A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma.

In the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expression score for predicting clinical benefit to the anti-PD-1 antibody nivolumab in the context of patients diagnosed with advanced clear cell RCC enrolled in the CheckMate-009, CheckMate-010, and CheckMate-025 clinical trials. First, a three-gene expression score (3GES) with prognostic value for overall survival integrating HMGA1, NUP62, and ARHGAP42 transcripts was developed in a cohort of patients treated with nivolumab. Its prognostic value was then validated in the TCGA-KIRC cohort. Second, the predictive value for nivolumab was confirmed in a set of patients from the CheckMate-025 phase 3 clinical trial. Lastly, we explored the correlation of our 3GES with different clinical, molecular, and immune tumor characteristics. If the results of this study are definitively validated in other retrospective and large-scale, prospective studies, the 3GES will represent a valuable tool for guiding the design of ICB-based clinical trials in the aRCC scenario in the near future.

Correlates of protection and determinants of SARS-CoV-2 breakthrough infections 1 year after third dose vaccination.

BACKGROUND: The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. METHODS: We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. RESULTS: Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26-0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. CONCLUSIONS: Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections.

Outcomes of Drug Interactions Between Antiretrovirals and Co-Medications, Including Over-the-Counter Drugs: A Real-World Study.

INTRODUCTION: The objective was to characterize real-world outcomes of drug-drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and treatment outcomes in clinical practice. METHODS: www.clinicalcasesDDIs.com is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023. RESULTS: A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case). CONCLUSIONS: Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through www.clinicalcasesDDIs.com serves as a valuable resource for assessing the clinical relevance of DDIs.

Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort.

BACKGROUND: In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational age (AGA) newborns from the LARGAN cohort. RESULTS: We found 1672 differentially methylated CpGs (DMCs) with a nominal p < 0.05 and 48 differentially methylated regions (DMRs) with a corrected p < 0.05 between the LGA and AGA groups. A systems biology approach identified several biological processes significantly enriched with genes in association with DMCs with FDR < 0.05, including regulation of transcription, regulation of epinephrine secretion, norepinephrine biosynthesis, receptor transactivation, forebrain regionalization and several terms related to kidney and cardiovascular development. Gene ontology analysis of the genes in association with the 48 DMRs identified several significantly enriched biological processes related to kidney development, including mesonephric duct development and nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched in gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys, and metabolism. CONCLUSIONS: Our study identified several DMCs/DMRs in association with fetal overgrowth. The use of cord blood as a material for the identification of DNA methylation biomarkers gives us the possibility to perform follow-up studies on the same patients as they grow. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness.

Hypothermic Protection in Neocortex Is Topographic and Laminar, Seizure Unmitigating, and Partially Rescues Neurons Depleted of RNA Splicing Protein Rbfox3/NeuN in Neonatal Hypoxic-Ischemic Male Piglets.

The effects of hypothermia on neonatal encephalopathy may vary topographically and cytopathologically in the neocortex with manifestations potentially influenced by seizures that alter the severity, distribution, and type of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia (HT) with continuous electroencephalography (cEEG) for seizures. Neonatal male piglets received HI-normothermia (NT), HI-HT, sham-NT, or sham-HT treatments. Randomized unmedicated sham and HI piglets underwent cEEG during recovery. Survival was 2-7 days. Normal and pathological neurons were counted in different neocortical areas, identified by cytoarchitecture and connectomics, using hematoxylin and eosin staining and immunohistochemistry for RNA-binding FOX-1 homolog 3 (Rbfox3/NeuN). Seizure burden was determined. HI-NT piglets had a reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to sham-NT and sham-HT piglets with differing severities in the anterior and posterior motor, somatosensory, and frontal cortices. Neocortical neuropathology was attenuated by HT. HT protection was prominent in layer III of the inferior parietal cortex. Rbfox3 immunoreactivity distinguished cortical neurons as: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had an increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT piglets. Neuronal Rbfox3 depletion was partly rescued by HT. Seizure burdens in HI-NT and HI-HT piglets were similar. We conclude that the neonatal HI piglet neocortex has: (1) suprasylvian vulnerability to HI and seizures; (2) a limited neuronal cytopathological repertoire in functionally different regions that engages protective mechanisms with HT; (3) higher seizure burden, insensitive to HT, that is correlated with more panlaminar ischemic-necrotic neurons in the somatosensory cortex; and (4) pathological RNA splicing protein nuclear depletion that is sensitive to HT. This work demonstrates that HT protection of the neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores neuronal depletion of RNA splicing factor.

