Low-cost, versatile, and highly reproducible microfabrication pipeline to generate 3D-printed customised cell culture devices with complex designs.

Cell culture devices, such as microwells and microfluidic chips, are designed to increase the complexity of cell-based models while retaining control over culture conditions and have become indispensable platforms for biological systems modelling. From microtopography, microwells, plating devices, and microfluidic systems to larger constructs such as live imaging chamber slides, a wide variety of culture devices with different geometries have become indispensable in biology laboratories. However, while their application in biological projects is increasing exponentially, due to a combination of the techniques, equipment and tools required for their manufacture, and the expertise necessary, biological and biomedical labs tend more often to rely on already made devices. Indeed, commercially developed devices are available for a variety of applications but are often costly and, importantly, lack the potential for customisation by each individual lab. The last point is quite crucial, as often experiments in wet labs are adapted to whichever design is already available rather than designing and fabricating custom systems that perfectly fit the biological question. This combination of factors still restricts widespread application of microfabricated custom devices in most biological wet labs. Capitalising on recent advances in bioengineering and microfabrication aimed at solving these issues, and taking advantage of low-cost, high-resolution desktop resin 3D printers combined with PDMS soft lithography, we have developed an optimised a low-cost and highly reproducible microfabrication pipeline. This is thought specifically for biomedical and biological wet labs with not prior experience in the field, which will enable them to generate a wide variety of customisable devices for cell culture and tissue engineering in an easy, fast reproducible way for a fraction of the cost of conventional microfabrication or commercial alternatives. This protocol is designed specifically to be a resource for biological labs with limited expertise in those techniques and enables the manufacture of complex devices across the µm to cm scale. We provide a ready-to-go pipeline for the efficient treatment of resin-based 3D-printed constructs for PDMS curing, using a combination of polymerisation steps, washes, and surface treatments. Together with the extensive characterisation of the fabrication pipeline, we show the utilisation of this system to a variety of applications and use cases relevant to biological experiments, ranging from micro topographies for cell alignments to complex multipart hydrogel culturing systems. This methodology can be easily adopted by any wet lab, irrespective of prior expertise or resource availability and will enable the wide adoption of tailored microfabricated devices across many fields of biology.

Concordance between two models of stratification for patients living with HIV infection to providing pharmaceutical care.

OBJECTIVE: To determine the degree of agreement of 2 differents stratification models for pharmaceutical care to people living with HIV. METHODS: This was a single-center observational prospective cohort study of patients with regular follow-up in pharmaceutical care consultations according to the Capacity-Motivation-Opportunity methodology, conducted between January 1 and March 31, 2023. Patients received the pharmacotherapeutic interventions applied routinely to ambulatory care patients according to this model. As part of the usual clinical practice, the presence or absence of the variables that apply to both stratification models were collected. The scores obtained and the corresponding stratification level were collected for each patient according to both stratification models published (ST-2017 and ST-2022). To analyze the reliability between the measurements of 2 numerical score models of the stratification level with both tools, their degree of concordance was calculated using the intraclass correlation coefficient. Likewise, reliability was also evaluated from a qualitative perspective by means of Cohen's Kappa coefficient. Additionally, the existence of correlation between the scores of the 2 models was assessed by calculating Pearson's correlation coefficient. RESULTS: Of the total of 758 patients being followed in the cohort, finally, 233 patients were enrolled. The distribution of patients for each stratification model was: ST-2017: 59.7% level-3, 25.3% level-2, and 15.0% level-1, while for ST-2022: 60.9% level-3, 26.6% level-2, and 12.4% level-1. It was observed that the reclassification was symmetrical (P=.317). The qualitative analysis of the agreement between the models showed a good Cohen's kappa value, (K=0.66). A value of 0.563 was found as the intraclass correlation coefficient. Finally, the correlation analysis between the quantitative scores of the 2 models yielded a Pearson correlation coefficient of 0.86. CONCLUSIONS: The concordance between the 2 models was good, which confirms that the multidimensional adaptation and simplification of the model were correct and that its use can be extended in routine clinical practice.

Safe nanomaterials: from their use, application, and disposal to regulations.

