METAPHOR: Metabolic evaluation through phasor-based hyperspectral imaging and organelle recognition for mouse blastocysts and oocytes.

Only 30% of embryos from in vitro fertilized oocytes successfully implant and develop to term, leading to repeated transfer cycles. To reduce time-to-pregnancy and stress for patients, there is a need for a diagnostic tool to better select embryos and oocytes based on their physiology. The current standard employs brightfield imaging, which provides limited physiological information. Here, we introduce METAPHOR: Metabolic Evaluation through Phasor-based Hyperspectral Imaging and Organelle Recognition. This non-invasive, label-free imaging method combines two-photon illumination and AI to deliver the metabolic profile of embryos and oocytes based on intrinsic autofluorescence signals. We used it to classify i) mouse blastocysts cultured under standard conditions or with depletion of selected metabolites (glucose, pyruvate, lactate); and ii) oocytes from young and old mouse females, or in vitro-aged oocytes. The imaging process was safe for blastocysts and oocytes. The METAPHOR classification of control vs. metabolites-depleted embryos reached an area under the ROC curve (AUC) of 93.7%, compared to 51% achieved for human grading using brightfield imaging. The binary classification of young vs. old/in vitro-aged oocytes and their blastulation prediction using METAPHOR reached an AUC of 96.2% and 82.2%, respectively. Finally, organelle recognition and segmentation based on the flavin adenine dinucleotide signal revealed that quantification of mitochondria size and distribution can be used as a biomarker to classify oocytes and embryos. The performance and safety of the method highlight the accuracy of noninvasive metabolic imaging as a complementary approach to evaluate oocytes and embryos based on their physiology.

Development and initial validation of parent and child versions of the Juvenile Arthritis Disease Activity Score.

OBJECTIVE: To develop parent- and child-centered versions of the Juvenile Arthritis Disease Activity Score (JADAS) and to provide preliminary evidence of their validity. METHODS: Validation analyses were conducted on two large multinational datasets of patients with juvenile idiopathic arthritis (JIA) and included assessment of construct validity, internal consistency and structure, discriminative validity, responsiveness to change, and predictive validity. RESULTS: The parJADAS and patJADAS include four parent/patient-reported outcomes, each measured on a 0-10 scale: assessment of overall disease activity; rating of pain intensity; assessment of activity of joint disease; duration of morning stiffness. Both scores are calculated as the simple linear sum of the scores of their 4 components, which yields for both of them a global score of 0-40. The parJADAS and patJADAS demonstrated good construct validity, yielding high correlations with other JIA composite disease activity measures and moderate correlations with physician global rating and joint counts. Internal consistency was satisfactory, with Cronbach' s alpha > 0.80, and exploratory factor analysis showed that both indices are monodimensional. Both instruments discriminated well between different disease states, with discriminative ability being not affected by the presence of damage, proved able to predict important disease outcomes, and showed fair responsiveness to clinically important change, with standardized response mean of 0.71. CONCLUSION: Both parJADAS and patJADAS were found to possess good measurement properties and to serve as surrogate of physicians' evaluations. Regular home completion of the two instruments through digital technologies offers a suitable and pragmatic approach to deliver remote symptom monitoring and telehealth.

[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Clopidogrel-induced thrombotic microangiopathy: a case report.

Thrombotic microangiopathy is a serious condition that can be precipitated by exposure to certain medications. Although rare, it is life threatening and requires a high index of clinical suspicion, appropriate laboratory testing and immediate cessation of the offending agent. We present a case of a 75-year-old man with a history of ischaemic heart disease treated with clopidogrel and aspirin. One month after initiating the treatment he developed microangiopathic haemolytic anaemia and thrombocytopenia. Extensive clinical and laboratory investigations suggested thrombotic microangiopathy secondary to clopidogrel. The drug was immediately discontinued and treatment with intravenous corticosteroids was started. Within a week the patient's laboratory parameters normalised, indicating successful recovery. This case highlights the role of early detection and immediate discontinuation of suspected medication in the effective management of clopidogrel-induced thrombotic microangiopathy. Healthcare professionals should consider drug-induced thrombotic microangiopathy as a possible diagnosis in patients receiving clopidogrel who present with thrombocytopenia and microangiopathic haemolytic anaemia.

