Review of the anticancer properties of 6-shogaol: Mechanisms of action in cancer cells and future research opportunities.

Cancer is a major global health challenge that affects every nation and accounts for a large portion of the worldwide disease burden. Furthermore, cancer cases will rise significantly in the next few decades. The Food and Drug Administration has approved more than 600 drugs for treating diverse types of cancer. However, many conventional anticancer medications cause side effects, and drug resistance develops as the treatment proceeds with a concomitant impact on patients' quality of life. Thus, exploring natural products with antitumor properties and nontoxic action mechanisms is essential. Ginger (Zingiber officinale Roscoe) rhizome has a long history of use in traditional medicine, and it contains biologically active compounds, gingerols and shogaols. The main ginger shogaol is 6-shogaol, whose concentration dramatically increases during the processing of ginger, primarily due to the heat-induced conversion of 6-gingerol. Some studies have demonstrated that 6-shogaol possesses biological and pharmacological properties, such as antioxidant, anti-inflammatory, and anticancer activities. The mechanism of action of 6-shogaol as an anticancer drug includes induction of paraptosis, induction of apoptosis, increase in the production of reactive oxygen species, induction of autophagy, and the inhibition of AKT/mTOR signaling. Despite this knowledge, the mechanism of action of 6-shogaol is not fully understood, and the scientific data on its therapeutic dose, safety, and toxicity are not entirely described. This review article examines the potential of 6-shogaol as an anticancer drug, addressing the limitations of current medications; it covers 6-shogaol's attributes, mechanism of action in cancer cells, and opportunities for future research.

Urinary Incontinence Care in the Academic and Safety-Net Primary Care Settings: Opportunities to Improve Quality of Care.

OBJECTIVE: To compare the quality of urinary incontinence care for women in the safety-net and non-safety-net settings prior to referral to a specialist. METHODS: We performed a retrospective review of 200 women from two non-safety-net hospitals and 188 women from two safety-net hospitals who were referred to Urogynecology and Reconstructive Surgery specialists for bothersome UI between March 2017 and March 2020. We evaluated the care that women received 12-months prior to referral, by measuring adherence to a set of previously developed quality indicators (QIs), for example the performance of a urinalysis or pelvic exam. RESULTS: Women seen in safety-net hospitals were more likely to receive QI-compliant care than women in the non-safety-net hospitals prior to referral, with 55.53% of appropriate care given in the safety-net vs. 40.3% in the non-safety-net setting (p<0.01). Clinicians in the safety-net hospitals were more likely to adhere to QIs in patients with general, stress, and urgency incontinence. CONCLUSIONS: Women were more likely to receive timely, quality-based UI care in the safety net compared to the non-safety-net setting. This may be in part due to aspects unique to the safety-net system, including an eConsult referral system, which guides referring clinicians in appropriate management steps that should be taken prior to the specialist visit, as well as women's health focused primary care clinics.

New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives.

Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL-6/JAK/STAT3, ER-α36, and NF-κB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug.

Human adenovirus-associated health risk in the recreational waters of the Yal-ku lagoon in the Mexican Caribbean.

The study objective was to evaluate human faecal contamination impacts in the Yal-ku lagoon in the Mexican Caribbean and to estimate adenovirus infection and illness risks associated with recreational exposure during water activities. A total of 20 water samples (10 from each site × two sites) (50 L) were collected monthly over a period of 12 months from two selected sampling sites in the swimming area of the Yal-ku lagoon. The occurrence of faecal-associated viruses was explored, and human adenovirus (HAdV) and pepper mild mottle virus (PMMoV) concentrations were quantified. A quantitative microbial risk assessment (QMRA) model was used to estimate exposure and subsequent adenovirus infection and illness risk for 1 h of swimming or snorkelling. Somatic and F + -specific coliphages occurred in 100% of the samples. Both HAdV and PMMoV were detected at a 60% frequency thereby indicating persistent faecal inputs. PMMoV concentrations (44-370 GC/L) were relatively lower than the concentrations of HAdV (64-1,000 GC/L). Estimated mean adenovirus risks were greater for snorkelling than for swimming by roughly one to two orders of magnitude and estimated mean illness risks for snorkelling were >32/1,000. Human faecal contamination is frequent in the Yal-ku lagoon, which is associated with human gastrointestinal illness.

