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Introduction: Prefrontal serotonin plays a role in the expression of flexible behavior during reversal learning tasks as its depletion delays reversal learning. However, the mechanisms by which serotonin modulates the prefrontal cortex functions during reversal learning remain unclear. Nevertheless, serotonin has been shown to modulate theta activity during spatial learning and memory., Methods: We evaluated the effects of prefrontal serotonin depletion on theta activity in the prefrontal infralimbic, prelimbic, and orbitofrontal (IL, PL, and OFC) subregions of male rats during a spatial reversal learning task in an aquatic T-maze., Results: Prefrontal serotonin depletion delayed spatial reversal learning and increased theta activity power in the PL and OFC. Furthermore, animals with serotonin depletion had increased functional coupling between the OFC and the IL and PL cortices compared with the control group., Discussion: These results indicate that serotonin regulates reversal learning through modulation of prefrontal theta activity by tuning both the power and functional synchronization of the prefrontal subregions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Estrada-Reyes, Cervantes-Alfaro, López-Vázquez and Olvera-Cortés.)

Incidental visuospatial learning acquired under incidental conditions is more vulnerable to aging than in the intentional case. The theta and gamma correlates of the coding and retrieval of episodic memory change during aging. Based on the vulnerability of incidental coding to aging, different theta and gamma correlates could occur under the incidental versus intentional coding and retrieval of visuospatial information. Theta and gamma EEG was recorded from the frontotemporal regions, and incidental/intentional visuospatial learning was evaluated in young (25-60 years old) and elderly (60-85 years old) participants. The EEG recorded during encoding and retrieval was compared between incidental low-demand, incidental high-demand, and intentional conditions through an ANCOVA considering the patient's gender, IQ, and years of schooling as covariates. Older adults exhibited worse performances, especially in place-object associations. After the intentional study, older participants showed a further increase in false-positive errors. Higher power at the theta and gamma bands was observed for frontotemporal derivations in older participants for both encoding and retrieval. Under retrieval, only young participants had lower power in terms of errors compared with correct responses. In conclusion, the different patterns of power and coherence support incidental and intentional visuospatial encoding and retrieval in young and elderly individuals. The correlates of power with behavior are sensitive to age and performance.

Objective: To evaluate the relationship between social needs and metformin use among adults with type 2 diabetes (T2D)., Research Design and Methods: In a prospective cohort study of adults with T2D (n = 722), we linked electronic health record (EHR) and Surescripts (Surescripts, LLC) prescription network data to abstract data on patient-reported social needs and to calculate metformin adherence based on expected refill frequency using a proportion of days covered methodology., Results: After adjusting for demographics and clinical complexity, two or more social needs (-0.046; 95% CI -0.089, 0.003), being uninsured (-0.052; 95% CI -0.095, -0.009) and while adjusting for other needs, being without housing (-0.069; 95% CI -0.121, -0.018) and lack of access to medicine/health care (-0.058; 95% CI -0.115, -0.000) were associated with lower use., Conclusions: We found that overall social need burden and specific needs, particularly housing and health care access, were associated with clinically significant reductions in metformin adherence among patients with T2D., (© 2023 by the American Diabetes Association.)

