Intramammary administration of lipopolysaccharides at parturition does not affect the transfer of passive immunity in goat kids.

This study evaluated the effect of feeding colostrum obtained from an intramammary administration (IA) of LPS from Escherichia coli (O55:B5) to dairy goats at parturition, on goat kids performance, biochemical parameters (i.e., calcium, LDH, glucose, total proteins, albumin, and urea) and immune status (i.e., IgG and IgM) during the first month of life. At birth, goat kids were weighted (d 0) and immediately allocated into either the LPS group (n = 15) or the CON group (n = 21) based on the experimental group of the dam. At parturition, 20 multiparous dairy goats were allocated in one of the 2 experimental groups (LPS vs. CON). The LPS group received an IA of saline solution (2 mL) containing 50 µg of LPS in each half udder whereas goats in the CON group received an IA of saline solution (2 mL) without LPS. Goat kids were bottle-fed dam colostrum equivalent to 10% of the birth BW divided in 2 meals (i.e., at 3 and 12 h relative to birth), and then fed twice daily with milk replacer ad libitum. Individual milk intake (MI) and BW were recorded on d 7, 15, 21 and 30 of life. Blood samples were collected on d 0, 1, 2, 4, 7, 15, 21 and 30 after birth. Data was analyzed using the MIXED procedure of SAS (9.4). The model included IA, time (T) and the interaction (IA x T) as fixed effects and sex and litter size as random effects. Both groups showed similar MI, except on d 7 relative to birth as the LPS group showed higher MI than the CON group (910.5 ± 69.77 and 683.9 ± 59.64 mL, respectively). No differences in BW or rectal temperature were observed between groups, neither in plasma IgG nor IgM concentrations. Despite the IA did not affect calcium, glucose, LDH, total protein, and albumin concentrations an interaction between the IA and T was observed for urea concentration, showing the LPS group higher urea concentrations than the CON group on d 0 (20.1 ± 1.34 and 20.0 ± 1.25 mg/dL, respectively). In conclusion, feeding colostrum from goats that received an IA of LPS at parturition does not affect goat kid performance, plasma immunoglobulin concentrations and serum metabolites during the first month of life.

The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain.

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

Optimizing semen cryopreservation in Calomys laucha: a step forward in rodent reproductive research.

BACKGROUND: Examining semen cryopreservation in Calomys laucha offers valuable insights for reproductive research and species conservation. OBJECTIVE: To determine the most effective sugar for the cryopreservation of C. laucha semen. MATERIALS AND METHODS: Using 36 epididymides from C. laucha, semen samples were diluted in a 3% skimmed milk medium supplemented with one of four sugars (glucose, fructose, lactose, or sucrose) at a concentration of 0.3 M. These mixtures underwent a conditioning phase at 37 degree C for 10 min, cooled to -80 degree C for another 10 min, and were subsequently stored in liquid nitrogen. RESULTS: Upon thawing, samples treated with lactose and glucose solutions show superior sperm motility, achieving 8.2% and 10.0% respectively, in contrast to the fructose (2.0%) and sucrose (4.1%) mixtures. Furthermore, samples preserved in glucose registered the highest sperm penetration rates, reaching 44.9%. CONCLUSION: Our findings suggest that a cryopreservation medium containing 0.3 M glucose can contribute to the safeguarding C. laucha rodent semen. https://doi.org/10.54680/fr24210110612.

Intramammary administration of lipopolysaccharides at parturition enhances immunoglobulin concentration in goat colostrum.

