Impact of COVID-19 on the degree of compliance with hand hygiene: a repeated cross-sectional study.

Hand hygiene (HH) is the paramount measure used to prevent healthcare-associated infections. A repeated cross-sectional study was undertaken with direct observation of the degree of compliance on HH of healthcare personnel during the SARS-CoV-2 pandemic. Between, 2018-2019, 9,083 HH opportunities were considered, and 5,821 in 2020-2022. Chi squared tests were used to identify associations. The crude and adjusted odds ratios were used along with a logistic regression model for statistical analyses. Compliance on HH increased significantly (p < 0.001) from 54.5% (95% CI: 53.5, 55.5) to 70.1% (95% CI: 68.9, 71.2) during the COVID-19 pandemic. This increase was observed in four of the five key moments of HH established by the World Health Organization (WHO) (p < 0.05), except at moment 4. The factors that were significantly and independently associated with compliance were the time period considered, type of healthcare-personnel, attendance at training sessions, knowledge of HH and WHO guidelines, and availability of hand disinfectant alcoholic solution in pocket format. Highest HH compliance occurred during the COVID-19 pandemic, reflecting a positive change in healthcare-personnel's behaviour regarding HH recommendations.

Mechanical Complications of Proximal Femur Fractures Treated with Intramedullary Nailing: A Retrospective Study.

Background and Objectives: This retrospective cohort study analyzes mechanical complications in hip fracture surgery using the Trochanteric Fixation Nail-Advanced (TFNA) implant. It investigates the correlation of these complications with demographic, intraoperative, and radiological factors, aiming to identify associated risk factors and suggest improvements in clinical surveillance and treatment strategies. Materials and Methods: We enrolled 253 patients diagnosed with pertrochanteric hip fractures treated between 2017 and 2021, with 126 meeting the criteria for a minimum 6-month follow-up. Data on demographics, American Anesthesia Association Classification (ASA), comorbidities, AO/OTA [AO (Arbeitsgemeinschaft für Osteosynthesefragen)/OTA (Orthopedic Trauma Association)] fracture classification, procedural details, and time to failure were collected. Radiographs were evaluated for reduction quality, the tip-apex distance (TAD), progressive varus deviation, and identification of mechanical complications. Statistical analysis was performed using SPSS software. Results: The predominant AO/OTA fracture classification was 31A2 in 67 cases (52.7%). Reduction quality was deemed good or acceptable in 123 cases (97.6%). The mean time to failure was 4.5 months (range: 2.2-6). The average TAD was 18 mm (range: 1.2-36), with a mean progressive varus deviation of 2.44° (range: 1.30-4.14). A good or acceptable reduction quality was observed in 97.6% of cases. Mechanical complications occurred in 21.4% of patients, with significant associations found with the lateral cortex fracture, use of a TFNA implant with a 130° angle, open reduction, and absence of prior osteoporosis treatment. Conclusions: The study provides insights into mechanical complications in proximal femur fractures treated with the TFNA nail, emphasizing the need for enhanced clinical and radiographic surveillance, especially in patients without osteoporosis treatment. Our findings support the necessity for further clinical studies comparing these outcomes with other implant designs and underscore the importance of personalized treatment strategies to reduce complication rates.

Nirmatrelvir/ritonavir for the treatment of immunocompromised adult patients with early-stage symptomatic COVID-19: A real-life experience.

Regardless of vaccination status, progression to severe coronavirus disease 2019 (COVID-19) is still a relevant cause of morbidity among immunocompromised patients. Despite the proven efficacy of nirmatrelvir/ritonavir (NMV/r), concerns remain regarding the potential for drug-to-drug interactions (DDIs) and the safety in this at-risk population. We aimed to evaluate the clinical outcomes of immunocompromised patients treated with NMV/r, as well as the occurrence of DDIs and treatment-emergent adverse events (TEAEs). This retrospective observational study included all the patients with some form of immunosuppression and laboratory-confirmed COVID-19 that received NMV/r at our center from April to August 2022. The main outcome was worsening of the clinical status (increase of ≥1 point from baseline in a validated clinical progression scale) by Days +7 and +28 after the initiation of therapy. Safety outcomes included the rates of any TEAE and potentially severe DDIs. We included 110 patients. Main causes of immunosuppression were hematological malignancy (58.2%) (mainly multiple myeloma [22.7%] and non-Hodgkin lymphoma [13.6%]), active chemotherapy (30.0%) and hematopoietic stem cell transplantation (14.5%). Clinical worsening by Days +7 and +28 was observed in four (3.6%) and five patients (4.5%), respectively. Only one patient had a positive SARS-CoV-2 polymerase chain reaction test at Day +28. At least one potentially severe DDI was observed in 56.4% of the patients. The rate of attributable TEAEs was 10.9%, although only two patients (1.8%) required premature discontinuation of NMV/r. Early initiation of NMV/r therapy should be considered in immunocompromised patients with COVID-19, with particular attention to interacting medications.