Non-arteritic anterior ischemic optic neuropathy as the only manifestation of a malignant hypertensive crisis: Report of a case.

Non-arteritic anterior ischemic optic neuropathy (NAION) is after glaucoma the most common optic neuropathy in patients over 50 years. It is known that high blood pressure (HBP) is an important risk factor for the development of NAION. It is also known that malignant arterial hypertension (MAH) could be accompanied by optic disc edema. However, MAH has not classically been considered a cause of NAION. We report the case of a 32-year-old patient who presented irreversible visual loss with a pattern compatible with NAION as the only manifestation of a hypertensive crisis.

Identifying Dietary Timing of Organic Trace Minerals to Reduce the Incidence of Osteomyelitis Lameness in Broiler Chickens Using the Aerosol Transmission Model.

Our prior research demonstrated a 20% to 25% reduction in bacterial chondronecrosis with osteomyelitis (BCO) lameness in broilers with organic Zn, Mn, and Cu (Availa® ZMC) supplementation. Expanding on this, we investigated the optimal timing for Availa® ZMC feeding to mitigate BCO lameness and reduce feed additive costs in the poultry industry. In this study, we compared the application of 0.15% Availa® ZMC for 56 days, the first 28 days, and the last 28 days. The experimental design was a randomized block design involving 1560 one-day-old chicks distributed across two wire-floor pens as BCO source infection and four treatment groups with six replicates. The source of BCO infection exhibited a cumulative lameness incidence of 83%, whereas the negative control group showed a 77% cumulative incidence of lameness (p = 0.125). Administering 0.15% of Availa® ZMC during the initial 28 d resulted in a 41.3% reduction in BCO incidence, significantly different from the supplementation during the last 28 d (p < 0.05). However, this reduction did not differ substantially (p > 0.05) from the 56d application period. Hence, administering 0.15% Availa® ZMC during the first four weeks emerges as the optimal timing protocol, providing a defense against lameness comparable to the continuous supplementation throughout the complete production duration. Implementing this feeding approach reduces the cost of feed additive, promotes the health of skeletal bones, and effectively protects against BCO lameness in broilers, offering a valuable consideration for producers seeking optimal outcomes in the poultry industry.

External validation of three diabetes prediction scores in a Spanish cohort: does adding high risk for depression improve the validation of the FINDRISC score (FINDRISC-MOOD)?

OBJECTIVES: To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD). DESIGN: Prospective population-based cohort study. SETTING: 10 primary healthcare centres in the north of the city of Madrid (Spain). PARTICIPANTS: A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose <200 mg/dL (<11.1 mmol/L) were followed up for 7.3 years (median) using their electronic health records (EHRs) and telephone contact. PRIMARY AND SECONDARY OUTCOME MEASURES: Diabetes risk scores (FINDRISC, DESIR, ADA), PHQ-9 questionnaire and 2-hour-OGTT were measured at baseline. Incident diabetes was defined as treatment for diabetes, fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L), new EHR diagnosis or self-reported diagnosis. External validation was performed according to optimal cut-off, sensitivity, specificity and Youden Index. Comparison between diabetes risk scores, including FINDRISC-MOOD (original FINDRISC score plus five points if PHQ-9 ≥10), was measured by area under the receiver operating characteristic curve (AUROC). RESULTS: During follow-up, 104 (8.4%; 95% CI, 6.8 to 9.9) participants developed diabetes and 185 had a PHQ-9 score ≥10. The AUROC values were 0.70 (95% CI, 0.67 to 0.72) for FINDRISC-MOOD and 0.68 (95% CI, 0.65 to 0.71) for the original FINDRISC. The AUROCs for DESIR and ADA were 0.66 (95% CI, 0.63 to 0.68) and 0.66 (95% CI, 0.63 to 0.69), respectively. There were no significant differences in AUROC between FINDRISC-MOOD and the other scores. CONCLUSIONS: The results of FINDRISC-MOOD were like those of the other risk scores and do not allow it to be recommended for clinical use.