Preoperative oral practices and incidence of postoperative complications in hospital medical-surgical procedures: A meta-analysis

Background: Oral decay prior to a hospital medical-surgical procedure is a risk factor for the development of postoperative complications. However, perioperative oral practices as a protective factor have not been studied. This review aims to evaluate the effectiveness of perioperative oral practices in the reduction of risk of developing postoperative complications in in-hospital medical surgical procedures. Material and methods: This review and meta-analysis was conducted according to Cochrane guidelines. Medline, Scopus, Scielo, and Cochrane were consulted. Articles of the previous 10 years concerning adult patients undergoing perioperative oral practices prior to hospital medical-surgical procedures, were included. Data of the type of perioperative oral practice, type of postoperative complication and measures of effect on the development of complications were extracted. Results: Of a pool of 1470 articles, 13 were included for systematic review and 10 for meta-analysis. The most common perioperative oral procedures were focalized approach (FA), referred to only the elimination of infectious foci in the oral cavity and comprehensive approach (CA), referred to a integral approach of the patient's oral health, both of which were mainly performed in oncologic surgeries, both were effective in the reduction of postoperative complications (RR=0.48, [95% CI 0.36 - 0.63]). The most reported postoperative complication was postoperative pneumonia. Conclusions: Perioperative oral management proved to be a protective factor against the development of postoperative complications. (AU)

Embriogénesis, desarrollo larval y sobrevivencia post-asentamiento del coral Orbicella annularis (Scleractinia: Merulinidae)

Introducción: Las poblaciones del coral Orbicella annularis han mostrado bajo reclutamiento en el Caribe. Uno de los cuellos de botella demográficos es la alta mortalidad en las primeras etapas de desarrollo. El conocimiento detallado del ciclo y las tasas de supervivencia de estas fases nos permitirá ayudar en la recuperación de la población y la restauración de los arrecifes. Objetivo: Describir la embriogénesis y estadios larvarios obtenidos por fertilización asistida y medir las tasas de asentamiento y supervivencia de las larvas en sustratos artificiales, antes de ser trasplantadas al arrecife. Métodos: Seis días después de la luna llena de septiembre de 2021, se recolectaron bolsas de gametos de ocho colonias de O. annularis en el Parque Nacional Natural Los Corales del Rosario y San Bernardo, Colombia, y se llevaron al laboratorio. Se realizó fecundación cruzada, se siguió el desarrollo embrionario y larvario hasta el asentamiento larval y se registró supervivencia hasta el día 41. Las larvas se mantuvieron en tres tanques con agua de mar filtrada con 126 sustratos marcados, previamente acondicionados con algas coralináceas costrosas. Luego, los sustratos se trasplantaron al arrecife. Resultados: El inicio del desarrollo embrionario ocurrió 1.11 hAF (horas después de la fertilización), cuando las células mostraron signos de la primera división, y duró hasta 104.59 hAF cuando comenzaron a metamorfosearse. El asentamiento de larvas se observó al sexto día AF. Veintiún días después de la fecundación se encontraron zooxantelas. La supervivencia de las larvas después del asentamiento fue de 27.5 %. Conclusión: En este primer esfuerzo de propagación sexual utilizando O. annularis en Colombia, 1.4 % de larvas competentes completaron todo el proceso de desarrollo. Aunque la tasa de supervivencia fue baja, estos resultados se suman a los esfuerzos de restauración de corales en el Caribe en los que se ayuda a las especies a aumentar la supervivencia de los corales en sus primeras etapas de desarrollo.

Introduction: Populations of the coral Orbicella annularis have shown low recruitment in the Caribbean. One of the demographic bottlenecks is the high mortality in the early stages of development. Detailed knowledge of the cycle and survival rates of these phases will allow us to assist in population recovery and reef restoration. Objective: To describe the embryogenesis and larval stages obtained by assisted fertilization and measure the settlement and survival rates of larvae on artificial substrates, before being outplanted to the reef. Methods: Six days after the full moon in September 2021, gamete bundles were collected from eight O. annularis colonies in Los Corales del Rosario and San Bernardo National Natural Park, Colombia and brought to the laboratory. Cross fertilization was carried out and embryonic and larval development were followed until larval settlement and survival was recorded until day 41. The larvae were kept in three tanks with filtered sea water with 126 tagged substrates, previously conditioned with crustose coralline algae. The substrates were then outplanted to the reef. Results: The onset of embryonic development occurred 1.11 hAF (hours after fertilization), when cells showed signs of the first cleavage, and lasted until 104.59 hAF when they began to metamorphose. Larvae settlement was observed on the sixth day AF. Twenty-one days after fertilization, zooxanthellae were found. Post-settlement larval survival was 27.5 %. Conclusions: In this first sexual propagation effort using O. annularis in Colombia, 1.4 % of competent larvae completed the entire development process. Although low survival rate, these results add to coral restoration efforts in the Caribbean in which species are assisted to increase the survival of corals in their early stages of development.

