Effect of Milk-Feeding Frequency and Calcium Gluconate Supplementation on Growth, Health, and Reproductive and Metabolic Features of Holstein Heifers at a Rearing Farm.

We compared the effects of milk-feeding in 288 Holstein calves (72 per group) which were fed twice (2F) or thrice (3F) daily, with or without the addition of hydrogenated fat-embedded calcium gluconate (G) supplemented in the starter food and in the daily diet up to the age of 9 months, on the calves' metabolism, growth, health, and reproductive efficiency up to first pregnancy. The calves received 6 L of milk replacer (130 g/L) and had ad libitum access to water and textured calf starter with or without gluconate. Gluconate supplementation promoted a "catch-up" in growth in supplemented calves compared to their counterparts that did not receive gluconate. Gluconate appeared to reduce animal metabolic stress during key events, such as weaning and transfer into open-door pens, reducing fructosamine (352.61 vs. 303.06 in 3FG and 3F, respectively; p = 0.028) and urea (3F revealed the highest values compared with the other three groups: 19.06 for 3F vs. 13.9 (2F), 13.7 (2FG), and 14.3 (3FG), respectively, p = 0.002) from weaning onwards. The feeding of dairy calves with milk replacer three rather than two times per day tended to be associated with better health from weaning to 4 months old; parameters such as ultrasound lung score and calf health score improved over time (p < 0.001). Thrice-daily feeding with milk replacer tended to reduce the number of artificial inseminations per pregnancy in heifers by 0.2 points (p = 0.092). We confirmed significant correlations between early health and growth parameters and reproductive efficiency and a positive correlation between body weight and average daily weight gain and the thickness of the back fat layer in young heifers (r = 0.245; p < 0.0001; r = 0.214; p < 0.0001 respectively). Our study was conducted on a commercial farm with reasonably effective animal management, so baseline welfare was likely satisfactory.

Shifts in uterine microbiome associated with pregnancy outcomes at first insemination and clinical cure in dairy cows with metritis.

Objectives were to assess differences in uterine microbiome associated with clinical cure and pregnancy outcomes in dairy cows treated for metritis. Cows with metritis (reddish-brownish, watery, and fetid vaginal discharge) were paired with cows without metritis based on parity and days postpartum. Uterine contents were collected through transcervical lavage at diagnosis, five days later following antimicrobial therapy (day 5), and at 40 days postpartum. Uterine microbiome was assessed by sequencing the V4 hypervariable region of the 16S rRNA gene. Although alpha-diversity based on Chao1, Shannon, and inverse Simpson indexes at diagnosis did not differ between cows with and without metritis, disease was associated with differences in beta-diversity. Prevalence of Porphyromonas, Bacteroides, and Veillonella was greater in cows with metritis. Streptococcus, Sphingomonas, and Ureaplasma were more prevalent in cows without metritis. Differences in beta-diversity between cows with and without metritis persisted on day 5. Uterine microbiome was not associated with clinical cure. Richness and alpha-diversity, but not beta-diversity, of uterine microbiome 40 days postpartum were associated with metritis and pregnancy. No relationship between uterine microbiome and pregnancy outcomes was observed. Results indicate that factors other than changes in intrauterine bacterial community underlie fertility loss and clinical cure in cows with metritis.

Real-time management of intra-hospital patient transport requests.

This paper addresses the management of patients' transportation requests within a hospital, a very challenging problem where requests must be scheduled among the available porters so that patients arrive at their destination timely and the resources invested in patient transport are kept as low as possible. Transportation requests arrive during the day in an unpredictable manner, so they need to be scheduled in real-time. To ensure that the requests are scheduled in the best possible manner, one should also reconsider the decisions made on pending requests that have not yet been completed, a process that will be referred to as rescheduling. This paper proposes several policies to trigger and execute the rescheduling of pending requests and three approaches (a mathematical formulation, a constructive heuristic, and a local search heuristic) to solve each rescheduling problem. A simulation tool is proposed to assess the performance of the rescheduling strategies and the proposed scheduling methods to tackle instances inspired by a real mid-size hospital. Compared to a heuristic that mimics the way requests are currently handled in our partner hospital, the best combination of scheduling method and rescheduling strategy produces an average 5.7 minutes reduction in response time and a 13% reduction in the percentage of late requests. Furthermore, since the total distance walked by porters is substantially reduced, our experiments demonstrate that it is possible to reduce the number of porters - and therefore the operating costs - without reducing the current level of service.