Effect of glucose variability on the mortality of adults aged 75 years and over during the first year of the COVID-19 pandemic.

BACKGROUND: To our knowledge, only one study has examined the association between glucose variability (GV) and mortality in the elderly population with diabetes. GV was assessed by HbA1c, and a J-shaped curve was observed in the relationship between HbA1c thresholds and mortality. No study of GV was conducted during the COVID-19 pandemic and its lockdown. This study aims to evaluate whether GV is an independent predictor of all-cause mortality in patients aged 75 years or older with and without COVID-19 who were followed during the first year of the COVID-19 pandemic and its lockdown measures. METHODS: This was a retrospective cohort study of 407,492 patients from the AGED-MADRID dataset aged 83.5 (SD 5.8) years; 63.2% were women, and 29.3% had diabetes. GV was measured by the coefficient of variation of fasting plasma glucose (CV-FPG) over 6 years of follow-up (2015-2020). The outcome measure was all-cause mortality in 2020. Four models of logistic regression were performed, from simple (age, sex) to fully adjusted, to assess the effect of CV-FPG on all-cause mortality. RESULTS: During follow-up, 34,925 patients died (14,999 women and 19,926 men), with an all-cause mortality rate of 822.3 per 10,000 person-years (95% confidence interval (CI), 813.7 to 822.3) (739 per 10,000; 95% CI 728.7 to 739.0 in women and 967.1 per 10,000; 95% CI 951.7 to 967.2 in men). The highest quartile of CV-FPG was significantly more common in the deceased group (40.1% vs. 23.6%; p < 0.001). In the fully adjusted model including dementia (Alzheimer's disease) and basal FPG, the odds ratio for mortality ranged from 1.88 to 2.06 in patients with T2DM and from 2.30 to 2.61 in patients with normoglycaemia, according to different sensitivity analyses. CONCLUSIONS: GV has clear implications for clinical practice, as its assessment as a risk prediction tool should be included in the routine follow-up of the elderly and in a comprehensive geriatric assessment. Electronic health records can incorporate tools that allow its calculation, and with this information, clinicians will have a broader view of the medium- and long-term prognosis of their patients.

Randomised, double-blind, placebo-controlled, parallel-group, multicentric, phase IIA clinical trial for evaluating the safety, tolerability, and therapeutic efficacy of daily oral administration of NFX88 to treat neuropathic pain in individuals with spinal cord injury.

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial. OBJECTIVE: To assess the safety and tolerability of oral administration of NFX-88 in subjects with chronic spinal cord injury (SCI) and explore its efficacy in pain control. SETTING: A total of 7 spinal cord injury rehabilitation units in Spain. METHODS: A total of 61 adult with traumatic complete or incomplete spinal cord injury (C4-T12 level), were randomised 1:1:1:1 to a placebo, NFX88 1.05 g, 2.1 g, 4.2 g/day for up to 12 weeks. The placebo or NFX-88 was administered as add-on therapy to pre-existing pregabalin (150-300 mg per day). Safety and tolerability were evaluated, and the Visual Analogue Scale (VAS) was the primary measure to explore the efficacy of NFX-88 in pain control. RESULTS: No severe treatment-related adverse effects were reported for any of the four study groups. 44 SCI individuals completed the study and were analysed. The data obtained from the VAS analysis and the PainDETECT Questionnaire (PD-Q) suggested that the combination of NFX88 with pregabalin is more effective than pregabalin with placebo at reducing neuropathic pain (NP) in individuals with SCI and that the dose 2.10 g/day causes the most dramatic pain relief. CONCLUSIONS: NFX88 treatment was found to be highly safe and well tolerated, with the dose of 2.10 g/day being the most effective at causing pain relief. Thus, the promising efficacy of this first-in-class lipid mediator deserves further consideration in future clinical trials.

Calcifediol or Corticosteroids in the Treatment of COVID-19: An Observational Study.

Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. OBJECTIVE: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. DESIGN, PATIENTS AND SETTING: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). INTERVENTIONS: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. MEASUREMENTS: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. RESULTS: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. INTERPRETATION: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation.

Effect of Cerebral Oximetry-Guided Treatment on Brain Injury in Preterm Infants as Assessed by Magnetic Resonance Imaging at Term Equivalent Age: An Ancillary SafeBoosC-III Study.

INTRODUCTION: The SafeBoosC-III trial investigated the effect of cerebral oximetry-guided treatment in the first 72 h after birth on mortality and severe brain injury diagnosed by cranial ultrasound in extremely preterm infants (EPIs). This ancillary study evaluated the effect of cerebral oximetry on global brain injury as assessed by magnetic resonance imaging (MRI) at term equivalent age (TEA). METHODS: MRI scans were obtained between 36 and 44.9 weeks PMA. The Kidokoro score was independently evaluated by two blinded assessors. The intervention effect was assessed using the nonparametric Wilcoxon rank sum test for median difference and 95% Hodges-Lehmann (HL) confidence intervals (CIs). The intraclass correlation coefficient (ICC) was used to assess the agreement between the assessors. RESULTS: A total of 210 patients from 8 centers were included, of whom 121 underwent MRI at TEA (75.6% of alive patients): 57 in the cerebral oximetry group and 64 in the usual care group. There was an excellent correlation between the assessors for the Kidokoro score (ICC agreement: 0.93, 95% CI: 0.91-0.95). The results showed no significant differences between the cerebral oximetry group (median 2, interquartile range [IQR]: 1-4) and the usual care group (median 3, IQR: 1-4; median difference -1 to 0, 95% HLCI: -1 to 0; p value 0.1196). CONCLUSIONS: In EPI, the use of cerebral oximetry-guided treatment did not lead to significant alterations in brain injury, as determined by MRI at TEA. The strong correlation between the assessors highlights the potential of the Kidokoro score in multicenter trials.

Preferences for neuromyelitis optica spectrum disorder treatments: A conjoint analysis with neurologists in Spain.

BACKGROUND: The treatment landscape for neuromyelitis optica spectrum disorder (NMOSD) has changed in recent years with the approval of therapies with different efficacy, safety and administration profiles. OBJECTIVE: The aim of this study was to assess neurologists' preferences for different NMOSD treatment attributes using conjoint analysis (CA). METHODS: We conducted an online, non-interventional, cross-sectional study in collaboration with the Spanish Society of Neurology. Our CA assessed five drugs' attributes: prevention of relapse, prevention of disability accumulation, safety risk, management during pregnancy, and route and frequency of administration. Participants were presented with eight hypothetical treatment scenarios to rank based on their preferences from the most preferred to the least. An ordinary least squares method was selected to estimate weighted preferences. RESULTS: A total of 104 neurologists were included. Mean age (standard deviation-SD) was 37.7 (10.3) years, 52.9 % were male, and median time (interquartile range) of experience managing NMOSD was 5.0 (2.9, 10.8) years. Neurologists placed the greatest importance on efficacy attributes, time to relapse (44.1 %) being the most important, followed by preventing disability accumulation (36.8 %). In contrast, route and frequency of administration (4.6 %) was the least important characteristic. Participants who prioritised efficacy attributes felt more comfortable in decision-making, had fewer past experiences of care-related regret and a lower attitude to risk taking than their counterparts. CONCLUSION: Neurologists' treatment preferences in NMOSD were mainly driven by efficacy attributes. These results may be useful to design policy decisions and treatment guidelines for this condition.

Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients.

