Twilight length alters growth and flowering time in Arabidopsis via LHY/CCA1.

Decades of research have uncovered how plants respond to two environmental variables that change across latitudes and over seasons: photoperiod and temperature. However, a third such variable, twilight length, has so far gone unstudied. Here, using controlled growth setups, we show that the duration of twilight affects growth and flowering time via the LHY/CCA1 clock genes in the model plant Arabidopsis. Using a series of progressively truncated no-twilight photoperiods, we also found that plants are more sensitive to twilight length compared to equivalent changes in solely photoperiods. Transcriptome and proteome analyses showed that twilight length affects reactive oxygen species metabolism, photosynthesis, and carbon metabolism. Genetic analyses suggested a twilight sensing pathway from the photoreceptors PHY E, PHY B, PHY D, and CRY2 through LHY/CCA1 to flowering modulation through the GI-FT pathway. Overall, our findings call for more nuanced models of day-length perception in plants and posit that twilight is an important determinant of plant growth and development.

Natural Hydrogels Support Kidney Organoid Generation and Promote In Vitro Angiogenesis.

To date, strategies aiming to modulate cell to extracellular matrix (ECM) interactions during organoid derivation remain largely unexplored. Here renal decellularized ECM (dECM) hydrogels are fabricated from porcine and human renal cortex as biomaterials to enrich cell-to-ECM crosstalk during the onset of kidney organoid differentiation from human pluripotent stem cells (hPSCs). Renal dECM-derived hydrogels are used in combination with hPSC-derived renal progenitor cells to define new approaches for 2D and 3D kidney organoid differentiation, demonstrating that in the presence of these biomaterials the resulting kidney organoids exhibit renal differentiation features and the formation of an endogenous vascular component. Based on these observations, a new method to produce kidney organoids with vascular-like structures is achieved through the assembly of hPSC-derived endothelial-like organoids with kidney organoids in 3D. Major readouts of kidney differentiation and renal cell morphology are assessed exploiting these culture platforms as new models of nephrogenesis. Overall, this work shows that exploiting cell-to-ECM interactions during the onset of kidney differentiation from hPSCs facilitates and optimizes current approaches for kidney organoid derivation thereby increasing the utility of these unique cell culture platforms for personalized medicine.

Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress.

Any deviation from the programmed processes of brain development may modify its formation and functions, thereby precipitating pathological conditions, which often become manifest in adulthood. Exposure to a challenge during crucial periods of vulnerability, such as adolescence, may reveal molecular changes preceding behavioral outcomes. Based on a previous study showing that prenatal fluoxetine (FLX) leads to the development of an anhedonic-like behavior in adult rats, we aimed to assess whether the same treatment regimen (i.e., fluoxetine during gestation; 15 mg/kg/day) influences the ability to respond to acute restraint stress (ARS) during adolescence. We subjected the rats to a battery of behavioral tests evaluating the development of various phenotypes (cognitive deficit, anhedonia, and anxiety). Furthermore, we carried out molecular analyses in the plasma and prefrontal cortex, a brain region involved in stress response, and whose functions are commonly altered in neuropsychiatric conditions. Our findings confirm that prenatal manipulation did not affect behavior in adolescent rats but impaired the capability to respond properly to ARS. Indeed, we observed changes in several molecular key players of the hypothalamic pituitary adrenal axis, particularly influencing genomic effects mediated by the glucocorticoid receptor. This study highlights that prenatal FLX exposure influences the ability of adolescent male rats to respond to an acute challenge, thereby altering the functionality of the hypothalamic-pituitary-adrenal axis, and indicates that the prenatal manipulation may prime the response to challenging events during this critical period of life.

Indole-3-Propionic Acid, a Gut Microbiota-Derived Tryptophan Metabolite, Promotes Endothelial Dysfunction Impairing Purinergic-Induced Nitric Oxide Release in Endothelial Cells.

