Avanzando Caminos (Leading Pathways): design and procedures of the Hispanic/Latino Cancer Survivorship Study.

Avanzando Caminos (Leading Pathways): The Hispanic/Latino Cancer Survivorship Cohort Study aims to examine the influence of sociocultural, medical, stress-related, psychosocial, lifestyle, behavioral, and biological factors on symptom burden, health-related quality of life, and clinical outcomes among Hispanics/Latinos who have been previously treated for cancer. Avanzando Caminos is a prospective, cohort-based study of 3000 Hispanics/Latinos who completed primary cancer treatment within the past 5 years that is representative of the general Hispanic/Latino population in the United States. Participants will complete self-report measures at baseline (time [T] 1), 6 months (T2), 1 year (T3), 2 years (T4), 3 years (T5), 4 years (T6), and 5 years (T7). Blood samples drawn for assessment of leukocyte gene expression, cardiometabolic markers, and genetic admixture will be collected at baseline (T1), 1 year (T3), 3 years (T5), and 5 years (T7). Medical and cancer characteristics and clinical outcomes will be extracted from the electronic medical record and/or state cancer registry at each time point. Data analysis will include general latent variable modeling and latent growth modeling. Avanzando Caminos will fill critical gaps in knowledge in order to guide future secondary and tertiary prevention efforts to mitigate cancer disparities and optimize health-related quality of life among Hispanic/Latino cancer survivors.

Associations between age and patient-reported outcomes, emergency department visits, and hospitalizations among lung cancer patients receiving immune checkpoint inhibitors.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) for lung cancer (LC) treatment have a more favorable safety profile and improved patient reported outcomes (PROs) compared to chemotherapy, suggesting that ICIs are advantageous for older populations. The impact of ICIs on PROs, clinical outcomes, and age in LC patients remains to be established. We examined associations between age and PROs, emergency department (ED) visits, and hospitalizations in LC patients receiving ICIs. METHODS: We performed retrospective analyses via My Wellness Check (MWC), an assessment and triage electronic medical record (EMR) integrated platform in LC patients receiving ICIs. Demographics, clinical characteristics, ED visits, and hospitalizations were extracted via EMR. Patient reported outcomes (PROMIS® anxiety, depression, fatigue, pain, physical function), and health-related quality of life (HRQOL; FACT-G7), were collected via MWC. We classified age into three categories (<65, 65-74, ≥75). Multiple regressions examined associations between PROs and age. Cox proportional hazards regressions assessed cumulative ED visits and hospitalizations. RESULTS: Among LC patients (N = 190) receiving ICIs, patients ≥75 had lower depression (ß = -5.80, p = 0.01) and higher HRQOL (ß = 2.47, p = 0.05) compared with patients <65. Relative to patients <65, patients 65-74 had lower anxiety (ß = -3.31, p = 0.05) and pain (ß = -4.18, p = 0.03). Patients 65-74 and ≥ 75 had lower risk of an ED visit (adjusted hazards ratio [aHR] = 0.45, p = 0.05 and aHR = 0.21, p = 0.05, respectively) and patients 65-74 had lower risk of hospitalization (aHR = 0.36, p = 0.02) relative to patients <65. CONCLUSIONS: Older LC patients (65-74; ≥75) have more favorable PROs and lower risk for negative clinical outcomes than younger (<65) patients.

Synthesis, biosimulation and pharmacological evaluation of benzimidazole derivatives with antihypertensive multitarget effect.

In this study, we synthesized a series of seven benzimidazole derivatives incorporating the structural acidic framework of angiotensin II (Ang II) type 1 receptor (AT1R) antagonists (ARA-II) employing a three-step reaction sequence. The chemical structures were confirmed by 1H NMR, 13C NMR and mass spectral data. Through biosimulation, compounds 1-7 were identified as computational safe hits, thus, best candidates underwent ex vivo testing against two distinct mechanisms implicated in hypertension: antagonism of the Ang II type 1 receptor and the blockade of calcium channel. Molecular docking studies helped to understand at the molecular level the dual vasorelaxant effects with the recognition sites of the AT1R and the L-type calcium channel. In an in vivo spontaneously hypertensive rat model (SHR), intraperitoneally administration of compound 1 at 20 mg/kg resulted in a 25 % reduction in systolic blood pressure, demonstrating both ex vivo vasorelaxant action and in vivo antihypertensive multitarget efficacy. ©2024 Elsevier.

