Melatonin for the Treatment of Sepsis: The Scientific Rationale

Sepsis affects 30 million people worldwide, leading to 6 million deaths every year (WHO), and despite decades of research, novel initiatives are drastically needed. According to the current literature, oxidative imbalance and mitochondrial dysfunction are common features of septic patients that can cause multiorgan failure and death. Melatonin, alongside its traditionally accepted role as the master hormonal regulator of the circadian rhythm, is a promising adjunctive drug for sepsis through its anti-inflammatory, antiapoptotic and powerful antioxidant properties. Several animal models of sepsis have demonstrated that melatonin can prevent multiorgan dysfunction and improve survival through restoring mitochondrial electron transport chain (ETC) function, inhibiting nitric oxide synthesis and reducing cytokine production. The purpose of this article is to review the current evidence for the role of melatonin in sepsis, review its pharmacokinetic profile and virtual absence of side effects. While clinical data is limited, we propose the adjunctive use of melatonin is patients with severe sepsis and septic shock

Do bilinguals have different concepts? The case of shape and material in Japanese L2 users of English

An experiment investigated whether Japanese speakers’ categorisation of objects and substances as shape or material is influenced by acquiring English, based on Imai and Gentner (1997). Subjects were presented with an item such as a cork pyramid and asked to choose between two other items that matched it for shape (plastic pyramid) or for material (piece of cork). The hypotheses were that for simple objects the number of shape-based categorisations would increase according to experience of English and that the preference for shape and material-based categorisations of Japanese speakers of English would differ from mono¬lingual speakers of both languages. Subjects were 18 adult Japanese users of English who had lived in English-speaking countries between 6 months and 3 years (short-stay group), and 18 who had lived in English-speaking countries for 3 years or more (long-stay group). Both groups achieved above criterion on an English vocabulary test. Results were: both groups preferred material responses for simple objects and substances but not for complex objects, in line with Japanese mono¬linguals, but the long-stay group showed more shape preference than the short-stay group and also were less different from Americans. These effects of acquiring a second language on categorisation have implications for conceptual representation and methodology

Deep phenotyping of cardiac function in heart transplant patients using cardiovascular systems models

Heart transplant patients are followed with periodic right heart catheterizations (RHCs) to identify post-transplant complications and guide treatment. Post-transplant positive outcomes are associated with a steady reduction of right ventricular and pulmonary arterial pressures, toward normal levels of right-side pressure (about 20mmHg) measured by RHC. This study shows more information about patient progression is obtained by combining standard RHC measures with mechanistic computational cardiovascular systems models. This study shows: to understand how cardiovascular system models can be used to represent a patient's cardiovascular state, and to use these models to track post-transplant recovery and outcome. To obtain reliable parameter estimates comparable within and across datasets, we use sensitivity analysis, parameter subset selection, and optimization to determine patient specific mechanistic parameter that can be reliably extracted from the RHC data. Patient-specific models are identified for ten patients from their first post-transplant RHC and longitudinal analysis is done for five patients. Results of sensitivity analysis and subset selection show we can reliably estimate seven non-measurable quantities including ventricular diastolic relaxation, systemic resistance, pulmonary venous elastance, pulmonary resistance, pulmonary arterial elastance, pulmonary valve resistance and systemic arterial elastance. Changes in parameters and predicted cardiovascular function post-transplant are used to evaluate cardiovascular state during recovery in five patients. Of these five patients, only one patient showed inconsistent trends during recovery in ventricular pressure-volume relationships and power output. At a four-year recovery time point this patient exhibited biventricular failure along with graft dysfunction while the remaining four exhibited no cardiovascular complications.Comment: 53 Pages (including supplement), 9 figures in manuscript, 9 figures in supplemen

Deep phenotyping of cardiac function in heart transplant patients using cardiovascular system models

