Synchrony between midbrain gene transcription and dopamine terminal regulation is modulated by chronic alcohol drinking.

Alcohol use disorder is marked by disrupted behavioral and emotional states which persist into abstinence. The enduring synaptic alterations that remain despite the absence of alcohol are of interest for interventions to prevent relapse. Here, 28 male rhesus macaques underwent over 20 months of alcohol drinking interspersed with three 30-day forced abstinence periods. After the last abstinence period, we paired direct sub-second dopamine monitoring via ex vivo voltammetry in nucleus accumbens slices with RNA-sequencing of the ventral tegmental area. We found persistent augmentation of dopamine transporter function, kappa opioid receptor sensitivity, and dynorphin release - all inhibitory regulators which act to decrease extracellular dopamine. Surprisingly, though transcript expression was not altered, the relationship between gene expression and functional readouts of these encoded proteins was highly dynamic and altered by drinking history. These results outline the long-lasting synaptic impact of alcohol use and suggest that assessment of transcript-function relationships is critical for the rational design of precision therapeutics.

Thermography Sensor to Assess Motor and Sensitive Neuromuscular Sequels of Brain Damage.

INTRODUCTION: The aim of this study was to observe the validity, diagnostic capacity, and reliability of the thermographic technique in the analysis of sensitive and motor sequelae in patients with chronic brain damage. METHOD: A longitudinal descriptive observational study was performed. Forty-five people with impairment in at least one anatomical region participated in and completed this study. All patients who had become infected by SARS-CoV-2 in the past year were excluded. Thermographic measurement was conducted, and the Modified Ashworth Scale and Pressure Pain Threshold was analyzed. RESULTS: A high correlation between two times of thermography data was observed. The Spearman correlations obtained between the Ashworth score on each leg and the temperature given by thermography were all significant. DISCUSSION AND CONCLUSIONS: Despite the above, the Spearman correlations obtained between the PPT in each leg and the temperature offered by thermography were not significant in any of the measurements. For this reason, thermography is a potential tool for the diagnosis and assessment of neuromuscular motor sequelae, but not for sensitive sequelae, after brain injury. Nevertheless, for the time being, no statistical relationship has been observed between the data reported by thermography and PPT; thus, future studies are needed to further investigate these results.

Cu(I) Coordination Compounds Conjugated to Au Nanorods for Future Applications in Drug Delivery: Insights in Molecular, Electronic and Cu Local Structure in Solid and Liquid Phase.

In the framework of the design, synthesis and testing of a library of copper complexes and nanostructured assemblies potentially endowed with antitumor and antiviral activity and useful for several applications, from drugs and related delivery systems to the development of biocidal nanomaterials, we present the detailed spectroscopic investigation of the molecular and electronic structure of copper-based coordination compounds and of a new conjugated system obtained by grafting Cu(I) complexes to gold nanorods. More in detail, the electronic and molecular structures of two Cu complexes and one AuNRs/Cu-complex adduct were investigated by X-ray photoelectron spectroscopy (XPS), synchrotron-induced XPS (SR-XPS) and near edge X-ray absorption spectroscopy (NEXAFS) in solid state, and the local structure around copper ion was assessed by X-ray absorption spectroscopy (XAS) both in solid state and water solution for the AuNRs/Cu-complex nanoparticles. The proposed multi-technique approach allowed to properly define the coordination geometry around the copper ion, as well as to ascertain the molecular structures of the coordination compounds, their stability and modifications upon interaction with gold nanoparticles, by comparing solid state and liquid phase data.

Daratumumab and Nelarabine Treatment as Salvage Therapy for T-Lymphoblastic Lymphoma: A Case Report.