Exploring parenthood in first episode of psychosis: the potential role of the offspring in the outcome of women.

PURPOSE: The study aimed to explore the role of parenthood at first episode of psychosis (FEP) on recovery, with a focus on potential sex differences. METHODS: Sociodemographic, clinical, and neurocognitive information was considered on 610 FEP patients form the PAFIP cohort (Spain). Baseline and three-year follow-up comparisons were carried out. Chi-square tests and ANCOVA analysis were performed controlling for the effect of age and years of education. RESULTS: Men comprised 57.54% of the sample, with only 5.41% having offspring when compared to 36.29% of women. Parenthood was related to shorter duration of untreated illness (DUI) in women with children (12.08 months mothers vs. 27.61 months no mothers), showing mothers better premorbid adjustment as well. Childless men presented the worst premorbid adjustment and the highest cannabis and tobacco consumption rates. Mothers presented better global cognitive function, particularly in attention, motor dexterity and executive function at three-year follow-up. CONCLUSIONS: Diminished parental rates among FEP men could be suggested as a consequence of a younger age of illness onset. Sex roles in caregiving may explain the potential role of parenthood on premorbid phase, with a better and heathier profile, and a more favorable long-term outcome in women. These characteristics may be relevant when adjusting treatment specific needs in men and women with and without offspring.

Processing speed in first episode of psychosis and first-degree relatives: A candidate endophenotype of spectrum schizophrenia disorders.

OBJECTIVE: The processing speed (PS) is highly impacted in individuals experiencing their first episode of psychosis (FEP). Conducting family studies can help to determine whether PS can serve as an endophenotype of schizophrenia spectrum disorders (SSDs), offering valuable insights into the prevention and diagnosis of SSDs. METHOD: A comprehensive cognitive battery, encompassing tests for PS, verbal memory, visual memory, working memory, executive functions, motor dexterity, and attention, was administered to a sample consisting of 133 FEP patients, 146 parents, 98 siblings, and 202 healthy controls (HCs). Univariate analyses (analysis of covariance [ANCOVA]) were conducted to compare the different cognitive domains between groups, utilizing sex, age, and years of education as covariates and Bonferroni corrections. Effect sizes (ESs) were calculated for estimating the magnitude of differences between groups. RESULTS: Group comparisons revealed significant differences in all cognitive domains. PS was the most impaired function in patients. Parents and siblings had intermediate PS performance between FEP patients and HC. Large ES were observed in PS between FEP versus siblings, FEP versus controls, parents versus controls, and parents versus siblings. CONCLUSIONS: Despite not meeting all the necessary criteria, the PS observed in FEP patients and their first-degree relatives suggests its potential as a promising endophenotype of SSDs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Síndrome cardiorrenal: diagnóstico y tratamiento / Cardiorenal syndrome: diagnosis and treatment