Heart transplant patients are followed with periodic right heart catheterizations (RHCs) to identify post‐transplant complications and guide treatment. Post‐transplant positive outcomes are associated with a steady reduction of right ventricular and pulmonary arterial pressures, toward normal levels of right‐side pressure (about 20 mmHg) measured by RHC. This study shows that more information about patient progression is obtained by combining standard RHC measures with mechanistic computational cardiovascular system models. The purpose of this study is twofold: to understand how cardiovascular system models can be used to represent a patient’s cardiovascular state, and to use these models to track post‐transplant recovery and outcome. To obtain reliable parameter estimates comparable within and across datasets, we use sensitivity analysis, parameter subset selection, and optimization to determine patient‐specific mechanistic parameters that can be reliably extracted from the RHC data. Patient‐specific models are identified for 10 patients from their first post‐transplant RHC, and longitudinal analysis is carried out for five patients. Results of the sensitivity analysis and subset selection show that we can reliably estimate seven non‐measurable quantities; namely, ventricular diastolic relaxation, systemic resistance, pulmonary venous elastance, pulmonary resistance, pulmonary arterial elastance, pulmonary valve resistance and systemic arterial elastance. Changes in parameters and predicted cardiovascular function post‐transplant are used to evaluate the cardiovascular state during recovery of five patients. Of these five patients, only one showed inconsistent trends during recovery in ventricular pressure–volume relationships and power output. At the four‐year post‐transplant time point this patient exhibited biventricular failure along with graft dysfunction while the remaining four exhibited no cardiovascular complications.Key pointsRight heart catheterization data from clinical records of heart transplant patients are used to identify patient‐specific models of the cardiovascular system.These patient‐specific cardiovascular models represent a snapshot of cardiovascular function at a given post‐transplant recovery time point.This approach is used to describe cardiac function in 10 heart transplant patients, five of which had multiple right heart catheterizations allowing an assessment of cardiac function over time.These patient‐specific models are used to predict cardiovascular function in the form of right and left ventricular pressure‐volume loops and ventricular power, an important metric in the clinical assessment of cardiac function.Outcomes for the longitudinally tracked patients show that our approach was able to identify the one patient from the group of five that exhibited post‐transplant cardiovascular complications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156242/2/tjp14120.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156242/1/tjp14120_am.pd

OC33 Chromatographic approaches to study pine nut skin: exploitation of its composition and bioactivities

Pine nut skin (PNS) is an unexploited and uncharacterized by-product recovered during pine nut processing. The exploitation of by-products as sources of valuable compounds agrees with the current demand for the reduction of waste, and a transition to more sustainable production and consumption1. Therefore, PNS characterization and bioactive potentialities were assessed. The utilization of several chromatographic techniques allowed the characterization of PNS phenolic compounds (HPLC-DAD-UV and HPLC-DAD-ESI-MSn), and the carbohydrates quantification and structural characterization, after specific derivatization (GC-FID and GC-MS). PNS subcritical water extraction using microwave was optimized and the obtained extracts, separated into low-molecularweight (rich in phenolic compounds) and high-molecular-weight (rich in carbohydrates), were evaluated regarding their digestibility and prebiotic activity. The prebiotic potential was assessed by quantifying the short-chain fatty acids (HPLC-UV) produced after the in vitro faecal fermentation. HPLC-DAD-ESI-MSn allowed to identify PNS phenolic compounds, namely protocatechuic, p-coumaric, and caffeic acids, while HPLC-DAD-UV enabled the monomers identification of proanthocyanidins ((epi)catechins) and hydrolysable tannins (protocatechuic acid), after acid methanolysis. GC techniques allowed to disclose the polysaccharides structures (xyloglucans and pectic polysaccharides) and their degradation by microbiota. The fermentation of both extracts rich in phenolic compounds and rich in polysaccharides resulted in an increased production of acetic, propionic, and butyric acids when compared to the commercial prebiotic inulin, proposing these PNS extracts as prebiotic agents.The work was supported through the projects UIDB/50006/2020 and UIDP/50006/2020, funded by FCT/MCTES through national funds. Soraia P. Silva, Alondra González and Dalila Roupar thank FCT/MCTES and ESF through NORTE 2020 for their PhD grants (ref. SFRH/BD/136471/2018, SFRH/BD/06268/2021 and SFRH/DB/139884/2018 respectively). Elisabete Coelho thanks the research contract (CDL-CTTRI-88-ARH/2018 – REF. 049-88-ARH/2018) funded by national funds (OE), through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Clarisse Nobre acknowledges FCT for the assistant research contract 2021.01234.CEECIND.info:eu-repo/semantics/publishedVersio

