed-effect model had a significantly higher area under the curve when using FWC-FA maps (AUC = 0.9) compared to noncorrected maps (AUC = 0.77, p < 0.001). This may reflect tumor infiltration that is not visible in conventional imaging, and may therefore reveal important information for personalized treatment decisions.

Antihypertensive Effects of Virgin Olive Oil (Unfiltered) Low Molecular Weight Peptides with ACE Inhibitory Activity in Spontaneously Hypertensive Rats.

The low molecular weight peptide composition of virgin olive oil (VOO) is mostly unknown. We hypothesised that unfiltered VOO could possess low molecular weight peptides with antihypertensive activity. We produced unfiltered VOO and obtained a water-soluble peptide extract from it. The peptides were separated by size-exclusion using fast protein liquid chromatography, and the low molecular weight fraction was analysed by nanoscale liquid chromatography-Orbitrap coupled with tandem mass spectrometry and de novo sequencing. We selected 23 peptide sequences containing between 6 and 9 amino acids and molecular masses ranging 698-1017 Da. Those peptides were chemically synthesised and their angiotensin-converting enzyme (ACE) inhibitory activity was studied in vitro. Seven peptides showed a strong activity, with half maximal inhibitory concentration (IC50) <10 µm. The antihypertensive effects of the four most active synthesised ACE inhibitor peptides were studied in spontaneously hypertensive rats (SHR). Acute oral administration of synthetic peptides RDGGYCC and CCGNAVPQ showed antihypertensive activity in SHR. We conclude that unfiltered VOO naturally contains low molecular weight peptides with specific ACE inhibitory activity and antihypertensive effects in SHR.