Renal Cell Carcinoma With Tumor Thrombus: A Case Series in Puerto Rico.

INTRODUCTION:  Renal cell carcinoma (RCC) is one of the most common types of kidney cancer. While RCC tends to present as a localized tumor, a notable proportion may present with distant metastasis. In some instances, RCC may also present with intravascular tumor extension, often called tumor thrombus (TT). Its presence confers a worse prognosis and has important implications for the tumor's staging and treatment. Despite extensive documentation of RCC TT in the US, limited data exists regarding its presentation, management, and outcomes in Puerto Rico (PR). This study aims to broaden the available information on RCC TT, emphasizing surgical management and outcomes. We also provide descriptive data on patient demographics and clinical presentation to improve decision-making among clinicians caring for Puerto Rican men and women. METHODS:  In this single-center, retrospective study, we evaluated patients who underwent partial or total nephrectomy at Saint Luke's Episcopal Medical Center between 2018 and 2022. Data was abstracted from electronic health records (EHR). Patients without documented evidence of TT during the peri-operative period were excluded from the study. A total of 220 patient records were evaluated, of which 12 met the inclusion criteria for the study. Cases were categorized using the latest RCC TT guidelines. Central tendency measurements were used to describe the sample distribution. The mean was considered to make assumptions regarding the prevalent observations, and the median was considered to rule out possible outliers. Categorical data were evaluated using proportion analyses, including TT extension level and BMI variables. Fisher's exact test evaluated the association between the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and TT extension level. RESULTS:  Most patients lacked TT-related symptoms. The most severe presenting symptom was a pulmonary embolism (8.3%). Hypertension (83.3%), BMI greater than 25 at the time of diagnosis (75%), and type 2 diabetes mellitus (66.7%) were the most common comorbid conditions within our cohort. Nearly 75% of patients underwent laparoscopic radical nephrectomy with TT resection. One left-sided level III case was managed by laparoscopic-assisted open radical nephrectomy with a right subcostal incision. There were zero intraoperative complications and two postoperative complications. The histopathological reports of all cases were consistent with clear cell carcinoma, and half of the cases (n=6) were WHO/ISUP G4. All patients are alive and free of disease. CONCLUSION:  RCC is a common renal neoplasm in PR that can present with intravascular tumor extension. Our findings do not establish a definitive association between BMI, tumor size, WHO/ISUP grading, and TT extension level. Our study shows that laparoscopic removal of RCC TT is a safe and effective approach. However, the generalizability of our findings is limited by the study's design and sample size. Future research should focus on identifying predictive markers, establishing effective screening protocols, and determining if our hybrid approach has comparable outcomes to the standard open approach.

Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study.