Fast profiling of primary, secondary, conjugated, and sulfated bile acids in human urine and murine feces samples.

Bile acids (BAs) are a complex class of metabolites that have been described as specific biomarkers of gut microbiota activity. The development of analytical methods allowing the quantification of an ample spectrum of BAs in different biological matrices is needed to enable a wider implementation of BAs as complementary measures in studies investigating the functional role of the gut microbiota. This work presents results from the validation of a targeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of 28 BAs and six sulfated BAs, covering primary, secondary, and conjugated BAs. The analysis of 73 urine and 20 feces samples was used to test the applicability of the method. Concentrations of BAs in human urine and murine feces were reported, ranging from 0.5 to 50 nmol/g creatinine and from 0.012 to 332 nmol/g, respectively. Seventy-nine percent of BAs present in human urine samples corresponded to secondary conjugated BAs, while 69% of BAs present in murine feces corresponded to primary conjugated BAs. Glycocholic acid sulfate (GCA-S) was the most abundant BA in human urine samples, while taurolithocholic acid was the lowest concentrated compound detected. In murine feces, the most abundant BAs were α-murocholic, deoxycholic, dehydrocholic, and ß-murocholic acids, while GCA-S was the lowest concentrated BA. The presented method is a non-invasive approach for the simultaneous assessment of BAs and sulfated BAs in urine and feces samples, and the results will serve as a knowledge base for future translational studies focusing on the role of the microbiota in health.

Emergency care carried out during the pandemic due to substance abuse in a Spanish province. / Atenciones urgentes realizadas durante la pandemia por consumo de tóxicos en una provincia española.

INTRODUCTION: During periods of isolation, people with substance use disorders may reduce tension, stress, uncertainty and possible distress by increasing the use of substances or practices that they have abused. The objective of this study was to evaluate the impact of the pandemic on emergency care and continuity of care for patients with substance use disorders. METHOD: Study carried out in the only psychiatric emergency service in the province at the Hospital Universitario Santa María de Lérida, which cares for 431,183 people. Sociodemographic, clinical and evolutionary variables were collected from all the patients treated during a period prior to lockdown (January 13, 2020, until March 14, 2020) and during the first (March 15, 2020 until June 20, 2020) and second states of emergency (from October 25, 2020 to May 9, 2021). RESULTS: 908 patients attended with substance use disorder, representing 23.8% of all visits. During the first state of emergency, visits increased (p < 0.001) with a decrease in the average age (p = 0.0023). During the second state of emergency, there was an increase in the use of alcohol with respect to the rest of toxic substances (p < 0.001) and an increase in the visits of patients without prior follow-up (p = 0.005). CONCLUSIONS: Substance use disorder consultations increased in the first state of emergency, with patients being younger and attending for reasons related to outpatient discontinuity, while in the second state of emergency, alcohol use increased in people without prior follow-up and with small social networks. Admissions in the first state of emergency were shorter, with no subsequent link to other detoxification treatment centers and with an earlier return to the emergency room, especially in female users.