Background and Objectives: The aim of this study was to analyze indirect costs of vaginal and laparoscopic routes for hysterectomy to determine whether this makes a difference in total costs when considering route for surgery., Methods: A five-year observational retrospective cohort study was conducted in an academic tertiary care center. A total of 517 patients scheduled for total laparoscopic hysterectomy (n = 137) and vaginal hysterectomy (n = 380) for benign conditions between January 1, 2008 and December 31, 2012 meeting inclusion criteria were reviewed., Results: Indirect costs were higher in the vaginal hysterectomy group compared to the laparoscopic hysterectomy group (mean cost €3,239.86 vs. €1,371.58; cost increase of €1,868.28; p < .001). Indirect costs due to lost-work-productivity were the most important, represented by 97.7% in the vaginal group and 93.6% in the laparoscopic group., Conclusion: Among women undergoing hysterectomy for benign disease, laparoscopic hysterectomy appears to be superior to vaginal hysterectomy when indirect costs are analyzed in a five-year temporal horizon. Laparoscopic hysterectomy is a good alternative to vaginal hysterectomy when technically feasible as both present comparable advantages. The surgical approach to hysterectomy should be decided in light of the relative benefits and hazards, which will depend on clinical circumstances and surgical expertise., (© 2022 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Background: Type 1 diabetes (T1D) is a complex disease with a higher incidence in Europeans than other populations. The Colombians Living in Medellin (CLM) is admixed with ancestry contributions from Europeans, Native Americans (NAT) and Africans (AFR)., Aim: Our aim was to analyze the genetic admixture component at candidate T1D loci in Colombian individuals with the disease., Methods: Seventy-four ancestry informative markers (AIMs), which tagged 41 T1D candidate loci/genes, were tested by studying a cohort of 200 Northwest Colombia diseased individuals. T1D status was classified by testing for glutamic acid decarboxylase (GAD-65 kDa) and protein tyrosine-like antigen-2 auto-antibodies in serum samples. Candidate loci/genes included HLA , INS , PTPN22 , CTLA4 , IL2RA , SUMO4 , CLEC16A , IFIH1 , EFR3B , IL7R , NRP1 and RNASEH1 , amongst others. The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM. As the data did not comply with a normal distribution, medians were compared between groups using the Mann-Whitney U -test., Results: Both T1D patients and individuals from CLM displayed mainly European ancestry (61.58 vs 62.06) followed by Native American (27.34 vs 27.46) and to a lesser extent the AFR ancestry (10.28 vs 10.65) components. However, compared to CLM, ancestry of T1D patients displayed a decrease of NAT ancestry at gene EFR3B (24.30 vs 37.10) and an increase at genes IFIH1 (32.07 vs 14.99) and IL7R (52.18 vs 39.18). Also, for gene NRP1 (36.67 vs 0.003), we observed a non-AFR contribution (attributed to NAT). Autoimmune patients (positive for any of two auto-antibodies) displayed lower NAT ancestry than idiopathic patients at the MHC region (20.36 vs 31.88). Also, late onset patients presented with greater AFR ancestry than early onset patients at gene IL7R (19.96 vs 6.17). An association analysis showed that, even after adjusting for admixture, an association exists for at least seven such AIMs, with the strongest findings on chromosomes 5 and 10 (gene IL7R , P = 5.56 × 10 -6 and gene NRP1 , P = 8.70 × 10 -19 , respectively)., Conclusion: Although Colombian T1D patients have globally presented with higher European admixture, specific T1D loci have displayed varying levels of Native American and AFR ancestries in diseased individuals., Competing Interests: Conflict-of-interest statement: None to declare., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: The HLA region strongly associates with autoimmune diseases, such as type 1 diabetes. An alternative way to test classical HLA alleles is by using tag SNP. A set of tag SNP for several classical HLA alleles has been reported as associated with susceptibility or resistance to this disease in Europeans. Objective: We aimed at validating the methodology based on tag SNP focused on the inference of classical HLA alleles, and at evaluating their association with type 1 diabetes mellitus in a sample of 200 families from Antioquia. Materials and methods: We studied a sample of 200 families from Antioquia. Each family had one or two children with T1D. We genotyped 13 SNPs using tetra-primer ARMS-PCR or PCRRFLP. In addition, we tested the validity of the tag SNP reported for Europeans in 60 individuals from a population of Colombians living in Medellín (CLM) from the 1000 Genomes Project database. Statistical analyses included the Hardy-Weinberg equilibrium, the transmission disequilibrium and the linkage disequilibrium tests. Results: The linkage disequilibrium was low in reported tag SNP and classical HLA alleles in this CLM population. Association analyses revealed both risk and protection factors to develop type 1 diabetes mellitus. Appropriate tag SNPs for the CLM population were determined by using the genotype information available in the 1000 Genome Project database. Conclusions: Although linkage disequilibrium patterns in this CLM population were different from those reported in Europeans, we did find strong evidence of the role of HLA in the development of type 1 diabetes mellitus in the study population.

