Charged Biological Membranes Repel Large Neutral Molecules by Surface Dielectrophoresis and Counterion Pressure.

Macromolecular crowding is the usual condition of cells. The implications of the crowded cellular environment for protein stability and folding, protein-protein interactions, and intracellular transport drive a growing interest in quantifying the effects of crowding. While the properties of crowded solutions have been extensively studied, less attention has been paid to the interaction of crowders with the cellular boundaries, i.e., membranes. However, membranes are key components of cells and most subcellular organelles, playing a central role in regulating protein channel and receptor functions by recruiting and binding charged and neutral solutes. While membrane interactions with charged solutes are dominated by electrostatic forces, here we show that significant charge-induced forces also exist between membranes and neutral solutes. Using neutron reflectometry measurements and molecular dynamics simulations of poly(ethylene glycol) (PEG) polymers of different molecular weights near charged and neutral membranes, we demonstrate the roles of surface dielectrophoresis and counterion pressure in repelling PEG from charged membrane surfaces. The resulting depletion zone is expected to have consequences for drug design and delivery, the activity of proteins near membrane surfaces, and the transport of small molecules along the membrane surface.

Tocilizumab en el tratamiento de la esclerosis sistémica difusa. A propósito de un caso / Tocilizumab in the treatment of diffuse systemic sclerosis. Report of clinical case

La esclerosis sistémica (ES) es una enfermedad autoinmune sistémica que se caracteriza por el desarrollo de alteraciones vasculares e inmunológicas, junto a una síntesis excesiva de colágeno en la matriz extracelular, que ocasiona una vasculopatía obliterante y fibrosis cutánea y visceral1. Los tratamientos disponibles tienen una efectividad limitada, entre los que se encuentran en primera línea fármacos inmunosupresores3. Recientemente se ha propuesto el tratamiento off-label con tocilizumab, anticuerpo monoclonal que inhibe la interleucina 6 (IL-6). Se describe el caso de una paciente con ES en tratamiento con tocilizumab, que aporta información sobre la efectividad y seguridad de tocilizumab en ES. (AU)

Systemic sclerosis (SS) is a systemic autoimmune disease characterized by the development of vascular and immunological alterations, together with an excessive synthesis of collagen in the extracellular matrix, which causes obliterative vasculopathy and cutaneous and visceral fibrosis. The available treatments have limited effectiveness, among which immunosuppressive drugs are the first line3. Off-label treatment with tocilizumab, a monoclonal antibody that inhibits interleukin 6 (IL-6), has recently been proposed. The case of a patient with SS undergoing treatment with tocilizumab is described, providing information on the effectiveness and safety of tocilizumab in SS. (AU)

Cross preferences and genetic diversity of Psidium interspecific hybrids through morphoagronomic traits and resistance to Meloidogyne enterolobii.

The introgression of M. enterolobii resistance-related genes in guava breeding programs can be compromised by incompatibility among Psidium species. This study aimed to evaluate the female parent preference and genetic diversity of Psidium interspecific hybrids using morphoagronomic traits and resistance to M. enterolobii. There were evaluated cross successes and germination from crosses between accesses of P. cattleyanum, P. guineense and P. guajava and the genetic diversity by Ward-MLM method of hybrids according to descriptors developed for the genus. Crosses were more successful when P. cattleyanum was the female parent. Germination was more successful in crosses involving P. cattleyanum and P. guajava. Four groups were formed. The group IV clustered the most resistant genotypes, composed by genotypes of P. cattleyanum x P. guineense, while the group II was the most susceptible. The groups I and III grouped some genotypes of P. cattleyanum x P. guajava with low levels of susceptibility. There are preferences of female parent species among crosses. Some individuals of groups I and III can be used as source of resistance genes for the breeding program, due the presence of favorable alleles inherited from guava parent. The high susceptibility leads to reduction in root development.

The Complex Proteolipidic Behavior of the SARS-CoV-2 Envelope Protein Channel: Weak Selectivity and Heterogeneous Oligomerization.