T-cell lymphoblastic lymphoma is an uncommon lymphoid neoplasm in adults, although more frequent in children and teenagers, that often affects the mediastinum and bone marrow, requiring intensive chemotherapy protocols. Its prognosis is poor if a cure is not achieved with first-line treatments. We present a case report of a 19-year-old man diagnosed with this type of lymphoma due to significant respiratory distress and a mediastinal mass. He received treatment according to the hyper-CVAD regimen, with a complete metabolic response. However, seven months later a new mediastinal growth was observed, leading to salvage treatment with a combination of nelarabine and daratumumab. We observed not only refractoriness, but also leukemization, which prompted consideration of hematopoietic stem cell transplantation. Based on this case, we conducted a review of pharmacological treatment options for refractory or relapsed lymphoblastic lymphoma, as well as the role of radiotherapy in managing mediastinal disease. This case report highlights the limited evidence available regarding later-line treatments, with unusual reports regarding employing our combination of daratumumab and nelarabine, and emphasizes the importance of achieving cures in the first line of treatment.

Urologists' and general practitioners' knowledge, beliefs and practice relevant for opportunistic prostate cancer screening: a PRISMA-compliant systematic review.

Background: Recent guidelines on opportunistic prostate cancer screening conclude that the decision to screen with prostate-specific antigen should be made by each patient individually together with the clinician. However, there is evidence of a lack of clinicians' awareness of prostate cancer screening. This study sought to assess the recent evidence of clinicians' knowledge, beliefs, and practice regarding opportunistic prostate cancer screening comparing urologists and generals practitioners. Methods: A systematic search was conducted in 3 online databases: MEDLINE, Web of Science and EMBASE (from January 1, 2015, to January 9th, 2023). Studies that explored clinicians' knowledge, beliefs, and practices regarding opportunistic prostate cancer screening were included. Studies were assessed for quality reporting according to the Strengthening the Reporting of Observational studies in Epidemiology guidelines. Results: A total of 14 studies met the inclusion criteria: ten studies included primary care health professionals, three studies included urologists, and one study included both. Studies involving general practitioners showed a generally low level of awareness of the recommended uses of the test, and urologists showed a greater knowledge of clinical practice guidelines. General practitioners' opinion of prostate-specific antigen was generally unfavourable in contrast to urologists' who were more likely to be proactive in ordering the test. Less than half of the included studies evaluated shared-decision making in practice and 50% of clinicians surveyed implemented it. Conclusion: General practitioners had less knowledge of prostate cancer risk factors and clinical practice guidelines in the use of PSA than urologists, which makes them less likely to follow available recommendations. A need to carry out education interventions with trusted resources based on the available evidence and the current guidelines was identified.

Effect of Acute Sodium Bicarbonate and Caffeine Coingestion on Repeated-Sprint Performance in Recreationally Trained Individuals: A Randomized Controlled Trial.

INTRODUCTION: The acute and isolated ingestion of sodium bicarbonate (NaHCO3) and caffeine (CAF) improves performance and delays fatigue in high-intensity tasks. However, it remains to be elucidated if the coingestion of both dietary supplements stimulates a summative ergogenic effect. This study aimed to examine the effect of the acute coingestion of NaHCO3 and CAF on repeated-sprint performance. METHODS: Twenty-five trained participants (age: 23.3 [4.0] y; sex [female/male]: 12/13; body mass: 69.6 [12.5] kg) participated in a randomized, double-blind, placebo (PLA) -controlled, crossover study. Participants were assigned to 4 conditions: (1) NaHCO3 + CAF, (2) NaHCO3, (3) CAF, or (4) PLA. Thus, they ingested 0.3 g/kg of NaHCO3, 3 mg/kg of CAF, or PLA. Then, participants performed 4 Wingate tests (Wt), consisting of a 30-second all-out sprint against an individualized resisted load, interspersed by a 1.5-minute rest period between sprints. RESULTS: Peak (Wpeak) and mean (Wmean) power output revealed a supplement and sprint interaction effect (P = .009 and P = .049, respectively). Compared with PLA, NaHCO3 + CAF and NaHCO3 increased Wpeak performance in Wt 3 (3%, P = .021) and Wt 4 (4.5%, P = .047), while NaHCO3 supplementation increased mean power performance in Wt 3 (4.2%, P = .001). In Wt 1, CAF increased Wpeak (3.2%, P = .054) and reduced time to Wpeak (-8.5%; P = .008). Plasma lactate showed a supplement plus sprint interaction (P < .001) when NaHCO3 was compared with CAF (13%, P = .031) and PLA (23%, P = .021). CONCLUSION: To summarize, although the isolated ingestion of CAF and NaHCO3 improved repeated-sprint performance, the coingestion of both supplements did not stimulate a synergic ergogenic effect.