Different gut microbiota-derived metabolites influence cardiovascular function, and, among all, the role of indole-3-propionic acid (IPA), from tryptophan metabolism, shows controversial effects. The aim of this study was to evaluate its role in endothelial dysfunction. IPA effects were studied on bovine aortic endothelial cells (BAE-1). First, IPA cytotoxicity was evaluated by an MTS assay. Then, the levels of intracellular reactive oxygen species (ROS) were evaluated by a microplate reader or fluorescence microscopy with the CellROX® Green probe, and nitric oxide (NO) production was studied by fluorescence microscopy with the DAR4M-AM probe after acute or chronic treatment. Finally, immunoblotting analysis for endothelial nitric oxide synthase (eNOS) phosphorylation (p-eNOS) was performed. In BAE-1, IPA was not cytotoxic, except for the highest concentration (5 mM) after 48 h of treatment, and it showed neither oxidant nor antioxidant activity. However, the physiological concentration of IPA (1 µM) significantly reduced NO released by adenosine triphosphate (ATP)-stimulated BAE-1. These last data were confirmed by Western blot analysis, where IPA induced a significant reduction in p-eNOS in purinergic-stimulated BAE-1. Given these data, we can speculate that IPA negatively affects the physiological control of vascular tone by impairing the endothelial NO release induced by purinergic stimulation. These results represent a starting point for understanding the mechanisms underlying the relationship between gut microbiota metabolites and cardiometabolic health.

The ERUS course on robot-assisted kidney transplantation.

PURPOSE: Robot-assisted kidney transplantation (RAKT) is being increasingly performed at selected referral institutions worldwide. Yet, surgical training in RAKT is still unstructured and not grounded into formal credentialing courses including simulation, lab facilities, and modular training with animal models. As such, developing standardized, modular training programs is warranted to provide surgeons with the RAKT-specific skillset needed for a "safe" learning curve. METHODS: The 3-day course on RAKT developed at the EAU Skills Center in Orsi Academy was designed as a standardized, modular, step-by-step approach aiming to provide theoretical and practical skills. The course is held by expert proctors with extensive experience in RAKT. To maximize the course's usefulness, a solid knowledge of robotics and transplantation is desirable for participants. RESULTS: From January 2016 to July 2023, 87 surgeons from 23 countries (of which 36% from extra-European countries) participated in the RAKT course performed at the EAU Skills Center in Orsi Academy. Of these, 58/87 (67%) were urologists, while 27/87 (31%) were general surgeons and 2/87 (2%) were vascular surgeons. To date, 18 participants (20.6%) are actively involved in RAKT programs at institutions included in the European Association of Urology (EAU) Robotic Urology Section (ERUS)-RAKT network. CONCLUSION: Leveraging the potential of simulation, wet-lab training, live porcine models, and experienced proctors, the RAKT course performed at the EAU Skills Center in Orsi Academy represents the first structured teaching effort aiming to offer surgeons a full immersion in RAKT to train the core technical skills.

Validity of Partner Reports of Recent Condomless Sex.

BACKGROUND: Prostate-specific antigen (PSA), a biomarker of vaginal semen exposure, is less susceptible to bias than self-reported condom use behaviors. We examined the agreement of self-reported recent condomless sex (RCS) within couples and how these reports related to PSA detection. METHODS: We analyzed data from a study conducted in Vietnam, 2017 to 2020, of 500 different-sex couples using condoms and no other contraceptive method to prevent pregnancy for 6 months. We assessed enrollment and 6-month data from vaginal swabs and questionnaires from both partners. We calculated Prevalence-Adjusted Bias-Adjusted Kappa (PABAK) to evaluate agreement of men's and women's reports. Among couples with detected PSA, we assessed partner concordance of RCS reporting. RESULTS: At enrollment (n = 499), 79.8% of couples reported no RCS, 16.4% reported RCS, and 3.8% had partner-discordant reports (PABAK, 0.93; 95% confidence interval, 0.91-0.97). At 6 months (n = 472), 91.7% reported no RCS, 5.7% reported RCS, and 2.5% had partner-discordant reports (PABAK, 0.98; 95% confidence interval, 0.96-1.0). Among couples with detected PSA at baseline (11%, n = 55), 36% reported no RCS, 55% reported RCS, and 6% had discordant reports; at 6 months (6.6%, n = 31), 58% reported no RCS, 35% reported RCS, and 3% had discordant reports. CONCLUSIONS: We observed high agreement regarding condomless sex within couples in a population using condoms as contraception in Vietnam; however, a high proportion of couples with detected PSA had both partners reporting no RCS, indicating that concordant reporting of no RCS does not indicate lack of semen exposure.

Prevalence and correlates of very rapid repeat pregnancy: Pregnancy Risk Assessment Monitoring System, United States, 2009-2020.