BACKGROUND: Galicia (Spain) was one of the first regions worldwide to incorporate nirsevimab for universal respiratory syncytial virus (RSV) prophylaxis in infants into its immunisation programme. The NIRSE-GAL longitudinal population-based study aimed to assess nirsevimab effectiveness in preventing hospitalisations (ie, admittance to hospital). METHODS: The 2023-24 immunisation campaign with nirsevimab in Galicia began on Sept 25, 2023, and concluded on March 31, 2024. The campaign targeted three groups: infants born during the campaign (seasonal group), infants younger than 6 months at the start of the campaign (catch-up group), and infants aged 6-24 months with high-risk factors at the start of the campaign (high-risk group). Infants in the seasonal group were offered immunisation on the first day of life before discharge from hospital. Infants in the catch-up and high-risk groups received electronic appointments to attend a public hospital or health-care centre for nirsevimab administration. For this interim analysis, we used data collected from Sept 25 to Dec 31, 2023, from children born up to Dec 15, 2023. Data were retrieved from public health registries. Nirsevimab effectiveness in preventing RSV-associated lower respiratory tract infection (LRTI) hospitalisations; severe RSV-related LRTI requiring intensive care unit admission, mechanical ventilation, or oxygen support; all-cause LRTI hospitalisations; and all-cause hospitalisations was estimated using adjusted Poisson regression models. Data from five past RSV seasons (2016-17, 2017-18, 2018-19, 2019-20, and 2022-23), excluding the COVID-19 pandemic period, were used to estimate the number of RSV-related LRTI hospitalisations averted along with its IQR. The number needed to immunise to avoid one case in the 2023-24 season was then estimated from the averted cases. Nirsevimab safety was routinely monitored. The NIRSE-GAL study protocol was registered on ClinicalTrials.gov (NCT06180993), and follow-up of participants is ongoing. FINDINGS: 9408 (91·7%) of 10 259 eligible infants in the seasonal and catch-up groups received nirsevimab, including 6220 (89·9%) of 6919 in the seasonal group and 3188 (95·4%) of 3340 in the catch-up group. 360 in the high-risk group were offered nirsevimab, 348 (97%) of whom received it. Only infants in the seasonal and catch-up groups were included in analyses to estimate nirsevimab effectiveness and impact because there were too few events in the high-risk group. In the catch-up and seasonal groups combined, 30 (0·3%) of 9408 infants who received nirsevimab and 16 (1·9%) of 851 who did not receive nirsevimab were hospitalised for RSV-related LRTI, corresponding to an effectiveness of 82·0% (95% CI 65·6-90·2). Effectiveness was 86·9% (69·1-94·2) against severe RSV-related LRTI requiring oxygen support, 69·2% (55·9-78·0) against all-cause LRTI hospitalisations, and 66·2% (56·0-73·7) against all-cause hospitalisations. Nirsevimab effectiveness against other endpoints of severe RSV-related LRTI could not be estimated because of too few events. RSV-related LRTI hospitalisations were reduced by 89·8% (IQR 87·5-90·3), and the number needed to immunise to avoid one RSV-related LRTI hospitalisation was 25 (IQR 24-32). No severe adverse events related to nirsevimab were registered. INTERPRETATION: Nirsevimab substantially reduced infant hospitalisations for RSV-associated LRTI, severe RSV-associated LRTI requiring oxygen, and all-cause LRTI when given in real-world conditions. These findings offer policy makers and health authorities robust, real-world, population-based evidence to guide the development of strategies for RSV prevention. FUNDING: Sanofi and AstraZeneca. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Exploring Cognitive Dysfunction in Long COVID Patients: Eye Movement Abnormalities and Frontal-Subcortical Circuits Implications via Eye-Tracking and Machine Learning.

BACKGROUND: Cognitive dysfunction is regarded as one of the most severe aftereffects following coronavirus disease 2019 (COVID-19). Eye movements, controlled by several brain areas, such as the dorsolateral prefrontal cortex and frontal-thalamic circuits, provide a potential metric for assessing cortical networks and cognitive status. We aimed to examine the utility of eye movement measurements in identifying cognitive impairments in long COVID patients. METHODS: We recruited 40 long COVID patients experiencing subjective cognitive complaints and 40 healthy controls and used a certified eye-tracking medical device to record saccades and antisaccades. Machine learning was applied to enhance the analysis of eye movement data. RESULTS: Patients did not differ from the healthy controls regarding age, sex, and years of education. However, the patients' Montreal Cognitive Assessment total score was significantly lower than healthy controls. Most eye movement parameters were significantly worse in patients. These included the latencies, gain (computed as the ratio between stimulus amplitude and gaze amplitude), velocities, and accuracy (evaluated by the presence of hypermetric or hypometria dysmetria) of both visually and memory-guided saccades; the number of correct memory saccades; the latencies and duration of reflexive saccades; and the number of errors in the antisaccade test. Machine learning permitted distinguishing between long COVID patients experiencing subjective cognitive complaints and healthy controls. CONCLUSION: Our findings suggest impairments in frontal subcortical circuits among long COVID patients who report subjective cognitive complaints. Eye-tracking, combined with machine learning, offers a novel, efficient way to assess and monitor long COVID patients' cognitive dysfunctions, suggesting its utility in clinical settings for early detection and personalized treatment strategies. Further research is needed to determine the long-term implications of these findings and the reversibility of cognitive dysfunctions.