Designing Digital COVID-19 Screening: Insights and Deliberations.

Due to the global COVID-19 pandemic, public health control and screening measures have been introduced at healthcare facilities, including those housing our most vulnerable populations. These warning measures situated at hospital entrances are presently labour-intensive, requiring additional staff to conduct manual temperature checks and risk-assessment questionnaires of every individual entering the premises. To make this process more efficient, we present eGate, a digital COVID-19 health-screening smart Internet of Things system deployed at multiple entry points around a children's hospital. This paper reports on design insights based on the experiences of concierge screening staff stationed alongside the eGate system. Our work contributes towards social-technical deliberations on how to improve design and deploy of digital health-screening systems in hospitals. It specifically outlines a series of design recommendations for future health screening interventions, key considerations relevant to digital screening control systems and their implementation, and the plausible effects on the staff who work alongside them.

Atoms in molecules in real space: a fertile field for chemical bonding.

In this perspective, we review some recent advances in the concept of atoms-in-molecules from a real space perspective. We first introduce the general formalism of atomic weight factors that allows unifying the treatment of fuzzy and non-fuzzy decompositions under a common algebraic umbrella. We then show how the use of reduced density matrices and their cumulants allows partitioning any quantum mechanical observable into atomic or group contributions. This circumstance provides access to electron counting as well as energy partitioning, on the same footing. We focus on how the fluctuations of atomic populations, as measured by the statistical cumulants of the electron distribution functions, are related to general multi-center bonding descriptors. Then we turn our attention to the interacting quantum atom energy partitioning, which is briefly reviewed since several general accounts on it have already appeared in the literature. More attention is paid to recent applications to large systems. Finally, we consider how a common formalism to extract electron counts and energies can be used to establish an algebraic justification for the extensively used bond order-bond energy relationships. We also briefly review a path to recover one-electron functions from real space partitions. Although most of the applications considered will be restricted to real space atoms taken from the quantum theory of atoms in molecules, arguably the most successful of all the atomic partitions devised so far, all the take-home messages from this perspective are generalizable to any real space decompositions.

Metadherin Regulates Inflammatory Breast Cancer Invasion and Metastasis.

Inflammatory breast cancer (IBC) is one of the most lethal subtypes of breast cancer (BC), accounting for approximately 1-5% of all cases of BC. Challenges in IBC include accurate and early diagnosis and the development of effective targeted therapies. Our previous studies identified the overexpression of metadherin (MTDH) in the plasma membrane of IBC cells, further confirmed in patient tissues. MTDH has been found to play a role in signaling pathways related to cancer. However, its mechanism of action in the progression of IBC remains unknown. To evaluate the function of MTDH, SUM-149 and SUM-190 IBC cells were edited with CRISPR/Cas9 vectors for in vitro characterization studies and used in mouse IBC xenografts. Our results demonstrate that the absence of MTDH significantly reduces IBC cell migration, proliferation, tumor spheroid formation, and the expression of NF-κB and STAT3 signaling molecules, which are crucial oncogenic pathways in IBC. Furthermore, IBC xenografts showed significant differences in tumor growth patterns, and lung tissue revealed epithelial-like cells in 43% of wild-type (WT) compared to 29% of CRISPR xenografts. Our study emphasizes the role of MTDH as a potential therapeutic target for the progression of IBC.

MSIMEP: Predicting microsatellite instability from microarray DNA methylation tumor profiles.