Introducción: Durante los períodos de aislamiento, las personas con trastornos por uso de sustancias pueden reducir la tensión, el estrés, la incertidumbre y la posible angustia aumentando el uso de sustancias o prácticas de las que han abusado. El objetivo de este estudio es evaluar el impacto de la pandemia en las atenciones urgentes y continuidad asistencial de pacientes con trastorno por uso de sustancias. Método: Estudio realizado en el único servicio de urgencias de Psiquiatría de la provincia en el Hospital Universitario Santa María de Lérida, que atiende a 431.183 personas. Se recogen variables sociodemográficas, clínicas y evolutivas de todos los pacientes atendidos durante un periodo previo al confinamiento (13 de enero de 2020, hasta el 14 de marzo de 2020) y durante el primer (15 de marzo de 2020 hasta su 20 de junio de 2020) y segundo estado de alarma (desde el 25 de octubre de 2020 hasta el 9 de mayo de 2021). Resultados: 908 pacientes atendidos con Trastorno por Uso de Sustancias, representa el 23,8% de todas las visitas. Durante el primer estado de alarma, aumento de las visitas (p < 0,001) con una disminución de la edad media (p = 0,023). Durante el segundo estado de alarma, aumento del consumo de OH respecto al resto de tóxicos (p < 0,001) y un aumento de las visitas de pacientes sin seguimiento previo (p = 0,005). Conclusiones: Aumentaron las consultas por trastorno por uso de sustancias en el primer estado de alarma siendo más jóvenes y acudiendo por motivos de consulta relacionados con la discontinuidad ambulatoria mientras en el segundo estado de alarma repuntó el consumo de alcohol en personas sin seguimiento previo y con escasa red social. Los ingresos del primer estado de alarma fueron más breves, sin vinculación posterior a otros centros terapéuticos de desintoxicación y con un retorno más precoz a urgencias sobre todo en mujeres consumidoras.

Holdemanella biformis improves glucose tolerance and regulates GLP-1 signaling in obese mice.

Impaired glucose homeostasis in obesity is mitigated by enhancing the glucoregulatory actions of glucagon-like peptide 1 (GLP-1), and thus, strategies that improve GLP-1 sensitivity and secretion have therapeutic potential for the treatment of type 2 diabetes. This study shows that Holdemanella biformis, isolated from the feces of a metabolically healthy volunteer, ameliorates hyperglycemia, improves oral glucose tolerance and restores gluconeogenesis and insulin signaling in the liver of obese mice. These effects were associated with the ability of H. biformis to restore GLP-1 levels, enhancing GLP-1 neural signaling in the proximal and distal small intestine and GLP-1 sensitivity of vagal sensory neurons, and to modify the cecal abundance of unsaturated fatty acids and the bacterial species associated with metabolic health. Our findings overall suggest the potential use of H biformis in the management of type 2 diabetes in obesity to optimize the sensitivity and function of the GLP-1 system, through direct and indirect mechanisms.

PSYCHOTIC DEPRESSION IN HEALTHCARE WORKERS DURING THE COVID-19 HEALTHCARE CRISIS: A CASE SERIES.

After the initial phases of the COVID-19 pandemic, new waves have occurred that have chronicled the epidemiological situation. This could especially affect the Mental Health of healthcare professionals with the appearance of serious conditions such as psychotic depression. The objective of this article is to describe a series of cases of psychotic depression in health professionals during the chronic phase of the sanitary crisis.

Mass testing after a single suspected or confirmed case of COVID-19 in London care homes, April-May 2020: implications for policy and practice.

INTRODUCTION: Previous investigations have identified high rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among residents and staff in care homes reporting an outbreak of coronavirus disease 2019 (COVID-19). We investigated care homes reporting a single suspected or confirmed case to assess whether early mass testing might reduce risk of transmission during the peak of the pandemic in London. METHODS: Between 18 and 27 April 2020, residents and staff in care homes reporting a single case of COVID-19 to Public Health England had a nasal swab to test for SARS-CoV-2 infection by reverse transcription polymerase chain reaction and subsequent whole-genome sequencing. Residents and staff in two care homes were re-tested 8 days later. RESULTS: Four care homes were investigated. SARS-CoV-2 positivity was 20% (65/333) overall, ranging between 3 and 59%. Among residents, positivity ranged between 3 and 76% compared with 3 and 40% in staff. Half of the SARS-CoV-2-positive residents (23/46, 50%) and 63% of staff (12/19) reported symptoms within 14 days before or after testing. Repeat testing 8 days later in two care homes with the highest infection rates identified only two new cases. Genomic analysis demonstrated a small number of introduction of the virus into care homes, and distinct clusters within three of the care homes. CONCLUSIONS: We found extensive but variable rates of SARS-CoV-2 infection among residents and staff in care homes reporting a single case of COVID-19. Although routine whole-home testing has now been adopted into practice, care homes must remain vigilant and should be encouraged to report a single suspected case, which should trigger appropriate outbreak control measures.