Characterization of an extremophile bacterial acid phosphatase derived from metagenomics analysis.

Acid phosphatases are enzymes that play a crucial role in the hydrolysis of various organophosphorous molecules. A putative acid phosphatase called FS6 was identified using genetic profiles and sequences from different environments. FS6 showed high sequence similarity to type C acid phosphatases and retained more than 30% of consensus residues in its protein sequence. A histidine-tagged recombinant FS6 produced in Escherichia coli exhibited extremophile properties, functioning effectively in a broad pH range between 3.5 and 8.5. The enzyme demonstrated optimal activity at temperatures between 25 and 50°C, with a melting temperature of 51.6°C. Kinetic parameters were determined using various substrates, and the reaction catalysed by FS6 with physiological substrates was at least 100-fold more efficient than with p-nitrophenyl phosphate. Furthermore, FS6 was found to be a decamer in solution, unlike the dimeric forms of crystallized proteins in its family.

A Comparative Analysis of Cognitive Deficits in Rheumatoid Arthritis and Fibromyalgia: Impact of Symptoms Severity and Its Clinical Implications.

Purpose: Fibromyalgia syndrome (FMS) and rheumatoid arthritis (RA) are chronic pain disorders, with clearly distinct pathogenetic mechanisms, frequently accompanied by symptoms like depression, fatigue, insomnia and cognitive problems. This study compared performance in various cognitive domains between patients with FMS and RA. The role of clinical symptoms severity in determine the differences in cognitive performance was also investigated. Patients and Methods: A cross-sectional study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. In total, 64 FMS patients, 34 RA patients and 32 healthy controls participated, all women. Using factor analysis, questionnaire scores were combined to yield a symptom severity factor, which was used as a control variable in the group comparisons. Results: Without controlling for symptom severity, both patient groups performed worse than controls in all the cognitive domains assessed (visuospatial memory; verbal memory; strategic planning and self-regulation; processing speed, attention and cognitive flexibility; and planning and organizational abilities); overall deficits were greater in FMS than in RA patients. FMS patients reported more severe clinical symptoms (current pain intensity, total pain, state anxiety, depression, fatigue and insomnia) than RA patients. After controlling for symptom severity, a large proportion of the cognitive test parameters no longer differed between FMS and RA patients. Conclusion: The study confirmed significant impairments in attention, memory, and higher cognitive functions in both FMS and RA. The greater deficits seen in FMS patients may at least partly be explained by more severe pain and secondary symptoms. Cognitive screening may facilitate the development of personalized treatment plans to optimize the quality of life of FMS and RA patients.

The investigation substantiated noteworthy impairments in attention, memory, and executive functions among individuals diagnosed with Fibromyalgia Syndrome (FMS) and Rheumatoid Arthritis (RA).The heightened cognitive deficits observed in FMS patients compared to those with RA could be attributed in part to the heightened severity of pain and secondary symptoms characteristic of FMS.Semantic clustering, by leveraging cognitive resources optimally, may serve as a compensatory mechanism for memory deficits and thus warrants inclusion in interventions aimed at assisting patients in coping with cognitive impairments.Incorporating cognitive deficit screenings into routine diagnostic protocols for FMS and RA is recommended, as it may facilitate the development of personalized treatment strategies aimed at enhancing the overall quality of life for affected individuals.

Body morphology and handgrip strength parameters of the female canoe slalom paddlers.