In newborn ruminants, transfer of passive immunity is essential to obtain protection against pathogens. This study aimed to increase the permeability of the blood-milk barrier using intramammary lipopolysaccharides (LPS) in goats at parturition to modulate colostrum composition. Twenty multiparous Majorera dairy goats were randomly allocated in one of the two experimental groups. The LPS group (n = 10) received an intramammary administration (IA) of saline (2 mL) containing 50 µg of LPS from Escherichia coli (O55:B5) in each half udder at parturition. The control group (n = 10) received an IA of saline (2 mL). Rectal temperature (RT) was recorded, and a blood sample was collected at parturition (before IA). In addition, RT was measured, and blood and colostrum/milk samples were collected on day (d) 0.125 (3 hours), 0.5 (12 hours), 1, 2, 4, 7, 15 and 30 relative to the IA. Goat plasma immunoglobulin G (IgG) and M (IgM) and serum ß-hydroxybutyrate, glucose, calcium, free fatty acids, lactate dehydrogenase and total protein concentrations were determined. Colostrum and milk yields as well as chemical composition, somatic cell count (SCC), IgG and IgM concentrations were measured. The MIXED procedure (SAS 9.4) was used, and the model included the IA, time, and the interaction between both fixed effects. Statistical significance was set as P < 0.05. Goats from the LPS group showed higher RT on d 0.125, 0.5 and 4 relative to the IA compared to the control group (PIA×Time = 0.007). Goat serum biochemical variables and plasma IgG and IgM concentrations were not affected by the IA. Colostrum and milk yield as well as chemical composition were not affected by the IA, except for milk lactose percentage that was lower in the LPS group compared to the control group (4.3 ± 0.08 and 4.6 ± 0.08%, respectively PIA = 0.026). Colostrum SCC was higher in the LPS group than in the control group (3.5 ± 0.09 and 3.1 ± 0.09 cells × 106/mL, respectively; PIA = 0.011). Similarly, milk SCC increased in the LPS group compared to the control group (PIA = 0.004). The LPS group showed higher IgG (PIA = 0.044) and IgM (PIA = 0.037) concentrations on colostrum than the control group (31.9 ± 4.8 and 19.0 ± 4.8 mg/mL, 0.8 ± 0.08 and 0.5 ± 0.08 mg/mL, respectively). No differences in milk IgG and IgM concentrations between groups were observed. In conclusion, the IA of LPS at parturition increases RT, SCC and IgG and IgM concentrations in colostrum without affecting either yield or chemical composition.

Sociodemographic disparities in oral health-related quality of life of schoolchildren in rural and urban areas.

OBJECTIVE: To assess the association between residence place, socioeconomic conditions and oral health-related quality of life (OHRQoL) among schoolchildren from southern Brazil. METHODS: Participants were 9-14-year-old schoolchildren from rural and urban municipal schools from Rosário do Sul, Brazil. The Child Perceptions Questionnaire (CPQ11-14) was used to assess OHRQoL. A structured questionnaire collected data on sociodemographic condition (family income), residence place (urban or rural), use of dental services, and behavioral variables. Clinical oral examination recorded the presence of missing teeth and the gingival bleeding index. Multilevel Poisson regression analysis with a hierarchical approach assessed the association between predictors and CPQ11-14 scores. Rate ratios (RR) and 95% confidence intervals (CI) were estimated. RESULTS: A total of 373 schoolchildren were included (rural area=122; urban area=251), with a mean CPQ11-14 score of 11.83, ranging from 0 to 42. Low-income schoolchildren living in rural areas had 15% higher CPQ11-14 scores than high-income schoolchildren living in urban areas. In urban areas, family income predicted OHRQoL, with low-income schoolchildren having 9% higher CPQ11-14 scores than high-income children. In rural areas, schoolchildren with low household income had 19% higher CPQ11-14 scores than high-income children. CONCLUSION: Schoolchildren from low-income families had a poorer OHRQoL irrespective of their area of residence (rural or urban). The association between family income and OHRQoL was more pronounced among children living in rural areas.

