Chemo-small extracellular vesicles released in cisplatin-resistance ovarian cancer cells are regulated by the lysosomal function.

Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.

Broad protection against invasive fungal disease from a nanobody targeting the active site of fungal b-1,3-glucanosyltransferases.

Invasive fungal disease accounts for ~3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal ß-1,3-glucanosyltransferases (Gel) involved in ß-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for ß-1,3-glucan remodelling in C. deneoformans survival. These findings add new insights about the role of b-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.

Draft genome of Bacillus subtilis sp. strain UAMC isolated from agricultural soil with historical use of pesticides in Argentina.

To understand microbial metabolism in horticultural soils exposed to pesticides, genome sequencing of Bacillus subtilis sp. strain UAMC was performed. A total of 7,892 genes distributed across 40 contigs were identified. Among these, those related to the degradation of endosulfan such as FMNH2 monooxygenase, or cytochrome p450 stand out.

A decentralized solid compound storage facility managed by a centralized electronic platform at a growing drug discovery company.

Within a growing drug discovery company, scientists acquire (either through in house synthesis or purchase) then store, retrieve, and ship solid compound samples daily between multiple locations. The efficient management and tracking of this entire process to support drug discovery is a significant challenge. This article describes a decentralized and cost-effective inventory facility that simplifies the solid compound storage and retrieval process. Standardized storage cabinets from the market are utilized, providing a cost-effective physical infrastructure. The cabinets can be distributed across storage rooms at multiple sites and arranged into spaces with a variety of dimensions, allowing the system to be retrofitted into existing facilities and scaled up easily. We can provide storage close to work areas at each location, minimizing both unnecessary movement of staff and transportation of substances. We have applied a systematic barcoding method to the compound batch identifier that correlates with its compound location. This simplifies the compound registration process as well as the process of finding and returning compounds. Additionally, a centralized electronic platform has been employed to store, update and track solid compound information, such as properties, location and quantity. Compound shipment may be initiated from different sites, and a centralized electronic platform assists the information retrieval process, ensuring each location possesses up-to-date information. The electronic platform we present streamlines the management of compound registration, location tracking, weight updates and shipment information, facilitating seamless record sharing among all stakeholders. Every step of the process can be tracked in real time by the project team. The platform can be flexibly configured to adapt to an evolving set of storage locations, with all information and processes being audited.

Comparison of MAF-32 and a One-Pot Synthesized Superparamagnetic Iron Oxide/MAF-32 Composite for the Adsorption of Diclofenac.

The global presence of pharmaceutical pollutants in water sources represents a burgeoning public health concern. Recent studies underscore the urgency of addressing this class of emerging contaminants. In this context, our work focuses on synthesizing a composite material, FexOy/MAF-32, through a streamlined one-pot reaction process, as an adsorbent for diclofenac, an emerging environmental contaminant frequently found in freshwater environments and linked to potential toxicity towards several organisms such as fish and mussels. A thorough characterization was performed to elucidate the structural composition of the composite. The material presents magnetic properties attributed to its superparamagnetic behavior, which facilitates the recovery efficiency of the composite post-diclofenac adsorption. Our study further involves a comparative analysis between the FexOy/MAF-32 and a non-magnetic counterpart, comprised solely of 2-ethylimidazolate zinc polymer. This comparison aims to discern the relative advantages and disadvantages of incorporating magnetic iron oxide nanoparticles in the contaminant removal process facilitated by a coordination polymer. Our findings reveal that even a minimal incorporation of iron oxide nanoparticles substantially enhanced the composite's overall performance in pollutant adsorption.

Functional imaging guided stereotactic ablative body radiotherapy (SABR) with focal dose escalation and bladder trigone sparing for intermediate and high-risk prostate cancer: study protocol for phase II safo trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. METHODS: Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. DISCUSSION: To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL SPONSOR: IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). STUDY SETTING: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL STATUS: Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

[Loxoscelism with acute compartment síndrome: A case report with successful conclusion]. / Loxoscelismo con síndrome compartimental agudo: reporte de un caso con desenlace exitoso.