T-cells and CD45-cells discovery in the central nervous system of healthy and nodavirus-infected teleost fish Dicentrarchuslabrax.

To achieve insights in antiviral immune defense of the central nervous system (CNS), we investigated T cells and CD45 cells in the marine fish model Dicentrarchus labrax infected with the CNS-tropic virus betanodavirus. By employing markers for pan-T cells (mAb DLT15) and CD45-cells (mAb DLT22) in immunofluorescence (IIF) of leukocytes from brain, we obtained 3,7 ± 2.3 % of T cells and 7.3 ± 3.2 % of CD45+ cells. Both IIF and immunoelectron microscopy confirmed a leukocyte/glial morphology for the immunoreactive cells. Quantitative immunohistochemistry (qIHC) of brain/eye sections showed 1.9 ± 0.8 % of T+ cells and 2 ± 0.9 % of CD45+ cells in the brain, and 3.6 ± 1.9 % and 4.1 ± 2.2 % in the eye, respectively. After in vivo RGNNV infection the number of T cells/CD45+ leukocytes in the brain increased to 8.3 ± 2.1 % and 11.6 ± 4.4 % (by IIF), and 26.1 ± 3.4 % and 45.6 ± 5.9 % (by qIHC), respectively. In the eye we counted after infection 8.5 ± 4.4 % of T cells and 10.2 ± 5.8 % of CD45 cells. Gene transcription analysis of brain mRNA revealed a strong increase of gene transcripts coding for: antiviral proteins Mx and ISG-12; T-cell related CD3ε/δ, TcRß, CD4, CD8α, CD45; and for immuno-modulatory cytokines TNFα, IL-2, IL-10. A RAG-1 gene product was also present and upregulated, suggesting somatic recombination in the fish brain. Similar transcription data were obtained in the eye, albeit with differences. Our findings provide first evidence for a recruitment and involvement of T cells and CD45+ leukocytes in the fish eye-brain axis during antiviral responses and suggest similarities in the CNS immune defense across evolutionary distant vertebrates.

Structural Determinants of Health and Markers of Immune Activation and Systemic Inflammation in Sexual Minority Men With and Without HIV.

Among sexual minority men (SMM), HIV and use of stimulants such as methamphetamine are linked with immune activation and systemic inflammation. Throughout the COVID-19 pandemic, SMM encountered financial challenges and structural obstacles that might have uniquely contributed to immune dysregulation and systemic inflammation, beyond the impacts of HIV and stimulant use. Between August 2020 and February 2022, 72 SMM with and without HIV residing in South Florida enrolled in a COVID-19 prospective cohort study. Multiple linear regression analyses examined unemployment, homelessness, and history of arrest as structural correlates of soluble markers of immune activation (i.e., sCD14 and sCD163) and inflammation (i.e., sTNF-α receptors I and II) at baseline after adjusting for HIV status, stimulant use, and recent SARS-CoV-2 infection. Enrolled participants were predominantly Latino (59%), gay-identified (85%), and with a mean age of 38 (SD, 12) years with approximately one-third (38%) of participants living with HIV. After adjusting for HIV status, SARS-CoV-2 infection, and recent stimulant use, unemployment independently predicted higher levels of sCD163 (ß = 0.24, p = 0.04) and sTNF-α receptor I (ß = 0.26, p = 0.02). Homelessness (ß = 0.25, p = 0.02) and history of arrest (ß = 0.24, p = 0.04) independently predicted higher levels of sCD14 after adjusting for HIV status, SARS-CoV-2 infection, and recent stimulant use. Independent associations exist between structural barriers and immune activation and systemic inflammation in SMM with and without HIV. Future longitudinal research should further elucidate complex bio-behavioral mechanisms linking structural factors with immune activation and inflammation.

Stress Management Interventions to Facilitate Psychological and Physiological Adaptation and Optimal Health Outcomes in Cancer Patients and Survivors.

Cancer diagnosis and treatment constitute profoundly stressful experiences involving unique and common challenges that generate uncertainty, fear, and emotional distress. Individuals with cancer must cope with multiple stressors, from the point of diagnosis through surgical and adjuvant treatments and into survivorship, that require substantial psychological and physiological adaptation. This can take a toll on quality of life and well-being and may also promote cellular and molecular changes that can exacerbate physical symptoms and facilitate tumor growth and metastasis, thereby contributing to negative long-term health outcomes. Since modifying responses tostressors might improve psychological and physiological adaptation, quality of life, and clinical health outcomes, several randomized controlled trials have tested interventions that aim to facilitate stress management. We review evidence for the effects of stress management interventions on psychological and physiological adaptation and health outcomes in cancer patients and survivors and summarize emerging research in the field to address unanswered questions.