The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), where virion budding takes place. Several reports claim that E protein promotes the formation of "cation-selective channels". However, whether this term represents specificity to certain ions (e.g., potassium or calcium) or the partial or total exclusion of anions is debatable. Herein, we discuss this claim based on the available data for SARS-CoV-1 and -2 E and on new experiments performed using the untagged full-length E protein from SARS-CoV-2 in planar lipid membranes of different types, including those that closely mimic the ERGIC membrane composition. We provide evidence that the selectivity of the E-induced channels is very mild and depends strongly on lipid environment. Thus, despite past and recent claims, we found no indication that the E protein forms cation-selective channels that prevent anion transport, and even less that E protein forms bona fide specific calcium channels. In fact, the E channel maintains its multi-ionic non-specific neutral character even in concentrated solutions of Ca2+ ions. Also, in contrast to previous studies, we found no evidence that SARS-CoV-2 E channel activation requires a particular voltage, high calcium concentrations or low pH, in agreement with available data from SARS-CoV-1 E. In addition, sedimentation velocity experiments suggest that the E channel population is mostly pentameric, but very dynamic and probably heterogeneous, consistent with the broad distribution of conductance values typically found in electrophysiological experiments. The latter has been explained by the presence of proteolipidic channel structures.

Consumer attitudes and perceptions towards chilled ready-to-eat foods: a multi-national study.

Understanding consumers' behavior and their handling of high-risk foods at home is essential for reducing the number of foodborne illnesses. This study shows the results of a cross-national analysis of consumers' perception from nine countries, and the identification of customers' clusters and its characteristics in order to understand customers' behavior, and to build safe chilled ready-to-eat (RTE) foods prevention strategies. The cluster analysis resulted in two clusters: (1) "Precautious consumers" characterized by the orientation towards pre-packed RTE foods, with consumers mainly coming from Bosnia and Herzegovina, India, Poland, Portugal, Spain, and Turkey. Their attitudes and self-reported practices may be categorized as less risky in terms of food-borne illnesses connected with the consumption of RTE foods; (2) "Unconcerned consumers" preferred cutting and slicing RTE foods freshly at the point of purchase, usually sold at the delicatessen department in a supermarket or at open markets. Those consumers mostly came from Croatia, Serbia and Slovenia and their attitudes and self-reported practices were riskier. These results allow a better understating of what characterizes consumers of RTE foods in different countries.

A novel approach to automatic seizure detection using computer vision and independent component analysis.

OBJECTIVE: Epilepsy is a neurological disease that affects ~50 million people worldwide, 30% of which have refractory epilepsy and recurring seizures, which may contribute to higher anxiety levels and poorer quality of life. Seizure detection may contribute to addressing some of the challenges associated with this condition, by providing information to health professionals regarding seizure frequency, type, and/or location in the brain, thereby improving diagnostic accuracy and medication adjustment, and alerting caregivers or emergency services of dangerous seizure episodes. The main focus of this work was the development of an accurate video-based seizure-detection method that ensured unobtrusiveness and privacy preservation, and provided novel approaches to reduce confounds and increase reliability. METHODS: The proposed approach is a video-based seizure-detection method based on optical flow, principal component analysis, independent component analysis, and machine learning classification. This method was tested on a set of 21 tonic-clonic seizure videos (5-30 min each, total of 4 h and 36 min of recordings) from 12 patients using leave-one-subject-out cross-validation. RESULTS: High accuracy levels were observed, namely a sensitivity and specificity of 99.06% ± 1.65% at the equal error rate and an average latency of 37.45 ± 1.31 s. When compared to annotations by health care professionals, the beginning and ending of seizures was detected with an average offset of 9.69 ± 0.97 s. SIGNIFICANCE: The video-based seizure-detection method described herein is highly accurate. Moreover, it is intrinsically privacy preserving, due to the use of optical flow motion quantification. In addition, given our novel independence-based approach, this method is robust to different lighting conditions, partial occlusions of the patient, and other movements in the video frame, thereby setting the base for accurate and unobtrusive seizure detection.

Plant compounds for obesity treatment through neuroendocrine regulation of hunger: A systematic review.