The tyrosine kinase Inhibitor (TKI) imatinib is approved for the treatment of the chronic phase of chronic myeloid leukemia (CP-CML). Pharmacokinetic studies have highlighted the importance of inter-patient variability on imatinib plasma trough concentrations (ima[C]min). In the OPTIM-imatinib trial, we demonstrated that therapeutic drug monitoring (TDM) is able to improve the molecular response of CP-CML patients treated with imatinib. Here, we analyzed the constitutional exomes and RNAseq data of these patients. We performed an association analysis between the constitutional genetic variants of the patients and their ima[C]min, measured after 12 weeks of treatment with 400 mg once daily. Using linear regression, we identified 50 SNPs that showed excess heterozygosity depending on the ima[C]min. Ten SNPs were from non-coding sequences, and among the 40 remaining, 30 (from 25 genes) could be split into two categories. The first group of 16 SNPs concerns genes encoding extracellular matrix, cell junction, and membrane proteins. Coincidentally, cell adhesion proteins were also identified by RNA-seq as being overexpressed in patients with high ima[C]min. The other group of 14 SNPs were from genes encoding proteins involved in transcription/translation. Although most of the SNPs are intronic variants (28), we also identified missense (3), synonymous (4), 5'/3' (2), splicing (1), and upstream (4) variants. A haplotype analysis of four genes showed a significant association with high ima[C]min. None of the SNPs were significantly associated with the response. In conclusion, we identified a number of ima[C]min-associated SNPs, most of which correspond to genes encoding proteins that could play a role in the diffusion and transit of imatinib through membranes or epithelial barriers.

Impact of specialized training for emergency department nurses screening or undetected HIV infection: the "Urgències VIHgila" project experience. / Impacto de una formación específica y generalizada de los profesionales de enfermería en el despistaje en urgencias de infección oculta por VIH: experiencia del proyecto "Urgències VIHgila".

OBJECTIVES: To evaluate the impact of specialized training for nurses on selective screening for undetected HIV infection in the emergency department. MATERIAL AND METHODS: The intervention group was comprised of 6 emergency departments that had been participating in a screening program (the "Urgències VIHgila" project) for at least 3 months. Nurses on all shifts attended training sessions that emphasized understanding the circumstances that should lead to suspicion of unidentified HIV infection and the need to order serology. Two studies were carried out: 1) a quasi-experimental pre-post study to compare the number of orders for HIV serology in each time period and measures of sensitivity, and 2) a case-control study to compare the changes made in the 6 hospitals where specialized training was provided (cases) vs 6 control hospitals in the HIV screening program where no training was given. RESULTS: A total of 280 HIV serologies were ordered for the 81015 patients (0.3%) attended during the period before training; 331 serologies were ordered for the 79620 patients in the period after training (0.4%). The relative increase in serologies was 20.3% (95% CI, 2.9% to 34.5%; P = .022). The relative increase in measures of sensitivity ranged between 19% and 39%, consistent with the main comparison. Serologies in the control group decreased between periods, from 0.9% to 0.8%, indicating a relative decrease of 15.7% (95% CI, -25.1% to -6.2%; P = .001). The absolute number of patients tested in the training group was 0.2% higher in the training hospitals (95% CI, 0.11% to 0.31%; P .001) than in the control hospitals. CONCLUSION: Training nurses to screen for undetected HIV infection in the emergency department increased the number of patients tested, according to the pre-post and case-control comparisons.

OBJETIVO: Evaluar el impacto de una formación específica para enfermería en el servicio urgencias (SU) sobre el despistaje selectivo de infección por VIH oculta. METODO: Participaron 6 SU adheridos al programa "Urgències VIHgila" con un mínimo de 3 meses y se realizaron sesiones formativas para los diferentes turnos. Las sesiones enfatizaban en qué circunstancias debía sospecharse infección oculta VIH y la necesidad de solicitar serología. Se realizaron dos estudios: 1) cuasiexperimental pre/post, que comparó la tasa de solicitudes VIH entre ambos periodos, con diversos análisis de sensibilidad; 2) caso-control, que comparó el cambio entre periodos de los 6 SU con formación (caso) con el cambio en otros 6 SU que no tuvieron formación (control). RESULTADOS: Se realizaron serologías de VIH a 280 de los 81.015 pacientes atendidos durante el periodo preintervención (0,3%) y a 331 de los 79.620 del periodo posintervención (0,4%). El incremento relativo fue del 20,3% (IC 95% de +2,9% a +34,5%; p = 0,022). Los análisis de sensibilidad mostraron incrementos relativos congruentes con el análisis principal (entre 19% y 39%). En el grupo control hubo descenso de solicitudes entre periodos, del 0,9% al 0,8% (descenso relativo del 15,7%, IC 95% de ­25,1% a­6,2%; p = 0,001). El grupo caso, en relación con el grupo control, tuvo un incremento absoluto de 0,2% (IC 95% de +0,11 a +0,31%, p 0,001) de pacientes testados. CONCLUSIONES: La formación de enfermería para despistaje de la infección VIH oculta en urgencias incrementa el número de pacientes investigados, tanto comparado con el periodo previo a la formación como comparado con SU sin formación específica para enfermería.