The Microbiota and the Gut-Brain Axis in Controlling Food Intake and Energy Homeostasis.

Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Gut microbiota-diet interactions might interfere in nutrient sensing and signalling from the gut to the brain, where the information is processed to control energy homeostasis. This gut microbiota-brain crosstalk is mediated by metabolites, mainly short chain fatty acids, secondary bile acids or amino acids-derived metabolites and subcellular bacterial components. These activate gut-endocrine and/or neural-mediated pathways or pass to systemic circulation and then reach the brain. Feeding time and dietary composition are the main drivers of the gut microbiota structure and function. Therefore, aberrant feeding patterns or unhealthy diets might alter gut microbiota-diet interactions and modify nutrient availability and/or microbial ligands transmitting information from the gut to the brain in response to food intake, thus impairing energy homeostasis. Herein, we update the scientific evidence supporting that gut microbiota is a source of novel dietary and non-dietary biological products that may beneficially regulate gut-to-brain communication and, thus, improve metabolic health. Additionally, we evaluate how the feeding time and dietary composition modulate the gut microbiota and, thereby, the intraluminal availability of these biological products with potential effects on energy homeostasis. The review also identifies knowledge gaps and the advances required to clinically apply microbiome-based strategies to improve the gut-brain axis function and, thus, combat obesity.

Hemophagocytic syndrome in patients living with HIV: a retrospective study.

Various infectious diseases can hyper-stimulate the immune system, causing hemophagocytic syndrome (HPS). Little is known regarding the accuracy of diagnostic criteria and epidemiological triggering factors in the acquired immunodeficiency syndrome (AIDS) setting. We investigated the major infectious disease triggers of HPS in patients living with human immunodeficiency virus (HIV)/AIDS and determined the accuracy of bone marrow aspiration (BMA). The inclusion criteria were (i) confirmed HIV diagnosis, (ii) bone marrow aspiration, and (iii) a minimum of four HPS criteria. Patients were further classified into those with four presumed HPS criteria, or ≥ 5 confirmed criteria. The disease triggers, accuracy of bone marrow aspiration, and prognosis markers were examined. Presumed HPS was observed in 15/36 patients (41%), and confirmed HPS in 58% (n = 21). The major etiological triggers were infection with Mycobacterium (34%), Cytomegalovirus (14%), Cryptococcus neoformans (11%), and hematological or tumoral disease (11%). BMA demonstrated 93% specificity on screening diagnosis (odds ratio [OR] 12.7, 95% confidence interval [CI] 1.4-115.1, P = 0.01). Ferritin > 5000 ng/mL correlated with probability of death in univariate analysis (OR 6.00, 95% CI 1.33-27.05, P = 0.02). Ferritin performance as test of death probability presented area under the curve as 0.74 (95% CI 0.56-0.91, P = 0.016). However, neither cluster of differentiation for lymphocyte count nor HIV viral load correlated with patient deaths. Mycobacterium spp. and Cytomegalovirus were the main factors triggering HPS, followed by Cryptococcus neoformans, and hematological and tumoral diseases. High ferritin levels were associated with increased death probability. High specificity was noted with BMA.

Hard Superconducting Gap in InSb Nanowires.

Topological superconductivity is a state of matter that can host Majorana modes, the building blocks of a topological quantum computer. Many experimental platforms predicted to show such a topological state rely on proximity-induced superconductivity. However, accessing the topological properties requires an induced hard superconducting gap, which is challenging to achieve for most material systems. We have systematically studied how the interface between an InSb semiconductor nanowire and a NbTiN superconductor affects the induced superconducting properties. Step by step, we improve the homogeneity of the interface while ensuring a barrier-free electrical contact to the superconductor and obtain a hard gap in the InSb nanowire. The magnetic field stability of NbTiN allows the InSb nanowire to maintain a hard gap and a supercurrent in the presence of magnetic fields (∼0.5 T), a requirement for topological superconductivity in one-dimensional systems. Our study provides a guideline to induce superconductivity in various experimental platforms such as semiconductor nanowires, two-dimensional electron gases, and topological insulators and holds relevance for topological superconductivity and quantum computation.