BACKGROUND: Loxoscelism is a toxic clinical condition caused by the bite of spiders of the genus Loxosceles, with wide distribution throughout the world.1 Phospholipase D is responsible for dermonecrosis, inflammation, platelet aggregation, hemolysis, alteration of vascular permeability, cytotoxicity, nephrotoxicity, acute renal failure, among other symptoms involved with this protein. CASE REPORT: 27-year-old male patient, who began with a sudden episode of intense pain in the right hand, in the metacarpus and metacarpophalangeal joints. On clinical examination, the upper extremity was noted to have increased volume, extensive edema, hyperemia, and increased local temperature; The lesion progressed to extensive necrosis. Fasciotomies were performed, from distal to proximal, and release of the second and third finger compartment through longitudinal radial and ulnar incisions. A skin autograft was placed, obtained from the anterior surface of the right thigh. Opioid analgesics, non-steroidal anti-inflammatory drugs, corticosteroids, and antibiotics were administered. The skin biopsy reported: inflammatory infiltrate with neutrophils, ulceration, and bacterial colonies. After 27 days he had a favorable evolution, so he was discharged to his home, with follow-up by staff from the Outpatient Service. CONCLUSION: Cutaneous loxoscelism, as a cause of acute compartment syndrome of the hand, is rare, but should be considered in an area endemic for Loxosceles spp. Surgical decompression of the affected compartments represents a decisive factor in the treatment of patients.

ANTECEDENTES: El loxoscelismo es un cuadro clínico tóxico provocado por la mordedura de arañas del género Loxosceles, con amplia distribución en todo el mundo.1 La fosfolipasa D es la responsable de la dermonecrosis, inflamación, agregación plaquetaria, hemólisis, alteración de la permeabilidad vascular, citotoxicidad, nefrotoxicidad, insuficiencia renal aguda, entre otros síntomas implicados con esta proteína. REPORTE DE CASO: Paciente masculino de 27 años, que inició con un cuadro repentino de dolor intenso en la mano derecha, en el metacarpo y las articulaciones metacarpofalángicas. Al examen clínico, la extremidad superior se percibió con aumento de volumen, edema extenso, hiperemia y aumento de la temperatura local; la lesión progresó a necrosis extensa. Se realizaron fasciotomías, de distal a proximal, y liberación del compartimento del segundo y tercer dedo a través de incisiones longitudinales radiales y cubitales. Se colocó un autoinjerto de piel, obtenido de la superficie anterior del muslo derecho. Se administraron analgésicos opioides, antiinflamatorios no esteroides, corticosteroides y antibióticos. La biopsia de piel reporto: infiltrado inflamatorio con neutrófilos, ulceración y colonias bacterianas. Luego de 27 días tuvo evolución favorable, por lo que se dio alta a su domicilio, con seguimiento por personal del servicio de Consulta externa. CONCLUSIÓN: El loxoscelismo cutáneo, como causa de síndrome compartimental agudo de la mano, es poco común, pero debe considerarse en un área endémica para Loxosceles spp. La descompresión quirúrgica de los compartimentos afectados representa un factor decisivo en el tratamiento de los pacientes.

Biophysical and structural study of La Crosse virus endonuclease inhibition for the development of new antiviral options.

The large Bunyavirales order includes several families of viruses with a segmented ambisense (-) RNA genome and a cytoplasmic life cycle that starts by synthesizing viral mRNA. The initiation of transcription, which is common to all members, relies on an endonuclease activity that is responsible for cap-snatching. In La Crosse virus, an orthobunyavirus, it has previously been shown that the cap-snatching endonuclease resides in the N-terminal domain of the L protein. Orthobunyaviruses are transmitted by arthropods and cause diseases in cattle. However, California encephalitis virus, La Crosse virus and Jamestown Canyon virus are North American species that can cause encephalitis in humans. No vaccines or antiviral drugs are available. In this study, three known Influenza virus endonuclease inhibitors (DPBA, L-742,001 and baloxavir) were repurposed on the La Crosse virus endonuclease. Their inhibition was evaluated by fluorescence resonance energy transfer and their mode of binding was then assessed by differential scanning fluorimetry and microscale thermophoresis. Finally, two crystallographic structures were obtained in complex with L-742,001 and baloxavir, providing access to the structural determinants of inhibition and offering key information for the further development of Bunyavirales endonuclease inhibitors.

