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Maura K Cosetti,1,2 James B Pinkston,3 Jose M Flores,4 David R Friedmann,5 Callie B Jones,3 J Thomas Roland Jr,5,6 Susan B Waltzman5 1Department of Otolaryngology – Head and Neck Surgery, 2Department of Neurosurgery, 3Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, 4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MA, 5Department of Otolaryngology, 6Department of Neurosurgery, New York University School of Medicine, New York, NY, USA Objective: The aim of this case series was to assess the impact of auditory rehabilitation with cochlear implantation on the cognitive function of elderly patients over time. Design: This is a longitudinal case series of prospective data assessing neurocognitive function and speech perception in an elderly cohort pre- and post-implantation. Setting: University cochlear implant center. Participants: The patients were post-lingually deafened elderly female (mean, 73.6 years; SD, 5.82; range, 67–81 years) cochlear implant recipients (n=7). Measurements: A neurocognitive battery of 20 tests assessing intellectual function, learning, short- and long-term memory, verbal fluency, attention, mental flexibility, and processing speed was performed prior to and 2–4.1 years (mean, 3.7) after cochlear implant (CI). Speech perception testing using Consonant–Nucleus–Consonant words was performed prior to implantation and at regular intervals postoperatively. Individual and aggregate differences in cognitive function pre- and post-CI were estimated. Logistic regression with cluster adjustment was used to estimate the association (%improvement or %decline) between speech understanding and years from implantation at 1 year, 2 years, and 3 years post-CI. Results: Improvements after CI were observed in 14 (70%) of all subtests administered. Declines occurred in five (25%) subtests. In 55 individual tests (43%), post-CI performance improved compared to a patient’s own performance before implantation. Of these, nine (45%) showed moderate or pronounced improvement. Overall, improvements were largest in the verbal and memory domains. Logistic regression demonstrated a significant relationship between speech perception and cognitive function over time. Five neurocognitive tests were predictive of improved speech perception following implantation. Conclusion: Comprehensive neurocognitive testing of elderly women demonstrated areas of improvement in cognitive function and auditory perception following cochlear implantation. Multiple neurocognitive tests were strongly associated with current speech perception measures. While these data shed light on the complex relationship between hearing and cognition by showing that CI may slow the expected age-related cognitive decline, further research is needed to examine the impact of hearing rehabilitation on cognitive decline. Keywords: cognitive function, cognitive impairment, dementia, aging, hearing loss, cochlear implant, neuropsychological testing

Abstract Background In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings. Methods BALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 106 and 1 × 105 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm3, four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm3 (27.0 C in 0.35 cm3) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm3, two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis. Results Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm3, respectively. Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory response, and a moderate peritumoral monocyte infiltration. The morphologic pattern of necrotic cell mass after direct electric current treatment is the coagulative necrosis. These findings were not observed in any of the untreated tumors. Conclusion The data presented indicate that electrotherapy with low-level DEC is feasible and effective in the treatment of the Ehrlich and fibrosarcoma Sa-37 tumors. Our results demonstrate that the sensitivity of these tumors to direct electric current and survival rates of the mice depended on both the amount of electrical charge and the type of tumor. Also the complete regression of each type of tumor is obtained for a threshold amount of electrical charge.