An Interactive Web-Based Lethal Means Safety Decision Aid for Suicidal Adults (Lock to Live): Pilot Randomized Controlled Trial

BACKGROUND: Counseling to reduce access to lethal means such as firearms and medications is recommended for suicidal adults but does not routinely occur. We developed the Web-based Lock to Live (L2L) decision aid to help suicidal adults and their families choose options for safer home storage. OBJECTIVE: This study aimed to test the feasibility and acceptability of L2L among suicidal adults in emergency departments (EDs). METHODS: At 4 EDs, we enrolled participants (English-speaking, community-dwelling, suicidal adults) in a pilot randomized controlled trial. Participants were randomized in a 13:7 ratio to L2L or control (website with general suicide prevention information) groups and received a 1-week follow-up telephone call. RESULTS: Baseline characteristics were similar between the intervention (n=33) and control (n=16) groups. At baseline, many participants reported having access to firearms (33/49, 67%), medications (46/49, 94%), or both (29/49, 59%). Participants viewed L2L for a median of 6 min (IQR 4-10 min). L2L also had very high acceptability; almost all participants reported that they would recommend it to someone in the same situation, that the options felt realistic, and that L2L was respectful of values about firearms. In an exploratory analysis of this pilot trial, more participants in the L2L group reported reduced firearm access at follow-up, although the differences were not statistically significant. CONCLUSIONS: The L2L decision aid appears feasible and acceptable for use among adults with suicide risk and may be a useful adjunct to lethal means counseling and other suicide prevention interventions. Future large-scale studies are needed to determine the effect on home access to lethal means. TRIAL REGISTRATION: ClinicalTrials.gov NCT03478501; https://clinicaltrials.gov/ct2/show/NCT03478501

Diabetes tipo 2 y depresión en guadalajara, méxico. 2005

Objetivo Determinar la prevalencia de depresión y comparar indicadoressociodemográficos, metabólicos y clínicos, en personas con diabetes tipo 2deprimidas y no deprimidas.Material y Métodos Se realizó un estudio transversal comparativo en una muestrade 450 personas con diabetes tipo 2, mayores de 30 años, con más de un año dediagnóstico y sin determinación de psicopatología. Aplicamos escala de Zungmodificada y encuesta sociodemográfica, evaluamos Hemoglobina glucosilada,índice de masa corporal (IMC), tensión arterial y glucemia de ayuno; registramosantigüedad diagnóstica y estadio clínico de diabetes.Resultados La prevalencia de depresión fue de 63 %, en una proporción de 3 a 1,mayor en mujeres que en hombres con razón de momios 3,17(IC 95 % 2,08-4,82)p=0,0000. Existen diferencias en escolaridad, estado civil y ocupación entredeprimidos y no deprimidos (p and lt;0.05), la edad no presenta diferencias, al igual quelas variables metabólicas, excepto IMC, antigüedad diagnóstica y estadio clínico 3y 4. En las variables socio-demográficas y clínico-metabólicas por sexo, noencontramos asociación en las primeras (p and gt;0.05), no obstante, antigüedad diagnostica y estadio clínico si se asocian con sexo, la primera de estas se asociósolo en hombres y la segunda en ambos sexos.Conclusiones La prevalencia de depresión es alta en las personas con diabetes ylas mujeres tienen mayor riesgo. La edad no muestra asociación entre personascon diabetes que están deprimidas, a diferencia de escolaridad, estado civil, y ocupación; la depresión se presentó más en personas con más antigüedad diagnóstica de diabetes y mayor IMC