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Review of / Reseña de: Guirao Mirón, Cristina. Transgresoras. Una historia cultural de las mujeres. Madrid: Catarata, 2024. 109 pp. ISBN: 978-84-1067-045-7

Lichen sclerosus (LS) is a chronic inflammatory condition predominantly affecting the anogenital region of postmenopausal women. It is associated with considerable aesthetic and functional impairments and an increased risk of squamous cell carcinoma. While high-potency topical corticosteroids remain the cornerstone of treatment, therapeutic options for patients with refractory LS are scarce. Fractional CO2 laser therapy has emerged as a potential second-line intervention aiming to mitigate symptoms and improve quality of life. This prospective observational study investigated the short-term efficacy and safety of fractional CO2 laser therapy in 75 women with refractory LS who underwent four treatment sessions between January 2022 and February 2024. Sixty-nine patients completed the protocol, demonstrating significant reductions in key symptoms, including pruritus (VAS score from 7.53 ± 3.02 to 4.08 ± 3.07), pain (5.83 ± 3.84 to 2.42 ± 2.85), and dyspareunia (8.26 ± 2.82 to 6.34 ± 3.30). Quality of life, sexual function, and psychological well-being also improved, as evidenced by reductions in Dermatology Life Quality Index (DLQI) scores (10.72 ± 7.25 to 5.94 ± 5.16), enhancements in sexual function (FSFI scores from 10.48 ± 8.46 to 15.52 ± 9.59), and decreased depression severity (BDI scores from 16.66 ± 12.64 to 5.94 ± 5.16). Importantly, no adverse effects were reported during the study period. Although these findings highlight the potential of fractional CO2 laser therapy as a safe and effective adjunct for refractory LS, it is essential to acknowledge the study’s limitations, particularly the relatively short follow-up period. Longer-term studies are warranted to confirm sustained benefits and to evaluate the broader applicability of this approach.

Background: Calcium is an essential ion for pathogen survival and virulence and is involved in the regulation of the inflammatory response. Hypocalcemia is a common laboratory finding in critically ill patients. Data regarding levels of calcium in SARS-CoV-2 infection is scarce. Patients with SARS-CoV-2 infection who present with hypocalcemia could have a worse outcome. Methods: We performed a retrospective analysis of hospitalized patients with SARS-CoV-2 infection and included all patients who had any serum calcium measurement in the first 72 h since hospital admission. The main objective was to investigate the relation of low serum calcium with adverse outcome, measured by the requirement of high oxygen support – defined as high flow nasal cannula oxygen, non-invasive mechanical ventilation and/or invasive ventilation – intensive care unit admission or death. Results: A total of 316 patients were included in the study. Median age was 65 years (IQR 55–74); 65% were men. Hypocalcemia within 72 h since hospital admission was present in 63% of patients. A higher number of patients in the hypocalcemia group required high oxygen support during hospitalization (49% vs 32%; p = 0,01) and were admitted to the ICU (42% vs 26%; p = 0,005). No differences in mortality were observed between groups. Conclusions: Hypocalcemia is frequent in hospitalized patients with SARS-CoV-2 infection and can identify patients who will have a worse outcome. More studies are needed to understand the role of calcium metabolism in SARS-CoV-2 infection and to address the clinical implications and therapeutic interventions it might have.