Introducción: Las enfermedades cardíacas y renales coexisten con frecuencia. El síndrome cardiorrenal es una entidad compleja; en ella, la disfunción primaria cardíaca produce daño renal (tipos 1 y 2) y viceversa (tipos 3 y 4) o efecto de una enfermedad sistémica que afecta a ambos órganos (tipo 5). Objetivo: Actualizar el diagnóstico y tratamiento de los pacientes con síndrome cardiorrenal. Métodos: Se utilizan métodos teóricos y empíricos para realizar análisis del conocimiento actualizado sobre el tema. Se ha definido la existencia de un síndrome cardiorrenal que compromete a ambos órganos, con interacción bidireccional. En su detección, el diagnóstico clínico es insuficiente y requiere marcadores bioquímicos; estas herramientas, junto con la medición del sodio urinario, permite vigilar la efectividad terapéutica. Otro recurso es la ultrafiltración, según complicaciones. Conclusiones: Se debe indicar tratamiento con base en la evidencia para mejorar la calidad de vida, reducir la mortalidad y retrasar el deterioro de la función renal y cardíaca a largo plazo; el trasplante renal se debe considerar en pacientes en diálisis con disfunción ventricular severa. Idealmente, deberían recibir un trasplante combinado: cardíaco y renal, lo cual es difícil; algunos pacientes sometidos exclusivamente a trasplante renal presentan una mejoría notable en su fracción de eyección y en la sobrevida.

Introduction: heart and kidney diseases frequently coexist. Cardiorenal syndrome is a complex entity in which primary cardiac dysfunction causes a kidney damage (types 1 and 2) and vice versa (types 3 and 4) or an effect of a systemic disease that affects both organs (type 5). Objective: to update the diagnosis and treatment of patients with cardiorenal syndrome. Methods: theoretical and empirical methods are used to carry out the analysis of updated knowledge on the subject. The existence of a cardiorenal syndrome that compromises both organs has been defined with bidirectional interaction. In its detection, clinical diagnosis is insufficient and requires biochemical markers; these tools, together with the measurement of urinary sodium, allow us to monitor therapeutic effectiveness. Another resource is ultrafiltration, according to complications. Conclusions: evidence-based treatment should be indicated to improve quality of life, reduce mortality, and delay the deterioration of renal and cardiac function in the long term; kidney transplantation should be considered in dialysis patients with severe ventricular dysfunction. Ideally, they should receive a combined transplant: heart and kidney, which is difficult; some patients undergoing exclusively a renal transplantation show a notable improvement in their ejection fraction and survival.

Biomarkers as proxies for cognitive reserve: The role of high density lipoprotein cholesterol in first episode of psychosis.

INTRODUCTION: The proxies used to compose cognitive reserve (CR) for patients of a first episode of psychosis (FEP) have varied in the literature. The development of FEP is linked to peripheral pathways of the central nervous system, yet despite this knowledge, no research has considered the introduction of biomarkers as proxies for CR. Meanwhile, schizophrenia has been linked to the metabolic system, indicating that alterations in the levels of biological parameters, in particular high-density lipoproteins (HDL), cause worse global functioning and cognitive impairment. For these reasons, the present study aimed to create a quantifiable and objective CR index that adjusts for the multifactorial nature of FEP. MATERIALS AND METHODS: We included 668 FEP patients and 217 healthy controls. Participants were assessed for sociodemographic information, years of education, employment status, premorbid IQ and biological parameters: waist circumference, hypertension, and levels of HDL, triglycerides, and glucose. RESULTS: The findings suggest that the years of education proxy showed correlational and higher relationship with HDL levels for both FEP patients (r=0.23, b=0.185) and controls (r=0.31, b=0.342). We found that the CR index composed of years of education and HDL levels showed a higher explanatory power for the phenomenon than the classic CR index composed of years of education, employment status and premorbid IQ. CONCLUSIONS: This article proposes an objective and quantifiable method to measure CR that is more the multifactorial nature of FEP.