Explorando la opinión de los especialistas españoles acerca de la utilidad de la radiómica en el área oncológica / Exploring the opinion of Spanish medical specialists about the usefulness of radiomics in oncology

Objetivo Describir el conocimiento y la opinión de los profesionales sanitarios relacionados con la oncología acerca de la radiómica. Métodos Se elaboró un cuestionario de 12 preguntas (respuestas de selección múltiple, de escala tipo Likert y respuesta abierta), dirigido a profesionales relacionados con el diagnóstico/tratamiento de enfermedades oncológicas (oncología, radiodiagnóstico, medicina nuclear, oncología-radioterápica, hematooncología, radiofísica y anatomía patológica). Los participantes se clasificaron en dos grupos según su grado de formación: adjuntos y residentes. Resultados Un total de 114 profesionales completaron la encuesta (54% residentes, principalmente de las especialidades medicina nuclear y radiodiagnóstico). Los adjuntos obtuvieron un mejor desempeño en el área de conocimiento respecto a los residentes. En ambos grupos los encuestados respondieron estar de acuerdo con la utilidad de la radiómica para ayudar a realizar diagnósticos más precisos, facilitando el trabajo de los equipos médicos. Las ideas más frecuentes relacionadas con las desventajas del uso de la radiómica se relacionaron con la falta de sistematización en la adquisición de imágenes y la extracción de parámetros, la necesidad de entrenamiento de los profesionales y la inquietud sobre el reemplazo del trabajo humano por herramientas tecnológicas. Conclusiones La radiómica es un campo de estudio novedoso, cuyos aspectos más generales son conocidos por los profesionales sanitarios. Los profesionales encuestados son optimistas en cuanto a los beneficios que entregan esta y otros tipos de herramientas. El principal problema detectado fue la falta de sistematización en su implementación. El reemplazo de los profesionales y la pérdida de trabajo es una preocupación presente, pero menos prevalente y que puede responder a un fenómeno generacional (AU)

Aim To describe the knowledge and opinion of health professionals regarding the usefulness of radiomics in oncology. Methods A 12-question questionnaire (multiple-choice responses, Likert-type scale, and open response) was developed and sent to professionals related to diagnosis/treatment of oncological diseases (Oncology, Radiodiagnosis, Nuclear Medicine, Radiation Oncology, Hematology-Oncology, Radiophysics and Pathology). Participants were classified into two groups according to their level of training: attending physicians and residents. Results 114 professionals completed the survey (54% residents, mostly from Nuclear Medicine and Radiodiagnostic specialties). Attending physicians obtained a better performance in the area pf knowledge compared to residents. Both groups of respondents agreed regarding the usefulness of radiomics to help make more accurate diagnoses and promoting the work of medical teams and the most frequent disadvantages were related to the lack of systematization in the acquisition of images and extraction of parameters, the need for the training of professionals and concern about the replacement of human work by technological tools. Conclusions Radiomics is a novel field and the most general aspects are known by health professionals. The professionals surveyed were optimistic about the benefits provided by radiomics and other types of tools. The main problem detected was the lack of systematization in its implementation. The replacement of professionals and job loss is a concern, albeit less prevalent, and may respond to a generational phenomenon (AU)

Feed restriction around parturition does not affect colostrum immunoglobulin G concentration in dairy fat-tailed sheep but does affect performance and blood metabolites in newborn lambs.