Evaluation of the Relation between Ictal EEG Features and XAI Explanations.

Epilepsy is a neurological disease with one of the highest rates of incidence worldwide. Although EEG is a crucial tool for its diagnosis, the manual detection of epileptic seizures is time consuming. Automated methods are needed to streamline this process; although there are already several works that have achieved this, the process by which it is executed remains a black box that prevents understanding of the ways in which machine learning algorithms make their decisions. A state-of-the-art deep learning model for seizure detection and three EEG databases were chosen for this study. The developed models were trained and evaluated under different conditions (i.e., three distinct levels of overlap among the chosen EEG data windows). The classifiers with the best performance were selected, then Shapley Additive Explanations (SHAPs) and Local Interpretable Model-Agnostic Explanations (LIMEs) were employed to estimate the importance value of each EEG channel and the Spearman's rank correlation coefficient was computed between the EEG features of epileptic signals and the importance values. The results show that the database and training conditions may affect a classifier's performance. The most significant accuracy rates were 0.84, 0.73, and 0.64 for the CHB-MIT, Siena, and TUSZ EEG datasets, respectively. In addition, most EEG features displayed negligible or low correlation with the importance values. Finally, it was concluded that a correlation between the EEG features and the importance values (generated by SHAP and LIME) may have been absent even for the high-performance models.

Hospital care direct costs due to ambulatory care sensitive conditions related to diabetes mellitus in the Mexican public healthcare system.

BACKGROUND: Hospitalizations for ambulatory care sensitive conditions (ACSC) incur substantial costs on the health system that could be partially avoided with adequate outpatient care. Complications of chronic diseases, such as diabetes mellitus (DM), are considered ACSC. Previous studies have shown that hospitalizations due to diabetes have a significant financial burden. In Mexico, DM is a major health concern and a leading cause of death, but there is limited evidence available. This study aimed to estimate the direct costs of hospitalizations by DM-related ACSC in the Mexican public health system. METHODS: We selected three hospitals from each of Mexico's main public institutions: the Mexican Social Security Institute (IMSS), the Ministry of Health (MoH), and the Institute of Social Security and Services for State Workers (ISSSTE). We employed a bottom-up microcosting approach from the healthcare provider perspective to estimate the total direct costs of hospitalizations for DM-related ACSC. Input data regarding length of stay (LoS), consultations, medications, colloid/crystalloid solutions, procedures, and laboratory/medical imaging studies were obtained from clinical records of a random sample of 532 hospitalizations out of a total of 1,803 DM-related ACSC (ICD-10 codes) discharges during 2016. RESULTS: The average cost per DM-related ACSC hospitalization varies among institutions, ranging from $1,427 in the MoH to $1,677 in the IMSS and $1,754 in the ISSSTE. The three institutions' largest expenses are LoS and procedures. Peripheral circulatory and renal complications were the major drivers of hospitalization costs for patients with DM-related ACSC. Direct costs due to hospitalizations for DM-related ACSC in these three institutions represent 1% of the gross domestic product (GDP) dedicated to health and social services and 2% of total hospital care expenses. CONCLUSIONS: The direct costs of hospitalizations for DM-related ACSC vary considerably across institutions. Disparities in such costs for the same ACSC among different institutions suggest potential disparities in care quality across primary and hospital settings (processes and resource utilization), which should be further investigated to ensure optimal supply utilization. Prioritizing preventive measures for peripheral circulatory and renal complications in DM patients could be highly beneficial.