Impact of social desirability bias on the CoPsoQ-ISTAS 21 psychosocial risk assessment questionnaire.

BACKGROUND: Self-reported test is one of the main psychosocial risk assessment tools. However, this test it is susceptible to certain sources of error, including social desirability. Since psychosocial risks are emerging, there are not many studies on their assessment. OBJECTIVE: The aim of this work is to analyze the impact of social desirability on the short version of the CopSoq-ISTAS 21 assessment tool. METHOD: A total of 563 workers (45.10% women and 54.90% men) participated in this study. The short version of the CoPsoQ-Istas21 questionnaire with four Likert scale questions as markers, which correspond to the Eysenck Personality Lie Scale Questionnaire Revised (EPQ-r), were used. The sample was divided into two halves, and both a confirmatory analysis and an exploratory analysis were carried out to find out the factorial structure of the scale and, with it, apply the bias filtering method. RESULTS: The results indicate that 10% of the scale is biased due to social desirability, and that there are significant differences between the group with bias clean scores and the group with scores without bias control. CONCLUSIONS: The effects of social desirability on the scale are verified, so it is concluded that in a psychosocial risk assessment is not enough to apply a self-report test and interpret its results, being necessary to minimize the sources of error.

Functional convergence of genomic and transcriptomic architecture underlies schooling behaviour in a live-bearing fish.

The organization and coordination of fish schools provide a valuable model to investigate the genetic architecture of affiliative behaviours and dissect the mechanisms underlying social behaviours and personalities. Here we used replicate guppy selection lines that vary in schooling propensity and combine quantitative genetics with genomic and transcriptomic analyses to investigate the genetic basis of sociability phenotypes. We show that consistent with findings in collective motion patterns, experimental evolution of schooling propensity increased the sociability of female, but not male, guppies when swimming with unfamiliar conspecifics. This finding highlights a relevant link between coordinated motion and sociability for species forming fission-fusion societies in which both group size and the type of social interactions are dynamic across space and time. We further show that alignment and attraction, the two major traits forming the sociability personality axis in this species, showed heritability estimates at the upper end of the range previously described for social behaviours, with important variation across sexes. The results from both Pool-seq and RNA-seq data indicated that genes involved in neuron migration and synaptic function were instrumental in the evolution of sociability, highlighting a crucial role of glutamatergic synaptic function and calcium-dependent signalling processes in the evolution of schooling.

A rapid and sensitive High-Performance Liquid Chromatography method with fluorescence detection for quantification of melatonin in small volume rat plasma samples: application to a preclinical study to determine the oral pharmacokinetics of melatonin under gestational conditions

Abstract A novel, simple and sensitive high-performance liquid chromatography with fluorescence detection method was developed and validated for the characterization of the preclinical pharmacokinetics of melatonin under pregnant conditions. Plasma samples (25 µL) were treated with 30 µL of ethanol absolute (containing the internal standard, IS). After a centrifugation process, aliquots of supernant (5 µL) were injected into the chromatographic system. Compounds were eluted on a Xbridge C18 (150 mm x 4.6 mm i.d., 5 µm particle size) maintained at 30°C. The mobile phase consisted in a mixture of aqueous solution of 0.4% phosphoric acid and acetonitrile (70:30 v/v). The wavelengths were set at 305 nm (excitation) and 408 nm (emission) and the total analysis time was 8 min/sample. All validation tests were obtained with accuracy and precision, according to FDA guidelines, over the concentration range of 0.005-20 µg/mL. Pharmacokinetic study showed that melatonin systemic exposure increased from day 14, with a significant difference at 19 days of gestation compared to the control group. Our findings suggest a decreased metabolism of melatonin as result of temporary physiological changes that occur throughout pregnancy. However, other maternal physiological changes cannot be ruled out.