This study aimed to investigate the effect of prepartum and postpartum feed restriction of fat-tailed dairy sheep on colostrum IgG concentration, and performance and blood metabolites of newborn fat-tailed lambs. Twenty fat-tailed dairy sheep were randomly allocated into control (Ctrl; n = 10) and feed restriction (FR; n = 10) groups. The Ctrl group received a diet that met 100% of energy requirements, both prepartum (from wk -5 to parturition) and postpartum (from parturition to wk 5). The FR group received a diet equivalent to 100, 50, 65, 80, and 100% of the energy requirements in wk -5, -4, -3, -2, and -1 relative to parturition, respectively. After parturition, the FR group received a diet equivalent to the 100, 50, 65, 80, and 100% of the energy requirements in wk 1, 2, 3, 4, and 5, respectively. At birth, lambs were assigned to their dam's experimental group. Both the Ctrl lambs (n = 10) and the FR lambs (n = 10) were allowed to suck colostrum and milk from the dams. Colostrum samples (50 mL) were collected at parturition (0 h) and then at 1, 12, 24, 36, 48, and 72 h postpartum. Blood samples were collected from all lambs before suckling colostrum (0 h) and then at 1, 12, 24, 36, 48, and 72 h after birth and weekly until the end of the experimental period (i.e., wk 5 relative to birth). The data were evaluated using the MIXED procedure of SAS (SAS Institute Inc.). The model included feed restriction, time, and the interaction feed restriction × time as fixed effects. The individual lamb was set as a repeated subject. Variables measured in colostrum and plasma were considered dependent variables, and significance was set at P < 0.05. Prepartum and postpartum feed restriction in fat-tailed dairy sheep did not affect colostrum IgG concentration. Consequently, no differences in blood IgG concentrations were observed in the lambs. In addition, the prepartum and postpartum feed restriction experienced by fat-tailed dairy sheep caused decreased body weight and milk intake in lambs from the FR group compared with the Ctrl group. Feed restriction also promoted increased concentration of blood metabolites such as triglycerides and urea in FR lambs compared with control lambs. In conclusion, prepartum and postpartum feed restriction in fat-tailed dairy sheep did not affect either colostrum IgG concentration or blood IgG concentration of the lambs. However, prepartum and postpartum feed restriction decreased lamb milk intake and, therefore, lamb body weight gain during the first 5 wk after birth.

Exploring the opinion of Spanish medical specialists about the usefulness of radiomics in oncology.

AIM: To describe the knowledge and opinion of health professionals regarding the usefulness of radiomics in oncology. METHODS: A 12-question questionnaire (multiple-choice responses, Likert-type scale, and open response) was developed and sent to professionals related to diagnosis/treatment of oncological diseases (Oncology, Radiodiagnosis, Nuclear Medicine, Radiation Oncology, Hematology-Oncology, Radiophysics and Pathology). Participants were classified into two groups according to their level of training: attending physicians and residents. RESULTS: 114 professionals completed the survey (54% residents, mostly from Nuclear Medicine and Radiodiagnostic specialties). Attending physicians obtained a better performance in the area pf knowledge compared to residents. Both groups of respondents agreed regarding the usefulness of radiomics to help make more accurate diagnoses and promoting the work of medical teams and the most frequent disadvantages were related to the lack of systematization in the acquisition of images and extraction of parameters, the need for the training of professionals and concern about the replacement of human work by technological tools. CONCLUSIONS: Radiomics is a novel field and the most general aspects are known by health professionals. The professionals surveyed were optimistic about the benefits provided by radiomics and other types of tools. The main problem detected was the lack of systematization in its implementation. The replacement of professionals and job loss is a concern, albeit less prevalent, and may respond to a generational phenomenon.

Does neoadjuvant treatment in resectable pancreatic cancer improve overall survival? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Neoadjuvant chemotherapy may improve overall survival (OS) in 'borderline' resectable pancreatic cancer (RPC). Whether the results are the same in upfront RPC is unknown. MATERIALS AND METHODS: To evaluate the association of neoadjuvant treatment and survival outcomes in RPC, a systematic literature review was carried out including prospective randomized trials of neoadjuvant treatment versus upfront surgery. Articles indexed in PubMed, Embase and Scopus were evaluated. Data regarding systemic treatment regimens, R0 resection rates, disease-free survival (DFS) and OS were extracted. The outcomes were compared using a random-effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. RESULTS: Of 3229 abstracts, 6 randomized controlled trials were considered eligible with a combined sample size of 805 RPC patients. Among the trials, PACT-15, PREP-02/JSAP-05 and updated long-term results from PREOPANC and NEONAX trials were included. Combining the studies with meta-analysis, we could see that neoadjuvant treatment in RPC does not improve DFS [hazard ratio (HR) 0.71 (0.46-1.09)] or OS [HR 0.76 (0.52-1.11)], without significant heterogeneity. Interestingly, R0 rates improved ∼20% with the neoadjuvant approach [HR 1.2 (1.04-1.37)]. It is important to note that most studies evaluated gemcitabine-based regimens in the neoadjuvant setting. CONCLUSIONS: Neoadjuvant chemotherapy or chemoradiation does not improve DFS or OS in RPC compared to upfront surgery followed by adjuvant treatment. Neoadjuvant treatment improves R0 rates by ∼20%. Randomized ongoing trials are eagerly awaited with more active combined regimens including modified FOLFIRINOX.