Several genetic polymorphisms of the innate immune system have been described to increase the risk of cytomegalovirus (CMV) infection in transplant patients. The aim of this study was to assess the impact of a polygenic score to predict CMV infection and disease in high risk CMV transplant recipients (heart, liver, kidney or pancreas). On hundred and sixteen CMV-seronegative recipients of grafts from CMV-seropositive donors undergoing heart, liver, and kidney or pancreas transplantation from 7 centres were prospectively included for this purpose during a 2-year period. All recipients received 100-day prophylaxis with valganciclovir. CMV infection occurred in 61 patients (53%) at 163 median days from transplant, 33 asymptomatic replication (28%) and 28 CMV disease (24%). Eleven patients (9%) had recurrent CMV infection. Clinically and/or functionally relevant single nucleotide polymorphisms (SNPs) from TLR2, TLR3, TLR4, TLR7, TLR9, AIM2, MBL2, IL28, IFI16, MYD88, IRAK2 and IRAK4 were assessed by real time polymerase chain reaction (RT-PCR) or sequence-based typing (PCR-SBT). A polygenic score including the TLR4 (rs4986790/rs4986791), TLR9 (rs3775291), TLR3 (rs3775296), AIM2 (rs855873), TLR7 (rs179008), MBL (OO/OA/XAO), IFNL3/IL28B (rs12979860) and IFI16 (rs6940) SNPs was built based on the risk of CMV infection and disease. The CMV score predicted the risk of CMV disease with an AUC of the model of 0.68, with sensitivity and specificity of 64.3 and 71.6%, respectively. Even though further studies are needed to validate this score, its use would represent an effective model to develop more robust scores predicting the risk of CMV disease in donor/recipient mismatch (D+/R-) transplant recipients.

ABSTRACT De novo mutations in the UL56 terminase subunit and its associated phenotypes were studied in the context of cytomegalovirus (CMV) transplant recipients clinically resistant to DNA-polymerase inhibitors, naive to letermovir. R246C was the only UL56 variant detected by standard and deep sequencing, located within the letermovir-resistance-associated region (residues 230–370). R246C emerged in 2/80 transplant recipients (1 hematopoietic and 1 heart) since first cytomegalovirus replication and responded transiently to various alternative antiviral treatments in vivo. Recombinant phenotyping showed R246C conferred an advanced viral fitness and was sensitive to ganciclovir, cidofovir, foscarnet, maribavir, and letermovir. These results demonstrate a low rate (2.5%) of natural occurring polymorphisms within the letermovir-resistant-associated region before its administration. Identification of high replicative capacity variants in patients not responding to treatment or experiencing relapses could be helpful to guide further therapy and dosing of antiviral molecules. IMPORTANCE We provide comprehensive data on the clinical correlates of both CMV genotypic follow-up by standard and deep sequencing and the clinical outcomes, as well as recombinant phenotypic results of this novel mutation. Our study emphasizes that the clinical follow-up in combination with genotypic and phenotypic studies is essential for the assessment and optimization of patients experiencing HCMV relapses or not responding to antiviral therapy. This information may be important for other researchers and clinicians working in the field to improve the care of transplant patients since drug-resistant CMV infections are an important emerging problem even with the new antiviral development.

Background: UVA1 phototherapy is a treatment used for multiple dermatological conditions. The optimal therapeutic regimens and dosing of UVA1 are a matter of debate. The dosages used vary widely between published studies and there are no evidence-based protocols that provide data on dosage, duration, or the role of maintenance therapy. The purpose of this study is to evaluate the experience in our medical center regarding treatment with UVA1, as well as the degree of patient satisfaction with the treatment according to their pathology. Methods: We present a retrospective evaluation of outcomes, treatment tolerability, and satisfaction in adult patients using a low dose of UVA1 phototherapy, administered in our dermatologic service between 2019 and 2022. Results: A total of 78 patients were treated with UVA1, of whom 46 patients (59%) were over 18 years old, completed treatment, and gave their consent. The overall objective clinical response rate was 91.30% (42/46), achieving a complete response in 17 (36.96%) patients, partial response in 25 (54.34%), and no response in 4 (8.70%). The complete response rates recorded were high in morphea, scleredema, or chronic hand eczema. In terms of the level of satisfaction objectively measured by TSQM-9 version 1.4, highlighting high scores obtained in mastocytosis, systemic sclerosis, morphea, scleredema, chronic hand eczema, or prurigo nodularis (over 65 points). Conclusions: We present a review of treatment with UVA1 phototherapy at low doses with good response in a wide variety of dermatological pathologies.