COVID-19 en las embarazadas. Riesgo de las complicaciones durante el embarazo y en el neonato / COVID-19 in pregnant women. Risk of complications during pregnancy and in the newborn

Sobre el tema COVID-19 se han publicado múltiples estudios que reflejan su elevada incidencia, transmisibilidad, morbilidad y mortalidad, con gran repercusión y severidad en los grupos poblacionales de riesgo. El embarazo no escapa a ello, y la inmunosupresión fisiológica que se presenta en esta condición, hace a la gestante y al neonato, ser más susceptibles a las enfermedades infecciosas. El objetivo de esta comunicación es profundizar en la fisiopatología y la repercusión de la enfermedad COVID-19 en las gestantes y el neonato, para mejorar el conocimiento relacionado con el tema, el cual repercutirá en un mejor manejo de estos pacientes. Para ello, se realizó una revisión de investigaciones publicadas en el período comprendido entre enero y diciembre de 2021, en las bases de datos: SciELO, SCOPUS, Medline, Dialnet, Cumed y Lilacs. De los 44 artículos obtenidos inicialmente, 33 cumplieron los criterios de inclusión.

Several studies on COVID-19 have been published reflecting its high incidence, transmissibility, morbidity and mortality, with great repercussions and severity in population groups at risk. Pregnancy does not escape from this, and the physiological immunosuppression that occurs in this condition makes the pregnant woman and the newborn more susceptible to infectious diseases. The objective of this communication is to deepen the pathophysiology and the repercussion of the COVID-19 disease in pregnant women and the newborn in order to improve knowledge related to the subject, which will have an impact on better management of these patients. For this, a review of research published between January and December 2021 was carried out in the databases such as SciELO, SCOPUS, Medline, Dialnet, Cumed and Lilacs. A number of 33 articles met the inclusion criteria from 44 initially obtained.

A Proxy Approach to Family Involvement and Neurocognitive Function in First Episode of Non-Affective Psychosis: Sex-Related Differences.

Schizophrenia spectrum disorders (SSD) often show cognitive deficits (CD) impacting daily life. Family support has been shown to be protective against CD, yet the relationship between these in psychotic patients remains complex and not fully understood. This study investigated the association between a subdomain of family support, namely, family involvement (estimated through a proxy measure), cognitive functioning, and sex in first-episode psychosis (FEP) patients. The sample included 308 patients enrolled in the Program for Early Phases of Psychosis (PAFIP), divided into 4 groups based on their estimated family involvement (eFI) level and sex, and compared on various variables. Women presented lower rates of eFI than men (37.1% and 48.8%). Higher eFI was associated with better cognitive functioning, particularly in verbal memory. This association was stronger in women. The findings suggest that eFI may be an important factor in FEP patients' cognitive functioning. This highlights the importance of including families in treatment plans for psychotic patients to prevent CD. Further research is needed to better understand the complex interplay between family support, sex, and cognitive functioning in psychotic patients and develop effective interventions that target these factors.

A simulation model for predicting hospital occupancy for Covid-19 using archetype analysis.

COVID-19 pandemic has sent millions of people to hospitals worldwide, exhausting on many occasions the capacity of healthcare systems to provide care patients required to survive. Although several epidemiological research works have contributed a variety of models and approaches to anticipate the pandemic spread, very few have tried to translate the output of these models into hospital service requirements, particularly in terms of bed occupancy, a key question for hospital managers. This paper proposes a tool for predicting the current and future occupancy associated with COVID-19 patients of a hospital to help managers make informed decisions to maximize the availability of hospitalization and intensive care unit (ICU) beds and ensure adequate access to services for confirmed COVID-19 patients. The proposed tool uses a discrete event simulation approach that uses archetypes (i.e., empirical models of trajectories) extracted from empirical analysis of actual patient trajectories. Archetypes can be fitted to trajectories observed in different regions or to the particularities of current and forthcoming variants using a rather small amount of data. Numerical experiments on realistic instances demonstrate the accuracy of the tool's predictions and illustrate how it can support managers in their daily decisions concerning the system's capacity and ensure patients the access the resources they require.

Pharmacy-based immunization: a systematic review.