Atmospheric absorption by brown carbon aerosol may play an important role in global radiative forcing. Brown carbon arises from both primary and secondary sources, but the mechanisms and reactions of the latter are highly uncertain. One proposed mechanism is the reaction of ammonia or amino acids with carbonyl products in secondary organic aerosol (SOA). We generated SOA in situ by reacting biogenic alkenes (α-pinene, limonene, and α-humulene) with excess ozone, humidifying the resulting aerosol, and reacting the humidified aerosol with gaseous ammonia. We determined the complex refractive indices (RI) in the 360-420 nm range for these aerosols using broadband cavity enhanced spectroscopy (BBCES). The average real part (n) of the measured spectral range of the NH3-aged α-pinene SOA increased from n = 1.50 (±0.01) for the unreacted SOA to n = 1.57 (±0.01) after 1.5 h of exposure to 1.9 ppm NH3, whereas the imaginary component (k) remained below k < 0.001((+0.002)(-0.001)). For the limonene and α-humulene SOA the real part did not change significantly, and we observed a small change in the imaginary component of the RI. The imaginary component increased from k = 0.000 to an average k = 0.029 (±0.021) for α-humulene SOA, and from k < 0.001((+0.002)(-0.001)) to an average k = 0.032 (±0.019) for limonene SOA after 1.5 h of exposure to 1.3 and 1.9 ppm of NH3, respectively. Collected filter samples of the aged and unreacted α-pinene SOA and limonene SOA were analyzed off-line by nanospray desorption electrospray ionization high resolution mass spectrometry (nano-DESI/HR-MS), and in situ using a Time-of-Flight Aerosol Mass Spectrometer (ToF-AMS), confirming that the SOA reacted and that various nitrogen-containing reaction products formed. If we assume that NH3 aging reactions scale linearly with time and concentration, which will not necessarily be the case in the atmosphere, then a 1.5 h reaction with 1 ppm NH3 in the laboratory is equivalent to 24 h reaction with 63 ppbv NH3, indicating that the observed aerosol absorption will be limited to atmospheric regions with high NH3 concentrations.

Contents The objective of this study was to investigate differences on the endometrial immunoexpression of type I IFN receptor subunit 1 (IFNAR1) and oxytocin receptor (OTR) during the time of maternal recognition of pregnancy in sheep, when oestrus is synchronized with either prostaglandin analogues (group PG) or conventional progestagens (group P). Plasma progesterone was measured from day 0 to 21 post-coitus (pc) (day 0 = day of oestrus). Immunohistochemistry was performed in samples of uterine horns from pregnant sheep on days 9pc, 13pc, 15pc, 17pc and 21pc to locate IFNAR1 and OTR expression in different endometrial compartments. Mean levels of plasma progesterone were different between treatments, obtaining higher levels in the PG group than in the P group (p < 0.05). Comparing days of pregnancy, IFNAR1 protein expression was different in the luminal epithelium (LE) (p < 0.05), while OTR was different in the LE and in the superficial glandular epithelium (SG) (p < 0.05). Temporal variation on the expression of both proteins from day 9pc to 21pc has been evidenced. IFNAR1 and OTR expression did not show significant differences between treatments. However, the response observed in the endometrium was highly inconsistent when prostaglandin analogues were used. Therefore, the protocol based on prostaglandin analogues still needs to be optimized before being considered as a better alternative to progestagens for oestrous synchronization in sheep. [ABSTRACT FROM AUTHOR]

The aim of the current study was to determine the possible effects of progestagen oestrous synchronization on vascular endothelial growth factor (VEGF) expression during sheep luteogenesis and the peri-implantation period and the relationship with luteal function. At days 9, 11, 13, 15, 17 and 21 of pregnancy, the ovaries from 30 progestagen treated and 30 ewes cycling after cloprostenol injection were evaluated by ultrasonography and, thereafter, collected and processed for immunohistochemical evaluation of VEGF; blood samples were drawn for evaluating plasma progesterone. The progestagen-treated group showed smaller corpora lutea than cloprostenol-treated and lower progesterone secretion. The expression of VEGF in the luteal cells increased with time in the cloprostenol group, but not in the progestagen-treated group, which even showed a decrease between days 11 and 13. In progestagen-treated sheep, VEGF expression in granulosa-derived parenchymal lobule capillaries was correlated with the size of the luteal tissue, larger corpora lutea had higher expression, and tended to have a higher progesterone secretion. In conclusion, the current study indicates the existence of deleterious effects from exogenous progestagen treatments on progesterone secretion from induced corpora lutea, which correlate with alterations in the expression of VEGF in the luteal tissue and, this, presumably in the processes of neoangiogenesis and luteogenesis. [ABSTRACT FROM AUTHOR]

This network pharmacology study represents a significant step in understanding the potential of Resveratrol as an antidiabetic agent and its molecular targets. Targets for Type 2 diabetes were obtained from the MalaCards and DisGeNET databases, while targets for Resveratrol were sourced from the STP and CTD databases. Subsequently, we performed matching to identify common disease-compound targets. The identified genes were analyzed using the ShinGO-0.76.3 database for functional enrichment analysis and KEGG pathway mapping. A protein-protein interaction network was then constructed using Cytoscape software, and hub genes were identified. These hub genes were subjected to molecular docking and dynamic simulations using AutoDock Vina and Gromacs software. According to functional enrichment and KEGG pathway analysis, Resveratrol influences insulin receptors, endoplasmic reticulum functions, and oxidoreductase activity and is involved in the estrogen and HIF-1 pathways. Ten hub genes were identified, including ESR1, PTGS2, SRC, NOS3, MMP9, IGF1R, CYP19A1, MTOR, MMP2, and PIK3CA. The proteins associated with these genes exhibited high interaction with Resveratrol in the molecular docking analysis, and molecular dynamics showed a stable interaction of Resveratrol with ESR1, MMP9, PIK3CA, and PTGS2. In conclusion, our work enhances the understanding of the antidiabetic activity of Resveratrol, which future studies should experimentally corroborate., (© 2024 Wiley Periodicals LLC.)