Familism, family cohesion, and health-related quality of life in Hispanic prostate cancer survivors.

BACKGROUND: Familism, the cultural value that emphasizes feelings of loyalty and dedication to one's family, has been related to both positive and negative outcomes in Hispanic cancer survivors. One potential source of observed inconsistencies may be limited attention to the family environment, as familism may be protective in a cohesive family whereas it can exacerbate distress in a conflictive family. PURPOSE: The current study explored the associations of familism with general and disease-specific health-related quality of life (HRQoL) in Hispanic men who completed prostate cancer (PC) treatment, and whether family cohesion may help explain these relationships. METHODS: Hispanic men treated for localized PC (e.g., radiation, surgery) were enrolled in a randomized controlled stress management trial and assessed prior to randomization. Familism (familial obligation) was assessed using Sabogal's Familism Scale and family cohesion was measured using the Family Environment Scale (ranging from high to low). The sexual, urinary incontinence, and urinary obstructive/irritative domains of the Expanded Prostate Cancer Index Composite - Short Form measured disease-specific HRQoL. The physical, emotional, and functional well-being subscales of the Functional Assessment of Cancer Therapy - General captured general HRQoL. Hierarchical linear regression and the SPSS PROCESS macro were used to conduct moderation analyses, while controlling for relevant covariates. RESULTS: Participants were 202 older men on average 65.7 years of age (SD = 8.0) who had been diagnosed with PC an average of 22 months prior to enrollment. Familism was not directly associated with general and disease-specific HRQoL. Moderation analyses revealed that greater familism was related to poorer urinary functioning in the incontinence (p = .03) and irritative/obstructive domains (p = .01), and lower emotional well-being (p = .02), particularly when family cohesion was low. CONCLUSIONS: These findings underscore the importance of considering contextual factors, such as family cohesion, in understanding the influence of familism on general and disease-specific HRQoL among Hispanic PC patients. The combined influence of familism and family cohesion predicts clinically meaningful differences in urinary functioning and emotional well-being during the posttreatment phase. Culturally sensitive psychosocial interventions to boost family cohesion and leverage the positive impact of familistic attitudes are needed to enhance HRQoL outcomes in this population.

Advance Care Planning With Black Women with Breast Cancer: A Community Health Worker Model.

BACKGROUND: Despite the importance of advance care planning (ACP), a process that optimizes future medical treatment and end-of-life care, for at-risk populations, rates of patient-provider ACP conversations are extremely low among Black women with breast cancer. Community health workers (CHWs) are well-positioned to support patients in engaging in ACP conversations with their providers; yet research on integrating CHWs to promote ACP is scant. The current study examined multilevel facilitators and barriers to successful ACP conversations among Black women from the perspective of providers and CHWs who serve this community. METHODS: Providers and CHWs were recruited from an academic medical center in a large urban city. Retrospective qualitative data on barriers and facilitators to ACP conversations, as well as CHWs' training needs, were collected from two focus groups (N = 5 providers, N = 5 CHWs) and one individual interview (N = 1 provider), and transcribed and coded for themes. RESULTS: All providers reported working primarily with Black patients, and identified stigma and time constraints as major barriers to ACP discussions; they also identified the structural barriers and injustices that their patients face during medical care. CHWs reported having a trusted relationship with their patients and flexibility in their care that would allow for ongoing ACP conversations, discussing their ability to serve as a bridge between the patient and provider. However, CHWs discussed that they lacked the tools and skills to have ACP conversations, largely because existing formal trainings in ACP are cost prohibitive. DISCUSSION: Competing priorities of the provider to discuss/treat the patient's disease and medical mistrust were major barriers to successful ACP conversations among Black women with breast cancer, leading to ACP completion occurring late in treatment. CHWs are uniquely qualified to overcome multilevel barriers to ACP and establish trusting relationships with patients in order to facilitate earlier and ongoing communication between patients and providers.

Predictors of cancer rehabilitation medicine referral and utilization based on the Moving Through Cancer physical activity screening assessment.