Deficiency in DNA MMR activity results in tumors with a hypermutator phenotype, termed microsatellite instability (MSI). Beyond its utility in Lynch syndrome screening algorithms, today MSI has gained importance as predictive biomarker for various anti-PD-1 therapies across many different tumor types. Over the past years, many computational methods have emerged to infer MSI using either DNA- or RNA-based approaches. Considering this together with the fact that MSI-high tumors frequently exhibit a hypermethylated phenotype, herein we developed and validated MSIMEP, a computational tool for predicting MSI status from microarray DNA methylation tumor profiles of colorectal cancer samples. We demonstrated that MSIMEP optimized and reduced models have high performance in predicting MSI in different colorectal cancer cohorts. Moreover, we tested its consistency in other tumor types with high prevalence of MSI such as gastric and endometrial cancers. Finally, we demonstrated better performance of both MSIMEP models vis-à-vis a MLH1 promoter methylation-based one in colorectal cancer.

Nurse, Give Me the News! Understanding Support for and Opposition to a COVID-19 Health Screening System.

Helping the sick and protecting the vulnerable has long been the credo of the health profession. In response to the coronavirus-disease-2019 (COVID-19 pandemic), hospitals and healthcare institutions have rapidly employed public health measures to mitigate patient and staff infection. This paper investigates staff and visitor responses to the COVID-19 eGate health screening system; a self-service technology (SST) which aims to protect health care workers and facilities from COVID-19. Our study evaluates the in situ deployment of the eGate, and employs a System Usability Scale (SUS) and questionnaire (n = 220) to understand staff and visitor's acceptance of the eGate. In detailing the themes relevant to those who advocate for the system and those who oppose it, we contribute towards a more detailed understanding of the use and non-use of health-screening SSTs. We conclude with a series of considerations for the design of future interactive screening systems within hospitals.

A Pilot of Brief Mindfulness-Based Intervention to manage emotions in patients with psoriasis / Un estudio piloto de intervención breve basada en Mindfulness para gestionar las emociones en pacientes con psoriasis

La psoriasis es una dermatosis de alta incidencia relacionada con el estrés, constituyendo las personas que lo padecen, un grupo objetivo adecuado para llevar a cabo intervenciones basadas en mindfulness, destinadas a ayudar a la regulación de las emociones. El objetivo del presente estudio es evaluar los efectos de la Técnica de Acompañamiento Emocional Compasivo (CEAT), como una intervención breve basada en mindfulness, sobre el afrontamiento emocional en pacientes con psoriasis grave, para determinar la eficacia del afrontamiento emocional tras la inducción de un estado emocional negativo. Cuarenta y cuatro adultos (el 59,1% mujeres) con edades comprendidas entre los 22 y los 71 años (M = 51,95, DT = 11,87), con psoriasis grave, fueron asignados aleatoriamente a un grupo de intervención con CEAT o a un grupo control de intervención de Revelación Emocional. Se evaluaron malestar subjetivo, capacidad cognitiva, afecto y frecuencia cardíaca, antes y después de las intervenciones, con dos seguimientos a las 48 horas y a los siete días. Los resultados muestran diferencias estadísticas significativas a favor de la intervención CEAT frente al grupo de Revelación Emocional, siendo más eficaz en el manejo emocional tras la inducción y el seguimiento. Estos resultados podrían favorecer la intervención en entornos clínicos con pacientes con psoriasis grave, y futuras investigaciones podrían considerar el uso de esta para mejorar la gestión emocional en este tipo de población.(AU)

Abstract: Psoriasis is a high incidence dermatosis related to stress, and its sufferers provide an appropriate target group to carry out interventions such as those based on mindfulness, aimed at helping emotion regulation. To assess the Compassionate Emotional Accompaniment Technique (CEAT) effects within a brief mindfulness-based intervention on emotion-al coping in patients with severe psoriasisto determine the efficacy of emotional coping after the induction of a negative emotional state. Forty-four adults(59.1% were women)aged 22 -71 years (M= 51.95, SD = 11.87) with severe psoriasis were assigned randomly to the CEAT group or the Emotional Disclosurecontrol group. Subjective discomfort, cognitive ability, affect, and heart rate were assessed before and after the interven-tions, with two follow-ups at 48 hours and seven days. The results show significant statistical differences in favour of the CEAT intervention versus the Emotional Disclosure group, being more effective in the emotional management after induction and follow-up. These results encourage inter-ventions in a clinical setting with patients with severe psoriasis, so future research should consider using this intervention type to improve emotional management with this population grou.(AU)

An allopurinol adherence tool using plasma oxypurinol concentrations.