Background: The coronavirus disease 2019 pandemic has prompted the exploration of new response strategies for such health contingencies in the near future. Over the last 15 years, several pharmacy-based immunization (PBI) strategies have emerged seeking to exploit the potential of pharmacies as immunization, medication sale, and rapid test centers. However, the participation of pharmacies during the last pandemic was very uneven from one country to another, suggesting a lack of consensus on the definition of their roles and gaps between the literature and practice. Purpose: This study aimed to consolidate the current state of the literature on PBI, document its progress over time, and identify the gaps not yet addressed. Moreover, this study seeks to (i) provide new researchers with an overview of the studies on PBI and (ii) to inform both public health and private organization managers on the range of possible immunization models and strategies. Methodology: A systematic review of scientific qualitative and quantitative studies on the most important scientific databases was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-analyzes guidelines were followed. Finally, this study discusses the trends, challenges, and limitations on the existing literature on PBI. Findings: Must studies concluded that PBI is a beneficial strategy for the population, particularly in terms of accessibility and territorial equity. However, the effectiveness of PBI is affected by the economic, political, and/or social context of the region. The collaboration between the public (government and health departments) and private (various pharmacy chains) sectors contributes to PBI's success. Originality: Unlike previous literature reviews on PBI that compiled qualitative and statistical studies, this study reviewed studies proposing mathematical optimization methods to approach PBI.

A systematic literature review on the utilization of extended operating room hours to reduce surgical backlogs.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Introduction: Hospital managers address elective patient surgical backlogs with different strategies: increasing installed capacity, managing demand and improving efficiency. Recently, and particularly since the COVID-19 elective surgery suspension, extended operating room hours has been used to reduce waiting lists by taking advantage of empty operating rooms and existing surgical teams. Methods: Two research questions are raised: (1) which are the scientific literature's insights related to the use of extended operating room hours to help reduce surgery backlogs? and (2) provided that a hospital decides to extend its operating room opening time, what are the main challenges and the key aspects to consider in the design and implementation of policies to manage extended operating room hours? A systematic review on Web of Science database was conducted to gather existing literature, published from January 2012 to December 2021, regarding strategies to reduce waiting lists using empty operating rooms outside regular working hours. Results: A total of 12 papers were selected as relevant to address the two research questions. Results were organized according to their main features, namely setting, type of strategy, methodology, and how human resources are handled. Discussion: The review suggests that extended operating room hours might be problematic if current staff is used and that a careful choice of patients should be made. However, its potential to reduce waiting times and its implications are discussed only superficially. Therefore, we analyze the implications of extending operating room hours from four different perspectives (management, staff, patients, and strategy deployment) and define some recommendations for policy makers and healthcare managers when implementing it in practice.

Effect of Lactose-Reduction in Murciano-Granadina Semi-Hard Goat Cheese on Physicochemical and Sensory Characteristics.

Semi-hard pressed goat's cheese, a traditional matured cheese in Andalusia, has a residual lactose content that may affect people with intolerance to that carbohydrate. Nowadays, lactose-free dairy products are characterized by presenting a scant sensory quality, far removed from their traditional profile for their pronounced sweet and bitter taste and aroma related to Maillard reactions. The aim of this work was to make a cheese with a similar sensory profile to that of the traditional Andalusian one but without lactose. For this purpose, the doses of the enzyme lactase that would be necessary to add to the milk were investigated so that, during the manufacturing of the cheese, there would remain enough lactose for the starter cultures to trigger lactic fermentation and, in turn, to spark the cheese's own maturity processes. The results show that the combined action of lactase (0.125 g/L, 0.250 g/L, 0.5 g/L, and 1 g/L) and of the lactic bacteria reduces the final content of lactose to below 0.01%, complying with the European Authority of Food Safety's recommendations for considering the cheeses as being under the denomination "lactose-free". The physicochemical and sensory values resulting from the different batches of cheese obtained indicate that the lowest dose studied (0.125 g/L) had very similar ones to those of the control cheese.

