Search

Excitotoxicity is classically defined as the neuronal damage caused by the excessive release of glutamate, and subsequent activation of excitatory plasma membrane receptors. In the mammalian brain, this phenomenon is mainly driven by excessive activation of glutamate receptors (GRs). Excitotoxicity is common to several chronic disorders of the Central Nervous System (CNS) and is considered the primary mechanism of neuronal loss of function and cell death in acute CNS diseases (e.g. ischemic stroke). Multiple mechanisms and pathways lead to excitotoxic cell damage including pro-death signaling cascade events downstream of glutamate receptors, calcium (Ca2+) overload, oxidative stress, mitochondrial impairment, excessive glutamate in the synaptic cleft as well as altered energy metabolism. Here, we review the current knowledge on the molecular mechanisms that underlie excitotoxicity, emphasizing the role of Nicotinamide Adenine Dinucleotide (NAD) metabolism. We also discuss novel and promising therapeutic strategies to treat excitotoxicity, highlighting recent clinical trials. Finally, we will shed light on the ongoing search for stroke biomarkers, an exciting and promising field of research, which may improve stroke diagnosis, prognosis and allow better treatment options. published

We aimed to evaluate the role of SARC-F and SARC-CalF scores as risk factors for mortality in adults over 60 years of age with cancer of the Centro Médico Naval (CEMENA) in Callao, Peru during 2012-2015.We performed a secondary analysis of data from a prospective cohort carried out from September 2012 to February 2013 in the Geriatrics Department of CEMENA. The outcome variable was mortality at two years of follow-up, while the exposure variable was the risk of sarcopenia assessed using the SARC-F and SARC-CalF scales. We carried out Cox proportional-hazards models to assess the role of SARC-F and SARC-CalF scores as risk factors for mortality. We estimated crude (cHR) and adjusted (aHR) hazard ratios (HR) with their respective 95% confidence intervals (95%CI). Likewise, we calculated the area under the curve (AUC) of both exposure variables in relation to mortality.We analyzed data from 922 elderly men with cancer; 43.1% (n=397) were between 60 and 70 years old. 21.5% (n=198) and 45.7% (n=421) were at risk of sarcopenia according to SARC-F and SARC-CalF, respectively, while the incidence of mortality was 22.9% (n=211). In the adjusted Cox regression model, we found that the risk of sarcopenia measured by SARC-F (aHR=2.51; 95%CI: 1.40-2.77) and SARC-CalF (aHR=2.04; 95%CI: 1.55-4.02) was associated with a higher risk of death in older men with cancer. In the diagnostic performance analysis, we found that the AUC for mortality prediction was 0.71 (95%CI: 0.68-0.75) for SARC-F and 0.80 (95%CI: 0.78-0.82) for SARC-CalF.The risk of sarcopenia evaluated by SARC-F and SARC-CalF scores was associated with an increased risk of mortality in older men with cancer. Both scales proved to be useful and accessible instruments for the identification of groups at risk of mortality.

Antibiotics are often prescribed to treat infections caused by group B Streptococcus; however, inappropriate use of antibiotics can develop resistance. Because of this, the research was carried out with the aim of evaluating the in vitro effect of the hydroalcoholic extract of Caesalpinia spinosa (Molina) Kuntze known as Taya or Tara on the viability of β-hemolytic streptococci; an experimental investigation of increasing stimulation was carried out. The hydroalcoholic extract of C. spinosa pods was worked in concentrations of 250, 500, 750, and 1000 mg/mL, which were placed on filter paper discs to perform the sensitivity test following the Kirby–Bauer method. The greatest inhibition of bacterial viability was observed in the penicillin control group (GPT-01) followed by the TCT-04 group (hydroalcoholic Tara extract 1000 mg/mL). In addition, it was found that these groups are statistically different from the rest (p < 0.05), while the lowest bacterial inhibition was obtained for the erythromycin group and the TCT-01 group (250–1000 mg/mL). It was concluded that the hydroalcoholic extract of the pods of C. spinosa (Molina) Kuntze affects the viability of β-hemolytic streptococci associated with strep pharyngitis and that this antimicrobial activity is due to the presence of tannins, steroidal flavonoid, and alkaloids. Likewise, the tested concentrations of hydroalcoholic Tara extract were found to have better antibacterial activity than erythromycin (15 µg/mL) against β-hemolytic streptococci. These results are hopeful for the traditional or herbal medicine field. However, future in vivo research is needed to determine its effectiveness in humans.