BACKGROUND: Food intake behavior is influenced by both physiological and psychological complex processes, such as appetite, satiety, and hunger. The neuroendocrine regulation of food intake integrates short- and long-term acting signals that modulate the moment of intake and energy storage/expenditure, respectively. These signals are classified as orexigenic, those that activate anabolic pathways and the desire of eating, and anorexigenic, those that activate the catabolic pathways and a sensation of satiety. Appetite control by natural vegetal compounds is an intense area of research and new pharmacological interventions have been emerging based on an understanding of appetite regulation pathways. Several validated psychometric tools are used to assess the efficacy of these plant ingredients. However, these data are not conclusive if they are not complemented with physiological parameters, such as anthropometric evaluations (body weight and composition) and the analysis of hormones related to adipose tissue and appetite in blood. PURPOSE: The purpose of this manuscript is the critical analysis of the plant compounds studied to date in the literature with potential for the neuroendocrine regulation of hunger in order to determine if the use of phytochemicals for the treatment of obesity constitutes an effective and/or promising therapeutic tool. METHODS: Relevant information on neuroendocrine regulation of hunger and satiety for the treatment of obesity by plant compounds up to 2022 in English and/or Spanish were derived from online databases using the PubMed search engine and Google Scholar with relevant keywords and operators. RESULTS: Accordingly, the comparison performed in this review between previous studies showed a high degree of experimental heterogeneity. Among the studies reviewed here, only a few of them establish comprehensively a potential correlation between the effect of the ingredient on hunger or satiety, body changes and a physiological response. CONCLUSIONS: More systematic clinical studies are required in future research. The first approach should be to decode the pattern of circulating hormones regulating hunger, satiety, and appetite in overweight/obese subjects. Thereafter, studies should correlate brain connectivity at the level of the hypothalamus, gut and adipose tissue with the hormone patterns modulating appetite and satiety. Extracts whose mode of action have been well characterized and that are safe, can be used clinically to perform a moderate, but continuous, caloric restriction in overweight patients to lose weight excess into a controlled protocol.

Biphasic concentration patterns in ionic transport under nanoconfinement revealed in steady-state and time-dependent properties.

Ion permeation across nanoscopic structures differs considerably from microfluidics because of strong steric constraints, transformed solvent properties, and charge-regulation effects revealed mostly in diluted solutions. However, little is known about nanofluidics in moderately concentrated solutions, which are critically important for industrial applications and living systems. Here, we show that nanoconfinement triggers general biphasic concentration patterns in a myriad of ion transport properties by using two contrasting systems: a biological ion channel and a much larger synthetic nanopore. Our findings show a low-concentration regime ruled by classical Debye screening and another one where ion-ion correlations and enhanced ion-surface interactions contribute differently to each electrophysiological property. Thus, different quantities (e.g., conductance vs noise) measured under the same conditions may appear contradictory because they belong to different concentration regimes. In addition, non-linear effects that are barely visible in bulk conductivity only in extremely concentrated solutions become apparent in nanochannels around physiological conditions.

Digging into the admixture strata of current-day Canary Islanders based on mitogenomes.

The conquest of the Canary Islands by Europeans began at the beginning of the 15th century and culminated in 1496 with the surrender of the aborigines. The collapse of the aboriginal population during the conquest and the arrival of settlers caused a drastic change in the demographic composition of the archipelago. To shed light on this historical process, we analyzed 896 mitogenomes of current inhabitants from the seven main islands. Our findings confirm the continuity of aboriginal maternal contributions and the persistence of their genetic footprints in the current population, even at higher levels (>60% on average) than previously evidenced. Moreover, the age estimates for most autochthonous founder lineages support a first aboriginal arrival to the islands at the beginning of the first millennium. We also revealed for the first time that the main recognizable genetic influences from Europe are from Portuguese and Galicians.

A Questionnaire Survey of Personal and Occupational Variables Associated With SARS-COV-2 Infection in Health Care Personnel of the Spanish Central Military Hospital.

INTRODUCTION: Spain is the country with the highest number of health care workers affected by coronavirus disease 2019 (COVID-19) in the world. The aim of this study was to describe the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection in health care worker (HCW) at the Gómez Ulla Military Hospital (HCDGU). MATERIALS AND METHODS: A case-control study was conducted during the first outbreak of COVID 19 at GUMH. The study was extended to the total number of HCW in the hospital who met the inclusion criteria. Health care worker of the HCDGU were civilian and military personnel that included nursing and medicine students of Spanish Military Academy, medicine specialty residents, and nursing residents of Medical Surgical Specialty in Operations (EMQO). A questionnaire of 33 items was prepared. The questionnaire was sent by e-mail to the entire population of study. With this questionnaire personnel were classified into sick (cases) or healthy. RESULTS AND CONCLUSIONS: One hundred fifty professionals answered the questionnaire. Cases were defined as those who tested positive in the diagnostic tests (n = 28, 20.7%) and no cases were those who tested negative (n = 107, 79.3%). Therefore, the percentage of SARS-CoV-2 in the GUMH was 20.7%. Of the total number of cases, 64.3% were men (P < .05), with a mean age of 47.1 years (SD 13.3), a mean BMI of 25.3 (SD 3.8), and 48.2% being overweight. Of the total cases, 59.3% had "A" blood group type and 69.2% were Rh positive. 50% were physicians, 32.1% were nurses, and 17.9% were auxiliary nurses (P < .05). Cases and controls with vitamin D deficiency and who took supplements had a lower risk of suffering COVID-19, with significant differences. Fever, cough, and diarrhea were found in at least 50% of the samples with significant differences.