Bladder Cancer and Probiotics: What Do We Know So Far?

Bladder cancer is around the 10th most diagnosed cancer, although has a considerable mortality. Recent research and new methodologies have discarded the historical dogma that the bladder (and urine) was sterile under normal conditions. Specifically, only a few studies have reported a detailed analysis of the urinary microbiota in patients with bladder cancer, thus exhibiting a remarkable variability due to the low biomass of the urinary microbiota and the influence of many factors. Nevertheless, this research shows us signals that urinary microbiota is a factor to be considered in the pathophysiology of bladder cancer. More importantly, probiotics could be useful as an adjuvant therapy to reduce the recurrence rate or increase the disease-free period after surgery. In vitro studies and animal assays have shown promising results, but the research in this context has also been scarce, and only a few studies have been conducted in humans. In summary, there is little evidence of the possible beneficial effect of probiotics in controlling the overgrowth of genera that could be involved in the carcinogenesis of bladder cancer. This narrative review aims to compile all the evidence to date on the therapeutic potential of probiotics injected directly into the bladder or orally administered.

Tetrazole derivatives as potent immunomodulatory agents in tumor microenvironment.

Twenty-seven compounds bearing a tetrazole ring as a central unit have been designed, synthetized and biologically evaluated. Studies have been performed in order to compare the effect of tetrazole derivatives bearing amine electron-donor or nitro electron-acceptor groups. The antiproliferative activity has been determined in monoculture studies on tumor cell lines HT-29, A-549, MCF-7 and on non-tumor cell line HEK-293 as well as in co-culture studies (HT-29/THP-1). All the compounds have been studied as PD-L1 (Programmed Death Ligand 1), VEGFR-2 (Vascular Endothelial Growth Factor 2), CD-47 (Cluster of Differentiation 47) and c-Myc inhibitors. The effect on TNF-α secretion has also been determined. Bromoderivatives 23, 24 and chloroderivatives 26, 27 have demonstrated an apoptotic effect on HT-29 cancer cells. Compounds bearing an amine group have shown very promising effects as TME immunomodulatory agents.

Aryl azoles based scaffolds for disrupting tumor microenvironment.

Thirty-nine aryl azoles, thirteen triazoles and twenty-seven tetrazoles, have been synthetized and biologically evaluated to determine their activity as tumor microenvironment disruptors. Antiproliferative studies have been performed on tumor cell lines HT-29, A-549 and MCF-7 and on non-tumor cell line HEK-293. It has been studied in HT-29 the expression levels of biological targets which are involved in tumor microenvironment processes, such as PD-L1, CD-47, c-Myc and VEGFR-2. In addition, antiproliferative activity was evaluated when HT-29 were co-cultured with THP-1 monocytes and the secretion levels of IL-6 were also determined in these co-cultures. The angiogenesis effect of some selected compounds on HMEC-1 was also evaluated as well as their action against vasculogenic mimicry on HEK-293. Compounds bearing an amino group in the phenyl ring and a halogen atom in the benzyl ring showed promising results as tumor microenvironment disrupting agents. The most outstanding compound decrease dramatically the population of HT-29 cells when co-cultured with THP-1 monocytes and the levels of IL-6 secreted, as well as it showed moderate effects over PD-L1, CD-47 and c-Myc.