This study assessed parental vaccine hesitancy in a metropolitan area of the United States. The study aimed to determine what characteristics and contributing factors influenced parental vaccine hesitancy and concerns regarding COVID-19.An online survey was used to recruit 93 parents to answer demographic and vaccine hesitancy information. Vaccine hesitancy was measured using the Parent Attitudes about Childhood Vaccines survey. The study was conducted between June 2020 and September 2020 during the COVID-19 pandemic.The rate of vaccine hesitancy was 15%. One hundred percent of vaccine hesitant parents were mothers, at least 30 years of age, married, and had completed at least some college. When characteristics of vaccine hesitant parents were compared to non-hesitant parents, the hesitant parents reported having more children, with 93% reporting two or more children compared to only 74% of non-hesitant parents (p = 0.046). Fifty percent of hesitant parents reported no concerns regarding COVID-19 compared to only 20% of non-hesitant parents (p = 0.006), and significantly less hesitant parents reported willingness to have their children receive a safe, effective COVID-19 vaccine if it were available compared to non-hesitant parents (p0.001).Our findings indicate that older mothers with two or more children are more likely to be vaccine hesitant and this hesitancy extends to the current COVID-19 pandemic.Healthcare providers can use the results of this study to identify parents at risk for vaccine hesitancy and initiate individualized education to promote on-time childhood vaccination.

OBJECTIVE: To explore the pattern of fetal cortical development in pregnancies complicated by pre-eclampsia (PE), with and without a small-for-gestational-age (SGA) fetus, compared to uncomplicated pregnancies. METHODS: This was a prospective observational study including singleton pregnancies complicated by normotensive SGA (birth weight < 10(th) centile) (n = 77), PE with an appropriate-for-gestational-age (AGA) fetus (n = 76) or PE with a SGA fetus (n = 67), and 128 uncomplicated pregnancies (normotensive AGA) matched by gestational age at ultrasound. All pregnancies underwent detailed neurosonography, using a transabdominal and transvaginal approach, at 31-35 weeks' gestation to assess the depth of the insula, Sylvian fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus. All measurements were adjusted for biparietal diameter (BPD). In addition, a grading score of cortical development was assigned to each brain structure, ranging from Grade 0 (no development) to Grade 5 (maximum development). Univariate and multiple regression analyses were conducted. RESULTS: Similar to findings in previous studies, normotensive pregnancies with a SGA fetus showed significant differences in cortical development compared with controls, with reduced Sylvian fissure depth adjusted for BPD (14.5 ± 2.4 vs 16.6 ± 2.3; P < 0.001) and increased insula depth adjusted for BPD (33.2 ± 2.0 vs 31.8 ± 2.0; P < 0.001). Interestingly, a similar cortical development pattern was observed in PE pregnancies with a SGA fetus and in PE pregnancies with an AGA fetus, manifested by reduced Sylvian fissure depth adjusted for BPD (14.2 ± 2.3 and 14.3 ± 2.3 vs 16.6 ± 2.3; P < 0.001 for both) and greater insula depth adjusted for BPD (33.2 ± 2.1 and 32.8 ± 1.7 vs 31.8 ± 2.0; P < 0.001 for both) compared with controls. No significant differences were observed in parieto-occipital, cingulate sulcus or calcarine sulcus depth across the study groups. The Sylvian fissure was scored as Grade 4 in significantly more (93.2% vs 59.5%) and as Grade 5 in significantly fewer (2.7% vs 37.3%) PE pregnancies with an AGA fetus compared with controls (P < 0.05 for both). These differences remained significant even after statistical adjustment for potential confounders, including ethnicity, low socioeconomic status, nulliparity, chronic hypertension, pregestational diabetes, assisted reproductive technologies, smoking and fetal gender, with the application of Benjamini-Hochberg procedure for multiple comparisons. CONCLUSIONS: PE with or without SGA is associated with a differential fetal cortical development pattern which is similar to that described previously in small fetuses. Future research is warranted to elucidate better the mechanism(s) underlying these changes. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Small unmanned aerial systems (UASs) are becoming a good candidate technology for solving the observational gap in the planetary boundary layer (PBL). Additionally, the rapid miniaturization of thermodynamic sensors over the past years has allowed for more seamless integration with small UASs and more simple system characterization procedures. However, given that the UAS alters its immediate surrounding air to stay aloft by nature, such integration can introduce several sources of bias and uncertainties to the measurements if not properly accounted for. If weather forecast models were to use UAS measurements, then these errors could significantly impact numerical predictions and hence influence the weather forecasters' situational awareness and their ability to issue warnings. Therefore, some considerations for sensor placement are presented in this study, as well as flight patterns and strategies to minimize the effects of UAS on the weather sensors. Moreover, advanced modeling techniques and signal processing algorithms are investigated to compensate for slow sensor dynamics. For this study, dynamic models were developed to characterize and assess the transient response of commonly used temperature and humidity sensors. Consequently, an inverse dynamic model processing (IDMP) algorithm that enhances signal restoration is presented and demonstrated on simulated data. This study also provides contributions on model stability analysis necessary for proper parameter tuning of the sensor measurement correction method. A few real case studies are discussed where the application and results of the IDMP through strong thermodynamic gradients of the PBL are shown. The conclusions of this study provide information regarding the effectiveness of the overall process of mitigating undesired distortions in the data sampled with a UAS to help increase the data quality and reliability.