Beef Nutritional Characteristics, Fat Profile and Blood Metabolic Markers from Purebred Wagyu, Crossbred Wagyu and Crossbred European Steers Raised on a Fattening Farm in Spain.

A high intramuscular fat content characterizes Wagyu (WY) cattle breed. Our objective was to compare beef from WY, WY-by-Angus, or Wangus (WN) steers with European, Angus-by-Charolais-Limousine crossbred steers (ACL), considering metabolic biomarkers pre-slaughtering and nutritional characteristics, including health-related indexes of the lipid fraction. The fattening system with olein-rich diets and no exercise restriction included 82 steers, 24 WY, 29 WN, and 29 ACL. The slaughter ages and weights were (median and interquartile range) 38.4 mo.-old (34.9-40.3 mo.) and 840 kg (785-895 kg) for WY; for WN, 30.6 mo. (26.9-36.5 mo.) and 832 kg (802-875 kg), and for ACL steers, 20.3 mo.-old (19.0-22.7 mo.) and 780 kg (715-852 kg). Blood lipid-related metabolites, except for non-esterified fatty acids (NEFA) and low-density level cholesterol (LDL), were higher in WY and WN than in ACL, while glucose was lower in WY and WN. Leptin was higher in WN than in ACL. Pre-slaughtering values of plasma HDL underscored as a possible metabolic biomarker directly related to beef quality. The amino-acid content in beef did not differ among experimental groups, except for more crude protein in ACL. Compared to ACL, WY steers showed higher intramuscular fat in sirloin (51.5 vs. 21.9%) and entrecote (59.6 vs. 27.6%), more unsaturated fatty acids in entrecote (55.8 vs. 53.0%), and more oleic acid in sirloin (46 vs. 41.3%) and entrecote (47.5 vs. 43.3%). Compared to ACL entrecote, WY and WN showed better atherogenic (0.6 and 0.55 vs. 0.69), thrombogenicity (0.82 and 0.92 vs. 1.1), and hypocholesterolemic/hypercholesterolemic index (1.9 and 2.1 vs. 1.7). Therefore, beef's nutritional characteristics depend on breed/crossbred, slaughtering age and cut, with WY and WN entrecote samples showing a healthier lipid fraction.

Portal hypertension has no role in perioperative bleeding during liver transplantation with systematic porto-caval shunt.

BACKGROUND: More than a half of patients undergoing liver transplantation (LT) receive intraoperative transfusion. Portal hypertension (PHT) may contribute to perioperative blood loss. We study the relationship between preoperative hepatic venous pressure gradient (HVPG) values and intraoperative transfusion requirements in adult patients undergoing LT. METHODS: 160 cirrhotic patients undergoing first elective LT (2009-2019) with an HVPG measurement within the previous 6 months were included. Surgical technique was piggyback with portocaval shunt (PCS). The association of HVPG and other variables with transfusion requirements and blood loss were studied. RESULTS: Blood loss (ml/kg) was positively correlated with HVPG, among other variables, but at multivariable analysis it only remained associated with MELD-Na and HCC indication. Regarding RBC transfusion, MELD-Na and hemoglobin were independently associated with the need and magnitude of RBC transfusion. Subanalysis by surgical stage (hepatectomy, anhepatic, neohepatic) and by serial HVPG cut-offs found no clear associations with either bleeding or transfusion. DISCUSSION: The severity of PHT plays a minor role on bleeding and transfusion during LT in a contemporary cohort with systematic PCS. Main determinants of transfusion are liver function and baseline hemoglobin, which would seem the suitable goal to optimize transfusion in LT.

Aqueous liquid chromatography with mobile phases of sodium dodecyl sulphate and ionic liquid.