The Adolescent Problem Gambling Prevalence Associated with Leisure-Time Activities and Risky Behaviors in Southern Spain.

Gambling addiction is increasing and is becoming a public health concern due to the rise of gambling-related harms affecting the youth. Previous studies suggest a strong link between problem gambling (PG) and substance use and psychosocial and familial factors. Our main objective was to analyze the association between PG and factors like sport, leisure-time activities, and risk-taking behaviors in adolescents. A survey on substance use and addictive behaviors was performed in 2019 on a representative sample of 2240 subjects (14-18 years) from the Southern Spain Region. Data variables like socio-demographic characteristics, sport, leisure and free time activities, family environment, PG (Lie-Bet Scale), compulsive internet use (CIUS Scale), and consumption of alcohol and cannabis were collected using a standardized questionnaire. Weighted PG prevalence was estimated in either sex, as well as the differences between various levels of PG using chi-square tests. Crude and adjusted weighted logistic regression models were used to identify predictors associated with PG. The prevalence of PG was associated with shopping frequency, compulsive internet use, cannabis use in the previous month, higher family economic status, and having a homemaker father which increased the likelihood of PG. On the contrary, cultural hobbies such as playing an instrument, painting, singing, and writing, and having a working mother were inversely associated with PG. Our results suggest that encouraging participation in creative activities along with supervised shopping and monitoring compulsive internet use and cannabis consumption may contribute some protection against adolescent PG. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-022-00950-7.

Treatment With a Three-Drug Regimen for Pulmonary Tuberculosis Based on Rapid Molecular Detection of Isoniazid Resistance: A Noninferiority Randomized Trial (FAST-TB).

Background: The rationale behind the use of ethambutol in the standard tuberculosis treatment is to prevent the emergence of resistance to rifampicin in case of primary resistance to isoniazid. We evaluated whether early detection of isoniazid resistance using molecular testing allows the use an ethambutol-free regimen. Methods: FAST-TB, a phase 4, French, multicenter, open-label, non-inferiority trial, compared 2 strategies: (1) polymerase chain reaction (PCR)-based detection of isoniazid and rifampicin resistance at baseline using Genotype MTBDRplus version 2.0 followed by ethambutol discontinuation if no resistance was detected (PCR arm) and (2) a standard 4-drug combination, pending phenotypic drug-susceptibility results (C arm). Adult patients with smear-positive pulmonary tuberculosis were enrolled. The primary endpoint was the proportion of patients with treatment success defined as bacteriological or clinical cure at the end of treatment. A non-inferiority margin of 10% was used. Results: Two hundred three patients were randomized, 104 in the PCR arm and 99 in the C arm: 26.6% were female, median age was 37 (interquartile range, 28-51) years, 72.4% were born in Africa, and 5.4% were infected with human immunodeficiency virus. Chest x-ray showed cavities in 64.5% of the cases. Overall, 169 patients met criteria of treatment success: 87 of 104 (83.7%) in the PCR arm and 82 of 99 (82.8%) in the C arm with a difference of +0.8% (90% confidence interval, -7.9 to 9.6), meeting the noninferiority criteria in the intention-to-treat population (P = .02). Conclusions: In a setting with low prevalence of primary isoniazid resistance, a 3-drug combination with isoniazid, rifampicin, and pyrazinamide, based on rapid detection of isoniazid resistance using molecular testing, was noninferior to starting the recommended 4-drug regimen.