Innovation in microbiome-based strategies for promoting metabolic health.

PURPOSE OF REVIEW: Update on the development of microbiome-based interventions and dietary supplements to combat obesity and related comorbidities, which are leading causes of global mortality. RECENT FINDINGS: The role of intestinal dysbiosis, partly resulting from unhealthy diets, in the development of obesity and metabolic disorders, is well documented by recent translational research. Human experimental trials with whole-faecal transplants are ongoing, and their results will be crucial as proof of concept that interventions intended to modulate the microbiome composition and function could be alternatives for the management of obesity and related comorbidities. Potential next-generation probiotic bacteria (Akkermansia, Bacteroides spp., Eubacterium halli) and microbiota-derived molecules (e.g. membrane proteins, short-chain fatty acids) are being evaluated in preclinical and clinical trials to promote the development of innovative dietary supplements. The fact that live or inactivated bacteria and their products can regulate pathways that increase energy expenditure, and reduce energy intake, and absorption and systemic inflammation make them attractive research targets from a nutritional and clinical perspective. SUMMARY: Understanding which are the beneficial bacteria and their bioactive products is helping us to envisage innovative microbiome-based dietary interventions to tackle obesity. Advances will likely result from future refinements of these strategies according to the individual's microbiome configuration and its particular response to interventions, thereby progressing towards personalized nutrition.

Underwater Electromagnetic Sensor Networks-Part I: Link Characterization.

Underwater Wireless Sensor Networks (UWSNs) using electromagnetic (EM) technology in marine shallow waters are examined, not just for environmental monitoring but for further interesting applications. Particularly, the use of EM waves is reconsidered in shallow waters due to the benefits offered in this context, where acoustic and optical technologies have serious disadvantages. Sea water scenario is a harsh environment for radiocommunications, and there is no standard model for the underwater EM channel. The high conductivity of sea water, the effect of seabed and the surface make the behaviour of the channel hard to predict. This justifies the need of link characterization as the first step to approach the development of EM underwater sensor networks. To obtain a reliable link model, measurements and simulations are required. The measuring setup for this purpose is explained and described, as well as the procedures used. Several antennas have been designed and tested in low frequency bands. Agreement between attenuation measurements and simulations at different distances was analysed and made possible the validation of simulation setups and the design of different communications layers of the system. This leads to the second step of this work, where data and routing protocols for the sensor network are examined.

Molecular Fountain.

The resolution of any spectroscopic or interferometric experiment is ultimately limited by the total time a particle is interrogated. Here we demonstrate the first molecular fountain, a development which permits hitherto unattainably long interrogation times with molecules. In our experiments, ammonia molecules are decelerated and cooled using electric fields, launched upwards with a velocity between 1.4 and 1.9 m/s and observed as they fall back under gravity. A combination of quadrupole lenses and bunching elements is used to shape the beam such that it has a large position spread and a small velocity spread (corresponding to a transverse temperature of <10 µK and a longitudinal temperature of <1 µK) when the molecules are in free fall, while being strongly focused at the detection region. The molecules are in free fall for up to 266 ms, making it possible, in principle, to perform sub-Hz measurements in molecular systems and paving the way for stringent tests of fundamental physics theories.

Underwater Electromagnetic Sensor Networks, Part II: Localization and Network Simulations.