Abstract Backgound In recent years we have witnessed an increase in infections due to multidrug-resistant organisms in kidney transplant recipients (KTR). In our setting, we have observed a dramatic increase in infections caused by extended-spectrum betalactamase-producing (ESBL) Enterobacteriaceae in KTR. In 2014 we changed surgical prophylaxis from Cefazolin 2 g to Ertapenem 1 g. Methods We compared bacterial infections and their resistance phenotype during the first post-transplant month with an historical cohort collected during 2013 that had received Cefazolin. Results During the study period 110 patients received prophylaxis with Cefazolin and 113 with Ertapenem. In the Ertapenem cohort we observed a non-statistically significant decrease in the percentage of early bacterial infection from 57 to 47%, with urine being the most frequent source in both. The frequency of infections caused by Enterobacteriaceae spp. decreased from 64% in the Cefazolin cohort to 36% in the Ertapenem cohort (p = 0.005). In addition, percentage of ESBL-producing strains decreased from 21 to 8% of all Enterobacteriaceae isolated (p = 0.015). After adjusted in multivariate Cox regression analysis, male sex (HR 0.16, 95%CI: 0.03–0.75), cefazolin prophylaxis (HR 4.7, 95% CI: 1.1–22.6) and acute rejection (HR 14.5, 95% CI: 1.3–162) were associated to ESBL- producing Enterobacteriaceae infection. Conclusions Perioperative antimicrobial prophylaxis with a single dose of Ertapenem in kidney transplant recipients reduced the incidence of early infections due to ESBL-producing Enterobacteriaceae without increasing the incidence of other multidrug-resistant microorganisms or C. difficile.

Importance Identifying undetected clinical signs is imperative in the prevention of SARS-CoV-2.Objective To establish the prevalence of clinical gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia. Clinical outcomes and recovery rates associated with gustatory and olfactory dysfunctions were also assessed.Design A prospective study was performed in 80 patients admitted to Hospital Clínic of Barcelona (Spain) for COVID-19 pneumonia. Patients were re-evaluated in the ward daily until discharge. Gustatory and olfactory dysfunction symptoms were retrospectively collected from emergency room (ER) charts after first assessments. Follow-up was performed in telemedicine consultation.Setting The single-centre study was performed in a hospitalisation ward at a university hospital.Participants Consecutive patients meeting hospitalisation criteria for COVID-19 pneumonia were eligible. Study exclusion criteria were patients who could not speak, had previous gustatory and olfactory dysfunctions or whose PCR tests for SARS-CoV-19 were negative.Interventions Systematic assessment of gustatory and olfactory symptoms with standardised questions.Outcome(s) Prevalence of gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia.Results Of the 80 study subjects, 62.5% were male and the median age was 57 years. Half of the cohort (n=40) presented with comorbidities. The prevalence of chemosensitive disorder was 73.8% (n=59) (95% CI: 63.8 to 83.8), although self-reported symptoms were recorded in only 26.3% (n=21) of patients in the ER. Gustatory and olfactory dysfunctions were observed in 58.8% (n=47) and 55% (n=44) of cases, respectively. They were also the first symptoms in 25% (n=20) of patients. Anosmia was associated with ageusia, OR: 7, 95% CI: 2.3 to 21.8, p=0.001). No differences in clinical outcomes were observed when patients with and without gustatory and olfactory dysfunctions were compared. Recovery rates were 20% (n=10) and 85% (n=42) at days 7 and 45, respectively.Conclusion The prevalence of gustatory and olfactory dysfunctions in COVID-19 pneumonia was much higher than in self-report. Presence of gustatory and olfactory dysfunctions was not a predictor of clinical outcomes.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.

In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% [CI 1.08-1.197]) higher levels of C-reactive protein (OR 3.068; 95% [CI 1.22-7.71]) and levels of serum creatinine on admission (OR 3.048 95% [CI 1.22-7.57]) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.