In conventional reversed-phase liquid chromatography (RPLC) with hydro-organic solvents, basic cationic solutes yield retained, broad, asymmetric peaks, owing to their interaction with free anionic silanols in the stationary phase. RPLC mobile phases to which the anionic surfactant sodium dodecyl sulphate (SDS), or an ionic liquid (IL) are added, have been proposed as solutions, since these additives are able to block the silanol effect thus improving the chromatographic performance. With these additives, it is however necessary to increase the elution strength by adding an organic solvent, such as an alcohol or acetonitrile. A novel aqueous liquid chromatographic mode (in the absence of organic solvent) is here proposed, where the mobile phases contain only a mixture of aqueous solutions of SDS and an IL derived from 1-alkyl-3-methylimidazolium associated to chloride, both environmentally friendly. When these reagents are added, the anionic surfactant adsorbed on the stationary phase is able to attract the cationic solutes, whereas the adsorbed IL cation repels them. The combination of both effects (attraction and repulsion) allows the modulation of retention, by varying the IL/SDS ratio. Given the character of the additives, a type of green liquid chromatography is achieved. In this work, the chromatographic behavior of six basic compounds of pharmaceutical interest, the ß-adrenoceptor antagonists acebutolol, atenolol, carteolol, metroprolol, oxprenolol and propranolol, is examined. In order to assess the chromatographic behavior of the mixed mobile phases containing SDS and IL, changes in retention, peak profile and resolution of mixtures of the analytes were explored at varying concentration of the additives.

Theory of Mind as an endophenotype for schizophrenia spectrum disorder: Study in first episode of psychosis patients and first-degree relatives.

BACKGROUND: Deficits in Theory of Mind (ToM) had been suggested as a possible endophenotype for unaffected relatives of first episode of psychosis (FEP) patients. There are a limited number of studies which have evaluated ToM deficits among the siblings and parents of FEP patients. AIM: This study aimed to explore ToM deficits and its correlates among FEP patients, their siblings, parents, and controls. METHODOLOGY: FEP patients (N=102), their parents (N=135), siblings (N=97), and controls (N=167) were evaluated on ToM performance with the Reading the Mind in the Eyes Test (Eyes Test). Interview for sociodemographic variables of age, sex, years of education, and IQ estimation and neurocognitive tests were administered to all groups. RESULTS: FEP patients had a significantly lower performance on the Eyes Test compared to their siblings and controls. However, no significant differences were found between siblings and parents or siblings and controls. CONCLUSION: Attending our results, we found no evidence for ToM deficits as an endophenotype of SSDs. Furthermore, ToM accuracy may be mediated by interaction with other cognitive domains and play a protective role against psychosis in unaffected siblings.

Conectividad funcional a partir de la perfusión cerebral en pacientes epilépticos y con enfermedad de Parkinson / Functional connectivity from cerebral perfusion in patients with epilepsy and Parkinson's disease

Introducción: La epilepsia y la enfermedad de Parkinson han sido descritos como trastornos de redes neurales. El estudio de la conectividad por modalidades moleculares puede ser más relevante fisiológicamente que los basados en señales hemodinámicas. Objetivo: Proponer una metodología para la descripción de patrones de conectividad funcional a partir de la perfusión cerebral por tomografía por emisión de fotón único. Métodos: La metodología incluye cuatro pasos principales: preprocesamiento espacial, corrección del volumen parcial, cálculo del índice de perfusión y obtención de la matriz de conectividad funcional mediante el coeficiente de correlación de Pearson. Se implementó en 25 pacientes con distintos trastornos neurológicos: 15 con epilepsia farmacorresistente y 10 con enfermedad de Parkinson. Resultados: Se encontraron diferencias significativas entre los índice de perfusión de varias regiones de los hemisferios ipsilateral y contralateral tanto en pacientes con epilepsia del lóbulo frontal como en pacientes con epilepsia del lóbulo temporal. Igual resultado se obtuvo en los pacientes con enfermedad de Parkinson con distintos estadios de la enfermedad. Para cada grupo se identificaron patrones de conectividad funcional que involucran a regiones relacionadas con la patología en estudio. Conclusiones: Con el desarrollo de esta metodología se ha demostrado que la tomografía por emisión de fotón único aporta información valiosa para estudiar la organización de las redes funcionales del cerebro. Futuras investigaciones con mayor número de pacientes contribuirían a hacer inferencias sobre los correlatos neurales de los distintos trastornos cerebrales(AU)