In the first part of the paper, we modeled and characterized the underwater radio channel in shallowwaters. In the second part,we analyze the application requirements for an underwaterwireless sensor network (U-WSN) operating in the same environment and perform detailed simulations. We consider two localization applications, namely self-localization and navigation aid, and propose algorithms that work well under the specific constraints associated with U-WSN, namely low connectivity, low data rates and high packet loss probability. We propose an algorithm where the sensor nodes collaboratively estimate their unknown positions in the network using a low number of anchor nodes and distance measurements from the underwater channel. Once the network has been self-located, we consider a node estimating its position for underwater navigation communicating with neighboring nodes. We also propose a communication system and simulate the whole electromagnetic U-WSN in the Castalia simulator to evaluate the network performance, including propagation impairments (e.g., noise, interference), radio parameters (e.g., modulation scheme, bandwidth, transmit power), hardware limitations (e.g., clock drift, transmission buffer) and complete MAC and routing protocols. We also explain the changes that have to be done to Castalia in order to perform the simulations. In addition, we propose a parametric model of the communication channel that matches well with the results from the first part of this paper. Finally, we provide simulation results for some illustrative scenarios.

Role of 18F-FDG-PET/CT in the management of Burkitt lymphoma.

UNLABELLED: Burkitt lymphoma (BL) is highly FDG-avid even though its usefulness in the management of these patients is still controversial. AIM: We analyzed the role of positron emission tomography/computerized tomography (PET/CT) in staging newly diagnosed patients with BL and evaluating disease after first-line chemotherapy. METHODS: Fifty-two PET/CTs were performed in 32 patients (20 at diagnosis, 27 after treatment, five to monitor residual disease). Involved areas were retrospectively compared with those observed in contrast-enhanced CT. RESULTS: Discrepancies were found in 64.7% of patients for whom results of both tests at diagnosis were available (n = 17), most of them involving extranodal sites. Regarding response assessment, discrepancies were observed in 38% of patients with both tests (5/13): residual masses detected by CT with negative PET/CT. Of 27 patients with post-treatment PET/CT, 22 were in complete remission whereas one true-positive and four false-positive lesions (two nodal and two extranodal) were detected. With a median follow-up of 27 months, 22 patients with negative PET/CT did not relapse. Thus, negative predictive value (NPV) was 100%. With respect to positive predictive value (PPV), one of five patients with positive assays after treatment died due to progression while the remaining four had false-positive lesions. Nevertheless, for these four patients, mean SUVmax at nodal sites was 4.1 vs. 14.9 at diagnosis, while mean SUVmax at extranodal sites was 3.8 vs. 12.1. Thus, with a cutoff value for SUVmax < 66% of that observed at diagnosis, PPV was also 100%. CONCLUSION: More accurate staging can be achieved using PET/CT. NPV reaches 100%, and using a ΔSUV < 66%, a high PPV is also observed.

Alkylating potential of styrene oxide: reactions and factors involved in the alkylation process.

The chemical reactivity of styrene-7,8-oxide (SO), an alkylating agent with high affinity for the guanine­N7 position and a probable carcinogen for humans, with 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, was investigated kinetically in water/dioxane media. UV­vis spectrophotometry and ultrafast liquid chromatography were used to monitor the reactions involved. It was found that in the alkylation process four reactions occur simultaneously: (a) the formation of a ß-NBP­SO adduct through an SN2 mechanism; (b) the acid-catalyzed formation of the stable α-NBP­SO adduct through an SN2' mechanism; (c) the base-catalyzed hydrolysis of the ß-adduct, and (d) the acid-catalyzed hydrolysis of SO. At 37.5 °C and pH = 7.0 (in 7:3 water/dioxane medium), the values of the respective reaction rate constants were as follows: kalkß = (2.1 ± 0.3) × 10­4 M­1 s­1, kalkα = (1.0 ± 0.1) × 10­4 M­1 s­1, khydAD = (3.06 ± 0.09) × 10­6 s­1, and khyd = (4.2 ± 0.9) × 10­6 s­1. These values show that, in order to determine the alkylating potential of SO, none of the four reactions involved can be neglected. Temperature and pH were found to exert a strong influence on the values of some parameters that may be useful to investigate possible chemicobiological correlations (e.g., in the pH 5.81­7.69 range, the fraction of total adducts formed increased from 24% to 90% of the initial SO, whereas the adduct lifetime of the unstable ß-adduct, which gives an idea of the permanence of the adduct over time, decreased from 32358 to 13313 min). A consequence of these results is that the conclusions drawn in studies addressing alkylation reactions at temperatures and/or pH far from those of biological conditions should be considered with some reserve.

Microbiota-Derived Short-Chain Fatty Acids Boost Antitumoral Natural Killer Cell Activity.