Background: With improved survival of adults with congenital heart disease (CHD) comes a need to understand the lifelong outcomes of this population. The aim of this paper is to describe the rationale and design of Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE), a study to determine long-term medical, neurocognitive, and psychosocial outcomes among adults with a history of intervention for CHD and to identify factors associated with those outcomes., Methods: CHD PULSE is a cross-sectional survey conducted from September 2021 to April 2023 among adults aged 18 and older with a history of at least one intervention for CHD at one of 11 participating U.S. centers in the Pediatric Cardiac Care Consortium. Participants with CHD were asked to complete a 99-question survey on a variety of topics including: demographics, surgeries, health insurance, health care, heart doctors, general health, height and weight, education and work history, reproductive health (for women only), and COVID-19. To construct a control group for the study, siblings of survey respondents were invited to complete a similar survey. Descriptive statistics for demographics, disease severity, center, and method of survey completion were computed for participants and controls. Comparisons were made between participants and non-participants to assess for response bias and between CHD participants and sibling controls to assess for baseline differences., Results: Among the 14,322 eligible participants, there were 3133 respondents (21.9%) from 48 U.S. states with surveys returned for inclusion in the study. Sibling contact information was provided by 691 respondents, with surveys returned by 326 siblings (47.2%). The median age of participants was 32.8 years at time of survey completion, with an interquartile range of 27.2 years to 39.7 years and an overall range of 20.1 to 82.9 years. Participants were predominantly female (55.1%) and of non-Hispanic White race/ethnicity (87.1%). There were no differences between participants and non-participants regarding severity of CHD. Compared to non-participants, participants were more likely to be female, of older age, and be of non-Hispanic White race/ethnicity. Enrolled siblings were more likely to be female and slightly younger than participants., Conclusions: With surveys from 3133 participants from across the U.S., CHD PULSE is poised to provide keen insights into the lifelong journey of those living with CHD, extending beyond mere survival. These insights will offer opportunities for informing strategies to enhance and improve future outcomes for this population of patients., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To quantify the risk of long-term post-radical prostatectomy (RP) erectile dysfunction (ED) in men with diabetes mellitus (DM)., Methods: We included men who underwent RP and were followed for ≥24 months at our institution; men were excluded if they received androgen deprivation therapy or radiation therapy. Erectile function recovery (EFR) was assessed using the International Index of Erectile Function (IIEF) Erectile Function Domain (EFD) score pre-RP and serially during follow-up. We performed logistic regression analysis to investigate a potential association between erectile function 24 months post-RP., Results: Of 2261 men included, 8% were diabetic. Men in the diabetic group tended to present with more vascular comorbidities. For men with DM, the median time from diagnosis was 4 years pre-RP, and the median hemoglobin A1c pre-RP was 6.7%. After 24 months post-RP, EFR was significantly lower among the diabetic group. The median EFD was 7. Men with DM had a lower proportion of functional EFR (17%) and a greater proportion of severe ED (57%). In the univariable logistic regression model to analyze DM diagnosis was a significant predictor of functional EFR (OR 0.43, P <.001) and severe ED (OR 1.85, P <.001) 24 months post-RP. Furthermore, this was not observed for a multivariable analysis., Conclusion: Twenty-four months after RP, EFR is compromised in individuals with DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Liver damage can progress through different stages, resulting in cirrhosis or hepatocellular carcinoma (HCC), conditions that are often associated with viral infections. Globally, 42% and 21% of cirrhosis cases correlate with HBV and HCV, respectively. In the Americas, the prevalence ranges from 1% to 44%. The WHO has the goal to eliminate viral hepatitis, but it is important to consider occult HBV infection (OBI), a clinical condition characterized by the presence of HBV genomes despite negative surface antigen tests. This review aims to provide an overview of recent data