Background: Benchmark data from the Trauma Quality Improvement Program (TQIP) identified an opportunity for improvement in our trauma programme. Our unexpected return to the intensive care unit (ICU) was found to be higher than the national averages and we also noticed that our readmission rate had increased. We chose to address these complications as continuous quality improvement projects. It was hypothesized that restructuring the workflow of the trauma advanced practice providers (APPs) to focus on the delivery of comprehensive clinical care would decrease return to ICU and readmission rates of trauma patients., Methods: The development of the APP programme occurred from 2012 to 2014. First, APP daily shifts were extended to mirror the resident physicians' coverage. Second, the APPs' original job description was expanded from 'task-oriented' workflow to providing comprehensive clinical care. Third, the APPs were involved in the evaluation and decision-making process for transferring trauma patients from the ICU. Finally, the APPs implemented a new discharge process that included all information in a standardized format and a follow-up phone call 24-48 hours after discharge. The trauma registry at our verified, academic level I trauma center was use to assess our ICU and hospital readmission rates during the time we instituted the new APP workflow programme., Results: In 2012, our ICU readmission rate was 5.7% (TQIP=1.9%) but then decreased to 4.4% in 2013 (TQIP=2.5%) and 2.1% in 2014 (TQIP=2.8%). Our hospital readmission rate was 2.0% in 2012 but then decreased to 1.38% and 0.96% over the next 2 years., Conclusions: After extending the APP service coverage, implementing a comprehensive clinical care model and standardizing the discharge process, our unplanned return to ICU rates have decreased to below the TQIP national average and hospital readmission rates have also decreased by half., Level of Evidence: III., Competing Interests: Competing interests: None declared.

Becker's nevus syndrome is part of the epidermal nevus syndromes and has been described with a phenotype that includes Becker's nevus, ipsilateral breast hypoplasia, and variable skeletal malformations. It is more frequent in males than in females (5 : 1) but is more relevant in females. The diagnosis is clinically based and the skin lesion must be present and no other numbered criteria have been established, but with more criteria being present the possibility of the diagnosis is higher. Regarding the treatment of breast hypoplasia, the use of antiandrogen medication has demonstrated adequate clinical response in a dose of 50 mg/day of spironolactone., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

The activating protein-1 transcription factor, in particular the Jun proteins play critical roles in the regulation of cell proliferation and tumor progression. To study the potential clinical relevance of interfering with JunB expression, we generated retroviruses expressing short hairpin RNA. Reduction of JunB levels causes increased proliferation and tumorigenicity in wild-type murine fibroblasts, whereas in c-Jun knockout cells p53-independent cell cycle arrest and apoptosis are induced. Using melanoma-derived B16-F10 cancer cells the combination of JunB knockdown and c-Jun/JNK inactivation leads to cell cycle arrest and apoptosis-inducing factor-dependent apoptosis. Furthermore, the combined treatment extends survival of mice inoculated with the tumor cells. These results indicate that in the absence of c-Jun, JunB can act as a tumor promoter and inactivation of both, c-Jun and JunB, could provide a valuable strategy for antitumor intervention.

Disseminated herpes simplex virus type 1 (HSV-1) infection during pregnancy is poorly described even though it is associated with high maternal and fetal morbidity and neonatal mortality in humans. In a previous paper using mice as a model, the authors demonstrated that HSV-1 is transmitted hematogenously from mother to offspring, the virus colonizing the central nervous system and provoking high mortality. In the present study, viral DNA levels in latently infected mothers were investigated during pregnancy and after delivery in mice. Samples from different organs were obtained before gestation (latency), three times during pregnancy (17, 4.5, and 1 day before delivery), and four times after delivery (1 day, 1 week, 1 and 2 months). A dramatic decrease in viral DNA concentration was observed during pregnancy, especially in the nervous system, with postnatal recovery to latent levels. All the brain regions studied showed similar trends. The viral copy numbers detected in mothers at delivery +1 day were independent of viral inoculum size. The spread of the virus to the above organs was examined immunohistochemically and, in general, more intense viral staining was observed after delivery in each. Because immunoglobulin levels can be modified by infections during pregnancy, the authors examined the levels of specific HSV-1 antibodies. Variation in HSV-1 DNA concentration was found to be associated with changes in the full spectrum of immunoglobulins (but especially immunoglobulin M [IgM]) over pregnancy, whereas at delivery -1 day a significant inverse relationship between immunoglobulins and HSV-1 DNA was observed. IgGs provided protection during the postnatal phase.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that causes severe disease and death in newborn humans but, to date, it remains unclear how neonatal infection occurs. We show here that the vertical transmission of HSV-1 in mice is mainly hematogenous and involves the colonization of the neonate central nervous system (CNS). HSV-1 DNA was mainly detected in the blood and CNS of the offspring born to latently infected mothers; no significant differences were seen between the viral DNA concentrations in the blood of these mothers and their female progeny (either neonate or adult). The administration of acyclovir during gestation reduced or eliminated both the maternal and the neonatal viral DNA in the blood. Embryo transfer was performed to ensure (as far as possible) that only vertical hematogenous infection took place. Immunohistochemical analysis detected viral proteins in the encephalon of the offspring. Immunofluorescence studies provided immunoreactive evidence of HSV-1 proteins in the neurons of the hippocampus and showed that these viruses can molecularly reactivate after hyperthermia. Neonatal HSV-1 infection therefore appears to be mainly caused by hematogenous vertical transmission, and the viruses that colonize the offspring CNS are capable of molecular reactivation after a period of latency.