Nanomaterials are structures with a wide range of applications in the medical, pharmaceutical, food, textile, and electronic industries, reaching more customers worldwide. As a relatively new technological field, the information about the associated risk of nanomaterials in environmental and human health must be addressed and consolidated to develop accurate legislations, frameworks, and guidelines to standardise their use in any field. This review aims to display and context the global applications of nanomaterials, their final disposal, as well as the perspective of the current efforts formulated by various countries (including Mexico and Latin American countries), international official departments and organisations directed to implement regulations on nanomaterials, nanotechnology, and nanoscience matters. In addition, the compiled information includes the tools, initiatives, and strategies to develop regulatory frameworks, such as life cycle assessments, risk assessments, technical tools, and biological models to evaluate their effects on living organisms. Finally, the authors point out the importance of implementing global regulations to promote nanotechnological research according to a precautionary principle focused on an environmental and health protection approach to ensure the use and application of nanotechnologies safely, and responsibly.

Mouth Breathing and Its Impact on Atypical Swallowing: A Systematic Review and Meta-Analysis.

The aim of this systematic review is the assessment of the effect of mouth breathing on the prevalence of tongue thrust. The review was performed according to the PRISMA 2020 checklist guidelines, and the protocol was registered with PROSPERO (CRD42022339527). The inclusion criteria were the following: studies of clinical trials and cross-sectional and longitudinal descriptive studies that evaluate the appearance of tongue thrust in patients with mouth breathing; healthy subjects of any age, race or sex; and studies with a minimum sample group of five cases. The exclusion criteria were the following: studies with syndromic patients, articles from case reports, and letters to the editor and/or publisher. Searches were performed in electronic databases such as The National Library of Medicine (MEDLINE via PUBMED), the Cochrane Central Register of Controlled Trials, Web of Science and Scopus, including studies published until November 2023, without a language filter. The methodological quality of the included case-control studies was assessed using the Newcastle-Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) tool was used for descriptive cross-sectional studies and cross-sectional prevalence studies. A meta-analysis was conducted on studies that provided data on patients' classification according to mouth breathing (yes/no) as well as atypical swallowing (yes/no) using Review Manager 5.4. From 424 records, 12 articles were selected, and 4 were eligible for meta-analysis. It was shown that there is no consensus on the diagnostic methods used for mouth breathing and tongue thrust. The pooled risk ratio of atypical swallowing was significantly higher in the patients with mouth breathing (RR: 3.70; 95% CI: 2.06 to 6.66). These studies have several limitations, such as the heterogeneity among the individual studies in relation to the diagnostic tools and criteria for the assessment of mouth breathing and atypical swallowing. Considering the results, this systematic review shows that patients with mouth breathing presented higher risk ratios for atypical swallowing.

Self-reported clinical features and treatment effectiveness of Papillon-Lefèvre syndrome patients from five Latin American countries: A cross-sectional online survey study.

BACKGROUND/OBJECTIVES: Most studies about Papillon-Lefèvre syndrome (PLS) are limited to case reports and patients of the same nationality. This study aimed to determine the self-reported prevalence of signs, symptoms and treatment effectiveness in PLS patients from five Latin American countries. METHODS: An online survey was conducted among adult and paediatric patients from Mexico, Argentina, Colombia and Brazil. Data were collected using multiple-choice, open-ended and image-chooser questions on demographics, signs and symptoms, perceived treatment effectiveness and quality of life. RESULTS: Seventeen patients (10 males and 7 females) aged 4-47 years were surveyed. All had palmoplantar hyperkeratosis. Other affected sites were the feet and hand dorsum (82.35%), Achilles tendon (88.24%), forearms (58.82%), legs (29.41%) and glutes (23.53%). They frequently presented hyperhidrosis and nail pitting. Four had a history of delayed umbilical cord separation. All used topical treatments, with moderate effectiveness; half used oral retinoids, perceived as highly effective. Most reported decreased quality of life and walking difficulties. CONCLUSIONS: The study's results align with prior research on PLS, but reveal new insights, including the impact on patients' quality of life and a history of delayed umbilical cord separation. These findings warrant consideration in future research and patient care.

Spontaneous regeneration of cholecystokinergic reticulospinal axons after a complete spinal cord injury in sea lampreys.