Enhanced amygdala-anterior cingulate white matter structural connectivity in Sahaja Yoga Meditators.

OBJECTIVE: To study the white matter connections between anterior cingulate cortex, anterior insula and amygdala as key regions of the frontal-limbic network that have been related to meditation. DESIGN: Twenty experienced practitioners of Sahaja Yoga Meditation and twenty nonmeditators matched on age, gender and education level, were scanned using Diffusion Weighted Imaging, using a 3T scanner, and their white matter connectivity was compared using diffusion tensor imaging analyses. RESULTS: There were five white matter fiber paths in which meditators showed a larger number of tracts, two of them connecting the same area in both hemispheres: the left and right amygdalae and the left and right anterior insula; and the other three connecting left anterior cingulate with the right anterior insula, the right amygdala and the left amygdala. On the other hand, non-meditators showed larger number of tracts in two paths connecting the left anterior insula with the left amygdala, and the left anterior insula with the left anterior cingulate. CONCLUSIONS: The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger white matter tracts strengthening interhemispheric connections between limbic regions and connections between cingulo-amygdalar and cingulo-insular brain regions related to top-down attentional and emotional processes as well as between top-down control functions that could potentially be related to the witness state perceived through the state of mental silence promoted with this meditation. On the other hand, reduced connectivity strength in left anterior insula in the meditation group could be associated to reduced emotional processing affecting top-down processes.

[Impact of self-reported periodontal status on oral health-related quality of life in adult population with Type 2 Diabetes from Mexico City]. / Impacto del estado periodontal autorreportado en la calidad de vida relacionada con la salud oral en población adulta con diabetes tipo 2 de la Ciudad de México.

OBJECTIVE: Periodontitis ranks sixth as a type 2 diabetes (T2D) complication. According to its severity, it may cause pain, discomfort and tooth loss. The aim of this study was to evaluate the impact of self-reported periodontal status on the Oral Health Related Quality of Life (OHRQoL) of people with T2D. METHODS: A cross-sectional study was conducted involving seventy-nine adults with T2D who visited the Metabolic Syndrome clinic at the Cosío Villegas National Institute of Respiratory Diseases in Mexico City between August and November 2010. The OHRQoL was evaluated with the shortened Oral Health Impact Profile (OHIP-EE14). Periodontitis was measured by self-report, probing depth (PD), and clinical attachment loss (CAL). The association between self-reported periodontal status and OHRQoL was evaluated with binomial regression models. RESULTS: Mean age of the participants was 60,4 years (SD=9,6); diabetes duration was 10,1 years (SD=6,6). The OHRQoL was associated with self-perception of bad breath (RR=1,58; p=0,025), self-perception of poor gum health (RR=1,66; p=0,016), dissatisfaction with chewing ability (RR=2,22; p≤0,001), tooth loss due to mobility (RR=1,74; p=0,019), and presence of 20 teeth or less (RR=1,57; p=0,045). CONCLUSIONS: OHRQoL is associated with self-report of bad breath, poor gum health and dissatisfaction with chewing ability in people with T2D, which suggests that self-perceived oral conditions represent signs and symptoms of functional and psychological impairment related to severe periodontitis.