AIMS: This study aimed to develop and evaluate an allopurinol adherence tool based on steady-state oxypurinol plasma concentrations, allopurinol's active metabolite. METHODS: Plasma oxypurinol concentrations were simulated stochastically from an oxypurinol pharmacokinetic model for allopurinol doses of 100-800 mg daily, accounting for differences in renal function, diuretic use and ethnicity. For each scenario, the 20th percentile for peak and trough concentrations defined the adherence threshold, below which imperfect adherence was assumed. Predictive performance was evaluated using both simulated low adherence and against data from 146 individuals with paired oxypurinol plasma concentrations and adherence measures. Sensitivity and specificity (S&S), negative and positive predictive values (NPV, PPV) and receiver operating characteristic (ROC) area under the curve (AUC) were determined. The predictive performance of the tool was evaluated using adherence data from an external study (CKD-FIX). RESULTS: The allopurinol adherence tool produced S&S values for trough thresholds of 89-98% and 76-84%, respectively, and 90%-98% and 76-83% for peak thresholds. PPV and NPV were 79-84% and 88-94%, respectively, for trough and 80-85% and 89-98%, respectively, for peak concentrations. The ROC AUC values ranged from 0.84 to 0.88 and from 0.86 to 0.89 for trough and peak concentrations, respectively. S&S values for the external evaluation were found to be 75.8% and 86.5%, respectively, producing an ROC AUC of 0.8113. CONCLUSION: A tool to identify people with gout who require additional support to maintain adherence using plasma oxypurinol concentrations was developed and evaluated. The predictive performance of the tool is suitable for adherence screening in clinical trials and may have utility in some clinical practice settings.

El papel del laboratorio de microbiología en la práctica clínica / The role of the microbiology laboratory in clinical practice

Los seres humanos albergamos en el cuerpo a cientos de miles de microbios (bacterias, virus, hongos, archaea). Con la mayoría convivimos armónicamente, y obtenemos beneficios mutuos. Ellos participan activamente en nuestros procesos metabólicos e inmunológicos, y nosotros les damos vivienda y nutrientes [1]. Si el equilibrio se altera, como ocurre cuando el sistema inmune se suprime, algunos de estos microorganismos aprovechan la oportunidad y desencadenan infección [2], siendo este el origen de la mayoría de las infecciones, pero no el único, pues los ambientes externos al cuerpo humano también están poblados de microbios, y si bien pocos se consideran patógenos, al entrar en contacto con ellos adquirimos infecciones que llamamos exógenas. De acuerdo con la Organización Mundial de la Salud (OMS), las enfermedades transmisibles están entre las 10 principales causas de muerte en el mundo, y excluyendo la infección por SARS-CoV-2 (COVID-19) en 2021, las infecciones respiratorias agudas fueron la cuarta causa más frecuente de defunción a nivel mundial [3]. El laboratorio de microbiología clínica tiene un papel crucial en el proceso diagnóstico, terapéutico y preventivo de las enfermedades infecciosas causadas por bacterias, hongos, virus y parásitos, pues determinar el agente causal de manera eficaz permite tomar acciones oportunas para definir el manejo individual de las personas infectadas y cortar la cadena de transmisión cuando se requiera [2]

Toward Reliable and Insightful Entropy Calculations on Flexible Molecules.

The absolute entropy of a flexible molecule can be approximated by the sum of a rigid-rotor-harmonic-oscillator (RRHO) entropy and a Gibbs-Shannon entropy associated to the Boltzmann distribution for the occupation of the conformational energy levels. Herein, we show that such partitioning, which has received renewed interest, leads to accurate entropies of single molecules of increasing size provided that the conformational part is estimated by means of a set of discretization and expansion techniques that are able to capture the significant correlation effects among the torsional motions. To ensure a reliable entropy estimation, we rely on extensive sampling as that produced by classical molecular dynamics simulations on the microsecond time scale, which is currently affordable for small- and medium-sized molecules. According to test calculations, the gas-phase entropy of simple organic molecules is predicted with a mean unsigned error of 0.9 cal/(mol K) when the RRHO entropies are computed at the B3LYP-D3/cc-pVTZ level. Remarkably, the same protocol gives small errors [<1 cal/(mol K)] for the extremely flexible linear alkane molecules (CnH2n+2, n = 14, 16, and 18). Similarly, we obtain well-converged entropies for a more challenging test of drug molecules, which exhibit more pronounced correlation effects. We also perform equivalent entropy calculations on a 76 amino acid protein, ubiquitin, by taking advantage of the cutoff-dependent formulation of an expansion technique (correlation-consistent multibody local approximation, CC-MLA), which incorporates genuine correlation effects among the neighboring dihedral angles. Moreover, we show that insightful descriptors of the coupled torsional motions can be obtained with the CC-MLA approach.