Inexpensive and Easy to Set Up Robotic Cardiac Simulator Offers "Unlimited" Endoscopic Coronary Artery Bypass Grafting Experience: Proof of Concept.

OBJECTIVE: Robotic totally endoscopic coronary artery bypass (TECAB) grafting is the least invasive form of coronary bypass surgery. However, despite its advantages, this approach has not gained widespread adoption. One possible reason is the advanced and complex robotic skills required to execute a totally endoscopic sutured coronary anastomosis. We prepared a novel, inexpensive, easy to set up robotic TECAB simulator. METHODS: A pig heart was placed in a cardboard box, and 3 holes were made on the side to mimic the exposure and surgical ergonomics of TECAB port placement. Four robotic ports were placed and docked to the da Vinci Si robot (Intuitive Surgical, Sunnyvale, CA, USA). Monofilament 7:0 suture (7 cm long) was used to perform the anastomosis to the left anterior descending artery using remnant conduit. Seven cardiac surgeons of various training levels participated and were asked to fill out a 10-point questionnaire. RESULTS: The cost of the simulator totaled $20 per session, with 20 min to assemble. Each session allowed each trainee to practice 3 to 4 coronary anastomoses. Three cardiac surgeons completed the survey and strongly agreed that the model was easy to set up, the anastomotic exercise was realistic, and that this practice helped them gain confidence. CONCLUSIONS: Our TECAB simulator is inexpensive, easy to set up, and allows trainees to practice endoscopic coronary suturing. We believe this to be a valuable training tool to learn how to do TECAB for established surgeons and that such a simulator may be of great value to cardiothoracic training programs and their trainees. Further studies are warranted.

3,3'-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways.

Dietary compounds in cancer prevention have gained significant consideration as a viable method. Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are heterocyclic and bioactive chemicals found in cruciferous vegetables like broccoli, cauliflower, cabbage, and brussels sprouts. They are synthesized after glycolysis from the glucosinolate structure. Clinical and preclinical trials have evaluated the pharmacokinetic/pharmacodynamic, effectiveness, antioxidant, cancer-preventing (cervical dysplasia, prostate cancer, breast cancer), and anti-tumor activities of I3C and DIM involved with polyphenolic derivatives created in the digestion showing promising results. However, the exact mechanism by which they exert anti-cancer and apoptosis-inducing properties has yet to be entirely understood. Via this study, we update the existing knowledge of the state of anti-cancer investigation concerning I3C and DIM chemicals. We have also summarized; (i) the recent advancements in the use of I3C/DIM as therapeutic molecules since they represent potentially appealing anti-cancer agents, (ii) the available literature on the I3C and DIM characterization, and the challenges related to pharmacologic properties such as low solubility, and poor bioavailability, (iii) the synthesis and semi-synthetic derivatives, (iv) the mechanism of anti-tumor action in vitro/in vivo, (v) the action in cellular signaling pathways related to the regulation of apoptosis and anoikis as well as the cell cycle progression and cell proliferation such as peroxisome proliferator-activated receptor and PPARγ agonists; SR13668, Akt inhibitor, cyclins regulation, ER-dependent-independent pathways, and their current medical applications, to recognize research opportunities to potentially use these compounds instead chemotherapeutic synthetic drugs.

hESC-derived striatal progenitors grafted into a Huntington's disease rat model support long-term functional motor recovery by differentiating, self-organizing and connecting into the lesioned striatum.