Doble revisión de colon derecho vs revisión simple durante lacolonoscopia para la detección de pólipos y adenomas de colon: revisión sistemática de la literatura

El tamizaje por colonoscopia es un método efectivo para prevenir cáncer de colon a traves de la detección de pólipos sobre los cuales se desarrolla en un mayor porcentaje el cáncer de colon; sin embargo la detección de estas lesiones varía en los diferentes segmentos del colon y de ellos en colon derecho su tasa detección suele ser menor. Objetivo: El objetivo de este estudio es evaluar si la doble revisión endoscópica de colon derecho durante la colonoscopia es un mecanismo para mejorar su rendimiento en cuanto a la tasa de detección de pólipos (TDP) y la tasa de detección de adenomas (TDA). Materiales y métodos: Revisión sistemática y metaanálisis de la literatura de estudios clínicos aleatorizados que realizaron una doble revisión del colon derecho por colonoscopia comparado con una revisión simple para mejorar la detección de pólipos y adenomas. El protocolo de esta revisión se publicó en PROSPERO bajo el código CRD42022356509. Resultados: Se incluyeron 5 estudios que incluyeron 2729 participantes. Se informó la detección de pólipos en 585/1197 pacientes (48,87%) después de la segunda revisión, en comparación con 537/1206 (44,52%) de los pacientes que recibieron una única examinación (p < 0,05), para un RR combinado de 1,09 (IC 95%: 0,97-1,23) (I2 fue de 44%). Se informó la detección de adenomas en 830/1513 pacientes (54,75%) después de la segunda revisión, en comparación con 779/1509 (51,62%) de los pacientes que recibieron una única examinación (p < 0,05), para un RR combinado de 1,06 (IC 95%: 1,00-1,13) (I2 fue de 0%). Conclusión: La segunda examinación del colon derecho por colonoscopia puede tener una modesta mejoría en la detección de pólipos y adenomas.

Colonoscopy screening is an effective method to prevent colon cancer through the detection of polyps on which colon cancer develops in a higher percentage; however, the detection of these lesions varies in the different segments of the colon and the detection rate of them in the right colon is usually lower. Objective: The objective of this study is to evaluate whether double endoscopic revision of the right colon during colonoscopy is a mechanism to improve its performance in terms of polyp detection rate (TDP) and adenoma detection rate (ADR). Materials and methods: Systematic review and meta-analysis of the literature including randomized clinical trials that evaluated repeat right-sight examination by colonoscopy compared to standard view to improve detection of polyps and adenomas. The protocol for this decision was published in PROSPERO under the code CRD42022356509. Results: Five studies involving 2729 participants were included. Polyp detection was reported in 585/1197 patients (48.87%) after the second review, compared with 537/1206 (44.52%) of patients who received a single examination (p< 0.05), for a combined RR of 1.09 (95% CI: 0.97-1.23) (I2 was 44%). Detection of adenomas was reported in 830/1513 patients (54.75%) after the second review, compared with 779/1509 (51.62%) of patients who received a single examination (p < 0.05), for a combined RR of 1.06 (95% CI: 1.00-1.13) (I2 was 0%). Conclusion: Second examination of the right colon by colonoscopy may have a modest improvement in the detection of polyps and adenomas.

Evolution of schooling drives changes in neuroanatomy and motion characteristics across predation contexts in guppies.

One of the most spectacular displays of social behavior is the synchronized movements that many animal groups perform to travel, forage and escape from predators. However, elucidating the neural mechanisms underlying the evolution of collective behaviors, as well as their fitness effects, remains challenging. Here, we study collective motion patterns with and without predation threat and predator inspection behavior in guppies experimentally selected for divergence in polarization, an important ecological driver of coordinated movement in fish. We find that groups from artificially selected lines remain more polarized than control groups in the presence of a threat. Neuroanatomical measurements of polarization-selected individuals indicate changes in brain regions previously suggested to be important regulators of perception, fear and attention, and motor response. Additional visual acuity and temporal resolution tests performed in polarization-selected and control individuals indicate that observed differences in predator inspection and schooling behavior should not be attributable to changes in visual perception, but rather are more likely the result of the more efficient relay of sensory input in the brain of polarization-selected fish. Our findings highlight that brain morphology may play a fundamental role in the evolution of coordinated movement and anti-predator behavior.