Introduction: Canoe slalom is a physically very demanding discipline, in which body constitution, body composition, and relative strength are significant factors in high performance. Although anthropometric and strength parameters are relatively well-studied in male athletes, there is a lack of evidence for any conclusions in women. Therefore, the objective of this study was to determine the morphology and upper-limb strength parameters of female canoe slalom paddlers and identify whether morphological differences exist between performance groups. Methods: Altogether, 63 female competitors of the 2023 ICF Canoe Slalom World Cup (n = 29) and 2023 ICF Canoe Slalom World Ranking Competition (n = 34) in Prague (Czech Republic) were examined with a battery of anthropometric tests, segmental bioimpedance analysis, and handgrip strength test. The athletes were divided into groups according to age and performance: elite athletes belonging to the world top 10 according to the ICF World Ranking (WORLD, n = 7), international-level athletes competing during the World Cup (ELITE, n = 22), international-level junior athletes competing in the World Ranking Race (JUNIOR, n = 17), and other lower performance-level athletes competing in the World Ranking Race (REST, n = 17). Results: Female slalom paddlers are, in general, of average body height (∼165 cm), lower body mass (∼60 kg), BMI (∼22 kg/m2), and body fat (∼20%) and without exceptional anthropometric dimensions and proportions. However, differences were detected when performance was factored in. Female paddlers belonging to the world TOP 10 have the largest circumferences of arms and forearms, and their somatotype is more mesomorphic, with a lower proportion of total body fat and a higher proportion of muscle mass. In addition, the WORLD group differs significantly in upper-limb strength. Discussion: The results shows the significance of muscular strength and power for canoe slalom athletes and the importance of well-developed musculature in operating the boat in the unstable environment. Being a successful female canoe slalom athlete requires a well-developed musculature, maximizing strength capabilities while maintaining a low body weight through limited hypertrophy of the lower limbs and a low level of body fat.

Epidemiological and clinical management aspects of pneumonias diagnosed in the emergency department in elderly patients in Spain: Results of the EDEN-29 study.

OBJECTIVES: To estimate the incidence of pneumonia diagnosis in elderly patients in Spanish emergency departments (ED), need for hospitalization, adverse events and predictive capacity of biomarkers commonly used in the ED. METHODS: Patients ≥65 years with pneumonia seen in 52 Spanish EDs were included. We recorded in-hospitaland 30-day mortality as adverse events, as well as intensive care unit (ICU) admission among hospitalizedpatients. Association of 10 predefined variables with adverse events was calculated and expressed as odds ratio (OR) with 95% confidence interval (CI), as well as predictive capacity of 5 commonly used biomarkers in the ED (leukocytes, hemoglobin, C-reactive protein, glucose, creatinine) was investigated using area under the receiver operating characteristic curve (AUC-ROC). RESULTS: 591 patients with pneumonia attended in the ED were included (annual incidence of 18,4 per 1000 inhabitants). A total of 78.0% were hospitalized. Overall, 30-day mortality was 14.2% and in-hospital mortality was 12.9%. Functional dependency was associated with both events (OR=4.453, 95%CI=2.361-8.400; and OR=3.497, 95%CI=1.578-7.750, respectively) as well as severe comorbidity (2.344, 1.363-4.030, and 2.463, 1.252-4.846, respectively). Admission to the ICU during hospitalization occurred in 3.5%, with no associated factors. The predictive capacity of biomarkers was only moderate for creatinine for ICU admission (AUC-ROC=0.702, 95% CI=0.536-0.869) and for leukocytes for post-discharge adverse event (0.669, 0.540-0.798). CONCLUSIONS: Pneumonia is a frequent diagnosis in elderly patients consulting in the ED. Their functional dependence and comorbidity is the factor most associated with adverse events. The biomarkers analyzed do not have a good predictive capacity for adverse events.

An Update of Kaempferol Protection against Brain Damage Induced by Ischemia-Reperfusion and by 3-Nitropropionic Acid.

Kaempferol, a flavonoid present in many food products, has chemical and cellular antioxidant properties that are beneficial for protection against the oxidative stress caused by reactive oxygen and nitrogen species. Kaempferol administration to model experimental animals can provide extensive protection against brain damage of the striatum and proximal cortical areas induced by transient brain cerebral ischemic stroke and by 3-nitropropionic acid. This article is an updated review of the molecular and cellular mechanisms of protection by kaempferol administration against brain damage induced by these insults, integrated with an overview of the contributions of the work performed in our laboratories during the past years. Kaempferol administration at doses that prevent neurological dysfunctions inhibit the critical molecular events that underlie the initial and delayed brain damage induced by ischemic stroke and by 3-nitropropionic acid. It is highlighted that the protection afforded by kaempferol against the initial mitochondrial dysfunction can largely account for its protection against the reported delayed spreading of brain damage, which can develop from many hours to several days. This allows us to conclude that kaempferol administration can be beneficial not only in preventive treatments, but also in post-insult therapeutic treatments.