In contrast to humans, lampreys spontaneously recover their swimming capacity after a complete spinal cord injury (SCI). This recovery process involves the regeneration of descending axons. Spontaneous axon regeneration in lampreys has been mainly studied in giant descending neurons. However, the regeneration of neurochemically distinct descending neuronal populations with small-caliber axons, as those found in mammals, has been less studied. Cholecystokinin (CCK) is a regulatory neuropeptide found in the brain and spinal cord that modulates several processes such as satiety, or locomotion. CCK shows high evolutionary conservation and is present in all vertebrate species. Work in lampreys has shown that all CCKergic spinal cord axons originate in a single neuronal population located in the caudal rhombencephalon. Here, we investigate the spontaneous regeneration of CCKergic descending axons in larval lampreys following a complete SCI. Using anti-CCK-8 immunofluorescence, confocal microscopy and lightning adaptive deconvolution, we demonstrate the partial regeneration of CCKergic axons (81% of the number of axonal profiles seen in controls) 10 weeks after the injury. Our data also revealed a preference for regeneration of CCKergic axons in lateral spinal cord regions. Regenerated CCKergic axons exhibit colocalization with synaptic vesicle marker SV2, indicative of functional synaptic connections. We also extracted swimming dynamics in injured animals by using DeepLabCut. Interestingly, the degree of CCKergic reinnervation correlated with improved swimming performance in injured animals, suggesting a potential role in locomotor recovery. These findings open avenues for further exploration into the role of specific neuropeptidergic systems in post-SCI spinal locomotor networks.

Language access research for community health: provider perspectives on language access techniques and the role of communication technology.

BACKGROUND: In the United States, 66 million people speak a language other than English at home. Patients with diverse language needs often face significant health disparities. Information and communication technologies have expanded the realm of modalities for patient-provider communication. However, the extent to which digital language access tools are utilized by healthcare providers is unknown. This research examines provider perspectives on language assistance techniques and the role of communication technology when serving patients with non-English language preference (NELP). METHODS: Between April and July 2019, an online survey was administered to 3,033 healthcare providers (doctors, nurse practitioners, pharmacists, and dentists) in Washington State. Providers reported on their language access practices and perspectives on communication technology. RESULTS: Most providers reported using ad hoc language access techniques when engaging patients with NELP, such as a patient's family member or friend (75.8%), a patient's child specifically (61.9%), or a bilingual staff member (64.3%). Professional techniques, such as in-person interpretation (53.5%), phone interpretation (57%), and video remote interpretation (38.8%), were used less often. Dissatisfaction with the language access processes of healthcare providers' place of work was associated with a higher reliance on a patient's family or friend for language interpretation. CONCLUSIONS: Findings suggest that providers might be under-utilizing professional and digital interpreter services while relying on ad hoc techniques. Such practices reveal systemic constraints on language access that might make it difficult for providers to access timely and reliable options for professional language interpretation, despite federal regulations that mandate such services for patients with NELP.

Assessment of an intervention for preventing pediatric overweight and obesity through the World Café technique: A qualitative study.

PURPOSE: To evaluate the self-reported perspectives of participants involved in the Previene Cádiz intervention for preventing pediatric overweight and obesity. DESIGN AND METHODS: This qualitative study collected information through the World Café technique. A purposive sample of 40 participants was used, of which 14 were schoolchildren, 12 were teachers, and 14 were parent volunteers. The data were segmented, and concepts were created and grouped into dimensions and categories. RESULTS: The participants confirmed they had learned new information and behaviors about healthy habits. Parental awareness was considered a crucial and necessary element in changing family habits; therefore, increasing the motivation of family members was deemed a critical task in public health interventions conducted in school settings. DISCUSSION: Despite the suitability of qualitative methodology to evaluate the perceptions of the main players in an educational intervention, scientific literature is scarce. Obtaining information from the educational community about an intervention is not always easy, so the perspectives of teachers, students, and families about the Previene Cádiz intervention through the World Café approach is considered a relevant contribution. CONCLUSIONS: The participants considered the intervention positive in terms of learning and fostering increased knowledge, awareness, and healthy behaviors. PRACTICE IMPLICATIONS: Future interventions should encourage the active participation of all social groups involved, integrating dynamic and collaborative training activities that are acceptable to all participants.