Background: The intestinal microbiota can regulate numerous host functions, including the immune response. Through fermentation, the microbiota produces and releases microbial metabolites such as short-chain fatty acids (SCFAs), which can affect host homeostasis. There is growing evidence that the gut microbiome can have a major impact on cancer. Specific gut microbial composition and metabolites are associated with tumor status in the host. However, their effects on the antitumor response have scarcely been investigated. Natural killer (NK) cells play an important role in antitumor immunity due to their ability to directly identify and eliminate tumor cells. Methods: The aim of this study was to investigate the effects of SCFAs on antitumoral NK cell activity, using NK-92 cell line. Results: Here, we describe how SCFAs can boost antitumoral NK cell activity. The SCFAs induced the release of NK extracellular vesicles and reduced the secretion of the anti-inflammatory cytokine IL-10. The SCFAs also increased the cytotoxicity of the NK cells against multiple myeloma cells. Conclusions: Our results indicate, for the first time, the enormous potential of SCFAs in regulating antitumoral NK cell defense, where modulation of the SCFAs' production could play a fundamental role in cancer immunotherapy.

The patient journey of fibromyalgia in Latin America.

OBJECTIVES: To explore the patient journey of people with fibromyalgia (FM) in Latin American countries in order to identify problems in health care and other areas that may be resolvable. METHODS: Qualitative study with phenomenological and content analysis approach through focus groups and patient journey (Ux; User Experience) methodology. Nine virtual focus groups were conducted with FM patients and healthcare professionals in Argentina, Mexico and Colombia recruited from key informants and social networks. RESULTS: Forty-three people participated (33 were clinicians and 10 were patients). The agents interacting with the patient in their disease journey are found in three spheres: healthcare (multiple medical specialists and other professionals), support and work life (including patient associations) and socioeconomic context. The line of the journey presents two large sections, two loops and a thin dashed line. The two major sections represent the time from first symptoms to medical visit (characterized by self-medication and denial) and the time from diagnosis to follow-up (characterized by high expectations and multiple contacts to make life changes that are not realized). The two loop phases include (1) succession of misdiagnoses and mistreatments and referrals to specialists and (2) new symptoms every so often, visits to specialists, diagnostic doubts, and impatience. Very few patients manage to reach the final phase of autonomy. CONCLUSION: The journey of a person with FM in Latin America is full of obstacles and loops. The desired goal is for all the agents involved to understand that self- management by the patient with FM is an essential part of success, and this can only be achieved with early access to resources and guidance from professionals.

The Ablation of Sensory Neurons Expressing the Nav1.8 Sodium Channel Improves Glucose Homeostasis and Amplifies the GLP-1 Signaling in Obese Female Mice.

SCOPE: Sensory neurons expressing the sodium channel Nav1.8 contain a repertoire of receptors for nutrient, hormonal, and inflammatory ligands. However, their function in key regulators of energy homeostasis control is not well understood and is completely unexplored in females. METHODS AND RESULTS: Mice lacking neurons expressing the sodium channel Nav1.8 were generated using an ablation strategy based on cre recombinase-mediated expression of diphtheria toxin fragment A (DTA) (Nav1.8-cre/DTA mice) to investigate whether these neurons modulate body weight, food intake, gut hormone secretion, gastrointestinal transit, and glucose tolerance in response to nutrient challenges in a sex-dependent manner. Male Nav1.8-cre/DTA mice show resistance to gain weight in response to high-fat high-sugar diet (HFHSD), whereas females lacking Nav1.8+ neurons have improved oral glucose tolerance accompanied by higher insulin levels and attenuated glucagon secretion after an oral glucose load. Female Nav1.8-cre/DTA mice also show higher fasting and postprandial glucagon like peptide-1 (GLP-1) levels with an increased number of GLP-1-positive cells. Finally, ablation of Nav1.8-expressing neurons accelerates the gastrointestinal transit in female mice under HFHSD. CONCLUSION: This data demonstrates sex-dependent differences in the Nav1.8-mediated regulation of energy metabolism, and provides new insights that may help in the design of sex-specific neuromodulation therapies for metabolic disorders induced by diets rich in fats and simple sugars.