Nanotechnology-Driven Cell-Based Therapies in Regenerative Medicine.

The administration of cells as therapeutic agents has emerged as a novel approach to complement the use of small molecule drugs and other biologics for the treatment of numerous conditions. Although the use of cells for structural and/or functional tissue repair and regeneration provides new avenues to address increasingly complex disease processes, it also faces numerous challenges related to efficacy, safety, and translational potential. Recent advances in nanotechnology-driven cell therapies have the potential to overcome many of these issues through precise modulation of cellular behavior. Here, we describe several approaches that illustrate the use of different nanotechnologies for the optimization of cell therapies and discuss some of the obstacles that need to be overcome to allow for the widespread implementation of nanotechnology-based cell therapies in regenerative medicine.

Mantenimiento del consumo de pescado rico en metilmercurio durante el embarazo: prevalencia, consejo profesional y características maternas asociadas / Maintaining methylmercury-rich fish consumption during pregnancy: prevalence, professional advice and associated maternal characteristics

Introducción: los objetivos de este estudio fueron estimar la prevalencia del consumo de pescado rico en metilmercurio (MeHg) durante el embarazo, la proporción de mujeres que recibieron recomendaciones sanitarias para evitar su consumo e identificar los factores asociados al mantenimiento del consumo. Material y métodos: en 2016 se realizó un estudio transversal siendo la población objetivo mujeres que habían dado a luz entre septiembre de 2015 y agosto de 2016 en Galicia (España). La información sobre el estado de la mujer seis meses antes del embarazo, durante el embarazo, en el momento del parto y en el momento de la encuesta se obtuvo con una entrevista telefónica estructurada. La prevalencia de consumo de pescados ricos en MeHg se estimó antes y durante la gestación y se ajustó un modelo de regresión logística para conocer las variables asociadas con el mantenimiento. Resultados: el consumo de pescado rico en MeHg fue del 30% durante los seis meses previos a la gestación y disminuyó a 7% durante esta. El mantenimiento del consumo se asoció con no vivir en entorno urbano, multiparidad, consumir más de una porción de pescado rico en MeHg/semana antes de la gestación y con no haber recibido recomendaciones profesionales para evitar el consumo; 5 de cada 10 mujeres recibieron estas recomendaciones durante los controles prenatales. Conclusiones: algunos factores asociados con continuar consumiendo pescados ricos en MeHg durante el embarazo son modificables y deben ser considerados en la elaboración de mensajes de salud pública destinados a promover una alimentación adecuada durante el embarazo (AU)

Introduction: Our aims were to estimate the prevalence of MeHg-rich fish consumption, the proportion of women who received healthcare recommendations to avoid their consumption and to identify the factors associated with the maintenance of consumption during pregnancy.Material and methods: In 2016, a cross-sectional study based on a random sampling of all the women who had given birth between September 2015 and August 2016 was conducted in Galicia, Spain. Information was collected through a structured telephone interview regarding the mother’s status 6 months before pregnancy, during pregnancy, at the time of delivery, and at the time of the survey. The prevalence of MeHg-rich fish consumption, was estimated before and during pregnancy and a logistic regression model was adjusted to ascertain variables associated with maintaining consumption during pregnancy.Results: The consumption of swordfish or bluefin, was 30% during the 6 months prior to pregnancy and decreased to 7% during pregnancy. Maintenance of MeHg-rich fish consumption during pregnancy was associated with not living in an urban environment, multiparity, consumption of over 1 portion of MeHg-rich fish per week prior pregnancy, and with not having received professional recommendations in order to avoid consumption; 5 out of 10 women received these recommendations during the prenatal check-ups.Conclusions: Some of the factors associated with continuing the consumption during pregnancy are modifiable and should be considered in the development of public health messages intended to promote an adequate diet during pregnancy. (AU)

Co-infections and superinfections complicating COVID-19 in cancer patients: A multicentre, international study.