on OBI, focusing on its role in the development of hepatic diseases and its significance in the WHO Viral Hepatitis Elimination Plan. Specific HBV gene mutations have been linked to HCC and other liver diseases. Factors related to the interactions between OBI and mutated viral proteins, which induce endoplasmic reticulum stress and oxidative DNA damage, and the potential role of HBV integration sites (such as the TERT promoter) have been identified in HCC/OBI patients. Health initiatives for OBI research in Latin American countries are crucial to achieving the WHO's goal of eradicating viral hepatitis by 2030, given the difficulty in diagnosing OBI and its unclear association with hepatic diseases.

Background: Vasculogenic erectile dysfunction is the most common type of erectile dysfunction, and penile Doppler ultrasound (PDUS) is a useful tool to assess erectile hemodynamics in the clinician's effort to discuss prognosis and management strategies with the patient., Aim: We herein describe the PDUS protocol used at our center, including indications, technique, and data interpretation., Methods: We describe our institutional experience with PDUS and discuss it in the context of a contemporary review of the literature for this investigation., Outcome: Our institutional PDUS protocol., Results: To perform PDUS properly, adequate training, equipment, setting, technique, and interpretation are critical. The accuracy of PDUS is entirely predicated on achieving complete cavernosal smooth muscle relaxation. A redosing protocol optimizes the reliability and reproducibility of the hemodynamic data acquired during PDUS. A rigidity-based assessment is performed, and patients are scanned according to the erection rigidity achieved (full hardness) or by administration of maximum dose of the vasoactive agent. Peak systolic velocity is considered a measure of arterial inflow (normal, >30 cm/s), while end diastolic velocity evaluates the veno-occlusive mechanism (normal, <5 cm/s). After the procedure, the patient is evaluated to confirm detumescence. If the patient has a persistent penetration rigidity erection, intracavernosal phenylephrine is administered; however, if detumescence is not achieved with intracavernosal phenylephrine injections alone, corporal aspiration is potentially performed., Conclusion: PDUS is a valuable minimally invasive tool for erectile hemodynamics assessment and an accurate assessment of such, provided that complete cavernosal smooth muscle relaxation is achieved., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objective of this study is to use GPS technology to determine if violent and property crime exposure to participants activity spaces affect outcomes of the HIV prevention and care continuum (PCC) among Young black sexually minoritized men (YBSMM) and transgender women (TGW), a subgroup at high vulnerability for new HIV diagnoses. Exposure to violent and property crime adversely affects a variety of acute and chronic medical conditions; however, the relationship between exposure to violent and property crime and HIV risk [e.g. preexposure prophylaxis (PrEP) nonuse] is unknown. Spatial analytic analysis using dynamic Global Position Systems (GPS) technology can accurately detect geospatial associations between the crime exposure and objective HIV-related outcomes., Methods: With the Neighborhoods and Networks (N2) Cohort Study, GPS technology to identify the activity space of 286 [123 people with HIV (PWH) and 163 people without HIV (PWoH)] YBSMM and TGW living in Chicago, Illinois, to identified spatial associations between violent and property crime exposures with HIV PCC outcomes., Results: We found that YBSMM and TGW with higher exposure areas with higher levels of violent crime were less likely to use HIV PrEP therapy [adjusted odds ratio (aOR) 0.76, 95% confidence interval (CI) 0.63-0.91, P  = 0.03]., Conclusion: This study demonstrates the importance of clinical providers to consider violent crime as a potential sociostructural barrier that may impact medication adherence and healthcare outcomes among vulnerable populations. Additionally, GPS technology offers an alternative data analytic process that may be used in future studies to assist in identifying barriers to ending the HIV epidemic., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chloride (Cl - ) is traditionally categorized as an antagonist of nitrate (NO 3 - ) because Cl - hinders plant NO 3 - transport and accumulation. However, we have recently defined Cl - as a beneficial macronutrient for higher plants, due to specific functions that lead to more efficient use of water, nitrogen (N) and CO 2 under optimal N and water supply. When