Membranous urethral length is the single independent predictor of urinary continence recovery at 12 months following Retzius-sparing robot-assisted radical prostatectomy.

The influence of anatomical parameters on urinary continence (UC) after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) remains uncharted. Our objective was to evaluate their association with UC at 3, 6 and 12 months post-operatively. Data from patients who underwent RS-RARP were prospectively collected. Continence was defined as no pad use. Anatomic variables were measured on preoperative magnetic resonance imaging (MRI). Regression analyses were performed to identify predictors of UC at each time point. We included 158 patients with a median age of 60 years, most of whom had a localized tumor (≤ cT2). On multivariate analyses, at 3 months post-surgery, urinary incontinence (UI) rises with age, odds ratio (OR) 1.07 [95% confidence interval (CI) 1.004-1.142] and with prostate volume (PV), OR 1.029 (95% CI 1.006-1.052); it reduces with longer membranous urethral length (MUL), OR 0.875 (95% CI 0.780-0.983) and with higher membranous urethral volume (MUV), OR 0.299 (95% CI 0.121-0.737). At 6 months, UI rises with PV, OR 1.033 (95% CI 1.011-1.056) and decreases with MUV, OR 0.1504 (95% CI 0.050-0.444). Significantly, at 12 months post-surgery, the only predictor of UI is MUL, OR 0.830 (95% CI 0.706-0.975), establishing a threshold associated with a risk of UI of 5% (MUL > 15 mm) in opposition to a risk of 25% (MUL < 10 mm). This single institutional study requires external validation. To our knowledge, this is the first prospective cohort study supporting MUL as the single independent predictor of UC at 12 months post-surgery. By establishing MUL thresholds, we enable precise patient counseling.

Extracellular acidification reveals the antiarrhythmic properties of amiodarone related to late sodium current-induced atrial arrhythmia.

BACKGROUND: Amiodarone (AMIO) is an antiarrhythmic drug with the pKa in the physiological range. Here, we explored how mild extracellular pH (pHe) changes shape the interaction of AMIO with atrial tissue and impact its pharmacological properties in the classical model of sea anemone sodium channel neurotoxin type 2 (ATX) induced late sodium current (INa-Late) and arrhythmias. METHOD: Isolated atrial cardiomyocytes from male Wistar rats and human embryonic kidney cells expressing SCN5A Na+ channels were used for patch-clamp experiments. Isolated right atria (RA) and left atria (LA) tissue were used for bath organ experiments. RESULTS: A more acidophilic pHe caused negative inotropic effects on isolated RA and LA atrial tissue, without modification of the pharmacological properties of AMIO. A pHe of 7.0 changed the sodium current (INa) related components of the action potential (AP), which was enhanced in the presence of AMIO. ATXinduced arrhythmias in isolated RA and LA. Also, ATX prolonged the AP duration and enhanced repolarization dispersion in isolated cardiomyocytes in both pHe 7.4 and pHe 7.0. Pre-incubation of the isolated RA and LA and isolated atrial cardiomyocytes with AMIO prevented arrhythmias induced by ATX only at a pHe of 7.0. Moreover, AMIO was able to block INa-Late induced by ATX only at a pHe of 7.0. CONCLUSION: The pharmacological properties of AMIO concerning healthy rat atrial tissue are not dependent on pHe. However, the prevention of arrhythmias induced by INa-Late is pHe-dependent. The development of drugs analogous to AMIO with charge stabilization may help to create more effective drugs to treat arrhythmias related to the INa-Late.

Effect of Far-Red Light on Biomass Accumulation, Plant Morphology, and Phytonutrient Composition of Ruby Streaks Mustard at Microgreen, Baby Leaf, and Flowering Stages.