BACKGROUND: Most rapid repeat pregnancies, defined as those occurring within 18 months of a previous birth, are unintended. These pregnancies are associated with later initiation of prenatal care and are more common among people with lower socio-economic status and among racially and ethnically minoritised populations. OBJECTIVES: To assess prevalence and correlate pregnancies occurring in the immediate period after a live birth in the United States, using the Pregnancy Risk Assessment Monitoring System (PRAMS). METHODS: We assessed data from the 2009-2020 PRAMS, a population-based survey of perinatal maternal characteristics of mothers of liveborn infants in US locations. We assessed pregnancies reported during the immediate postpartum period (approximately 2-6 months post-delivery), and term this 'very rapid repeat pregnancy' (VRRP). We assessed the adjusted prevalence of VRRP from 2009 to 2020. From 2016 to 2020, we calculated adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) for maternal characteristics. RESULTS: The adjusted prevalence of VRRP ranged from 0.38% (95% CI: 0.29, 0.48) in 2009 to 0.76% (95% CI: 0.61, 0.91) in 2020. Demographic characteristics associated with VRRP included younger age, lower educational attainment, and being unmarried. Black mothers had a higher prevalence of VRRP compared to white mothers. Mothers who attended a healthcare visit in the 12 months preconception had a lower prevalence of VRRP as did mothers who attended a postpartum check-up, compared to their counterparts without these visits. Among those receiving prenatal care, mothers whose prenatal healthcare provider asked about postpartum contraception birth had a lower prevalence of VRRP, compared to those not asked about postpartum contraception. CONCLUSIONS: VRRP appeared to increase over time in 2009-2020. Mothers who are younger, Black, have lower educational attainment, or who did not attend healthcare visits before or after pregnancy had a higher prevalence of VRRP and may comprise a population who would benefit from additional family planning resources.

Prevalence of lower urinary tract symptoms in taxi drivers: a cross-sectional web-based survey.

PURPOSE: Aim of the study was to evaluate the prevalence of LUTS in taxi drivers. METHODS: Between February 24th 2021 and March 26th 2021 a web based survey was administered to Taxi drivers in the city of Florence. Taxi drivers were evaluated with baseline characteristics such as: age, BMI, smoking, career length, comorbidities, and treatment. LUTS were evaluated using the international prostate symptom score (IPSS) and the overactive bladder (OAB) score. As well sexual function was evaluated using the international index erectile function (IIEF) and female sexual function index (FSFI) questionnaires. Risk factors for LUTS were evaluated using regression analysis. RESULTS: The overall response rate was 64.6% (537/830 taxi drivers filled the questionnaires). Among them, 449 (83.6%) were men and 88 (16.4%) females. Overall, median IPSS was 5 (2/9) and median OAB score was 10 (7/14). On multivariate binary regression analysis age > 50 (OR:1.60; p < 0,05), Smoking (OR:1.57; p < 0,05), chronic treatment (OR:1.57; p < 0,05), recurrent cystitis (OR: 2.66; p < 0,05) and chronic pelvic pain (OR:4.94; p < 0,05) were independent risk factors for moderate/severe LUTS. On multivariate binary logistic regression analysis, risk factors for erectile dysfunction were age older than 50 years (OR = 3.64; p < 0.05) and urinary incontinence (OR = 5.53; p = 0.005). CONCLUSIONS: According to our web-based survey, Taxi drivers in the metropolitan city of Florence had non-negligible symptomatic LUTS and even sexual dysfunction. Our data suggest as LUTS are particular influenced by several life-style and behavioural factors as type and duration of work.

Morbidity of Transrectal MRI-Fusion Targeted Prostate Biopsy at a Tertiary Referral Academic Centre: An Audit to Guide the Transition to the Transperineal Approach.