UNSTRUCTURED Only 5% of the molecules tested in oncology phase I trials reach the market after an average of 7.5 years of waiting and at a cost of tens of millions of euros. To reduce the cost and shorten the times of discovery of new treatments, “drug repurposing” (research with molecules already approved for another indication) and the use of secondary data (not collected for the purpose of research) have been proposed. Due to advances in informatics in clinical care, secondary data can, in some cases, be of equal quality to primary data generated through prospective studies. The objective of this study is to identify drugs currently marketed for other indications which may have an effect on the prognosis of cancer patients. For this purpose, a cohort of patients with high-lethality neoplastic diseases, treated in the public health system of Catalonia between 2006 and 2012, will be monitored retrospectively for survival for 5 years after diagnosis or until death. A control cohort, comprising people without neoplasms, will be also retrospectively monitored for 5 years. The following study variables will be extracted from different population databases: type of neoplasm (cancer patient cohort), date and cause of death, pharmacological treatment, sex, age and place of residence. In the first stage of the statistical analysis of the cancer patient cohort, the drugs consumed by the long-term survivors (alive at 5 years) will be compared with those consumed by nonsurvivors. In a second stage, the survival associated with the consumption of each relevant drug will be analysed. For the analyses, groups will be matched for potentially confounding variables, and multivariate analyses will be performed to adjust for residual confounding variables if necessary. The control cohort will be used to verify whether the associations found are exclusive to patients with neoplasms or whether they also occur in patients without cancer. All analyses are considered exploratory; therefore, the results will have to be confirmed in subsequent clinical trials; however, the results of this study may accelerate drug discovery in oncology.

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection.Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves.Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of

Full genome sequences of seven mycobacteriophages isolated from environmental soil samples are presented. These bacteriophages, with their respective cluster or subclusters, are Duplo (A2), Dynamo (P1), Gilberta (A11), MaCh (A11), Nikao (K1), Phloss (N), and Skinny (M1). All were temperate Siphoviridae, with genome sizes ranging from 43,107–82,071 bp.