Índice neutrófilo-linfocito e índice plaquetas-linfocito: herramientas pronósticas del cáncer de pulmón

El cáncer de pulmón es la neoplasia maligna que causa mayor mortalidad en el mundo. Dentro de los factores pronósticos de esta entidad, se encuentran el índice neutrófilo-linfocito y el índice plaquetas-linfocito, parámetros hematológicos que se utilizan para evaluar la inflamación y la respuesta inmunitaria en el cuerpo humano. Se realizó una revisión bibliográfica con el objetivo de exponer el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón, teniendo en cuenta la evidencia científica publicada hasta el momento. Se estudiaron 46 artículos, 28 de los cuales resultaron seleccionados para la elaboración de la investigación. Se emplearon como criterios de selección la calidad de los estudios, el nivel de actualización sobre el tema en cuestión, así como la fiabilidad de la fuente. Se usaron los recursos disponibles en la red Infomed para la selección de la información, entre ellos: PubMed, SciELO, EBSCO, Cumed, LILACS y Scopus, además de Medline, Academic Search Premier y MedicLatina. Se expuso el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón de células no pequeñas, en todos los estadios y con modalidades terapéuticas diferentes.

Lung cancer is the malignant neoplasm that causes higher mortality in the world. Among the prognostic factors of this entity are the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, hematological parameters that are used to assess inflammation and the immune response in the human body. A bibliographic review was carried out with the objective of exposing the value of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool for lung cancer, taking into account the scientific evidence published to date. A total of 46 articles were studied, of which 28 were selected for the development of the research. The quality of the studies, the level of updating on the subject in question, as well as the reliability of the source was used as selection criteria. The resources available in the Infomed network were used to select the information, including PubMed, SciELO and EBSCO, Cumed, LILACS and Scopus, as well as Medline, Academic Search Premier and MedicLatina databases. The value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool in non-small cell lung cancer at all stages and with different therapeutic modalities was exposed.

Identification of a HIV-1 circulating BF1 recombinant form (CRF75_BF1) of Brazilian origin that also circulates in Southwestern Europe.

Introduction: The high recombinogenic potential of HIV-1 has resulted in the generation of countless unique recombinant forms (URFs) and around 120 reported circulating recombinant forms (CRFs). Here we identify through analyses of near full-length genomes (NFLG) a new HIV-1 CRF derived from subtypes B and F1. Methods: HIV-1 protease-reverse transcriptase (Pr-RT) sequences were obtained by RT-PCR amplification from plasma RNA. Near full-length genome sequences were obtained after amplification by RT-PCR in 5 overlapping fragments. Phylogenetic sequence analyses were performed via maximum likelihood. Mosaic structures were analyzed by bootscanning and phylogenetic analyses of genome segments. Temporal and geographical estimations of clade emergence were performed with a Bayesian coalescent method. Results: Through phylogenetic analyses of HIV-1 Pr-RT sequences obtained by us from samples collected in Spain and downloaded from databases, we identified a BF1 recombinant cluster segregating from previously reported CRFs comprising 52 viruses, most from Brazil (n = 26), Spain (n = 11), and Italy (n = 9). The analyses of NFLG genomes of 4 viruses of the cluster, 2 from Spain and 2 from Italy, allowed to identify a new CRF, designated CRF75_BF1, which exhibits a complex mosaic structure with 20 breakpoints. All 4 patients harboring CRF75_BF1 viruses studied by us had CD4+ T-cell lymphocyte counts below 220/mm3 less than one year after diagnosis, a proportion significantly higher (p = 0.0074) than the 29% found in other patients studied in Spain by us during the same period. The origin of the clade comprising CRF75_BF1 and related viruses was estimated around 1984 in Brazil, with subsequent introduction of CRF75_BF1 in Italy around 1992, and migration from Italy to Spain around 1999. Conclusion: A new HIV-1 CRF, designated CRF75_BF1, has been identified. CRF75_BF1 is the 6th CRF of South American origin initially identified in Western Europe, reflecting the increasing relationship of South American and European HIV-1 epidemics. The finding of low CD4+ T-cell lymphocyte counts early after diagnosis in patients harboring CRF75_BF1 viruses warrants further investigation on the virulence of this variant.

Neurofeedback and Affect Regulation Circuitry in Depressed and Healthy Adolescents.