Far-red (FR) light influences plant development significantly through shade avoidance response and photosynthetic modulation, but there is limited knowledge on how FR treatments influence the growth and nutrition of vegetables at different maturity stages in controlled environment agriculture (CEA). Here, we comprehensively investigated the impacts of FR on the yield, morphology, and phytonutrients of ruby streaks mustard (RS) at microgreen, baby leaf, and flowering stages. Treatments including white control, white with supplementary FR, white followed by singularly applied FR, and enhanced white (WE) matching the extended daily light integral (eDLI) of FR were designed for separating the effects of light intensity and quality. Results showed that singular and supplemental FR affected plant development and nutrition similarly throughout the growth cycle, with light intensity and quality playing varying roles at different stages. Specifically, FR did not affect the fresh and dry weight of microgreens but increased those values for baby leaves, although not as effectively as WE. Meanwhile, FR caused significant morphological change and accelerated the development of leaves, flowers, and seedpods more dramatically than WE. With regard to phytonutrients, light treatments affected the metabolomic profiles for baby leaves more dramatically than microgreens and flowers. FR decreased the glucosinolate and anthocyanin contents in microgreens and baby leaves, while WE increased the contents of those compounds in baby leaves. This study illustrates the complex impacts of FR on RS and provides valuable information for selecting optimal lighting conditions in CEA.

Alzheimer's disease drug development pipeline: 2024.

INTRODUCTION: New therapies to prevent or delay the onset of symptoms, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed. METHODS: We interrogated clinicaltrials.gov including all clinical trials assessing pharmaceutical therapies for AD active in on January 1, 2024. We used the Common Alzheimer's Disease Research Ontology (CADRO) to classify the targets of therapies in the pipeline. RESULTS: There are 164 trials assessing 127 drugs across the 2024 AD pipeline. There were 48 trials in Phase 3 testing 32 drugs, 90 trials in Phase 2 assessing 81 drugs, and 26 trials in Phase 1 testing 25 agents. Of the 164 trials, 34% (N = 56) assess disease-modifying biological agents, 41% (N = 68) test disease-modifying small molecule drugs, 10% (N = 17) evaluate cognitive enhancing agents, and 14% (N = 23) test drugs for the treatment of neuropsychiatric symptoms. DISCUSSION: Compared to the 2023 pipeline, there are fewer trials (164 vs. 187), fewer drugs (127 vs. 141), fewer new chemical entities (88 vs. 101), and a similar number of repurposed agents (39 vs. 40). Highlights: In the 2024 Alzheimer's disease drug development pipeline, there are 164 clinical trials assessing 127 drugs.The 2024 Alzheimer's disease drug development pipeline has contracted compared to the 2023 Alzheimer pipeline with fewer trials, fewer drugs, and fewer new chemical entities.Drugs in the Alzheimer's disease drug development pipeline target a wide array of targets; the most common processes targeted include neurotransmitter receptors, inflammation, amyloid, and synaptic plasticity.The total development time for a potential Alzheimer's disease therapy to progress from nonclinical studies to FDA review is approximately 13 years.

Differential microbiota shift on whole romaine lettuce subjected to source or forward processing and on fresh-cut products during cold storage.

Romaine lettuce in the U.S. is primarily grown in California or Arizona and either processed near the growing regions (source processing) or transported long distance for processing in facilities serving distant markets (forward processing). Recurring outbreaks of Escherichia coli O157:H7 implicating romaine lettuce in recent years, which sometimes exhibited patterns of case clustering in Northeast and Midwest, have raised industry concerns over the potential impact of forward processing on romaine lettuce food safety and quality. In this study, freshly harvested romaine lettuce from a commercial field destined for both forward and source processing channels was tracked from farm to processing facility in two separate trials. Whole-head romaine lettuce and packaged fresh-cut products were collected from both forward and source facilities for microbiological and product quality analyses. High-throughput amplicon sequencing targeting16S rRNA gene was performed to describe shifts in lettuce microbiota. Total aerobic bacteria and coliform counts on whole-head lettuce and on fresh-cut lettuce at different storage times were significantly (p < 0.05) higher for those from the forward processing facility than those from the source processing facility. Microbiota on whole-head lettuce and on fresh-cut lettuce showed differential shifting after lettuce being subjected to source or forward processing, and after product storage. Consistent with the length of pre-processing delays between harvest and processing, the lettuce quality scores of source-processed romaine lettuce, especially at late stages of 2-week storage, was significantly higher than of forward-processed product (p < 0.05).

In vivo tebuconazole administration impairs heart electrical function and facilitates the occurrence of dobutamine-induced arrhythmias: involvement of reactive oxygen species.