BACKGROUND: Huntington's disease (HD) is a motor and cognitive neurodegenerative disorder due to prominent loss of striatal medium spiny neurons (MSNs). Cell replacement using human embryonic stem cells (hESCs) derivatives may offer new therapeutic opportunities to replace degenerated neurons and repair damaged circuits. METHODS: With the aim to develop effective cell replacement for HD, we assessed the long-term therapeutic value of hESC-derived striatal progenitors by grafting the cells into the striatum of a preclinical model of HD [i.e., adult immunodeficient rats in which the striatum was lesioned by monolateral injection of quinolinic acid (QA)]. We examined the survival, maturation, self-organization and integration of the graft as well as its impact on lesion-dependent motor alterations up to 6 months post-graft. Moreover, we tested whether exposing a cohort of QA-lesioned animals to environmental enrichment (EE) could improve graft integration and function. RESULTS: Human striatal progenitors survived up to 6 months after transplantation and showed morphological and neurochemical features typical of human MSNs. Donor-derived interneurons were also detected. Grafts wired in both local and long-range striatal circuits, formed domains suggestive of distinct ganglionic eminence territories and displayed emerging striosome features. Moreover, over time grafts improved complex motor performances affected by QA. EE selectively increased cell differentiation into MSN phenotype and promoted host-to-graft connectivity. However, when combined to the graft, the EE paradigm used in this study was insufficient to produce an additive effect on task execution. CONCLUSIONS: The data support the long-term therapeutic potential of ESC-derived human striatal progenitor grafts for the replacement of degenerated striatal neurons in HD and suggest that EE can effectively accelerate the maturation and promote the integration of human striatal cells.

Transsulfuration pathway: a targeting neuromodulator in Parkinson's disease.

The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, H2S, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine ß-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway. TSP metabolites are implicated in many physiological processes in the central nervous system and other tissues. TSP is important in controlling sulfur balance and optimal cellular functions such as glutathione synthesis. Alterations in the TSP and related pathways (transmethylation and remethylation) are altered in several neurodegenerative diseases, including Parkinson's disease, suggesting their participation in the pathophysiology and progression of these diseases. In Parkinson's disease many cellular processes are comprised mainly those that regulate redox homeostasis, inflammation, reticulum endoplasmic stress, mitochondrial function, oxidative stress, and sulfur content metabolites of TSP are involved in these damage processes. Current research on the transsulfuration pathway in Parkinson's disease has primarily focused on the synthesis and function of certain metabolites, particularly glutathione. However, our understanding of the regulation of other metabolites of the transsulfuration pathway, as well as their relationships with other metabolites, and their synthesis regulation in Parkinson´s disease remain limited. Thus, this paper highlights the importance of studying the molecular dynamics in different metabolites and enzymes that affect the transsulfuration in Parkinson's disease.

Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells.

Cancer treatment typically involves multiple strategies, such as surgery, radiotherapy, and chemotherapy, to remove tumors. However, chemotherapy often causes side effects, and there is a constant search for new drugs to alleviate them. Natural compounds are a promising alternative to this problem. Indole-3-carbinol (I3C) is a natural antioxidant agent that has been studied as a potential cancer treatment. I3C is an agonist of the aryl hydrocarbon receptor (AhR), a transcription factor that plays a role in the expression of genes related to development, immunity, circadian rhythm, and cancer. In this study, we investigated the effect of I3C on cell viability, migration, invasion properties, as well as mitochondrial integrity in hepatoma, breast, and cervical cancer cell lines. We found that all tested cell lines showed impaired carcinogenic properties and alterations in mitochondrial membrane potential after treatment with I3C. These results support the potential use of I3C as a supplementary treatment for various types of cancer.

Retrospective evaluation of wobbly hedgehog syndrome in 49 African pygmy hedgehogs (Atelerix albiventris): 2000-2020.