Enterobacteria species are common causes of hospital-acquired infections, which are associated with high morbidity and mortality rates. Immunocompromised patients such as solid organ transplant (SOT) recipients are especially at risk because they are frequently exposed to antibiotics in the course of their treatments. In this work, we used a collection of 106 Escherichia coli, 78 Klebsiella pneumoniae, 25 Enterobacter spp., and 24 Citrobacter spp. multidrug resistant strains isolated from transplant patients (hepatic, renal or renal/pancreatic) in order to examine their ability to adhere in vitro to HT-29 human colon cells, and to determine if some adhesive characteristics are associated with prevalence and persistence of these strains. A total of 33 E. coli (31%), 21 K. pneumoniae (27%), 7 Enterobacter spp. (28%), and 5 Citrobacter spp. (21%), adhered to the colon epithelial cells. Two main adherence patterns were observed in the four species analyzed, diffuse adherence, and aggregative adherence. Under transmission electronic microscopy (TEM), most bacteria lacked visible fimbria on their surface, despite their strong adherence to epithelial cells. None of the strains studied was able to induce any cytotoxic effect on HT-29 cells although some of them strongly colonizing both cells and glass coverslips at high density. Some of the strains failed to adhere to the epithelial cells but adhered strongly to the cover-slide, which shows that microscopy studies are mandatory to elucidate the adherence of bacteria to epithelial cells in vitro, and that quantitative assays using colony forming unit (CFUs) counting need to be supplemented with pictures to determine definitively if a bacterial strain adheres or not to animal cells in vitro. We report here, for the first time, the aggregative adherence pattern of two multidrug resistant (MDR) Citrobacter freundii strains isolated from human patients; importantly, biofilm formation in Citrobacter is totally dependent on the temperature; strong biofilms were formed at room temperature (RT) but not at 37°C, which can play an important role in the colonization of hospital surfaces. In conclusion, our results show that there is a great variety of adhesion phenotypes in multidrug-resistant strains that colonize transplanted patients.

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin whose main symptom is pruritus and may affect all age ranges. Regarding the prevalence, it has been estimated at around 10% of the world population. Many concomitant diseases have been associated with AD, but the causal relationship between AD and psychological impairment has not been clearly established. Scientific literature studying the probable association between male or female sexual dysfunction and dermatological pathology is limited, even more so in AD. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and the Cochrane Collaboration methodology for systematic reviews. All relevant articles in English were identified through a search from inception to 10 December 2020, including the following databases: Medline (via PubMed), Scopus, Web of Science Core Collection, and SciELO. The results of the search were compiled using the COVIDENCE software for systematic reviews. The methodological quality of the included studies was done using the “Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies” and the “Quality Assessment of Case-Control Studies” developed by the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH). Our search yielded potentially relevant studies. Five studies that evaluated the prevalence of sexual dysfunction in atopic dermatitis were retrieved after applying the selection criteria. The present systematic review achieved data from 8088 patients with atopic dermatitis from four articles. Sample sizes for atopic dermatitis patients ranged from 266 to 3997. We identified one cohort study with four years of follow-up, three studies with a cross-sectional design, and one case-control study. Three studies reported data disaggregated by the severity of atopic dermatitis. Two studies included healthy controls with a total sample size of 1,747,755 subjects. Two studies compared data with other dermatological conditions such as psoriasis. In conclusion, we can establish that unlike other psychological comorbidities such as anxiety and depression, sexual dysfunction is a field scarcely explored in the literature. This sexual dysfunction focuses on the male sex in large population studies and in clinical diagnoses without exploring it through specific and validated questionnaires in this regard. Further studies focused on both genders are needed. It is important to correlate this sexual dysfunction with the severity of the disease, previous treatments, and cardiovascular comorbidities.

Reconstruction of skin defects is often a challenging effort due to the currently limited reconstructive options. In this sense, tissue engineering has emerged as a possible alternative to replace or repair diseased or damaged tissues from the patient’s own cells. A substantial number of tissue-engineered skin substitutes (TESSs) have been conceived and evaluated in vitro and in vivo showing promising results in the preclinical stage. However, only a few constructs have been used in the clinic. The lack of standardization in evaluation methods employed may in part be responsible for this discrepancy. This review covers the most well-known and up-to-date methods for evaluating the optimization of new TESSs and orientative guidelines for the evaluation of TESSs are proposed.

ObjetivesThe aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance.MethodsUsing Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016.ResultsAmong 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in ConclusionsNGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.