accumulated in leaves at macronutrient levels, Cl - promotes growth through osmotic, physiological, metabolic, anatomical and cellular changes that improve plant performance under optimal NO 3 - nutrition. Nitrate over-fertilization in agriculture can adversely affect crop yield and nature, while its deficiency limits plant growth. To study the relationship between Cl - nutrition and NO 3 - availability, we have characterized different physiological responses such as growth and yield, N-use efficiency, water status, photosynthesis, leaf anatomy, pigments and antioxidants in tomato plants treated with or without 5 mM Cl - salts and increasing NO 3 - treatments (3-15 mM). First, we have demonstrated that 5 mM Cl - application can reduce the use of NO 3 - in the nutrient solution by up to half without detriment to plant growth and yield in tomato and other horticultural plants. Second, Cl - application reduced stress symptoms and improved plant growth under low-NO 3 - conditions. The Cl - -dependent resistance to low-N stress resulted from: more efficient use of the available NO 3 - ; improved plant osmotic and water status regulation; improved stomatal conductance and photosynthetic rate; and better antioxidant response. We proposed that beneficial Cl - levels increase the crop ability to grow better with lower NO 3 - requirements and withstand N deficiency, promoting a more sustainable and resilient agriculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: A high prevalence of low testosterone levels has been reported in men with prostate cancer. The use of testosterone therapy in men with a history of prostate cancer is still controversial, and there is uncertainty regarding the management of these patients., Methods: We analyzed the European and American guidelines on this topic and presented the clinical experience in the management of patients with low testosterone levels and a history of prostate cancer in one of the world's leading cancer centers., Results: According to the published evidence to date, testosterone therapy in men with prostate cancer does not increase the risk of prostate cancer recurrence in the short and medium term, but there is a lack of data on the long term. Symptomatic men with low testosterone levels who are candidates for this therapy need a thorough clinical evaluation before commencing testosterone therapy. Evaluation of prostate cancer history including type of treatment administered, pathologic stage of prostate cancer and prostate specific antigen should be requested before and during testosterone treatment to assess its trend., Conclusion: Prostate-specific antigen should remain undetectable after radical prostatectomy or stable after radiotherapy. Otherwise, it would be a sign of uncontrolled prostate cancer, and the patient may require cessation of testosterone therapy and referral to oncology for further evaluation., (Copyright © 2023 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Retention in care for people living with HIV (PLWH) is important for individual and population health. Preemptive identification of PLWH at high risk of lapsing in care may improve retention efforts. We surveyed providers at nine institutions throughout Chicago about their perspectives on using an electronic health record (EHR) tool to predict the risk of lapsing in care. Sixty-three percent (20/32) of providers reported currently assessing patients' risk for lapsing in care, and 91% (29/32) reported willingness to implement an EHR tool. When compared to those with other job roles, prescribers agreed (vs. neutral) that the tool would be less biased than personal judgment (OR 13.33, 95% CI 1.05, 169.56). Prescribers were also more likely to identify community health workers as persons who should deliver these interventions (OR 10.50, 95% CI 1.02, 108.58). Transportation, housing, substance use, and employment information were factors that providers wanted to be included in an EHR-based tool. Social workers were significantly more likely to indicate the inclusion of employment information as important (OR 10.50, 95% CI 1.11, 98.87) when compared to other participants. Acceptability of an EHR tool was high; future research should investigate barriers and evaluate the effectiveness of such a tool.

Background: Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as Streptococcus mutans and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and Streptococcus mutans ., Methods: We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking., Results: Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in Streptococcus mutans ., Conclusions: Curcumin affects both host carious processes and Streptococcus mutans .