Despite transrectal prostate biopsy (TRPB) being still widespread globally, the EAU Guidelines strongly recommend the transperineal approach, due to the reported lower infectious risk. Our study aims to evaluate the impact of a standardized clinical pathway for TRPB on post-operative complications. We prospectively collected data from all patients undergoing mpMRI-targeted TRPB at our Academic Centre from January 2020 to December 2022. All patients followed a standardized, structured multistep pathway. Post-procedural complications were collected and classified according to the Clavien-Dindo (CD) Classification. Among 458 patients, post-procedural adverse events were reported by 203 (44.3%), of which 161 (35.2%) experienced CD grade 1 complications (hematuria [124, 27.1%], hematochezia [22, 4.8%], hematospermia [14, 3.1%], or a combination [20, 4.4%]), and 45 (9.0%) reported CD grade 2 complications (acute urinary retention or hematuria needing catheterization, as well as urinary tract infections, of which 2 cases required hospitalization). No major complications, including sepsis, were observed. At uni- and multivariable analysis, age > 70 years and BMI > 25 kg/ m2 for patients were identified as predictors of post-operative complications. The results of our study confirm that TRPB is a safe and cost-effective procedure with a low risk of severe adverse events in experienced hands and following a standardized pathway.

Human N-acetyltransferase 2 (NAT2) gene variability in Brazilian populations from different geographical areas.

Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 (NAT2) gene and the predominant genotype-deduced acetylation profiles of Brazilians. Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon. Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G>A, c.282C>T, c.341T>C, c.481C>T, c.590G>A, c.803A>G and c.857G>A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states (p < 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast (p = 0.0396). The Southern region was significantly different from all other regions (p < 0.0001). Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions.

Phosphorylation mediated regulation of RNA splicing in plants.

For the past two decades, the study of alternative splicing (AS) and its involvement in plant development and stress response has grown in popularity. Only recently however, has the focus shifted to the study of how AS regulation (or lack-thereof) affects downstream mRNA and protein landscapes and how these AS regulatory events impact plant development and stress tolerance. In humans, protein phosphorylation represents one of the predominant mechanisms by which AS is regulated and thus the protein kinases governing these phosphorylation events are of interest for further study. Large-scale phosphoproteomic studies in plants have consistently found that RNA splicing-related proteins are extensively phosphorylated, however, the signaling pathways involved in AS regulation have not been resolved. In this mini-review, we summarize our current knowledge of the three major splicing-related protein kinase families in plants that are suggested to mediate AS phospho-regulation and draw comparisons to their metazoan orthologs. We also summarize and contextualize the phosphorylation events identified as occurring on splicing-related protein families to illustrate the high degree to which splicing-related proteins are modified, placing a new focus on elucidating the impacts of AS at the protein and PTM-level.

Redo Partial Nephrectomy for Local Recurrence After Previous Nephron-sparing Surgery. Surgical Insights and Oncologic Results from a High-volume Robotic Center.

Background: The role of redo partial nephrectomy (PN) for recurrent renal cell carcinoma (RCC) is still overlooked. Objective: To report our experience of salvage PN for local recurrence after previous nephron-sparing surgery (NSS). Design setting and participants: We prospectively gathered data from patients treated with robotic redo PN for locally recurrent RCC after previous NSS from January 2017 to January 2023. The type of surgical resection technique was assigned to the pathologic specimen according to the surface-intermediate-base (SIB) score. Surgical procedure: Redo PN was performed by using the Si Da Vinci robotic platform. Measurements: Operative time, warm ischemia time, and intra- and postoperative complications were recorded. The severity of postoperative complications and tumor stage were evaluated. Results and limitations: Overall, 26 patients entered the study. The median clinical diameter was 3.5 (interquartile range [IQR] 2.2-4.9) cm and the median Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score was 8 (IQR 7-9). In 14 (53.8%) cases, recurrence was at the level of previous tumor resection bed. The median operative time was 177 (IQR 148-200) min, and hilar clamping was performed in 14 (53.8%) cases with a median warm ischemia time of 16 (14.5-22) min. Pure enucleation (SIB score 0-1), hybrid enucleation (SIB score 2), and pure enucleoresection (SIB score 3) were recorded in 13 (50%), eight (30.8%), and five (19.2%) cases, respectively. The totality of recurrent RCC far from previous tumor resection bed received a SIB score of 0-1, while in 57.1% and 35.8% of recurrent RCC on previous tumor resection a hybrid enucleation and a pure enucleoresection were performed, respectively. At a median follow-up of 37 (IQR 16-45) mo, five (19%) patients experienced disease recurrence, being local and systemic in three (11.5%) and two (7.7%) patients, respectively. Conclusions: Our study highlights the feasibility and safety of redo PN for the treatment of locally recurrent RCCs after NSS, either on previous tumor resection bed or elsewhere in the kidney. Patient summary: Robotic redo partial nephrectomy is a challenging procedure. The surgeon needs to tailor the surgical strategy and tumor resection technique case by case, given the heterogeneity of clinical scenarios and the need to achieve maximal functional preservation while ensuring oncologic efficacy.