Nucleic acid-loaded poly(beta-aminoester) nanoparticles for cancer nano-immuno therapeutics: the good, the bad, and the future.

Immunotherapy has emerged as a promising approach to cancer treatment, offering improved survival rates and enhanced patients' quality of life. However, realizing the full potential of immunotherapy in clinical practice remains a challenge, as there is still plenty of room for modulating the complexity of the human immune system in favor of an antitumor immunogenicity. Nanotechnology, with its unique properties, holds promise in augmenting the efficacy of cancer immunotherapies in biotherapeutic protection and site- and time-controlled delivery of the immune modulator biologicals. Polymeric nanoparticles are promising biomaterials among different nanocarriers thanks to their robustness, versatility, and cost-efficient design and production. This perspective paper overviews critical concepts in nanometric advanced delivery systems applied to cancer immunotherapy. We focus on a detailed exploration of the current state of the art and trends in using poly(beta-aminoester) (pBAE) polymers for nucleic acid-based antitumor immunotherapies. Through different examples of the use of pBAE polymers reported in the literature, we revise the main advantages these polymers offer and some challenges to overcome. Finally, the paper provides insights and predictions on the path toward the clinical implementation of cancer nano-immunotherapies, highlighting the potential of pBAE polymers for advancements in this field.

Impact of breastfeeding on ICU admissions and need for mechanical ventilation in infants younger than 6 months with RSV+ bronchiolitis. An observational study.

INTRODUCTION: This work aimed to analyze whether breastfeeding is a predictive factor for admission to ICU or needing mechanical ventilation in children under 6 months with RSV+ respiratory infection. METHODS: A retrospective cohort study was performed in three hospitals. Binary and multiple logistic regression analyses were performed to evaluate the association of variables with admission to the ICU or receiving mechanical ventilation. RESULTS: We analyzed 414 admissions, of which 293 (70.8%) had received breastfeeding, 43 (8.1%) were admitted to the ICU, and 26 (5.4%) required mechanical ventilation. Bivariate analysis showed that breastfeeding for at least 15 days and a longer duration of breastfeeding were associated with a lower risk of admission to the ICU and requiring mechanical ventilation. Multivariate analysis showed that not having been breastfed for at least 1 month was predictive of ICU admission; not having been breastfed for at least 2 months was predictive of needing mechanical ventilation. CONCLUSIONS: Breastfeeding for as little as 15-28 days could be associated with a lower risk of ICU admission and requiring mechanical ventilation in infants younger than 6 months admitted for RSV+ bronchiolitis. Since breastfeeding is one of the few protective factors that can be promoted, this finding is relevant for current clinical practice and the development of health promotion programs. Future studies can compare their results to ours.

Mutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.