Tebuconazole (TEB), a widely used pesticide in agriculture to combat fungal infections, is commonly detected in global food, potable water, groundwater, and human urine samples. Despite its known in vivo toxicity, its impact on heart function remains unclear. In a 28-day study on male Wistar rats (approximately 100 g), administering 10 mg/kg/day TEB or a vehicle (control) revealed no effect on body weight gain or heart weight, but an increase in the infarct area in TEB-treated animals. Notably, TEB induced time-dependent changes in in vivo electrocardiograms, particularly prolonging the QT interval after 28 days of administration. Isolated left ventricular cardiomyocytes exposed to TEB exhibited lengthened action potentials and reduced transient outward potassium current. TEB also increased reactive oxygen species (ROS) production in these cardiomyocytes, a phenomenon reversed by N-acetylcysteine (NAC). Furthermore, TEB-treated animals, when subjected to an in vivo dobutamine (Dob) and caffeine (Caf) challenge, displayed heightened susceptibility to severe arrhythmias, a phenotype prevented by NAC. In conclusion, TEB at the no observed adverse effect level (NOAEL) dose adversely affects heart electrical function, increases arrhythmic susceptibility, partially through ROS overproduction, and this phenotype is reversible by scavenging ROS with NAC.

Violência contra as mulheres no estado de Pernambuco ­ Brasil: perfil das agredidas e características das ocorrências notificadas entre 2015 e 2019

Objetivo: Descrever as características epidemiológicas das notificações das mulheres que sofreram violências, residentes em Pernambuco, no período 2014 a 2019. Métodos: Estudo epidemiológico, transversal, com dados das notificações do Sistema de Informação de Agravos de Notificação. Resultado: Identificamos 31.439 casos. Predominaram mulheres na faixa etária dos 10 a 29 anos (16.730), raça/cor parda (20.384). As solteiras foram as que mais sofreram violências (14.405). A zona urbana (26.005) foi a mais frequente. Quanto ao local de ocorrência, predominou a residência (19.013). No que diz respeito à natureza das violências, os maiores registros foram física (19.049), psicológica (9.609) e sexual (4.983). A força corporal/espancamento alcançou (13.662). Os parceiros íntimos foram os autores mais prováveis (9.964), frequentemente do sexo masculino (17.879). Conclusão: Por meio da notificação completa e adequada é possível conhecer o perfil da violência, identificar os fatores de risco e realizar um planejamento estratégico, tendo em vista a prevenção e assistência de qualidade às mulheres que sofrem violência.

A monster into the heart: an unusual presentation of cardiac leiomyosarcoma.

BACKGROUND: Malignant primary cardiac tumors are infrequent and can lead to an unfavorable prognosis if not identified and treated promptly. Early detection and prompt treatment of malignant primary cardiac tumors are crucial for a better prognosis. This article presents a case of primary cardiac leiomyosarcoma and reviews the literature on this topic. CASE PRESENTATION: Female patient that developed recurrent pericardial effusion and hemodynamic instability caused by a cardiac tumor, later identified as leiomyosarcoma. Multidisciplinary treatment was administered to the patient. CONCLUSIONS: The initial approach to this type of pathology should include multimodality imaging to establish a prompt diagnosis leading to complete standard treatment, to minimize risks to the patient's heart function which may include resection with complete margins of the neoplasm, otherwise the prognosis may be poor.

Mining the Penicillium expansum Genome for Virulence Genes: A Functional-Based Approach to Discover Novel Loci Mediating Blue Mold Decay of Apple Fruit.

Blue mold, a postharvest disease of pome fruits, is caused by the filamentous fungus Penicillium expansum. In addition to the economic losses caused by P. expansum, food safety can be compromised, as this pathogen is mycotoxigenic. In this study, forward and reverse genetic approaches were used to identify genes involved in blue mold infection in apple fruits. For this, we generated a random T-DNA insertional mutant library. A total of 448 transformants were generated and screened for the reduced decay phenotype on apples. Of these mutants, six (T-193, T-275, T-434, T-588, T-625, and T-711) were selected for continued studies and five unique genes were identified of interest. In addition, two deletion mutants (Δt-625 and Δt-588) and a knockdown strain (t-434KD) were generated for three loci. Data show that the ∆t-588 mutant phenocopied the T-DNA insertion mutant and had virulence penalties during apple fruit decay. We hypothesize that this locus encodes a glyoxalase due to bioinformatic predictions, thus contributing to reduced colony diameter when grown in methylglyoxal (MG). This work presents novel members of signaling networks and additional genetic factors that regulate fungal virulence in the blue mold fungus during apple fruit decay.