A novel and efficient strategy for the biodegradation of di(2-ethylhexyl) phthalate by Fusarium culmorum.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is used worldwide and raises concerns because of its prevalence in the environment and potential toxicity. Herein, the capability of Fusarium culmorum to degrade a high concentration (3 g/L) of DEHP as the sole carbon and energy source in solid-state fermentation (SSF) was studied. Cultures grown on glucose were used as controls. The biodegradation of DEHP by F. culmorum reached 96.9% within 312 h. This fungus produced a 3-fold higher esterase activity in DEHP-supplemented cultures than in control cultures (1288.9 and 443.2 U/L, respectively). In DEHP-supplemented cultures, nine bands with esterase activity (24.6, 31.2, 34.2, 39.5, 42.8, 62.1, 74.5, 134.5, and 214.5 kDa) were observed by zymography, which were different from those in control cultures and from those previously reported for cultures grown in submerged fermentation. This is the first study to report the DEHP biodegradation pathway by a microorganism grown in SSF. The study findings uncovered a novel biodegradation strategy by which high concentrations of DEHP could be biodegraded using two alternative pathways simultaneously. F. culmorum has an outstanding capability to efficiently degrade DEHP by inducing esterase production, representing an ecologically promising alternative for the development of environmental biotechnologies, which might help mitigate the negative impacts of environmental contamination by this phthalate. KEY POINTS: • F. culmorum has potential to tolerate and remove di(2-ethylhexyl) phthalate (DEHP) • Solid-state fermentation is an efficient system for DEHP degradation by F. culmorum • High concentrations of DEHP induce high levels of esterase production by F. culmorum.

Timely Assessment of Breathing-Related Distress in Community Palliative Care: A Multidisciplinary Collaborative Quality Improvement Project.

Background: Breathlessness is a common symptom for palliative patients that can cause distress and decrease function and quality of life. Palliative care services in Australia aim to routinely assess patients for breathing-related distress, but timely reassessment is not always achieved. Objective: To improve the timeliness of breathlessness reassessment in a home-based community palliative care service in New South Wales for people with moderate-to-severe breathing-related distress. Breathing-related distress was defined as a Symptom Assessment Score for "breathing problems" of four or more. Methods: This collaborative quality improvement (QI) project between SPHERE Palliative Care CAG, Stanford University mentors, and a Sydney metropolitan specialist palliative care service included a: (1) retrospective chart audit; (2) cause and effect analyses using a fishbone diagram; (3) development and implementation of key drivers and interventions; and (4) a pre-and-post evaluation of the timeliness of reassessment of breathing-related distress and changes in Symptom Assessment Scale scores for "breathing problems." Results: Key interventions included multidisciplinary education sessions to facilitate buy-in, with nurses as case managers responsible for breathlessness reassessment and documentation of scores, access and training in electronic palliative care data entry software, fortnightly monitoring and reporting of breathing-related distress scores, and development of an educational flowchart. The proportion of patients reassessed within seven days of an initial nursing assessment of moderate-to-severe breathing-related distress increased from 34% at baseline to 92% at six months. Conclusion: A local QI project increased the proportion of patients with a timely reassessment of their breathing-related distress in a community palliative care service.

Long-Term Results of Cortical Motor Stimulation for Neuropathic Peripheral and Central Pain: Real-World Evidence From Two Independent Centers.