PURPOSE: Cancer survivors experience high rates of physical inactivity that often go unaddressed. The My Wellness Check program (MWC) is an EHR-integrated screening and referral system that includes surveillance of physical activity and triage to cancer rehabilitation medicine services. This study examined assessment of physical activity and subsequent referrals to cancer rehabilitation medicine. METHODS: A secondary analysis was performed for survivors who completed the MWC between April 2021 and January 2022. Univariable and multivariable logistic regression modeled determinants of qualification for a physical activity referral and provider completion of referral to cancer rehabilitation medicine. Referral was based on responses to the Moving Through Cancer questionnaire. Adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95% CI) were calculated. RESULTS: There were 1,174 survivors who completed the assessment, of which 46% (n = 540) reported physical inactivity. After controlling for group differences, individuals with moderate-severe physical dysfunction (aOR: 1.750; 95% CI: 1.137, 2.693) had higher odds, and self-reporting Hispanic or Latino ethnicity (aOR: 0.720; CI: 0.556, 0.932) had lower odds of physical inactivity. Only 31% (n = 168) received a completed physician referral to cancer rehabilitation medicine following identification of physical inactivity. No patient-level factors were associated with receiving a physician referral. Following referral, 8% (n = 13) utilized cancer rehabilitation medicine services. CONCLUSIONS: Patient-level and clinical factors may predict qualification for physical activity referrals; however, they don't appear to predict referral completion to cancer rehabilitation medicine. Future research should focus on potential provider- and organization-level factors that interact and influence access to cancer rehabilitation medicine services.

Comorbidity burden and health-related quality of life in men with advanced prostate cancer.

PURPOSE: Identifying clinically relevant comorbidities and their effect on health-related quality of life (HRQoL) outcomes among men with advanced prostate cancer (APC) can inform patient care and improve outcomes; however, this is poorly understood. The aim of this observational study was to examine the prevalence of comorbidities, and the relationship of comorbidity burden to HRQoL and other patient-reported outcomes (PROs) among men with APC. METHODS: Participants were 192 men (average age 68.8) with APC (stage III or IV) who completed a psychosocial battery including measures of sociodemographic factors, HRQoL and other PROs, and the Charlson Comorbidity Index (CCI). Hierarchical multiple regression analysis was used to examine the relationships between CCI, HRQOL, and PROs. RESULTS: The vast majority (82%) of participants had at least one comorbidity, with the most common being: hypertension (59%), connective tissue disease or arthritis (31%), diabetes (24%), and problems with kidneys, vision, or another organ (24%). After controlling for covariates, regressions showed that a higher CCI score was significantly associated with worse HRQoL (p < 0.001), lower levels of positive affect (p < 0.05), and higher levels of depression (p < 0.05), fatigue (p < 0.001), pain (p < 0.01), stress (p < 0.01), and cancer-specific distress (p < 0.05). CONCLUSIONS: Comorbidities were common among men with APC, and a greater CCI score was associated with detriments in several domains of HRQoL and other PROs. Our findings show the need to address comorbidities in the presence of a cancer diagnosis and subsequent treatment. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT03149185.

Cardiometabolic comorbidities in Hispanic/Latino cancer survivors: prevalence and impact on health-related quality of life and supportive care needs.

PURPOSE: The aim of this study was to characterize the prevalence of cardiometabolic comorbidities (i.e., diabetes, peripheral vascular disease, myocardial infarction, congestive heart failure, cerebrovascular disease) among Hispanic/Latino cancer survivors and examine the impact of cardiometabolic comorbidities on health-related quality of life (HRQoL), unmet supportive care needs, patient-provider communication self-efficacy, satisfaction with cancer care, and increases in healthy behaviors. METHODS: Hispanics/Latinos diagnosed with breast, prostate, or colorectal cancer (N = 288) were assessed within 15 months of primary treatment completion. RESULTS: One-quarter (24.7%) of survivors were diagnosed with diabetes and one-fifth (20.8%) were diagnosed with peripheral vascular disease. Survivors with at least one cardiometabolic comoribidity were older (t(278) = -.3.622, p < .001) and more likely to have a household income of less than $25,000 (X2 = 8.369, p = .004). When adjusting for sociodemographic and medical covariates, survivors with cardiometabolic comorbidities demonstrated worse overall HRQoL (B = -4.792, p = .050), emotional (B = -1.479, p = .018) and physical (B = -2.228, p = .005) wellbeing, a higher odds of unmet psychological (OR = 2.095, p = .027) and sexuality (OR = 2.898, p = .004) needs, and greater patient-provider communication self-efficacy (B = .179, p = .045). There were no differences in healthy behavior changes or satisfaction with cancer care. CONCLUSIONS: Cardiometabolic comorbidities may be highly prevalent among Hispanic/Latino cancer survivors and increase the risk of worse HRQoL and unmet supportive care needs. Targeted interventions are needed to optimize health among Hispanic/Latino cancer survivors with cardiometabolic comorbidities.