Neurodevelopmental psychopathology seeks to understand higher-order emotion regulation circuitry to develop new therapies for adolescents with depression. Depressed (N = 34) and healthy youth (N = 19) completed neurofeedback (NF) training and exhibited increased bilateral amygdala and hippocampus activity in the region of interest (ROI) analyses by recalling positive autobiographical memories. We tested factors supportive of the engagement of emotion regulation's neural areas during NF (i.e., parental support, medication, and gender effects upon anterior cingulate cortex (ACC) engagement). Whole-brain analyses yielded effects of NF vs. control condition and effects of diagnosis. Youth showed higher amygdala and hippocampus (AMYHIPPO) activity during the NF vs. control condition, particularly in the left hippocampus. ACC's activity was also higher during NF vs. control. Higher average ACC activity was linked to better parental support, absent depression, female gender, and absent medication. Control youth showed higher average AMYHIPPO and ACC activity throughout the task and a faster decline in activity vs. depressed youths. Whole-brain level analyses showed higher activity in the frontotemporal network during the NF vs. control conditions, suggesting targeting their connectivity in future neurofeedback trials.

Agreement between pharmacists and physicians on the assessment of appropriateness of antimicrobial prescribing.

INTRODUCTION: Audits for monitoring the quality of antimicrobial prescribing are a main tool in antimicrobial stewardship programs; however, interobserver reliability has not been conclusively assessed. Our objective was to measure the level of agreement between pharmacists and physicians on the appropriateness of antimicrobials prescribing in hospitals. METHODS: A national multicenter, cross-sectional study was conducted of patients who were receiving antimicrobials one day of April 2021. Hospital participation was voluntary, and the study population was randomly selected. Pharmacists and physicians performed a simultaneous, independent assessment of the quality of antimicrobial prescriptions. The observers used an assessment method by which all indicators of the quality of antimicrobial use were considered. Finally, an algorithm was used to rate overall antimicrobial prescribing as appropriate, suboptimal, inappropriate, or not assessable. Gwet's AC1 coefficient was used to assess interobserver agreement. RESULTS: In total, 101 hospitals participated, and 411 hospital antimicrobial prescriptions were reviewed. The strength of agreement was moderate regarding the overall quality of prescribing (AC1=0.51; 95%CI=[0.44-0.58]). A very good level of agreement (AC1>0.80) was observed between pharmacists and physicians in all indicators of the quality, except for duration of treatment, rated as good (AC1=0.79; 95%CI=[0.75-0.83]), and registration on the medical record, rated as fair (AC1=0.34; 95%CI=[0.26-0.43]). The agreement was greater in critical care, onco-hematology, and pediatric units than in medical and surgery units. CONCLUSIONS: In this point prevalence study, a moderate level of agreement was observed between pharmacists and physicians in the evaluation of the appropriateness of antimicrobials prescribing in hospitals.

On the Effect of High Stimulation Rates on Temporal Loudness Integration in Cochlear Implant Users.

Long stimuli have lower detection thresholds or are perceived louder than short stimuli with the same intensity, an effect known as temporal loudness integration (TLI). In electric hearing, TLI for pulse trains with a fixed rate but varying number of pulses, i.e. stimulus duration, has mainly been investigated at clinically used stimulation rates. To study the effect of an overall effective stimulation rate at 100% channel crosstalk, we investigated TLI with (a) a clinically used single-channel stimulation rate of 1,500 pps and (b) a high stimulation rate of 18,000 pps, both for an apical and a basal electrode. Thresholds (THR), a line of equal loudness (BAL), and maximum acceptable levels (MALs) were measured in 10 MED-EL cochlear implant users. Stimulus durations varied from a single pulse to 300 ms long pulse trains. At 18,000 pps, the dynamic range (DR) increased by 7.36±3.16 dB for the 300 ms pulse train. Amplitudes at THR, BAL, and MAL decreased monotonically with increasing stimulus duration. The decline was fitted with high accuracy with a power law function (R2=0.94±0.06). Threshold slopes were -1.05±0.36 and -1.66±0.30 dB per doubling of duration for the low and high rate, respectively, and were shallower than for acoustic hearing. The electrode location did not affect the amplitudes or slopes of the TLI curves. THR, BAL, and MAL were always lower for the higher rate and the DR was larger at the higher rate at all measured durations.

Unravelling the functional development of vertebrate pathways controlling gaze.