Herpes simplex virus type 1 (HSV-1) causes disease in humans and animals. Infection usually occurs via the neural route and possibly occurs via the hematogenous route. The latter, however, is the main route by which immunosuppressed individuals and neonates are infected. Gender-dependent differences in the incidence and severity of some viral infections have been reported. To detect differences between the sexes with respect to HSV-1 colonization and disease, the characteristics of both acute and latent infections in hematogenously infected male and female mice were compared. In acute infection, the female mice had a poorer outcome: HSV-1 colonization was more effective, especially in the gonads and brain. In the encephalon, the midbrain had the highest viral load. In latent infection, brain viral loads were not significantly different with respect to sex. Significant differences were seen, however, in the blood and trigeminal ganglia: HSV-1 seroprevalence was observed in females, with no virus detected in males. In brain dissections, only the cerebral cortex of the females had viral loads statistically higher than those observed in the males. The spread of the virus to several organs of interest during acute infection was examined immunohistochemically. Female mice showed greater viral immunostaining, especially in the adrenal cortex, gonads, and midbrain. In male mice, HSV-1 was detected predominantly in the adrenal cortex. It was also found that apolipoprotein E promotes virus colonization of the ovaries, the APOE gene dose being directly related to viral invasiveness.

Background: So far there have been no reports on the expression pattern of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) in human breast cells and its relationship to the estrogen receptors, ER-alpha and ER-beta, and the androgen receptor (AR)., Methods: In this study we evaluated, by immunohistochemistry and Western blot analysis, the presence and distribution of DAX-1 in benign breast disease (BBD), in situ carcinoma (CIS), and ductal and lobular breast carcinomas., Results: In BBD and breast carcinomas, DAX-1 was present in both the nuclei and the cytoplasm of epithelial cells, although in infiltrative carcinomas the percentage of nuclear immunoreaction was higher than in CIS. An important relation was observed between DAX-1 and AR expression and between this orphan receptor and nodal status., Conclusion: DAX-1 might modify the AR and ER-beta intracellular location, and because a direct positive relation between the expression of these three receptors was found it could be assumed that the presence of DAX-1 in neoplastic cells might indicate a possible failure of endocrine therapies.

The aim of this study was to evaluate the presence and distribution of retinoid X receptors (RXRs) alpha, beta, and gamma in normal, hyperplastic (nodular, basal cell, and atrophic hyperplasia), and carcinomatous human prostates in order to elucidate the relationship among these receptors and the onset and development of prostatic adenocarcinoma. RXRalpha and RXRgamma were immunodetected in all samples of normal, nodular, and basal cell hyperplasia, as well as carcinomatous prostates. In atrophic glands, the expression of both receptors was found in 22.5% of samples. Positive immunostaining for RXRbeta was observed in 53.3% of normal prostates, 100% of samples showed basal cell hyperplasia, and were negative in nodular and atrophic hyperplasia. In prostatic adenocarcinoma, only 3 of 25 samples (the 3 diagnosed as well-differentiated) were positive for RXRbeta. Results suggest that diminished RXRbeta expression might be related to prostate cancer progression and because the responsiveness to retinoic acid treatments depends on the expression of different receptors, it is important to study their expression before therapy.

Expression of androgen receptor (AR), estrogen receptor alpha (ER-alpha) and estrogen receptor beta (ER-beta) in the testis of the marbled newt (Triturus marmoratus marmoratus) was investigated, with special attention to changes during the annual testicular cycle, using light microscopy immunohistochemistry and Western blot analysis. Primordial germ cells, primary and secondary spermatogonia and spermatocytes showed a positive reaction to the 3 receptor antibodies during the annual reproductive cycle. Follicular cells were positive to AR, ER-alpha and ER-beta during the spermiogenesis and quiescence periods in the glandular tissue. Interstitial cells showed reactivity to AR, ER-alpha and ER-beta in the spermiogenesis and the quiescence periods, and presented no labelling to these receptors in the proliferative period. These findings suggest that, as in mammals, there is an androgen-estrogen regulation of the function and development of the newt testis.