QM/MM Energy Decomposition Using the Interacting Quantum Atoms Approach.

The interacting quantum atoms (IQA) method decomposes the quantum mechanical (QM) energy of a molecular system in terms of one- and two-center (atomic) contributions within the context of the quantum theory of atoms in molecules. Here, we demonstrate that IQA, enhanced with molecular mechanics (MM) and Poisson-Boltzmann surface-area (PBSA) solvation methods, is naturally extended to the realm of hybrid QM/MM methodologies, yielding intra- and inter-residue energy terms that characterize all kinds of covalent and noncovalent bonding interactions. To test the robustness of this approach, both metal-water interactions and QM/MM boundary artifacts are characterized in terms of the IQA descriptors derived from QM regions of varying size in Zn(II)- and Mg(II)-water clusters. In addition, we analyze a homologous series of inhibitors in complex with a matrix metalloproteinase (MMP-12) by carrying out QM/MM-PBSA calculations on their crystallographic structures followed by IQA energy decomposition. Overall, these applications not only show the advantages of the IQA QM/MM approach but also address some of the challenges lying ahead for expanding the QM/MM methodology.

Peptides recovery from egg yolk lipovitellins by ultrafiltration and their in silico bioactivity analysis.

The lipoproteins that remain after the extraction of phosvitin from the egg yolk granular fraction possess low industrial applicability. In this study, these lipoproteins were hydrolysed using trypsin, and the bioactivity of the resulting peptides was assessed by in silico analysis. In addition, in order to isolate the most valuable previously detected peptides, their transmission through a polyethersulfone (PES) membrane and a stabilised cellulose (SC) based membrane was also evaluated at several pHs. A pH of 4.0 gave the highest observed transmission of peptides through both membranes for every peptide identified in the permeate streams. Regarding the PES membrane, six peptide sequences detected in the permeate were predicted to be antihypertensive, although only one of them showed a bioactivity score higher than 0.5 according to Peptide Ranker. When the SC membrane was assessed, five peptides with a bioactivity score higher than 0.5 were detected in the permeate streams and eight peptides were predicted as antihypertensive. The in silico analysis performed showed that K.VQWGIIPSWIK.K was the most promising antihypertensive peptide found in the permeates.

Prevention and Treatment of SARS-CoV2 Infection in People Living with HIV: The Need for Specific Data.

The HIV pandemic has led to close to 40 million people living with HIV (PLWH) worldwide. To date, SARS-CoV2 has affected > 220 million people, and unprecedented global efforts have resulted in almost 6000 million doses of SARS-CoV2 vaccines being administered. Although several specific COVID-19 antiviral and anti-inflammatory treatments and SARS-CoV2 vaccines have been approved, the data available to support their use in specific populations such as PLWH remain limited. PLWH includes a range of individuals from practically unaffected immunity to severely immunocompromised individuals, and preventive and therapeutic interventions should be tailored for these subgroups . However, in most randomized clinical trials regarding antivirals, immunomodulators and vaccines for COVID-19, PLWH have been excluded or only enrolled in small numbers leading to a paucity of data. We briefly discuss the current evidence for prevention and treatment of COVID-19 in PLWH and identify key areas where more information is required.

[Design of a real and perceived academic workload measurement instrument for health care undergraduate students]. / Diseño y validación de un instrumento de medición de la carga académica de estudiantes de carreras de la salud.

BACKGROUND: A high academic workload may have adverse consequences among university students. AIM: To design and validate an instrument to measure both real and perceived academic workload for health care students. MATERIAL AND METHODS: The questionnaire was designed based on a bibliographic revision and the conduction of two focus groups conformed by undergraduate students from a Faculty of Medicine. Afterwards, it was submitted to qualitative pre-tests. The final instrument consists of a self-applied questionnaire with both a characterization section (10 questions) and one concerning academic workload by subject and semester (five and two questions, respectively). A national and international panel of 14 experts evaluated the survey content's validity. The analysis was performed according to the Content Validity Ratio and the Content Validity Index. RESULTS: The complete instrument was validated with an 84% consensus between the judges. Each section of the instrument was approved separately with a 77% and a 94% agreement, respectively. After being individually analyzed by the judges, each question was validated. The wording of questions was improved taking the experts comments into consideration. CONCLUSIONS: The proposed instrument constitutes a contribution for the measurement of real and perceived academic workload for students.