Animals constantly redirect their gaze away or towards relevant targets and, besides these goal-oriented responses, stabilizing movements clamp the visual scene avoiding image blurring. The vestibulo-ocular (VOR) and the optokinetic reflexes are the main contributors to gaze stabilization, whereas the optic tectum integrates multisensory information and generates orienting/evasive gaze movements in all vertebrates. Lampreys show a unique stepwise development of the visual system whose understanding provides important insights into the evolution and development of vertebrate vision. Although the developmental emergence of the visual components, and the retinofugal pathways have been described, the functional development of the visual system and the development of the downstream pathways controlling gaze are still unknown. Here, we show that VOR followed by light-evoked eye movements are the first to appear already in larvae, despite their burrowed lifestyle. However, the circuits controlling goal-oriented responses emerge later, in larvae in non-parasitic lampreys but during late metamorphosis in parasitic lampreys. The appearance of stabilizing responses earlier than goal-oriented in the lamprey development shows a stepwise transition from simpler to more complex visual systems, offering a unique opportunity to isolate the functioning of their underlying circuits.

Cross-species transmission and PB2 mammalian adaptations of highly pathogenic avian influenza A/H5N1 viruses in Chile.

H5N1 highly pathogenic avian influenza viruses (HPAIV) emerged in wild birds in Chile in December 2022 and spilled over into poultry, marine mammals, and one human. Between December 9, 2022 - March 14, 2023, a coordinated government/academic response detected HPAIV by real-time RT-PCR in 8.5% (412/4735) of samples from 23 avian and 3 mammal orders. Whole-genome sequences obtained from 77 birds and 8 marine mammals revealed that all Chilean H5N1 viruses belong to lineage 2.3.4.4b and cluster monophyletically with viruses from Peru, indicating a single introduction from North America into Peru/Chile. Mammalian adaptations were identified in the PB2 segment: D701N in two sea lions, one human, and one shorebird, and Q591K in the human and one sea lion. Minor variant analysis revealed that D701N was present in 52.9 - 70.9% of sequence reads, indicating the presence of both genotypes within hosts. Further surveillance of spillover events is warranted to assess the emergence and potential onward transmission of mammalian adapted H5N1 HPAIV in South America.

An online home-based exercise program improves autonomic dysfunction in breast cancer survivors.

Introduction: Exercise interventions for breast cancer survivors have proved their potential to improve clinical, physical, and psychosocial outcomes. However, limited studies have explored exercise effects on autonomic dysfunction and the measurement of exercise tolerance and progression through daily heart rate variability (HRV). Purpose: To analyze the effects of a 16-wk exercise intervention on the autonomic modulation of breast cancer survivors, as well as to examine the evolution of daily measured HRV and its interaction with exercise sessions in this population. Methods: A total of 29 patients who had undergone chemotherapy and radiotherapy were randomly assigned to the exercise group or to the control group. The exercise intervention was delivered remotely through online meetings and consisted of supervised training resistance and cardiovascular exercise 3 times per week. During the intervention all patients measured their HRV daily obtaining the napierian logarithm of the root mean square of successive differences between normal heartbeats (lnrMSSD) and the napierian logarithm of the standard deviation of the interbeat interval of normal sinus beats (lnSDNN) values at four moments: day 0 (the morning of the training sessions), 24, 48, and 72 h after exercise. Results: The results revealed a significant interaction between group and months during the intervention period for lnrMSSD and lnSDNN (p < 0.001). Additionally, there were significant differences in lnSDNN recovery time between months (p < 0.05), while differences in lnrMSSD become apparent only 24 h after exercise (p = 0.019). The control group experienced a significant decrease in both variables monthly (p < 0.05) while exercise group experienced a significant increment (p < 0.05). Conclusion: HRV is daily affected by exercise training sessions in cancer patients. Although results strongly support the role of exercise as a post-chemotherapy and radiotherapy rehabilitation strategy for breast cancer survivors to improve autonomic imbalance, further research is necessary to validate these initial findings.

[Community health. Innovating in the training of family and community medicine residents]. / Salud comunitaria. Innovando en la formación de residentes de medicina familiar y comunitaria.

OBJECTIVE: To know the opinions of the agents involved in the training of family and community medicine residents in order to improve the training process of the «Project to Support the Revitalization of Primary Care; Assets for Community Health¼ (PARAC) taking into account its adequacy, contextualization and the methodologies used. METHOD: Qualitative interpretative-explanatory study of phenomenological orientation, multilevel and multicenter, in which the opinion of the participants is analyzed. Between 2018 and 2020, 12 focus groups and 24 semi-structured interviews were carried out, with the participation of sixty-seven professionals from six health districts of Andalusia (Spain), who were involved in the PARAC training process. RESULTS: The participants consider it necessary to broaden training in community health for residents. To this end, they consider it necessary to make changes in the training plan of the specialty, giving more importance to primary health care than to hospital rotations. They value positively the methodologies used in the PARAC training process, which they consider «novel¼, and the choice of young teachers to serve as references. In order for their interventions in the territory to be carried out with quality and safety for the population, they ask that specific times and spaces be guaranteed for community health, as well as adequate supervision to help ensure the coherence and continuity of their interventions. CONCLUSIONS: Training in community health for family and community medicine residents requires a pedagogical, didactic and curricular effort that prepares them for work with the community, as well as the guarantee of organizational conditions that allow this work.