Avirulent Isolates of Penicillium chrysogenum to Control the Blue Mold of Apple Caused by P. expansum.

Blue mold is an economically significant postharvest disease of pome fruit that is primarily caused by Penicillium expansum. To manage this disease and sustain product quality, novel decay intervention strategies are needed that also maintain long-term efficacy. Biocontrol organisms and natural products are promising tools for managing postharvest diseases. Here, two Penicillium chrysogenum isolates, 404 and 413, were investigated as potential biocontrol agents against P. expansum in apple. Notably, 404 and 413 were non-pathogenic in apple, yet they grew vigorously in vitro when compared to the highly aggressive P. expansum R19 and Pe21 isolates. Whole-genome sequencing and species-specific barcoding identified both strains as P. chrysogenum. Each P. chrysogenum strain was inoculated in apple with the subsequent co-inoculation of R19 or Pe21 simultaneously, 3, or 7 days after prior inoculation with 404 or 413. The co-inoculation of these isolates showed reduced decay incidence and severity, with the most significant reduction from the longer establishment of P. chrysogenum. In vitro growth showed no antagonism between species, further suggesting competitive niche colonization as the mode of action for decay reduction. Both P. chrysogenum isolates had incomplete patulin gene clusters but tolerated patulin treatment. Finally, hygromycin resistance was observed for both P. chrysogenum isolates, yet they are not multiresistant to apple postharvest fungicides. Overall, we demonstrate the translative potential of P. chrysogenum to serve as an effective biocontrol agent against blue mold decay in apples, pending practical optimization and formulation.

Interaction of the antiarrhythmic drug Amiodarone with the sodium channel Nav1.5 depends on the extracellular pH.

INTRODUCTION: Amiodarone (AMD) is a clinically used drug to treat arrhythmias with significant effect upon the cardiac sodium channel Nav1.5. AMD has a pKa of 6.56, and changes in extracellular pH (pHe) may alter its pharmacological properties. Here we explored how changes in pHe impacts the pharmacological properties of AMD upon human-Nav1.5-sodium-current (INa) and in ex vivo rat hearts. METHODS: Embryonic-human-kidney-cells (HEK293) were used to transiently express the human alpha-subunit of NaV1.5 channels and the isolated heart of Wistar rats were used. Patch-Clamp technique was deployed to study INa and for electrocardiogram (ECG) evaluation the ex vivo heart preparation in the Langendorff system was applied. RESULTS: The potency of AMD upon peak INa was ∼25x higher in pHe 7.0 when compared to pHe 7.4. Voltage dependence for activation did not differ among all groups. AMD shifted the steady-state inactivation curve to more hyperpolarized potentials, with similar magnitudes for both pHes. The recovery from INa inactivation was delayed in the presence of AMD with similar profile in both pHes. Interestingly, the use-dependent properties of AMD was distinct at pHe 7.0 and 7.4. Finally, AMD was able to change the ex vivo ECG profile, however at pHe 7.0+AMD a larger increase in the RR and QRS duration and in the QT interval when compared to pHe 7.4 was found. CONCLUSIONS: The pharmacological properties of AMD upon NaV1.5 and isolated heart preparation depends on the pHe and its use in vivo during extracellular acidosis may cause a distinct biological response in the heart tissue.

Isolated Left Atrium Morphofunctional Study of an Experimental Pulmonary Hypertension Model in Rats. / Estudo Morfofuncional do Átrio Esquerdo Isolado de um Modelo Experimental de Hipertensão Pulmonar em Ratos.