OBJECTIVE: La periodontitis es la sexta complicación de la diabetes tipo 2 (DT2); dependiendo de su severidad puede causar dolor, incomodidad o hasta pérdida dental. El objetivo del estudio fue evaluar el impacto del estado periodontal autorreportado en la Calidad de Vida Relacionada con la Salud Oral (CVRSO) en personas con DT2. METHODS: Se realizó un estudio transversal que incluyó a setenta y nueve adultos con DT2 atendidos en la Clínica de Síndrome Metabólico del Instituto Nacional de Enfermedades Respiratorias Cosío Villegas en la Ciudad de México, entre agosto y noviembre de 2010. La CVRSO se evaluó con el cuestionario Perfil de Impacto en la Salud Bucal acortado (OHIP-EE14). La periodontitis se evaluó por autorreporte, profundidad al sondeo (PS) y pérdida de inserción clínica (PIC). La asociación entre estado periodontal autorreportado y CVRSO se evaluó con modelos de regresión binomial negativa. RESULTS: La edad promedio fue de 60,4 años (DE=9,6); la duración de diabetes de 10,1 años (DE=6,6). La CVRSO se asoció con la autopercepción de mal aliento (RR=1,58, p=0,025), autopercepción de mala salud de las encías (RR=1,66, p=0,016), insatisfacción de la habilidad para masticar (RR=2,22, p≤0,001), pérdida de algún diente con movilidad previa (RR=1,74, p=0,019) y 20 dientes presentes o menos (RR=1,57, p=0,045). CONCLUSIONS: La CVRSO se asocia con el autorreporte de mal aliento, mala salud de las encías e insatisfacción de la habilidad para masticar en personas con DT2; esto sugiere que las condiciones bucales autopercibidas representan signos y síntomas de deterioro funcional y psicológico relacionados con la periodontitis severa.

Targets and Effects of Common Biocompounds of Hibiscus sabdariffa (Delphinidin-3-Sambubiosid, Quercetin, and Hibiscus Acid) in Different Pathways of Human Cells According to a Bioinformatic Assay.

The utilization of food as a therapeutic measure for various ailments has been a prevalent practice throughout history and across different cultures. This is exemplified in societies where substances like Hibiscus sabdariffa have been employed to manage health conditions like hypertension and elevated blood glucose levels. The inherent bioactive compounds found in this plant, namely, delphinidin-3-sambubioside (DS3), quercetin (QRC), and hibiscus acid (HA), have been linked to various health benefits. Despite receiving individual attention, the specific molecular targets for these compounds remain unclear. In this study, computational analysis was conducted using bioinformatics tools such as Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb to identify the molecular targets, pathways, and hub genes. Supplementary results were obtained through a thorough literature search in PubMed. DS3 analysis revealed potential genetic alterations related to the metabolism of nitrogen and glucose, inflammation, angiogenesis, and cell proliferation, particularly impacting the PI3K-AKT signaling pathway. QRC analysis demonstrated interconnected targets spanning multiple pathways, with some overlap with DS3 analysis and a particular focus on pathways related to cancer. HA analysis revealed distinct targets, especially those associated with pathways related to the nervous system. These findings emphasize the necessity for focused research on the molecular effects of DS3, QRC, and HA, thereby providing valuable insights into potential therapeutic pathways.

Suicidal Ideation and Behavior Among Mexican University Students Before and During the COVID-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic has affected the mental health of populations around the world, but few longitudinal studies of its impact on suicidal thoughts and behaviors have been published especially from low- and middle-income countries. METHODS: This is a prospective cohort study of 1,385 first-year students from 5 Universities in Mexico followed-up for 1 year. We report 1-year cumulative incidence of suicidal thoughts and behaviors before (September 19, 2019-March 29, 2020) and during the COVID-19 period (March 30, 2020-June 30, 2020), focusing on those in the COVID-19 period with risk conditions and positive coping strategies during the pandemic. RESULTS: There was an increase in the incidence of suicidal ideation during the COVID-19 period compared to the pre-COVID-19 period (RR 1.65, 95%CI 1.08-2.50). This increase was mostly found among students with heightened sense of vulnerability (RR 1.95), any poor coping behavior (RR 2.40) and a prior mental disorder (RR 2.41). While we found no evidence of an increased risk of suicidal planning or attempts, there was evidence that those without lifetime mental health disorders were at greater risk of suicidal plans than those with these disorders especially if they had poor coping strategies (RR 3.14). CONCLUSION: In the short term, how students deal with the pandemic, being at high risk and having poor coping behavior, increased the new occurrence of suicidal thoughts and behaviors. Studies with longer follow-up and interventions to reduce or enhance these behaviors are needed.HIGHLIGHTSSuicidal ideation increased during the COVID-19 periodThose with heightened sense of vulnerability and poor coping were more affectedStudies with longer follow-up are needed.