BACKGROUND: We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19. METHODS: International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections. RESULTS: 684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa. Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections. CONCLUSIONS: Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized.

Elucidating venlafaxine metabolism in the Mediterranean mussel (Mytilus galloprovincialis) through combined targeted and non-targeted approaches.

Exposure of aquatic organisms to antidepressants is currently well documented, while little information is available on how wild organisms cope with exposure to these pharmaceutical products. Studies on antidepressant metabolism in exposed organisms could generate information on their detoxification pathways and pharmacokinetics. The goal of this study was to enhance knowledge on the metabolism of venlafaxine (VEN)-an antidepressant frequently found in aquatic ecosystems-in Mytilus galloprovincialis, a bivalve that is present worldwide. An original tissue extraction technique based on the cationic properties of VEN was developed for further analysis of VEN and its metabolites using targeted and non-targeted approaches. This extraction method was assessed in terms of recovery and matrix effects for VEN metabolites. Commercial analytical standards were applied to characterize metabolites found in mussels exposed to 10 µg/L VEN for 3 and 7 days. Targeted and non-targeted approaches using liquid chromatography (LC) combined with high-resolution mass spectrometry (HRMS) were implemented to screen for expected metabolites based on the literature on aquatic species, and for metabolites not previously documented. Four venlafaxine metabolites were identified, namely N-desmethylvenlafaxine and O-desmethylvenlafaxine, which were clearly identified using analytical standards, and two other metabolites revealed by non-target analysis. According to the signal intensity, hydroxy-venlafaxine (OH-VEN) was the predominant metabolite detected in mussels exposed for 3 and 7 days.

Non-viral reprogramming of human nucleus pulposus cells with FOXF1 via extracellular vesicle delivery: an in vitro and in vivo study.

Intervertebral disc (IVD) degeneration is characterized by decreased cellularity and proteoglycan synthesis and increased inflammation, catabolism, and neural/vascular ingrowth. Regenerative methods for IVD degeneration are largely cell-therapy-based or involve viral vectors, which are associated with mutagenesis and undesired immune responses. The present study used bulk electroporation and engineered extracellular vesicles (EVs) to deliver forkhead-box F1 (FOXF1) mRNA to degenerate human nucleus pulposus (NP) cells as a minimally invasive therapeutic strategy for IVD regeneration. Bulk electroporation was used to investigate FOXF1 effects on human NP cells during a 4-week culture in 3D agarose constructs. Engineered EV delivery of FOXF1 into human IVD cells in monolayer was determined, with subsequent in vivo validation in a pilot mouse IVD puncture model. FOXF1 transfection significantly altered gene expression by upregulating healthy NP markers [FOXF1, keratin 19 (KRT19)], decreasing inflammatory cytokines [interleukin (IL)-1ß, -6], catabolic enzymes [metalloproteinase 13 (MMP13)] and nerve growth factor (NGF), with significant increases in glycosaminoglycan accumulation in human NP cells. Engineered EVs loaded with FOXF1 demonstrated successful encapsulation of FOXF1 cargo and effective uptake by human NP cells cultured in monolayer. Injection of FOXF1-loaded EVs into the mouse IVD in vivo resulted in a significant upregulation of FOXF1 and Brachyury, compared to controls at 7 d post-injection, with no evidence of cytotoxicity. This is the first study to demonstrate non-viral delivery of FOXF1 and reprogramming of human NP cells in vitro and mouse IVD cells in vivo. This strategy represents a non-addictive approach for treating IVD degeneration and associated back pain.

Estatus epiléptico no convulsivo secundario a encefalopatía hiperamonémica inducida por valproato / Non-convulsive status epilepticus secondary to valproate-induced hyperammonaemic encephalopathy

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