Meloidogyne enterolobii-induced Changes in Guava Root Exudates Are Associated With Root Rotting Caused by Neocosmospora falciformis.

Despite the worldwide importance of disease complexes involving root-feeding nematodes and soilborne fungi, there have been few in-depth studies on how these organisms interact at the molecular level. Previous studies of guava decline have shown that root exudates from Meloidogyne enterolobii-parasitized guava plants (NP plants), but not from nematode-free plants (NF plants), enable the fungus Neocosmospora falciformis to rot guava roots, leading to plant death. To further characterize this interaction, NP and NF root exudates were lyophilized; extracted with distinct solvents; quantified regarding amino acids, soluble carbohydrates, sucrose, phenols, and alkaloids; and submitted to a bioassay to determine their ability to enable N. falciformis to rot the guava seedlings' roots. NP root exudates were richer than NF root exudates in amino acids, carbohydrates, and sucrose. Only the fractions NP-03 and NP-04 enabled fungal root rotting. NP-03 was then sequentially fractionated through chromatographic silica columns. At each step, the main fractions were reassessed in bioassay. The final fraction that enabled fungal root rotting was submitted to analysis using high performance liquid chromatography, nuclear magnetic resonance, mass spectrometry, energy-dispersive X-ray fluorescence, and computational calculations, leading to the identification of 1,5-dinitrobiuret as the predominant substance. In conclusion, parasitism by M. enterolobii causes an enrichment of guava root exudates that likely favors microorganisms capable of producing 1,5-dinitrobiuret in the rhizosphere. The accumulation of biuret, a known phytotoxic substance, possibly hampers root physiology and the innate immunity of guava to N. falciformis.

[Classification of continuous multilevel vertebral fractures]. / Clasificación de las fracturas vertebrales multinivel continuas.

Currently there is still little information about multilevel vertebral fractures (MVF), in addition to the fact that there are no classifications that help us group them in a simpler way, and guide us on their prognosis. The objective of this work is to propose a new classification of continuous type MVF, based on the number of end plates injured of the vertebral bodies and their severity, where we form four groups. A review of continuous MVF cases that we found in our hospital over a 6-year period was carried out, managing to designate 100% of the fractures, by their characteristics, to the corresponding group. In addition, we observed a better neurological prognosis in group 1. This classification is a proposal that will help us to group these injuries, that can be very varied, in only four groups; with the aim of later creating a more standardized management proposal, and knowing its neurological prognosis.

Actualmente aún existe poca información acerca de las fracturas vertebrales multinivel (MVF), además de que no hay clasificaciones que nos ayuden a agruparlas de una manera más sencilla y nos orienten sobre su pronóstico. El objetivo del presente trabajo es proponer una nueva clasificación de MVF del tipo continuas, basada en el número de plataformas lesionadas de los cuerpos vertebrales y su gravedad, donde formamos cuatro grupos. Se realizó la revisión de casos de MVF continuas que encontramos en nuestro hospital en un período de seis años; logrando designar cada fractura, debido a sus características, al grupo correspondiente en 100% de los casos. Además, se observó un mejor pronóstico neurológico en el grupo 1. Esta clasificación es una propuesta que nos ayudará a agrupar estas lesiones, que pueden ser muy variadas, en sólo cuatro grupos; con el objetivo de posteriormente crear una propuesta de manejo más estandarizado y conocer su pronóstico neurológico.