OBJECTIVE: To retrospectively evaluate the prevalence and clinical progression of wobbly hedgehog syndrome (WHS) and concurrent incidence of neoplasia in a cohort of African pygmy hedgehogs (Atelerix albiventris). ANIMALS: 49 hedgehogs. CLINICAL PRESENTATION AND PROCEDURES: Medical records of hedgehogs from 7 institutions across the US over a 20-year period (2000 to 2020) were retrospectively reviewed. Inclusion criteria were hedgehogs of any sex or age with postmortem CNS histopathology consistent with WHS. Collected data included sex, age at onset and euthanasia, major histopathologic findings, reported neurologic clinical signs, and treatments administered. RESULTS: 24 males and 25 females were included. Fifteen of 49 (31%) individuals had subclinical WHS with no reported antemortem neurologic clinical signs. In neurologically affected (clinical) hedgehogs (n = 34), the mean ± SD age at onset was 3.3 ± 1.5 years with a median (range) time from onset to euthanasia of 51 days (1 to 319 days). In neurologically affected hedgehogs, the most commonly reported clinical signs were ataxia (n = 21) and pelvic limb paresis (16) and the most commonly administered treatment was meloxicam (13). Overall, 31 of 49 (63%) hedgehogs had a concurrent histopathologic diagnosis of neoplasia outside of the CNS. CLINICAL RELEVANCE: The prognosis for hedgehogs with WHS is poor. No treatment had a significant effect on survival time, and neoplasia was a common comorbidity in the current cohort. A small but clinically relevant subset of neurologically normal hedgehogs had a histopathologic diagnosis of WHS.

Lithium: A Promising Anticancer Agent.

Lithium is a therapeutic cation used to treat bipolar disorders but also has some important features as an anti-cancer agent. In this review, we provide a general overview of lithium, from its transport into cells, to its innovative administration forms, and based on genomic, transcriptomic, and proteomic data. Lithium formulations such as lithium acetoacetate (LiAcAc), lithium chloride (LiCl), lithium citrate (Li3C6H5O7), and lithium carbonate (Li2CO3) induce apoptosis, autophagy, and inhibition of tumor growth and also participate in the regulation of tumor proliferation, tumor invasion, and metastasis and cell cycle arrest. Moreover, lithium is synergistic with standard cancer therapies, enhancing their anti-tumor effects. In addition, lithium has a neuroprotective role in cancer patients, by improving their quality of life. Interestingly, nano-sized lithium enhances its anti-tumor activities and protects vital organs from the damage caused by lipid peroxidation during tumor development. However, these potential therapeutic activities of lithium depend on various factors, such as the nature and aggressiveness of the tumor, the type of lithium salt, and its form of administration and dosage. Since lithium has been used to treat bipolar disorder, the current study provides an overview of its role in medicine and how this has changed. This review also highlights the importance of this repurposed drug, which appears to have therapeutic cancer potential, and underlines its molecular mechanisms.

Experiences of Women With Interstitial Cystitis/Bladder Pain Syndrome: What Can We Learn From Women's Online Discussions?

PURPOSE: Interstitial cystitis/bladder pain syndrome is a debilitating chronic condition that disproportionately affects women at a ratio of 5:1. We sought to capture women's experiences with interstitial cystitis/bladder pain syndrome by conducting a large-scale digital ethnographic analysis of anonymous posts on Internet forums. MATERIALS AND METHODS: Online posts were identified using condition-specific keywords and data mining extraction services. Once posts were identified, a random sample of 200 online posts was coded and analyzed by hand using qualitative methods. A Latent Dirichlet Allocation probabilistic topic model was applied to the complete dataset to substantiate the qualitative analysis and allow for further thematic discovery. RESULTS: A total of 6,842 posts written by 3,902 unique users from 224 websites were identified. There was a significant overlap between the hand coding and Latent Dirichlet Allocation themes. Our analysis yielded the following themes: online community engagement, triggers and disease etiologies, medical comorbidities, quality of life impact, patient experience with medical care, and alternative therapies and self-management strategies. Additionally, our population appeared to have a high burden of nonurological associated syndromes. We identified barriers to patient-centered care and found that online peer support was important for women. CONCLUSIONS: Our digital ethnographic analysis is a novel application of qualitative methods using online sources. Social media analytics appears to capture a broader patient population than that typically included in clinic-based qualitative studies, such as patient interviews and focus groups. Understanding patient behaviors and concerns are important to guide strategies for improving care and the overall experience with this difficult-to-treat condition.