BACKGROUND AND OBJECTIVES: Cortical motor stimulation (CMS) is used to modulate neuropathic pain. The literature supports its use; however, short follow-up studies might overestimate its real effect. This study brings real-world evidence from two independent centers about CMS methodology and its long-term outcomes. METHODS: Patients with chronic refractory neuropathic pain were implanted with CMS. The International Classification of Headache Disorders 3rd Edition was used to classify craniofacial pain and the Douleur Neuropathique en 4 Questions Scale score to explore its neuropathic nature. Demographics and clinical and surgical data were collected. Pain intensity at 6, 12, and 24 months and last follow-up was registered. Numeric rating scale reduction of ≥50% was considered a good response. The Clinical Global Impression of Change scale was used to report patient satisfaction. RESULTS: Twelve males (38.7%) and 19 females (61.3%) with a mean age of 55.8 years (±11.9) were analyzed. Nineteen (61.5%) were diagnosed from painful trigeminal neuropathy (PTN), and seven (22.5%) from central poststroke pain. The mean follow-up was 51 months (±23). At 6 months, 42% (13/31) of the patients were responders, all of them being PTN (13/19; 68.4%). At last follow-up, only 35% (11/31) remained responders (11/19 PTN; 58%). At last follow-up, the global Numeric rating scale reduction was 34% ( P = .0001). The Clinical Global Impression of Change scale punctuated 2.39 (±0.94) after 3 months from the surgery and 2.95 (±1.32) at last follow-up ( P = .0079). Signs of suspicious placebo effect were appreciated in around 40% of the nonresponders. CONCLUSION: CMS might show long-term efficacy for neuropathic pain syndromes, with the effect on PTN being more robust in the long term. Multicentric clinical trials are needed to confirm the efficacy of this therapy for this and other conditions.

Intermediate science knowledge predicts overconfidence.

Lackner et al. found science overconfidence peaks at intermediate levels of knowledge. Those with intermediate knowledge also hold the most negative attitudes toward scientists. In doing so, they provide a novel measure of overconfidence that measures the tendency to give incorrect answers as opposed to answering, 'I don't know'.

Impact of First Wave of COVID-19 Pandemic on Mortality at Emergency Department in Older Patients with COVID and Non-COVID Diagnoses.

INTRODUCTION: Mortality in emergency departments (EDs) is not well known. This study aimed to assess the impact of the first-wave pandemic on deaths accounted in the ED of older patients with COVID and non-COVID diseases. METHODS: We used data from the Emergency Department and Elderly Needs (EDEN) cohort (pre-COVID period) and from the EDEN-COVID cohort (COVID period) that included all patients ≥65 years seen in 52 Spanish EDs from April 1 to 7, 2019, and March 30 to April 5, 2020, respectively. We recorded patient characteristics and final destination at ED. We compared older patients in the pre-COVID period, with older patients with non-COVID and with COVID-19. ED-mortality (before discharge or hospitalization) is the prior outcome and is expressed as an adjusted odds ratio (aOR) with 95% interval confidence. RESULTS: We included 23,338 older patients from the pre-COVID period (aged 78.3 [8.1] years), 6,715 patients with non-COVID conditions (aged 78.9 [8.2] years) and 3,055 with COVID (aged 78.3 [8.3] years) from the COVID period. Compared to the older patients, pre-COVID period, patients with non-COVID and with COVID-19 were more often male, referred by a doctor and by ambulance, with more comorbidity and disability, dementia, nursing home, and more risk according to qSOFA, respectively (p < 0.001). Compared to the pre-COVID period, patients with non-COVID and with COVID-19 were more often to be hospitalized from ED (24.8% vs. 44.3% vs. 79.1%) and were more often to die in ED (0.6% vs. 1.2% vs. 2.2%), respectively (p < 0.001). Compared to the pre-COVID period, aOR for age, sex, comorbidity and disability, ED mortality in elderly patients cared in ED during the COVID period was 2.31 (95% confidence interval [CI]: 1.76-3.06), and 3.75 (95% CI: 2.77-5.07) for patients with COVID. By adding the variable qSOFA to the model, such OR were 1.59 (95% CI: 1.11-2.30) and 2.16 (95% CI: 1.47-3.17), respectively. CONCLUSIONS: During the early first pandemic wave of COVID-19, more complex and life-threatening older with COVID and non-COVID diseases were seen compared to the pre-COVID period. In addition, the need for hospitalization and the ED mortality doubled in non-COVID and tripled in COVID diagnosis. This increase in ED mortality is not only explained by the complexity or severity of the elderly patients but also because of the system's overload.