Perfil de pacientes grandes consumidores de fentanilo de liberación rápida en un área sanitaria de Córdoba / Profile of patients with abusive consumption of quick-release fentanyl in a health area of Cordoba

Objetivo: Describir el tipo de pacientes que superan la dosis diaria definida (DDD) de fentanilo de liberación inmediata en un área sanitaria.Material y métodos: Estudio observacional, descriptivo, realizado en un área sanitaria de 256.807 habitantes en el que se incluyeron todos los pacientes que superaban la DDD de fentanilo de liberación inmediata en diciembre de 2019.Resultados: Se detectaron 29 pacientes, 58,6% mujeres, con una mediana de edad de 59 (31-87) años, que superaban una media de 3 (1,1-10) veces la DDD de fentanilo de liberación inmediata, en sus distintas presentaciones, siendo la indicación en el 69% de los casos dolor crónico no oncológico (DCNO). La mayoría de los pacientes tomaba benzodiacepinas (79,3%) y el mayor porcentaje de primeras prescripciones de fentanilo de liberación rápida procedía de atención primaria (38%).Conclusiones: En nuestro estudio el uso inadecuado o posible abuso de fentanilo de liberación inmediata se da en mayor proporción en pacientes con DCNO, y en la mayoría de los casos la primera prescripción se realizó en atención primaria. No observamos relación clara con patología psiquiátrica ni otras adicciones. (AU)

Objective: To describe the type of patients that exceed the defined daily dose (DDD) of immediate-release fentanyl in a health area.Material and methods: Observational, descriptive study, carried out in a health area of ​​256,807 inhabitants, which included all patients who passed the immediate-release fentanyl DDD in December 2019.Results: 29 patients were detected, 58.6% female, with a median age of 59 (31-87) years, who exceeded an average of 3 (1.1-10) times the immediate-release fentanyl DDD, in its different presentations, being the indication in 69% of cases chronic non-cancer pain (CNCP). The majority of patients took benzodiazepines (79.3%) and the highest percentage of first-prescriptions for inmediate-release fentanyl came from primary care (38%).Conclusions: In our study, the inappropriate use or possible abuse of immediate-release fentanyl occurs in a greater proportion in patients with CNCP, and in most cases the first prescription was made in primary care. We did not observe a clear relationship with psychiatric pathology or other addictions. (AU)

Retinol-Loaded Poly(vinyl alcohol)-Based Hydrogels as Suitable Biomaterials with Antimicrobial Properties for the Proliferation of Mesenchymal Stem Cells.

Polyvinyl alcohol (PVA) hydrogels are well-known biomimetic 3D systems for mammalian cell cultures to mimic native tissues. Recently, several biomolecules were intended for use in PVA hydrogels to improve their biological properties. However, retinol, an important biomolecule, has not been combined with a PVA hydrogel for culturing bone marrow mesenchymal stem (BMMS) cells. Thus, for the first time, the effect of retinol on the physicochemical, antimicrobial, and cell proliferative properties of a PVA hydrogel was investigated. The ability of protein (3.15 nm) and mineral adsorption (4.8 mg/mL) of a PVA hydrogel was improved by 0.5 wt.% retinol. The antimicrobial effect of hydrogel was more significant in S. aureus (39.3 mm) than in E. coli (14.6 mm), and the effect was improved by increasing the retinol concentration. The BMMS cell proliferation was more upregulated in retinol-loaded PVA hydrogel than in the control at 7 days. We demonstrate that the respective in vitro degradation rate of retinol-loaded PVA hydrogels (RPH) (75-78% degradation) may promote both antibacterial and cellular proliferation. Interestingly, the incorporation of retinol did not affect the cell-loading capacity of PVA hydrogel. Accordingly, the fabricated PVA retinol hydrogel proved its compatibility in a stem cell culture and could be a potential biomaterial for tissue regeneration.

Impact of Non-Thermal Technologies on the Quality of Nuts: A Review.

Nuts are widely consumed worldwide, mainly due to their characteristic flavor and texture, ease of consumption, and their functional properties. In addition, consumers increasingly demand natural or slightly processed foods with high quality. Consequently, non-thermal treatments are a viable alternative to thermal treatments used to guarantee safety and long shelf life, which produce undesirable changes that affect the sensory quality of nuts. Non-thermal treatments can achieve results similar to those of the traditional (thermal) ones in terms of food safety, while ensuring minimal loss of bioactive compounds and sensory properties, thus obtaining a product as similar as possible to the fresh one. This article focuses on a review of the main non-thermal treatments currently available for nuts (cold plasma, high pressure, irradiation, pulsed electric field, pulsed light, ultrasound and ultraviolet light) in relation to their effects on the quality and safety of nuts. All the treatments studied have shown promise with regard to the inhibition of the main microorganisms affecting nuts (e.g., Aspergillus, Salmonella, and E. coli). Furthermore, by optimizing the treatment, it is possible to maintain the organoleptic and functional properties of these products.