Se evaluó el efecto de la temperatura (29, 32 y 35ºC) y del tiempo (2, 4 y 6 días) de curado, a humedades relativas de 85 a 95%, sobre las propiedades térmicas de los almidones de camote, variedad INA-100, cuyas raíces estuvieron 50 días almacenadas entre 12.8 a 15.6°C y 85 a 90% de humedad relativa. Se evaluaron las muestras de nueve tratamientos de curado y una muestra testigo que no fue curada, en tres repeticiones. Se determinó que la entalpía de gelatinización (ΔH) en el almidón de camote no vario por efecto del curado, disminuyendo en promedio ligeramente (-1.17J/g) respecto al testigo. También, la temperatura inicial (To) y pico (Tp) de gelatinización se incrementaron en promedio por efecto del curado; mientras que la temperatura final (Te) disminuyó ligeramente y el rango de la temperatura de gelatinización (Te-To) disminuyó en todos los tratamientos. El curado podría ser considerado una tecnología que modifica los almidones de camote, incrementando la To y Tp, y disminuyendo la Te y el (Te-To). Esta forma de modificar los almidones no tiene impacto ambiental y es más segura que las modificaciones químicas.

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A partir de una reflexión clínica de los trastornos límite se introduce un faro de orientación que permite dilucidar, en su seno, la neurosis y la psicosis.

Background Although a significant number of cases of Staphylococcus aureus bacteraemia (SAB) are managed at non-referral community hospitals, the impact of a bundle-of-care intervention in this setting has not yet been explored. Methods We performed a quasi-experimental before–after study with the implementation of a bundle of care for the management of SAB at five non-referral community hospitals and a tertiary care university hospital. Structured recommendations for the five indicators selected to assess quality of care were provided to investigators before the implementation of the bundle and monthly thereafter. Primary endpoints were adherence to the bundle intervention and treatment failure, defined as death or relapse at 90 days of follow-up. Results One hundred and seventy patients were included in the pre-intervention period and 103 in the intervention period. Patient characteristics were similar in both periods. Multivariate analysis controlling for potential confounders showed that performance of echocardiography was the only factor associated with improved adherence to the bundle in the intervention period (adjusted OR 2.13; 95% CI 1.13–4.02). Adherence to the bundle, performance of follow-up blood cultures, and adequate duration of antibiotic therapy for complicated SAB presented non-significant improvements. The intervention was not associated with a lower rate of 90 day treatment failure (OR 1.11; 95% CI 0.70–1.77). Conclusions A bundle-of-care intervention for the management of SAB at non-referral community hospitals increased adherence to quality indicators, but did not significantly reduce rates of 90 day mortality or relapse. [ABSTRACT FROM AUTHOR]

Brown adipose tissue, known produce heat by metabolizing fat, is also secretes molecules capable of communicating with other organs. Here the authors show that brown adipose tissue secretes kininogen, a component of heat system regulation, that provides auto-regulatory inhibitory signaling in brown adipose tissue.

Nicotine reduces food intake and increases energy expenditure in brown adipose tissue. Here the authors show that nicotine also induces white adipose tissue browning via central kappa opioid receptor action.