Immunosuppressants alter the immune response associated with Glucantime® treatment for Leishmania infantum infection in a mouse model.

Background: Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop. Objectives: To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses. Results: Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment. Conclusion: The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.

Coaching leaders toward favorable trajectories of burnout and engagement.

Existing literature on executive coaching has shown beneficial outcomes for leaders. Indeed, executive coaching can positively affect an individual's psychological well-being and quality of work life. However, while burnout among leaders is on the rise, to our knowledge no prior study has investigated the influence of executive coaching on the dimensions of burnout and engagement concurrently. Therefore, the aim of the current study is to examine if an executive coaching intervention has positive effects on managerial burnout and engagement. We implemented a ten-week coaching intervention for leaders, where questionnaire data were collected at two time points. Participants (N = 92; Mage = 42; 64% male) were randomly assigned to an intervention or a wait-list control group. Self-reported levels of engagement and burnout were collected at the start of the study protocol (T1) and at the end (T2). Coaching sessions for the intervention group were one hour once per week. The control group did not receive coaching. Repeated measures ANOVAs examined the extent to which the intervention influences the leader's engagement and burnout. Analyses revealed that all three dimensions of burnout significantly decreased for the intervention group over time while vigor increased. Findings did not reveal an increase in dedication and absorption. Consistent with prior literature, this study supports that executive coaching can improve a leader's well-being. Specifically, this study shows that an executive coaching intervention can decrease burnout symptoms and increase vigor in leaders. Adding a follow-up survey to the design would allow for further exploration of the intervention on engagement.

Impact of the ABO and RhD Blood Groups on the Evaluation of the Erythroprotective Potential of Fucoxanthin, ß-Carotene, Gallic Acid, Quercetin and Ascorbic Acid as Therapeutic Agents against Oxidative Stress.

Previous studies detail that different blood groups are associated with incidence of oxidative stress-related diseases such as certain carcinomas. Bioactive compounds represent an alternative for preventing this oxidative stress. The aim of this study was to elucidate the impact of blood groups on the erythroprotective potential of fucoxanthin, ß-Carotene, gallic acid, quercetin and ascorbic acid as therapeutic agents against oxidative stress. The impact of ABO blood groups on the erythroprotective potential was evaluated via the antioxidant capacity, blood biocompatibility, blood susceptibility and erythroprotective potential (membrane stabilization, in vitro photostability and antihemolytic activity). All tested antioxidants exhibited a high antioxidant capacity and presented the ability to inhibit ROO•-induced oxidative stress without compromising the cell membrane, providing erythroprotective effects dependent on the blood group, effects that increased in the presence of antigen A. These results are very important, since it has been documented that antigen A is associated with breast and skin cancer. These results revealed a probable relationship between different erythrocyte antigens with erythroprotective potential, highlighting the importance of bio-targeted drugs for groups most susceptible to certain chronic-degenerative pathologies. These compounds could be applied as additive, nutraceutical or encapsulated to improve their bioaccessibility.

Validation of the anxiety subscale of the Spanish version of the Edinburgh Postnatal Depression Scale (EPDS-A).