Topoisomeric Membrane-Active Peptides: A Review of the Last Two Decades.

In recent decades, bioactive peptides have been gaining recognition in various biomedical areas, such as intracellular drug delivery (cell-penetrating peptides, CPPs) or anti-infective action (antimicrobial peptides, AMPs), closely associated to their distinct mode of interaction with biological membranes. Exploiting the interaction of membrane-active peptides with diverse targets (healthy, tumoral, bacterial or parasitic cell membranes) is opening encouraging prospects for peptides in therapeutics. However, ordinary peptides formed by L-amino acids are easily decomposed by proteases in biological fluids. One way to sidestep this limitation is to use topoisomers, namely versions of the peptide made up of D-amino acids in either canonic (enantio) or inverted (retroenantio) sequence. Rearranging peptide sequences in this fashion provides a certain degree of native structure mimicry that, in appropriate contexts, may deliver desirable biological activity while avoiding protease degradation. In this review, we will focus on recent accounts of membrane-active topoisomeric peptides with therapeutic applications as CPP drug delivery vectors, or as antimicrobial and anticancer candidates. We will also discuss the most common modes of interaction of these peptides with their membrane targets.

Perinatal serotonergic manipulation shapes anhedonic and cognitive behaviors in a sex- and age-dependent manner: Identification of related biological functions at central and peripheral level.

Poor knowledge about psychiatric disorders often results in similar diagnoses for patients with different symptoms, thus limiting the effectiveness of the available medications. As suggested by several lines of evidence, to improve these shortcomings, it is essential to identify biomarkers associated with specific symptoms and to stratify patients into more homogeneous populations taking a further step toward personalized medicine. Here, we aimed to associate specific behavioral phenotypes with specific molecular alterations by employing an animal model based on the pharmacological manipulation of the serotonergic system, which mimics a condition of vulnerability to develop psychiatric disorders. In particular, we treated female and male rats with fluoxetine (FLX 15 mg/kg dissolved in drinking water) during prenatal or early postnatal life, and we evaluated different pathological-like phenotypes (cognitive deficit, anhedonia, and anxiety) by exposing the rats to a battery of behavioral tests during adolescence and adulthood. In addition, we carried out molecular analyses on specific brain areas and in the blood. Our results showed that perinatal FLX administration determined age- and sex-dependent effects, with males being more sensitive to prenatal manipulation and manifesting anhedonic-like behavior and females to early postnatal exposure, exhibiting cognitive deficits and a less anxious phenotype. Furthermore, we identified, peripherally and centrally, biological functions altered by perinatal serotonin modulation regardless of the timing of exposure and sex, and other pathways specific for the pathological-like phenotypes. The results presented here provide new insights into potential biomarkers associated with specific behavioral phenotypes that may be useful for broadening knowledge about psychiatric conditions.

Venlafaxine's effect on resilience to stress is associated with a shift in the balance between glucose and fatty acid utilization.

Brain metabolism is a fundamental process involved in the proper development of the central nervous system and in the maintenance of the main higher functions in humans. As consequence, energy metabolism imbalance has been commonly associated to several mental disorders, including depression. Here, by employing a metabolomic approach, we aimed to establish if differences in energy metabolite concentration may underlie the vulnerability and resilience in an animal model of mood disorder named chronic mild stress (CMS) paradigm. In addition, we have investigated the possibility that modulation of metabolite concentration may represent a pharmacological target for depression by testing whether repeated treatment with the antidepressant venlafaxine may normalize the pathological phenotype by acting at metabolic level. The analyses were conducted in the ventral hippocampus (vHip) for its key role in the modulation of anhedonia, a core symptom of patients affected by depression. Interestingly, we showed that a shift from glycolysis to beta oxidation seems to be responsible for the vulnerability to chronic stress and that vHip metabolism contributes to the ability of the antidepressant venlafaxine to normalize the pathological phenotype, as shown by the reversal of the changes observed in specific metabolites. These findings may provide novel perspectives on metabolic changes that could serve as diagnostic markers and preventive strategies for the early detection and treatment of depression as well as for the identification of potential drug targets.