Prácticas socioformativas para la gestión de competencias investigativas en el médico general integral utilizando Telegram / Socioformative practices for the management of investigative skills in the comprehensive general practitioner using Telegram

Fundamento: las tecnologías de la información y las comunicaciones ofrecen herramientas que facilitan la formación de competencias investigativas en los médicos generales integrales con la utilización de Telegram en el contexto de la sociedad del conocimiento. Objetivo: valorar la efectividad en la transformación de la práctica socioformativa para la gestión de las competencias investigativas en el médico general integral, haciendo uso de Telegram en el curso de Metodología de la Investigación durante el periodo septiembre 2021-2022. Métodos: se realizó un estudio cuasiexperimental, en la Filial de Ciencias Médicas "Julio Trigo López" de Palma Soriano. Se utilizaron métodos teóricos: histórico-lógico, análisis-síntesis, enfoque de sistema, abstracción-concreción y el hermenéutico-dialéctico; empíricos: análisis documental, observación, cuestionario y el criterio de expertos. Resultados: se alcanzó mayor eficiencia en la transformación de la práctica socioformativa para la gestión de las competencias investigativas en el médico general integral, haciendo uso de Telegram en los aspectos relacionados con la realización de tareas grupales, interacción promotora y conocimientos sobre cómo confeccionar el proyecto de investigación para la solución de los problemas en la comunidad. Conclusiones: se valora como factible y novedosa la transformación de la práctica socioformativa para la gestión de las competencias investigativas en el médico general integral, haciendo uso de Telegram como herramienta para el aprendizaje colaborativo como protagonista en este entorno virtual de interacción.

Background: information and communication technologies offer tools that facilitate the formation of investigative skills in comprehensive general practitioners in the context of the knowledge society. Objective: to assess the effectiveness in the transformation of the socioformative practice for the management of investigative skills in the comprehensive general practitioner, using Telegram in the Research Methodology course during the period September 2021-2022. Methods: a quasi-experimental study was carried out at the "Julio Trigo López" Medical Sciences Branch in Palma Soriano. Theoretical methods were used: historical-logical, analysis-synthesis, system approach, abstraction-concretion and hermeneutic-dialectical; Empirical: documentary analysis, observation, questionnaire and expert criteria. Results: greater efficiency was achieved in the transformation of the socio-formative practice for the management of investigative skills in the comprehensive general practitioner, making use of Telegram in aspects related to carrying out group tasks, promoting interaction and knowledge on how to prepare the project. Research to solve problems in the community. Conclusions: the transformation of the socio-formative practice for the management of investigative skills in the comprehensive general practitioner is valued as feasible and novel, making use of Telegram as a tool for collaborative learning as a protagonist in this virtual environment of interaction.

Información, narrativas y vivencias de los equipos de salud del Hospital Vilardebó ante la nueva Ley de Salud Mental No 19529 / Information, narratives and experiences of the health teams of the Hospital Vilardebó before the new Law of Mental Health N.o 19.529

La nueva Ley de Salud Mental N.o 19.529 promueve el cierre paulatino de los establecimientos asilares y monovalentes en todo el país. Dentro del sector público se encuentra el Hospital Vilardebó. En esta investigación se exploraron los significados que los equipos de salud de dicho hospital construyen sobre la implementación de la Ley N.o 19.529. Para esto se diseñó un estudio descriptivo. A partir de un muestreo teórico estratificado, la población quedó conformada por 69 personas con formación en medicina general, psiquiatría, psicología, trabajo social y enfermería. A través de un cuestionario autoadministrado, se indagó la información sobre la nueva ley, el reconocimiento de cambios institucionales, la modificación de las prácticas laborales, y los afectos movilizados. De los resultados se destaca un manejo heterogéneo de la información sobre la nueva normativa. Se advierte, asimismo, un proceso de transición institucional donde se observan narrativas contradictorias sobre los cambios en curso.