Introduction: There is a need to implement routine perinatal mental health screening in Spain. Therefore, it is necessary to systematise the detection of depressive and anxious symptoms in pregnancy and postpartum using the same instrument. The Edinburgh Postnatal Stress Depression Scale (EPDS) is frequently used as a rapid, effective and cross-culturally validated screening tool for perinatal depression. In several countries, an Anxiety subscale, the EPDS-A, was identified within the EPDS. Although the factorial structure of the EPDS has been investigated in Spanish population, the EPDS-A has not yet been validated. This study aimed to validate the EPDS-A as a measure of perinatal anxiety in Spanish population. Methods: 161 women were evaluated with the EPDS and the State-Trait Anxiety Inventory (STAI) during pregnancy and postpartum. Confirmatory factor analysis (CFA) was used to confirm the trifactorial structure of the EPDS, comprising the dimensions of Depression, Anhedonia and Anxiety. Likewise, the invariance of the trifactorial model between pregnancy and postpartum was tested. Finally, the correlations between the EPDS-A and the STAI subscales (State Anxiety and Trait Anxiety) were calculated. Results: The Exploratory factor analysis (EFA) driven three-factor structure of the EPDS, consisting of an Anhedonia factor (Items 1, 2, and 10), an Anxiety factor (Items 3, 4, 5, and 6) and a Depression factor (Items 7, 8, and 9), was the best measurement model for the current data compared to the alternative model tested [χ2 = 34.592, df = 32, p = 0.34; χ2/df = 1.08; RMSEA = 0.023, 90% Confidence Interval [CI] [0.000, 0.064], CFI = 0.996, GFI = 0.960]. The model's invariance between pregnant and postpartum women was confirmed. The existence of an Anxiety subscale within the EPDS was also confirmed. The scores obtained with the EPDS-A correlated moderately with scores on both subscales of the STAI during pregnancy and after delivery. Using the STAI as a criterion and prioritising the instrument's sensitivity, a cut-off point of 4 points was established for the EPDS-A. Conclusion: Our results confirm the trifactorial structure of the EPDS in Spanish population. The Anxiety subscale was validated for routine perinatal mental health screening.

Active and Intelligent Packaging: A Review of the Possible Application of Cyclodextrins in Food Storage and Safety Indicators.

Natural cyclodextrins (CDs) can be formed by 6, 7, or 8 glucose molecules (α-, ß-, and γ-, respectively) linked in a ring, creating a cone shape. Its interior has an affinity for hydrophobic molecules, while the exterior is hydrophilic and can interact with water molecules. This feature has been used to develop active packaging applied to food, interacting with the product or its environment to improve one or more aspects of its quality or safety. It also provides monitoring information when food is optimal for consumption, as intelligent packaging is essential for the consumer and the merchant. Therefore, this review will focus on discerning which packaging is most appropriate for each situation, solubility and toxicological considerations, characterization techniques, effect on the guest properties, and other aspects related to forming the inclusion complex with bioactive molecules applied to packaging.

Novel Insights into the Molecular Mechanisms Governing Embryonic Epicardium Formation.

The embryonic epicardium originates from the proepicardium, an extracardiac primordium constituted by a cluster of mesothelial cells. In early embryos, the embryonic epicardium is characterized by a squamous cell epithelium resting on the myocardium surface. Subsequently, it invades the subepicardial space and thereafter the embryonic myocardium by means of an epithelial-mesenchymal transition. Within the myocardium, epicardial-derived cells present multilineage potential, later differentiating into smooth muscle cells and contributing both to coronary vasculature and cardiac fibroblasts in the mature heart. Over the last decades, we have progressively increased our understanding of those cellular and molecular mechanisms driving proepicardial/embryonic epicardium formation. This study provides a state-of-the-art review of the transcriptional and emerging post-transcriptional mechanisms involved in the formation and differentiation of the embryonic epicardium.

A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care.

INTRODUCTION: The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion. PATIENTS AND METHODS: The efficacy of oral domperidone plus standard of care (SOC; n = 87) versus placebo plus SOC (n = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes. RESULTS: A significant reduction in the viral load was observed (p < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized. CONCLUSION: Results do not prove the use of domperidone as antiviral in patients with COVID-19.

A 28-day double-blind clinical trial was performed to investigate the antiviral effect of domperidone, 30 mg/day for 7 days (n = 87) versus placebo (n = 86) in outpatients with mild-to-moderate COVID-19.The primary efficacy endpoint was the reduction of viral load on day 4 as compared with baseline, estimated as the cycle thresholds to detect ORF1ab, N Protein and S Protein genes by RT-qPCR in saliva samples.The study findings do not prove the use of domperidone as antiviral in patients with COVID-19.