BACKGROUND: The high incidence of atrial arrhythmias in pulmonary hypertension (PH) might be associated with poor prognosis, and the left atrium (LA) may play a role in this. An important finding in PH studies is that LA remodeling is underestimated. OBJECTIVE: This study investigated LA morphology and mechanical function, as well as the susceptibility to develop arrhythmias in a monocrotaline-induced PH (MCT-PH) model. METHODS: Wistar rats aged 4 weeks received 50 mg/kg of MCT. Electrocardiography and histology analysis were performed to evaluate the establishment of the MCT-PH model. The tissue was mounted in an isolated organ bath to characterize the LA mechanical function. RESULTS: Compared with the control group (CTRL), the MCT-PH model presented LA hypertrophy and changes in cardiac electrical activity, as evidenced by increased P wave duration, PR and QT interval in MCT-PH rats. In LA isolated from MCT-PH rats, no alteration in inotropism was observed; however, the time to peak contraction was delayed in the experimental MCT-PH group. Finally, there was no difference in arrhythmia susceptibility of LA from MCT-PH animals after the burst pacing protocol. CONCLUSION: The morphofunctional remodeling of the LA did not lead to increased susceptibility to ex vivo arrhythmia after application of the burst pacing protocol.

FUNDAMENTO: A alta incidência de arritmias atriais na hipertensão pulmonar (HP) pode estar associada a um prognóstico ruim, e o átrio esquerdo (AE) pode desempenhar um papel neste quadro. Um achado importante nos estudos de HP é que a remodelação do AE é subestimada. OBJETIVO: Este estudo investigou a morfologia e a função mecânica do AE, bem como a suscetibilidade ao desenvolvimento de arritmias em um modelo de HP induzida por monocrotalina (HP-MCT). MÉTODOS: Ratos Wistar com 4 semanas de idade receberam 50 mg/kg de MCT. Foram realizadas análises eletrocardiográficas e histológicas para avaliar o estabelecimento do modelo de HP-MCT. O tecido foi montado em banho de órgão isolado para caracterizar a função mecânica do AE. RESULTADOS: Em comparação com o grupo controle, o modelo de HP-MCT apresentou hipertrofia do AE e alterações da atividade elétrica cardíaca, conforme evidenciadas pelo aumento da duração da onda P, PR e intervalo QT. Não foi observada alteração no inotropismo do AE isolado de ratos com HP-MCT; no entanto, o tempo para atingir a contração máxima foi atrasado. Finalmente, não observamos diferença na suscetibilidade à arritmia no AE dos ratos com HP-MCT após o protocolo de estimulação intermitente. CONCLUSÃO: A remodelação morfofuncional do AE não levou ao aumento da suscetibilidade à arritmia ex vivo após a aplicação do protocolo de estimulação intermitente.

Niti-S Esophageal Mega-Stent: An Emerging Endoscopic Tool with Different Applications in the Management of Surgical Anastomotic Leaks.

Introduction: Anastomotic leak (AL) is a dangerous complication in the early postoperative period after total gastrectomy or esophagectomy being associated with high mortality. Self-expandable metal stents (SEMS) play a significant role in AL management. Only one case report described the use of Mega-Stent in AL setting. The authors report a two-case series with different applications of a Niti-S esophageal Mega-Stent in AL management. Case Report: Case 1 is a 67-year-old male who underwent an esophagectomy due to a squamous cell carcinoma of the distal esophagus. The early postoperative period was complicated with AL and gastropleural fistula. Initially, an OTSC was deployed in the dehiscence but failed to resolve AL. The esophageal Mega-Stent was further placed in-between the esophagus and the bulbus. Post-stenting contrast studies confirmed no further AL.Case 2 is an 86-year-old woman who underwent total gastrectomy with roux-en-y esophagojejunostomy due to a gastric adenocarcinoma, complicated with AL. A partially covered metal stent (PCMS) was placed to cover the anastomosis. Computed tomography confirmed leakage persistence and a second PCMS was deployed, resolving the AL. Several weeks later, both PCMSs presented ingrowth from granulation tissue. An esophageal Mega-Stent was placed (stent-in-stent technique) and 2 weeks later, all stents were removed, with no AL recurrence. Discussion/Conclusion: SEMS placement for AL is a safe, well-established therapeutic technique. Limitations include stent migration and incomplete cover of large AL. Mega-Stent can be an emerging tool for endoscopic AL management.