Introduction: Epilepsy and Parkinson's disease have been described as disorders of neural networks. The study of connectivity by molecular modalities may be more physiologically relevant than those based on hemodynamic signals. Aim: The aim of the present work is to propose a methodology for the description of functional connectivity patterns from brain perfusion by single photon emission tomography. Methods: The methodology includes four main steps: spatial preprocessing, partial volume correction, calculation of the perfusion index and obtaining the functional connectivity matrix using Pearson's correlation coefficient. It was implemented in 25 patients with different neurological disorders: 15 with drug-resistant epilepsy and 10 suffering Parkinson's disease. Results: Significant differences were found between the perfusion indexes of various regions of the ipsilateral and contralateral hemispheres in both patients with frontal lobe epilepsy and patients with temporal lobe epilepsy. The same result was obtained in Parkinson's disease patients with different stages of the disease. For each group, functional connectivity patterns involving regions related to the pathology under study were identified. Conclusions: With the development of this methodology, it has been demonstrated that single photon emission tomography provides valuable information to study the organization of functional brain networks. Future research with a larger number of patients would contribute to make inferences about the neural correlates of the different brain disorders(AU)

pH-Responsive Metal-Organic Framework Thin Film for Drug Delivery.

In this work, surface-supportive MIL-88B(Fe) was explored as a pH-stimuli thin film to release ibuprofen as a model drug. We used surface plasmon resonance microscopy to study the pH-responsive behaviors of MIL-88B(Fe) film in real time. A dissociation constant of (6.10 ± 0.86) × 10-3 s-1 was measured for the MIL-88B(Fe) film in an acidic condition (pH 6.3), which is about 10 times higher than the dissociation of the same film in a neutral pH condition. MIL-88B(Fe) films are also capable of loading around 6.0 µg/cm2 of ibuprofen, which was measured using a quartz crystal microbalance (QCM). Drug release profiles were compared in both acidic and neutral pH conditions (pH 6.3 and 7.4) using a QCM cell to model the drug release in healthy body systems and those containing inflammatory tissues or cancerous tumors. It was found that the amount of drug released in acidic environments had been significantly higher compared to that in a neutral system within 55 h of testing time. The pH-sensitive chemical bond breaking between Fe3+ and the carboxylate ligands is the leading cause of drug release in acidic conditions. This work exhibits the potential of using MOF thin films as pH-triggered drug delivery systems.

Alternative Excipients for Protein Stabilization in Protein Therapeutics: Overcoming the Limitations of Polysorbates.

Given their safety and efficiency in protecting protein integrity, polysorbates (PSs) have been the most widely used excipients for the stabilization of protein therapeutics for years. In recent decades, however, there have been numerous reports about visible or sub-visible particles in PS-containing biotherapeutic products, which is a major quality concern for parenteral drugs. Alternative excipients that are safe for parenteral administration, efficient in protecting different protein drugs against various stress conditions, effective in protein stabilization in high-concentrated liquid formulations, stable under the storage conditions for the duration of the product's shelf-life, and compatible with other formulation components and the primary packaging are highly sought after. The aim of this paper is to review potential alternative excipients from different families, including surfactants, carbohydrate- and amino acid-based excipients, synthetic amphiphilic polymers, and ionic liquids that enable protein stabilization. For each category, important characteristics such as the ability to stabilize proteins against thermal and mechanical stresses, current knowledge related to the safety profile for parenteral administration, potential interactions with other formulation components, and primary packaging are debated. Based on the provided information and the detailed discussion thereof, this paper may pave the way for the identification or development of efficient excipients for biotherapeutic protein stabilization.