Optimization of Enterotoxigenic Escherichia coli (ETEC) Outer Membrane Vesicles Production and Isolation Method for Vaccination Purposes.

The study addresses Enterotoxigenic Escherichia coli (ETEC), a significant concern in low-income countries. Despite its prevalence, there is no licensed vaccine against ETEC. Bacterial vesicle-based vaccines are promising due to their safety and diverse virulence factors. However, cost-effective production requires enhancing vesicle yield while considering altered properties due to isolation methods. The proposed method involves heat treatment and ultrafiltration to recover vesicles from bacterial cultures. Two vesicle types, collected from heat-treated (HT-OMV) or untreated (NT-OMV) cultures, were compared. Vesicles were isolated via ultrafiltration alone ("complete") or with ultracentrifugation ("sediment"). Preliminary findings suggest complete HT-OMV vesicles are suitable for an ETEC vaccine. They express important proteins (OmpA, OmpX, OmpW) and virulence factors (adhesin TibA). Sized optimally (50-200 nm) for mucosal vaccination, they activate macrophages, inducing marker expression (CD40, MHCII, CD80, CD86) and Th1/Th2 cytokine release (IL-6, MCP-1, TNF-α, IL12p70, IL-10). This study confirms non-toxicity in RAW 264.7 cells and the in vivo ability of complete HT-OMV to generate significant IgG2a/IgG1 serum antibodies. Results suggest promise for a cost-effective ETEC vaccine, requiring further research on in vivo toxicity, pathogen-specific antibody detection, and protective efficacy.

Gold nanorods derivatized with CTAB and hydroquinone or ascorbic acid: spectroscopic investigation of anisotropic nanoparticles of different shapes and sizes.

Gold nanorods stabilized by binary ligand mixtures of cetyltrimethylammonium bromide (CTAB, primary ligand) and ascorbic acid or hydroquinone were investigated by complementary synchrotron radiation-induced spectroscopies and microscopies, with the aim to find evidence of the influence of the secondary ligand molecular and chemical structure on the nanorod shapes and size ratios. Indeed, as it is well known that the CTAB interaction with Ag(i) ions at the NR surface plays a key role in directing the anisotropic growth of nanorods, the possibility to finely control the NR shape and dimension by opportunely selecting the secondary ligands opens new perspectives in the design and synthesis of anisotropic nanoparticles.

Use of Tenecteplase in Acute Ischemic Stroke in the Time of SARS-CoV-2.

Tenecteplase (TNK) is a fibrinolytic drug that is administrated in a single bolus, recommended in eligible patients with acute ischemic stroke prior to mechanical thrombectomy. This study explores its usefulness in adverse situations, such as the SARS-CoV-2 pandemic. We conducted a retrospective study involving consecutive patients with suspected acute ischemic stroke treated either with intravenous fibrinolysis with alteplase during 2019 or with TNK (.25 mg/kg) between March 2020 and February 2021. A comparative analysis was made to compare patient treatment times and prognosis. A total of 117 patients treated with alteplase and 92 with TNK were included. No significant differences were observed in age, main vascular risk factors or previous treatments. The median National Institutes of Health Stroke Scale was 8 in the alteplase group and 10 in those treated with TNK (P = .13). Combined treatment with mechanical thrombectomy was performed in 47% in the alteplase group and 46.7% in the TNK group; Thrombolysis In Cerebral Infarction scale 2b-3 recanalization was achieved in 83% and 90.7%, respectively (P = .30). There was a decrease in onset-to-needle median time (165 min vs 140 min, P < .01) and no significant variations in door-needle median time. There was no significant difference in the incidence of symptomatic hemorrhagic transformation in mortality or functional independence at 3 months. The easier administration of TNK has improved the accessibility of fibrinolytic therapy, even in adverse circumstances, such as the COVID-19 pandemic. Its use appears to be safe and effective, even in patients who are not candidates for mechanical thrombectomy.