Introdução: A deiscência anastomótica (DA) é uma complicação grave no pós-operatório precoce da esofagectomia e gastrectomia total, pela sua elevada mortalidade. As próteses metálicas autoexpansíveis (PMAE) desempenham um papel fundamental no tratamento das DA. Na literatura, há apenas um caso descrito sobre a utilização de um Mega-Stent no contexto de DA, que não complicação bariátrica. Os autores reportam uma série de dois casos com diferente aplicação do Mega-Stent esofágico no tratamento de DA. Descrição do caso: Caso 1: Homem de 67 anos, submetido a esofagectomia por carcinoma epidermóide do esófago distal. O período pós-operatório precoce foi complicado de DA com fístula gastro-pleural. Inicialmente foi colocado um clip OTSC no orifício da deiscência com insucesso técnico e clínico, sendo posteriormente utilizado o Mega-Stent, posicionado desde o esófago até ao bulbo duodenal. Estudos contrastados posteriores confirmaram resolução da DA. Caso 2: Mulher de 86 anos, submetida a gastrectomia total com reconstrução em Y-Roux e esofagojejunostomia por adenocarcinoma gástrico, complicada de DA. Neste contexto foi colocada uma PMAE parcialmente coberta (PMAE-PC) sobre a área da anastomose. A tomografia computorizada subsequente demonstrou persistência de extravasamento. Foi colocada uma segunda PMAE-PC, com posterior resolução da DA. Semanas depois, ambas as PMAE-PC apresentavam tecido de granulação nos topos, tendo sido colocado o Mega-Stent (técnica stent-in-stent) e decorridas duas semanas, todas as próteses foram facilmente extraídas, confirmando-se sucesso no tratamento da DA. Discussão/conclusão: A utilização de PMAE nas DA constitui uma técnica terapêutica segura e bem estabelecida, contudo passível de apresentar limitações tais como a migração ou incapacidade de cobrir totalmente DA de maiores dimensões. O Mega-Stent esofágico pode constituir uma ferramenta útil na terapêutica endoscópica destes doentes.

Bubble plastic use in rats hernioplasty: Uso do plástico bolha em hernioplastias de ratos.

Purpose: Despite the high frequency of hernioplasties worldwide, their complications and recurrences are still a challenge to be overcome. The search for prostheses that aim to promote the correction of hernia defects has been a challenge. For this purpose, the materials used in hernioplasties must be biocompatible, promote the formation of little or no peritoneal adhesion, possess compatible texture and flexibility, providing the necessary resistance to protect the viscera and allow the movement of the abdomen. Methods: The aim of the present study was to evaluate the effectiveness of bubble plastic (low density polyethylene, LDPE) as a material for the correction of hernia in the abdominal wall. For this, twenty male rats (Rattus norvegicus, Wistar variety) were used and divided into four groups of five animals. The animals were evaluated at 7, 15, 30 and 90 days after surgery according to clinical, thermographic and morphological parameters (macroscopic and microscopic). Results: The results showed that the bubble plastic induced inflammatory reaction in the initial period (7 day), followed by a reduction (30 day) to increase considerably at 90 days after the operation. Conclusion: So, bubble plastic can be used for temporary implants (up to 30 days).

Eugenol delays the onset of ouabain-induced ventricular cardiac arrhythmias in guinea pigs.

Eugenol is an aromatic compound used in the manufacture of medicines, perfumes, cosmetics and as an anaesthetic due to the ability of the drug to block the neuronal isoform of voltage-gated Na+ channels (NaV ). Some arrhythmias are associated with gain of function in the sodium current (INa ) found in cardiomyocytes, and antiarrhythmic sodium channel blockers are commonly used in the clinical practice. This study sought to elucidate the potential mechanisms of eugenol's protection in the arrhythmic model of ouabain-induced arrhythmias in guinea pig heart. Ex vivo arrhythmias were induced using 50 µM of ouabain. The antiarrhythmic properties of eugenol were evaluated in the ex vivo heart preparation and isolated ventricular cardiomyocytes. The compound's effects on cardiac sodium current and action potential using the patch-clamp technique were evaluated. In all, eugenol decreased the ex vivo cardiac arrhythmias induced by ouabain. Furthermore, eugenol showed concentration dependent effect upon peak INa , left-shifted the stationary inactivation curve and delayed the recovery from inactivation of the INa . All these aspects are considered to be antiarrhythmic. Our findings demonstrate that eugenol has antiarrhythmic activity, which may be partially explained by the ability of eugenol to change de biophysical properties of INa of cardiomyocytes.