The new Mental Health Law N 19.529 promotes gradual closure of asylums and monovalent institutions throughout the country. Hospital Vilardebó is the public health psychiatric hospital. This research explores the meanings that health teams assign to this law's implemen tation by means of a descriptive study. Based on a theoretical stratified sample, 69 workers with training in general medicine, psychiatry, psychology, social work and nursing answered a self-administered questionnaire regarding the new law, institutional and work practice changes, and affects involved. The results highlight a heterogeneous handling of information on new regulations. Likewise, an institutional transitional process is noted, with contradictory narratives regarding ongoing changes.

Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest.

Cervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host cell differentiation by targeting retinoblastoma tumor suppressor. The host cell can ubiquitinate E6 and E7 through UBE2L3, whose expression depends on the interaction between the aryl hydrocarbon receptor (AhR) with Xenobiotic Responsive Elements (XREs) located in the UBE2L3 gene promoter. In this study, we used cell culture to determine the effect of indole-3-carbinol (I3C) over cellular viability, apoptosis, cell proliferation, and mRNA levels of UBE2L3 and CYP1A1. In addition, patients' samples were used to determine the mRNA levels of UBE2L3 and CYP1A1 genes. We found that I3C promotes the activation of AhR and decreases cell proliferation, possibly through UBE2L3 mRNA induction, which would result in the ubiquitination of HPV E7. Since there is a strong requirement for selective and cost-effective cancer treatments, natural AhR ligands such as I3C could represent a novel strategy for cancer treatment.

Rapid, site-specific labeling of "off-the-shelf" and native serum autoantibodies with T cell-redirecting domains.

Extensive antibody engineering and cloning is typically required to generate new bispecific antibodies. Made-to-order genes, advanced expression systems, and high-efficiency cloning can simplify and accelerate this process, but it still can take months before a functional product is realized. We developed a simple method to site-specifically and covalently attach a T cell-redirecting domain to any off-the-shelf, human immunoglobulin G (IgG) or native IgG isolated from serum. No antibody engineering, cloning, or knowledge of the antibody sequence is required. Bispecific antibodies are generated in just hours. By labeling antibodies isolated from tumor-bearing mice, including two syngeneic models, we generated T cell-redirecting autoantibodies (TRAAbs) that act as an effective therapeutic. TRAAbs preferentially bind tumor tissue over healthy tissue, indicating a previously unexplored therapeutic window. The use of autoantibodies to direct the tumor targeting of bispecific antibodies represents a new paradigm in personalized medicine that eliminates the need to identify tumor biomarkers.

LKB-1 Expression and High-Risk Histopathology are Independent Prognostic Factors for Patients with Oral Cavity Carcinoma.

BACKGROUND: The expression of liver kinase B1 (LKB-1) has been associated with prognosis in squamous cell carcinoma of the oral cavity (SCCOC). This study aimed to define the prognostic role of LKB-1 expression for patients with SCCOC and the suitability of its integration into a multivariate prognostic model. METHODS: A retrospective cohort study of patients with SCCOC was conducted in a cancer center. Expression of LKB-1 was evaluated by immunohistochemistry, and multivariate analysis defined prognostic factors associated with recurrence, recurrence-free survival (RFS), and overall survival (OS). The logistic regression model was used to construct a predictive computer software program. RESULTS: Of the 201 patients in this study, 104 (51.7%) experienced recurrence of their disease. Lower expression of LKB-1, high-risk histopathology, and advanced tumor-node-metastasis (TNM) stages were independent factors via multivariate analysis associated with the increased recurrence risk, poor RFS, and poor OS. If lack of LKB-1 expression is considered the reference category, the factors independently associated with recurrence were low (odds ratio [OR], 0.157; 95% confidence interval [CI], 0.044-0.557), intermediate (OR, 0.073; 95% CI, 0.017-0.319), and intense (OR, 0.047; 95% CI, 0.007-0.304) expression of LKB-1. This model permitted construction of a computer software program capable of prediction with receiver operating characteristic analysis (area under the curve, 0.925) and led to the definition of five prognostic groups with a biologic gradient. CONCLUSION: These results suggest that LKB-1 expression in patients with SCCOC is of robust prognostic value and complements the TNM staging system. The proposed model requires external validation in prospective observational studies.