Major depression (MD) and obesity are complex genetic disorders that are frequently comorbid. However, the study of both diseases concurrently remains poorly addressed and therefore the underlying genetic mechanisms involved in this comorbidity remain largely unknown. Here we examine the contribution of common and rare variants to this comorbidity through a next-generation sequencing (NGS) approach. Specific genomic regions of interest in MD and obesity were sequenced in a group of 654 individuals from the PISMA-ep epidemiological study. We obtained variants across the entire frequency spectrum and assessed their association with comorbid MD and obesity, both at variant and gene levels. We identified 55 independent common variants and a burden of rare variants in 4 genes (PARK2, FGF21, HIST1H3D and RSRC1) associated with the comorbid phenotype. Follow-up analyses revealed significantly enriched gene-sets associated with biological processes and pathways involved in metabolic dysregulation, hormone signaling and cell cycle regulation. Our results suggest that, while risk variants specific to the comorbid phenotype have been identified, the genes functionally impacted by the risk variants share cell biological processes and signaling pathways with MD and obesity phenotypes separately. To the best of our knowledge, this is the first study involving a targeted sequencing approach toward the study of the comorbid MD and obesity. The framework presented here allowed a deep characterization of the genetics of the co-occurring MD and obesity, revealing insights into the mutational and functional profile that underlies this comorbidity and contributing to a better understanding of the relationship between these two disabling disorders.

Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms 2 years after hospitalization: The VIPER study.

The SARS-CoV-2 VIrus PERsistence (VIPER) study investigated the presence of long-lasting SARS-CoV-2 RNA in plasma, stool, urine, and nasopharyngeal samples in COVID-19 survivors. The presence of SARS-CoV-2 RNA reverse transcription polymerase chain reactions (RT-PCR) were analyzed within plasma, stool, urine, and nasopharyngeal swab samples in COVID-19 survivors with post-COVID symptoms and a comparison group of COVID-19 survivors without post-COVID symptoms matched by age, sex, body mass index and vaccination status. Participants self-reported the presence of any post-COVID symptom (defined as a symptom that started no later than 3 months after the initial infection). Fifty-seven (57.9% women, age: 51.1, standard deviation [SD]: 10.4 years) previously hospitalized COVID-19 survivors with post-COVID symptoms and 55 (56.4% women, age: 50.0, SD: 12.8 years) matched individuals who had a past SARS-CoV-2 infection without post-COVID symptoms were evaluated 27 (SD 7.5) and 26 (SD 8.7) months after hospital discharge, respectively. The presence of SARS-CoV-2 RNA was identified in three nasopharyngeal samples of patients with post-COVID symptoms (5.2%) but not in plasma, stool, or urine samples. Thus, SARS-CoV-2 RNA was not identified in any sample of survivors without post-COVID symptoms. The most prevalent post-COVID symptoms consisted of fatigue (93%), dyspnea, and pain (both, 87.7%). This study did not find SARS-CoV-2 RNA in plasma, stool, or urine samples, 2 years after the infection. A prevalence of 5.2% of SARS-CoV-2 RNA in nasopharyngeal samples, suggesting a potential active or recent reinfection, was found in patients with post-COVID symptoms. These results do not support the association between SARS-CoV-2 RNA in plasma, stool, urine, or nasopharyngeal swab samples and post-COVID symptomatology in the recruited population.

The relationship between BDNF and physical activity on depression.

BACKGROUND/OBJECTIVE: Major depressive disorder (MDD) is one of the leading causes of disease burden and disability worldwide. Brain-derived neurotrophic factor (BDNF) seems to have an important role in the molecular mechanisms underlying MDD aetiology, given its implication in regulating neuronal plasticity. There is evidence that physical activity (PA) improves depressive symptoms, with a key role of BDNF in this effect. We aim to perform a systematic review examining the relationship between the BDNF Val66Met polymorphism and the BDNF protein, PA and MDD. METHODS: Both observational and experimental design original articles or systematic reviews were selected, according to the PRISMA statement. RESULTS: Six studies evaluated the Val66Met polymorphism, suggesting a greater impact of physical activity on depression depending on the Val66Met genotype. More discordant findings were observed among the 13 studies assessing BDNF levels with acute or chronic exercise interventions, mainly due to the high heterogeneity found among intervention designs, limited sample size, and potential bias. CONCLUSIONS: Overall, there is cumulative evidence supporting the potential role of BDNF in the interaction between PA and MDD. However, this review highlights the need for further research with more homogeneous and standardised criteria, and pinpoints important confounding factors that must be considered in future studies to provide robust conclusions.