Coping strategies and psychosocial resources among women living with metastatic breast cancer: A qualitative study.

Objective: Despite more women living with metastatic breast cancer (MBC), this population is underrepresented in cancer survivorship research. Few studies have assessed how women with MBC cope with their cancer experience. This qualitative study describes the coping strategies and psychosocial resources utilized by women living with MBC.Methods: Twenty-two women with MBC participated in four focus groups. Transcripts were analyzed using a general inductive approach. Codes derived from participants' responses were subsequently condensed into themes.Results: We identified 12 coping strategies and psychosocial resources and grouped them into five themes: Behavioral Coping Strategies (i.e. stress management, active coping and planning); Cognitive Coping Strategies and Psychological Resources (i.e. cognitive reappraisal, optimism, mindfulness, positive thinking, and religious coping); Existential Approach-Oriented Coping (i.e. acceptance, values-based living, and identity integration); Avoidance (i.e. avoidant coping); and Interpersonal Resources and Seeking Social Support (i.e. social support).Conclusions: Women living with MBC utilize several engagement and disengagement coping strategies, as well as intrapersonal and interpersonal resources. This study provides useful perspectives of women living with MBC that may inform the development of psychosocial interventions. Further research is needed to assess coping strategies and psychosocial resources across different subgroups of MBC patients and determine their impact on cancer outcomes.

Who benefits from an eHealth-based stress management intervention in advanced prostate cancer? Results from a randomized controlled trial.

OBJECTIVE: Conduct a secondary analysis to examine the effects of a tablet-delivered, group-based cognitive-behavioral stress management (CBSM) intervention for reducing symptom burden among men with advanced prostate cancer (APC) and elevated baseline levels of symptom burden. METHODS: A total of 192 men with APC were randomized to either a CBSM or a health promotion condition and followed for one year. Six analytical samples were included in our study, each including participants who reported elevated levels of burden for the corresponding outcome at baseline. Outcomes included five domains of symptom-related quality of life (urinary incontinence n = 98; urinary irritation n = 61; bowel function n = 43; sexual function n = 177; and hormonal function n = 149) and depression (n = 31). Repeated measures mixed models were used to detect within- and between-group changes in outcomes. RESULTS: Regardless of condition, participants with elevated symptom burden or mild-to-severe depression showed short-term (6-month) improvements in urinary irritation, bowel function, hormonal function, and depression scores. Only participants in the CBSM condition showed short-term (6-month) improvements in urinary incontinence, and long-term (12-month) improvements in urinary irritation, bowel function, hormonal function, and depression scores. CONCLUSIONS: Our findings suggest that targeting a web-based CBSM intervention to recipients most likely to benefit (elevated levels of symptom burden) can improve several domains of symptom-related quality of life and depressive symptoms in men with APC.

Cytokine-like activity of European sea bass ISG15 protein on RGNNV-infected E-11 cells.

IFN-I generates an antiviral state by inducing the expression of numerous genes, called IFN-stimulated genes, ISGs, including ISG15, which is the only ISG with cytokine-like activity. In a previous study, we developed the Dl_ISG15_E11 cell line, which consisted of E11 cells able to express and secrete sea bass ISG15. The current study is a step forward, analysing the effect of secreted sea bass ISG15 on RGNNV replication in E11 cells, and looking into its immunomodulatory activity in order to corroborate its cytokine-like activity. The medium from ISG15-produccing cells compromised RGNNV replication, as it has been demonstrated both, by reduction in the viral genome synthesis and, specially, in the yield of infective viral particles. The implication of sea bass ISG15 in this protection has been demonstrated by ISG15 removal, which decreased the percentage of surviving cells upon viral infection, and by incubation of RGNNV-infected cells with a recombinant sea bass ISG15 protein, which resulted in almost full protection. Furthermore, the immunomodulatory activity of extracellular sea bass ISG15 has been demonstrated, which reaffirms a cytokine-like role for this protein.