Cognitive flexibility impairment in temporal lobe epilepsy: The impact of epileptic foci lateralization on executive functions.

INTRODUCTION: Temporal Lobe Epilepsy (TLE) has been associated with memory impairments, which are typically linked to hippocampal and mesial temporal cortex lesions. Considering the presence of extensive bidirectional frontotemporal connections, it can be hypothesized that executive dysfunction in TLE is modulated by the lateralization of the epileptic foci. MATERIAL AND METHODS: A comprehensive neuropsychological executive functions protocol was administered to 63 participants, including 42 individuals with temporal lobe epilepsy (20 with right-TLE and 22 with left-TLE) and 21 healthy controls aged 20-49. RESULTS: The results indicate that TLE patients exhibit poorer executive performance compared to healthy controls in working memory (F(2,60) = 4.18, p <.01), planning (F(2,60) = 4.71, p <.05), set shifting (F(2,60) = 10.1, p <.001), phonetic verbal fluency (F(2,60) = 11.71, p <.01) and semantic verbal fluency (F(2,60) = 9.61, p <.001. No significant differences were found in cognitive inhibition. Furthermore, right-TLE patients showed lower performance than left-TLE in set shifting (F(1,61) = 6.45, p <.05), while no significant differences were observed in working memory, planning, inhibition, and verbal fluency. CONCLUSIONS: This research emphasize the importance of considering the lateralization of the temporal lobe focus to achieve a more accurate neuropsychological characterization. The cognitive differences between left and right TLE patients highlight the need for individualized approaches in their treatment and care.

Monitoring the neural activity associated with praying in Sahaja Yoga meditation.

BACKGROUND: Sahaja Yoga Meditation draws on many religious traditions and uses a variety of techniques including Christian prayer to reach a state known as thoughtless awareness, or mental silence. While there are many studies on the neural correlates of meditation, few studies have focused on the neural correlates of praying. Thus, the aim of our research was to study the neural activity associated with the prayer practices in Sahaja Yoga Mediation, which have not been studied before, to explore effects beyond repetitive speech or "mantra effects". Sixteen experienced Sahaja Yoga Meditation practitioners were scanned using task based functional Magnetic Resonance Imaging while performing formalised and improvised forms of praying and their equivalent secular tasks. RESULTS: Our results showed the deactivation of bilateral thalamus during both prayers compared to secular conditions and the activation in the medial prefrontal cortex that was reduced by religious and formalised secular speech conditions but increased during improvised secular speech; similarly, frontal regions were deactivated when comparing prayers to their secular equivalents. DISCUSSION: These results seem to depict two important factors related with praying in Sahaja Yoga Meditation merging inner concentration and social cognition. First, the perception of the surroundings mediated by the thalamus may be decreased during these prayers probably due to the establishment of inner concentration and, second, frontal deactivation effects could be related to reduced social judgement and 'mentalizing', particularly in the medial prefrontal cortex. Our findings suggest that praying by Sahaja Yoga Meditation practitioners is neurophenomenologically different from the social cognitive attempt of praying within Christian praying practices.

Design and validation of indicators for the comprehensive measurement of quality of care for type 2 diabetes and acute respiratory infections in ambulatory health services.