The Disruption of a Nuclear Export Signal in the C-Terminus of the Herpes Simplex Virus 1 Determinant of Pathogenicity UL24 Protein Leads to a Syncytial Plaque Phenotype.

UL24 of herpes simplex virus 1 (HSV-1) has been shown to be a determinant of pathogenesis in mouse models of infection. The N-terminus of UL24 localizes to the nucleus and drives the redistribution of nucleolin and B23. In contrast, when expressed alone, the C-terminal domain of UL24 accumulates in the Golgi apparatus; its importance during infection is unknown. We generated a series of mammalian expression vectors encoding UL24 with nested deletions in the C-terminal domain. Interestingly, enhanced nuclear staining was observed for several UL24-deleted forms in transient transfection assays. The substitution of a threonine phosphorylation site had no effect on UL24 localization or viral titers in cell culture. In contrast, mutations targeting a predicted nuclear export signal (NES) significantly enhanced nuclear localization, indicating that UL24 is able to shuttle between the nucleus and the cytoplasm. Recombinant viruses that encode UL24-harboring substitutions in the NES led to the accumulation of UL24 in the nucleus. Treatment with the CRM-1-specific inhibitor leptomycin B blocked the nuclear export of UL24 in transfected cells but not in the context of infection. Viruses encoding UL24 with NES mutations resulted in a syncytial phenotype, but viral yield was unaffected. These results are consistent with a role for HSV-1 UL24 in late cytoplasmic events in HSV-1 replication.

Remdesivir and SARS-CoV-2 monoclonal antibodies to prevent COVID-19 progression in hematological patients: an observational study.

BACKGROUND: Patients with hematological malignancies (HM) are at high risk of COVID-19 progression. Hence, early treatments to prevent progression are needed. The aim of our work was to evaluate the effectiveness and safety of remdesivir (RDV) and SARS-CoV-2 monoclonal antibodies (mAb) in patients with HM and mild-to-moderate disease in real clinical practice. METHODS: We conducted a prospective study in a tertiary hospital in 55 HM patients with mild-to-moderate SARS-CoV-2 disease diagnosed between August 2021 and July 2022 and who received RDV or mAb to prevent COVID-19 progression (related death or hospitalization). The primary endpoint was COVID-19 progression on day 28. Other outcomes were COVID-19 progression beyond day 28 and viral load evolution. RESULTS: RDV was administered to 44 (80.0%) patients and mAb to 11 (20.0%) patients. Death occurred in 1 (1.8%) patient and hospitalization in 9 (16.4%) patients by day 28, respectively; 3 patients (5.5%) required intensive care and 8 (14.5%), oxygen support. Of note, 5 additional patients [15, (27.3%) in total] died or required hospitalization after day 28. Two hazard Cox regression models yielded the absence of anti-SARS-CoV-2 antibodies, age over 65 years, and ECOG-performance status ≥ 2 as the main risk factors for COVID-19-related death or hospitalization. CONCLUSION: Our results from clinical practice suggest that RDV and SARS-CoV-2 mAb therapies elicit worse outcomes in hematological patients than those reported for high-risk population in clinical trials.

Vibrio vulnificus mutation rate: an in vitro approach.

Vibrio vulnificus is a multi-host pathogenic species currently subdivided into five phylogenetic lineages (L) plus one pathovar with the ability to infect fish due to a transmissible virulence plasmid. This plasmid (or a fragment of it) has been transmitted between lineages within the species, contributing to the evolution of V. vulnificus. This study aimed to provide an experimental approximation to the V. vulnificus mutation rate by determining spontaneous mutation rates from bacterial cultures of representants of the different lineages by whole-genome sequencing. To this purpose, synonymous SNP differences, i.e., spontaneous mutation not subjected to the evolutive forces, between initial and final culture after serial growth were evaluated and used for mutation rate calculation.