Pain, cancer-related distress, and physical and functional well-being among men with advanced prostate cancer.

PURPOSE: Men with advanced prostate cancer (APC) experience high levels of pain, which contribute to poor psychosocial and functional outcomes. Cancer-related distress explains the relationship between pain severity and interference, yet specificity of distress characteristics (e.g., hyperarousal, intrusive, or avoidant symptoms) in explaining associations between pain experiences and well-being has not been explored within APC. This study examined men with APC entering a clinical trial and tested associations of baseline pain, cancer-related distress, and physical and functional well-being. METHODS: One hundred ninety men with APC enrolled in a randomized-controlled trial and were assessed prior to randomization. The McGill Pain Questionnaire assessed pain severity, and the Functional Assessment of Cancer Therapy-General captures physical and functional well-being. The Impact of Events Scale-Revised measured cancer-specific distress symptoms, including hyperarousal, avoidance, and intrusion symptoms. Controlling for age, cancer stage at diagnosis, income, education, and race/ethnicity, mediation models (SPSS PROCESS, model 4) tested whether cancer-specific distress accounted for the associations between pain severity and physical and functional well-being. RESULTS: Men were on average 68 years of age, White non-Hispanic, with stage IV cancer. Pain severity was related to poorer physical (p < .001) and functional well-being (p < .001). Associations between pain severity and physical and functional well-being were partially mediated by greater intrusive and hyperarousal symptoms but not avoidant symptoms. CONCLUSION: For men with APC, intrusive and hyperarousal symptoms may partially explain the relationship between pain severity and decrements in physical and functional well-being. APC pain management should attend to such distress symptoms, which may contribute to interference if left unaddressed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03149185.

How do patients interpret and respond to a single-item global indicator of cancer treatment tolerability?

BACKGROUND: There is increasing interest in patient-reported measures of cancer treatment tolerability. A global measure of bother, the FACT GP5 item ("I am bothered by side effects of treatment") is potentially useful for regulatory, research, and clinical use. To understand this item's appropriateness for capturing treatment tolerability, we conducted cognitive interviews on this item with 3 samples of cancer patients. METHODS: Patients with ovarian cancer (Study 1: N = 21; on treatment), lymphoma (Study 2: N = 14; on treatment), and colorectal or lung cancer (Study 3: N = 16; treatment naïve) were interviewed about GP5's understandability and relevance to their treatment side effects. What patients think about when answering GP5 was also assessed. In all studies, the interview included both structured and open-ended questions. Qualitative data were coded to extract themes and responses to structured questions were tallied. RESULTS: Most patients on treatment (Studies 1 and 2) reported that the GP5 item wording is appropriate (88%) and its meaning is clear (97%). They were very confident or confident in their response (97%) and stated that GP5 was relevant to their cancer experience (97%). When answering GP5, patients considered their treatment and specific side effects. A large proportion (40%) of the treatment-naïve (Study 3) patients reported that GP5 was not relevant to their cancer treatment, and the largest proportion responded to GP5 thinking of negative side effect expectancies. CONCLUSION: This study provides assurance that GP5 is a useful indicator of treatment tolerability, and is meaningful to people with cancer, especially once they have started treatment.

Morphology and cyclooxygenase-2 and renin expression in the kidney of young spontaneously hypertensive rats.

The kidneys play an important role in blood pressure regulation under normal and pathological conditions. We examined the histological changes and expression patterns of cyclooxygenase-2, renin, and (pro)renin receptor (PRR) in the renal cortex of prehypertensive spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). Moreover, blood pressure and plasma urea, creatinine, angiotensin II, and angiotensin (1-7) levels were measured. The results showed that both strains had similar blood pressure and plasma urea and creatinine levels. The glomerular area, basement membrane thickness, collagen fiber content, and arterial wall thickness were greater in SHRs than in WKYs. By immunohistochemistry, cyclooxygenase-2 was localized in the macula densa and renal tubules of both strains. In SHRs, cyclooxygenase-2 was detected in a larger number of tubules, and the cortical expression of cyclooxygenase-2 was also increased. In both strains, PRR and renin were localized in the tubular epithelium and juxtaglomerular cells, respectively. In SHRs, PRR immunolocalization was increased in the glomerulus. The cortical expression of immature renin was markedly increased in SHRs compared to that in WKYs, while renin was significantly decreased. These changes were associated with higher plasma angiotensin II levels and lower plasma angiotensin (1-7) levels in SHRs. The results indicate that the kidneys of SHRs showed morphological changes and variations in cortical expression patterns of PRR, cyclooxygenase-2, and renin before the development of hypertension.