Developing ambulatory health services (AHS) of optimal quality is a pending issue for many health systems at a global level, especially in middle- and low-income countries. An effective health response requires indicators to measure the quality of care that are context-specific and feasible for routine monitoring. This paper aimed to design and validate indicators for assessing the technical and interpersonal quality dimensions for type 2 diabetes (T2D) and acute respiratory infections (ARI) care in AHS. The study was conducted in two stages. First, technical and user-centered-based indicators of quality of care for T2D and ARI care were designed following international recommendations, mainly from the American Diabetes Association standards and the National Institute for Health and Care Excellence guidelines. We then assessed the validity, reliability, relevance, and feasibility of the proposed indicators implementing the modified Delphi technique. A panel of 17 medical experts from five countries scored the indicators using two electronic questionnaires, one for each reason for consultation selected, sent by email in two sequential rounds of rating. We defined the levels of consensus according to the overall median for each performance category, which was established as the threshold. Selected indicators included those with scores equal to or higher than the threshold. We designed 36 T2D indicators, of which 16 were validated for measuring the detection of risks and complications, glycemic control, pharmacological treatment, and patient-centered care. Out of the 22 indicators designed for ARI, we validated 10 for diagnosis, appropriate prescription of antimicrobials, and patient-centered care. The validated indicators showed consistency for the dimensions analyzed. Hence, they proved to be a potentially reliable and valuable tool for monitoring the performance of the various T2D and ARI care processes in AHS. Further research will be needed to verify the applicability of the validated indicators in routine clinical practice.

Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination.

Lyme disease is the most common vector-borne disease in North America and Europe. The clinical manifestations of Lyme disease vary based on the genospecies of the infecting Borrelia burgdorferi spirochete, but the microbial genetic elements underlying these associations are not known. Here, we report the whole genome sequence (WGS) and analysis of 299 B. burgdorferi (Bb) isolates derived from patients in the Eastern and Midwestern US and Central Europe. We develop a WGS-based classification of Bb isolates, confirm and extend the findings of previous single- and multi-locus typing systems, define the plasmid profiles of human-infectious Bb isolates, annotate the core and strain-variable surface lipoproteome, and identify loci associated with disseminated infection. A core genome consisting of ~900 open reading frames and a core set of plasmids consisting of lp17, lp25, lp36, lp28-3, lp28-4, lp54, and cp26 are found in nearly all isolates. Strain-variable (accessory) plasmids and genes correlate strongly with phylogeny. Using genetic association study methods, we identify an accessory genome signature associated with dissemination in humans and define the individual plasmids and genes that make up this signature. Strains within the RST1/WGS A subgroup, particularly a subset marked by the OspC type A genotype, have increased rates of dissemination in humans. OspC type A strains possess a unique set of strongly linked genetic elements including the presence of lp56 and lp28-1 plasmids and a cluster of genes that may contribute to their enhanced virulence compared to other genotypes. These features of OspC type A strains reflect a broader paradigm across Bb isolates, in which near-clonal genotypes are defined by strain-specific clusters of linked genetic elements, particularly those encoding surface-exposed lipoproteins. These clusters of genes are maintained by strain-specific patterns of plasmid occupancy and are associated with the probability of invasive infection.

Energy-saving pretreatments affect pelagic Sargassum composition and DNA metabarcoding reveals the microbial community involved in methane yield.

Sargassum spp. flood the Caribbean coastline, causing damage to the local economy and environment. Anaerobic digestion (AD) has been proposed as an attractive option for turning macroalgae into valuable resources. Sargassum spp. has a complex composition that affects the microbial composition involved in AD which generates a low methane yield. This study aimed to improve the methane yield of pelagic Sargassum, using different energy-saving pretreatments and identifying the microbial community associated with methane production. We applied different energy-saving pretreatments to algal biomass and assessed the methane yield using a biomethane potential (BMP) test. The microbial communities involved in the AD of the best- and worst-performing methanogenic systems were analyzed by high-throughput sequencing. The results showed that pretreatment modified the content of inorganic compounds, fibers, and the C:N ratio, which had a strong positive correlation with BMP. The water washing pretreatment resulted in the best methane yield, with an increase of 38%. DNA metabarcoding analysis revealed that the bacterial genera Marinilabiliaceae_uncultured, DMER64, Treponema, and Hydrogenispora, as well as the archaea genera Methanosarcina, RumEn_M2, Bathyarchaeia, and Methanomassiliicocus, dominated the microbial community with a high methane yield. This study is the first to demonstrate the microbial community structure involved in the AD of Sargassum spp. The pretreatments presented in this study can help overcome the limitations associated with methane yield.