Sleep disorders (SD) in children is a topic of great relevance due to their impact on a child's general health. This has led us to study their prevalence and the factors that disturb them in the developing population. Using a validated Likert-type questionnaire, different behaviors observed by the parents during the different phases of their children's sleep were evaluated during the last 6 months. A total of 206 children between the ages of 7 and 17 who attended a dental office participated in the study. The prevalence of SD was 47.6%. There were no significant differences regarding the SD in relation to sex ( p = 0.796). The mean total score for children aged 7 to 11 years old was 42.3 (±14.25) compared to 45.44 (±15.51) for the group consisting of children aged 12 to 17 years old, reporting a statistically significant difference among both age groups ( p = 0.01). The most frequent disorder was related to initiating and maintaining sleep (64.9%) while the least prevalent were the respiratory sleep disorders (27.2%). Given the high prevalence of these disorders, it is necessary to intercept them during childhood and establish educational guidelines in this regard throughout primary care.

Background: Testosterone (T) plays a crucial role in various physiological functions in men, and understanding the variations in T levels during the day is essential for diagnosing and treating testosterone deficiency (TD)., Aim: We sought to evaluate the reduction in serum total T (TT) levels throughout the day in men with symptoms of testosterone deficiency and to determine the variables having an impact on the extent of this decline., Methods: The study population consisted of a group of men who within 3 months of each other had all undergone both early morning and afternoon TT level measurements. We did not include patients with a history of a prior orchiectomy, testosterone levels below 100 ng/dL or above 1000 ng/dL, a history of androgen deprivation therapy, or patients on T therapy. Statistical analyses were conducted using descriptive statistics, t-tests, chi-square tests, and correlation calculations. Liquid chromatography-tandem mass spectrometry was used to measure TT, and a change in TT levels greater than 100 ng/dL was considered significant. Using multivariable and univariable analysis, we attempted to define predictors of a decrease in afternoon TT levels., Outcomes: The majority of men showed no significant difference in T levels between morning and afternoon., Results: In total, 506 men with a median age of 65 years were analyzed. The most common comorbidities were hypertension and hyperlipidemia. Levels of TT were measured in the morning and afternoon, and no significant differences in mean T levels based on the time of the test were found. Age was not significantly associated with T levels., Clinical Implications: There was a weak negative correlation between age and the difference between morning and afternoon T levels, with younger men showing more significant variations in T levels. The most considerable differences in T levels were observed in men younger than 30 years. There were no predictors of the magnitude of the T decrease in the afternoon., Strengths and Limitations: Strengths of the study include the number of subjects and the use of liquid chromatography-tandem mass spectrometry for T measurement. Limitations include failure to measure morning and afternoon T levels on the same day, the retrospective nature of the study, and a smaller sample size of patients younger than 30 years., Conclusion: In this study we found no strong link between age and daily T fluctuation, but we observed a decrease in the magnitude of variation with aging. The group experiencing the most significant decline in daily T had higher morning and consistently normal afternoon T levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In pathogen recognition, the nucleotide-binding domain (NBD) and leucine rich repeat receptors (NLRs) have noteworthy functions in the activation of the innate immune response. These receptors respond to several viral infections, among them NOD2, a very dynamic NLR, whose role in dengue virus (DENV) infection remains unclear. This research aimed to determine the role of human NOD2 in THP-1 macrophage-like cells during DENV-2 infection. NOD2 levels in DENV-2 infected THP-1 macrophage-like cells was evaluated by RT-PCR and Western blot, and an increase was observed at both mRNA and protein levels. We observed using confocal microscopy and co-immunoprecipitation assays that NOD2 interacts with the effector protein MAVS (mitochondrial antiviral signaling protein), an adaptor protein promoting antiviral activity, this occurring mainly at 12 h into the infection. After silencing NOD2 , we detected increased viral loads of DENV-2 and lower levels of IFN-α in supernatants from THP-1 macrophage-like cells with NOD2 knock-down and further infected with DENV-2, compared with mock-control or cells transfected with Scramble-siRNA. Thus, NOD2 is activated in response to DENV-2 in THP-1 macrophage-like cells and participates in IFN-α production, in addition to limiting virus replication at the examined time points.