Symptom burden profiles in men with advanced prostate cancer undergoing androgen deprivation therapy.

To identify symptom burden profiles among men with advanced prostate cancer undergoing androgen-deprivation therapy and examine their association with baseline sociodemographic and medical characteristics and psychosocial outcomes over time. Latent profile analysis was employed to identify distinct groups based on the Expanded Prostate Index Composite and the McGill Pain Questionnaire at baseline. Psychosocial outcomes were assessed at baseline, 6- and 12-month follow-ups. Three profiles emerged: "high symptom burden," "high sexual bother," and "low symptom burden." Men with "high symptom burden" were younger and exhibited higher baseline levels of depression, stress, cancer-specific distress, and anxiety than men in the other two groups. However, men with "high symptom burden" also demonstrated improvement in these psychosocial outcomes over time. Men with advanced prostate cancer who experience multiple co-occurring symptoms demonstrate worse psychosocial adjustment. Patients with substantial symptom burden, and specifically young men, may benefit from prompt referral to supportive care services.

Citalopram improves vasomotor syndrome and urogenital syndrome of menopause in Mexican women: a randomized clinical trial.

PURPOSE: This study aimed to determine the efficacy of non-hormonal therapy with citalopram vs fluoxetine for treating vasomotor syndrome (VMS) and urogenital syndrome of menopause (GSM) in Mexican women. METHODS: A parallel prospective randomized clinical trial was conducted in 91 postmenopausal women with a total score on the Menopause Rating Scale (MRS) ≥ 17 and with the clinical diagnosis of VSM and GSM. Patients were randomly assigned to receive citalopram (n = 49) or fluoxetine (n = 42). Follow-up was carried out at 3 and 6 months. RESULTS: The citalopram group experienced a significant improvement compared to the fluoxetine group in the MRS total score (p < 0.01), as well as in the psychological (p < 0.001) and somatic (p < 0.0001) domains at 3 and 6 months of follow-up. After 6 months of follow-up, the group that received citalopram decreased the relative risk (RR) to present VMS symptoms (RR = 0.30, CI 0.19-0.5, p = 0.0001), depressed mood (RR = 0.31, CI 0.15-0.6, p = 0.0002), irritability (RR = 0.40, CI 0.22-0.73, p = 0.002), anxiety (RR = 0.30, CI 0.13-0.69, p = 0.003), physical and mental exhaustion (RR = 0.35, CI 0.18-0.67, p = 0.001), sexual problems (RR = 0.18, CI 0.06-0.48, p = 0.0001), vaginal dryness (RR = 0.34, CI 0.14-0.80, p = 0.01), and urinary problems (RR = 0.36, CI 0.14-0.92, p = 0.043). CONCLUSION: We conclude that citalopram tends to improve VSM and GSM symptoms in postmenopausal Mexican women. Thus, we recommend the daily use of citalopram 20 mg. However, further studies will be required to support the results of the present work. These should include a larger number of patients and a placebo group. CLINICAL TRIAL REGISTRATION: This clinical trial was retrospectively registered by the United States National Library of Medicine in the www. CLINICALTRIALS: gov database on 04/20/2022. The given test Registration Number is NCT05346445.

Recent Analytical Approaches for the Study of Bioavailability and Metabolism of Bioactive Phenolic Compounds.

The study of the bioavailability of bioactive compounds is a fundamental step for the development of applications based on them, such as nutraceuticals, functional foods or cosmeceuticals. It is well-known that these compounds can undergo metabolic reactions before reaching therapeutic targets, which may also affect their bioactivity and possible applications. All recent studies that have focused on bioavailability and metabolism of phenolic and terpenoid compounds have been developed because of the advances in analytical chemistry and metabolomics approaches. The purpose of this review is to show the role of analytical chemistry and metabolomics in this field of knowledge. In this context, the different steps of the analytical chemistry workflow (design study, sample treatment, analytical techniques and data processing) applied in bioavailability and metabolism in vivo studies are detailed, as well as the most relevant results obtained from them.