Improving endothelial health with food-derived H2S donors: an in vitro study with S-allyl cysteine and with a black-garlic extract enriched in sulfur-containing compounds.

A healthy vascular endothelium plays an essential role in modulating vascular tone by producing and releasing vasoactive factors such as nitric oxide (NO). Endothelial dysfunction (ED), the loss of the endothelium physiological functions, results in the inability to properly regulate vascular tone, leading to hypertension and other cardiovascular risk factors. Alongside NO, the gasotransmitter hydrogen sulfide (H2S) has emerged as a key molecule with vasodilatory and antioxidant activities. Since a reduction in H2S bioavailability is related to ED pathogenesis, natural H2S donors are very attractive. In particular, we focused on the sulfur-containing amino acid S-allyl cysteine (SAC), a bioactive metabolite, of which black garlic is particularly rich, with antioxidant activity and, among others, anti-diabetic and anti-hypertensive properties. In this study, we analyzed the protective effect of SAC against ED by evaluating reactive oxygen species level, H2S release, eNOS phosphorylation, and NO production (by fluorescence imaging and western blot analysis) in Bovine Aortic Endothelial cells (BAE-1). Furthermore, we chemically characterized a Black Garlic Extract (BGE) for its content in SAC and other sulfur-containing amino acids. BGE was used to carry out an analysis on H2S release on BAE-1 cells. Our results show that both SAC and BGE significantly increase H2S release. Moreover, SAC reduces ROS production and enhances eNOS phosphorylation and the consequent NO release in our cellular model. In this scenario, a natural extract enriched in SAC could represent a novel therapeutic approach to prevent the onset of ED-related diseases.

Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene Nr4a1 in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine.

Despite several antidepressant treatments being available in clinics, they are not effective in all patients. In recent years, N-acetylcysteine (NAC) has been explored as adjunctive therapy for many psychiatric disorders, including depression, for its antioxidant properties. Given the promising efficacy of this compound for the treatment of such pathologies, it is fundamental to investigate, at the preclinical level, the ability of the drug to act in the modulation of neuroplastic mechanisms in basal conditions and during challenging events in order to highlight the potential features of the drug useful for clinical efficacy. To this aim, adult male Wistar rats were treated with the antidepressant venlafaxine (VLX) (10 mg/kg) or NAC (300 mg/kg) for 21 days and then subjected to 1 h of acute restraint stress (ARS). We found that NAC enhanced the expression of several immediate early genes, markers of neuronal plasticity in the ventral and dorsal hippocampus, prefrontal cortex and amygdala, and in particular it mediated the acute-stress-induced upregulation of Nr4a1 expression more than VLX. These data suggested the ability of NAC to induce coping strategies to face external challenges, highlighting its potential for the improvement of neuroplastic mechanisms for the promotion of resilience, in particular via the modulation of Nr4a1.

Prevalence, Resistance Patterns and Biofilm Production Ability of Bacterial Uropathogens from Cases of Community-Acquired Urinary Tract Infections in South Italy.

Community-acquired urinary tract infections represent the most common infectious diseases in the community setting. Knowing the antibiotic resistance patterns of uropathogens is crucial for establishing empirical treatment. The aim of the current study is to determine the incidence of the causative agents of UTIs and their resistance profiles. Patients of all ages and both sexes were enrolled in the study, and admitted to San Ciro Diagnostic Center in Naples between January 2019 and Jun 2020. Bacterial identification and antibiotic susceptibility testing were carried out using Vitek 2 system. Among the 2741 urine samples, 1702 (62.1%) and 1309 (37.9%) were negative and positive for bacterial growth, respectively. Of 1309 patients with infection, 760 (73.1%) were females and 279 (26.9%) were males. The greatest number of positive cases were found in the in the elderly (>61 years). Regarding uropathogens, 1000 (96.2%) were Gram-negative while 39 (3.8%) were Gram-positive strains. The three most isolated pathogenic strains were Escherichia coli (72.2%), Klebsiella pneumoniae (12.4%), and Proteus mirabilis (9.0%). Strong biofilm formation ability was observed in about 30% of the tested isolates. The low resistance rates recorded against nitrofurantoin, fosfomycin, piperacillin-tazobactam, and gentamicin could suggest them as the most appropriate therapies for CA-UTIs.