RNA sequencing in a penile cancer cohort: an investigation of biomarkers of cisplatin resistance and potential therapeutic drug targets.

OBJECTIVE: Chemoresistance in distant micrometastatic lesions may account for diminished durable response rates in advanced penile cancer. However, there are limited studies on new therapeutic targets and the identification of biomarkers that predict chemotherapy response in this population. Thus, we examine the expression of candidate biomarkers of cisplatin resistance, ERCC1 and E2F1, and perform next-generation sequencing on the cancer transcriptome in a penile cancer cohort. MATERIALS AND METHODS: In this retrospective cohort study, we identified 71 patients treated for penile squamous cell carcinoma between 2009 and 2019. Immunohistochemistry staining for ERCC1 and E2F1 was performed. H-scores were measured for patient specimens obtained from adjacent normal skin, primary tumor and metastatic lymph node specimens and correlated with RNA expression data obtained through next-generation sequencing. RESULTS: Of the 71 patients identified, 51 and 8 had available surgical specimens for immunohistochemistry and RNA sequencing, respectively. Median H-scores for ERCC1 in adjacent normal skin, primary and metastatic tumors were 17.04, 3.15, and 7.9 respectively compared to E2F1 (43.95, 15.54, 7.9). The median H-score for E2F1 was higher in poorly differentiated primary tumors (24.86) compared to well (7.62) and moderately differentiated (9.55, p = 0.055). Next generation sequencing showed no difference in RNA expression of E2F1 nor ERCC1 between primary tumors and metastatic lesions however did demonstrate elevated RNA expression of genes such as MMP1, and MMP10 in primary tumors compared to adjacent normal skin. CONCLUSION: We identify potential drug targets for metastatic penile cancer through next-generation RNA sequencing.

The Impact of Provider Sex and Experience on the Quality of Care Provided for Women with Urinary Incontinence.

BACKGROUND: Although specialists are skilled in the management of urinary incontinence, primary care clinicians are integral in early diagnosis and initiation of management in order to decrease overuse of specialty care and improve the quality of specialist visits. We measured the quality of incontinence care provided by primary care clinicians prior to referral to a specialist and evaluated the impact of provider variables on quality of care. METHODS: We performed a retrospective review of 200 women referred for urinary incontinence to a Female Pelvic Medicine and Reconstructive Surgery specialist between March 2017 and July 2018. We measured primary care adherence to 12 quality indicators in the 12 months prior to specialist consultation. We stratified adherence to quality indicators by clinician sex and years of experience. RESULTS: Half of women with incontinence underwent a pelvic examination or had a urinalysis ordered. Few patients with urge urinary incontinence were recommended behavioral therapy (14%) or prescribed medication (8%). When total aggregate scores were compared, female clinicians performed the recommended care 47% ± 25% of the time, compared with 35% ± 23% for male clinicians (P = .003). Increasing years of experience was associated with worse overall urinary incontinence care (r -0.157, P = .02). CONCLUSIONS: We found low rates of adherence to a set of quality indicators for women with urinary incontinence, with male clinicians performing significantly worse than female clinicians. Improvement of incontinence care in primary care could significantly reduce costs of care and preserve outcomes.