Background: While the impact of metformin in hepatocytes leads to fatty acid (FA) oxidation and decreased lipogenesis, hepatic microRNAs (miRNAs) have been associated with fat overload and impaired metabolism, contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methods: We investigated the expression of hundreds of miRNAs in primary hepatocytes challenged by compounds modulating steatosis, palmitic acid and compound C (as inducers), and metformin (as an inhibitor). Then, additional hepatocyte and rodent models were evaluated, together with transient mimic miRNAs transfection, lipid droplet staining, thin-layer chromatography, quantitative lipidomes, and mitochondrial activity, while human samples outlined the translational significance of this work. Findings: Our results show that treatments triggering fat accumulation and AMPK disruption may compromise the biosynthesis of hepatic miRNAs, while the knockdown of the miRNA-processing enzyme DICER in human hepatocytes exhibited increased lipid deposition. In this context, the ectopic recovery of miR-30b and miR-30c led to significant changes in genes related to FA metabolism, consistent reduction of ceramides, higher mitochondrial activity, and enabled β-oxidation, redirecting FA metabolism from energy storage to expenditure. Interpretation: Current findings unravel the biosynthesis of hepatic miR-30b and miR-30c in tackling inadequate FA accumulation, offering a potential avenue for the treatment of NAFLD. Funding: Instituto de Salud Carlos III (ISCIII), Govern de la Generalitat (PERIS2016), Associació Catalana de Diabetis (ACD), Sociedad Española de Diabetes (SED), Fondo Europeo de Desarrollo Regional (FEDER), Xunta de Galicia, Ministerio de Economía y Competitividad (MINECO), “La Caixa” Foundation, and CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN). Keywords: MicroRNAs, AMPK, Hepatocytes, Fatty acid homeostasis, Steatosis

Background/Aims: Thyroid hormones have been recently linked to senescence and longevity. Given the recent description of TSHB mRNA in human adipose tissue (AT), we aimed to investigate the relationship between local AT TSH and adipose tissue senescence. Methods: TSHB mRNA (measured by real-time PCR) and markers of adipose tissue senescence [BAX, DBC1, TP53, TNF (real-time PCR), telomere length (Telo TAGGG Telomere Length Assay) and lipidomics (liquid chromatography mass spectrometry)] were analysed in subcutaneous (SAT) and visceral (VAT) AT from euthyroid subjects. The chronic effects of TSH were also investigated in AT from hypothyroid rats and after recombinant human TSH (rhTSH) administration in human adipocytes. Results: Both VAT and SAT TSHB gene expression negatively correlated with markers of AT cellular senescence (BAX, DBC1, TP53, TNF gene expression and specific glucosylceramides) and positively associated with telomere length. Supporting these observations, both rhTSH administration in human adipocytes and increased TSH in hypothyroid rats resulted in decreased markers of cellular senescence (Bax and Tp53 mRNA) in both gonadal and subcutaneous white adipose tissue. Conclusion: These data point to a possible role of TSH in AT cellular senescence.

The best immunosuppressive regimen in HIV-infected renal transplant recipients has not been established. Thymoglobulin has been associated with an increased risk of serious bacterial infections in HIV-negative patients and, for this reason, there is some concern over its use in the HIV-infected population. We describe three consecutive HIV-infected renal transplant recipients who received thymoglobulin as induction therapy, and we compared their progress with a cohort of 23 HIV-negative recipients. Median follow-up was 24 and 11 months, respectively. Nadir lymphocytopenia was observed at 1 week in both groups, and their absolute lymphocyte count recovery was similar. An early and deep (<30 cellsmm3) CD4T cell lymphocytopenia was seen in two of the three HIV-infected patients. No opportunistic infections were diagnosed in HIV-positive patients. One HIV-positive patient had a bacterial infection and five HIV-negative patients had one or more bacterial infections. Thymoglobulin was safe in our three HIV-infected renal transplant recipients. Until those data are confirmed in larger studies, close monitoring is recommended during the thymoglobulin-induced CD4T cell lymphocytopenia period. [ABSTRACT FROM AUTHOR]

Summary: Compelling evidence has shown that, besides its putative effect on the regulation of the gonadal axis, estradiol (E2) exerts a dichotomic effect on the hypothalamus to regulate food intake and energy expenditure. The anorectic effect of E2 is mainly mediated by its action on the arcuate nucleus (ARC), whereas its effects on brown adipose tissue (BAT) thermogenesis occur in the ventromedial nucleus (VMH). Here, we demonstrate that central E2 decreases hypothalamic ceramide levels and endoplasmic reticulum (ER) stress. Pharmacological or genetic blockade of ceramide synthesis and amelioration of ER stress selectively occurring in the VMH recapitulate the effect of E2, leading to increased BAT thermogenesis, weight loss, and metabolic improvement. These findings demonstrate that E2 regulation of ceramide-induced hypothalamic lipotoxicity and ER stress is an important determinant of energy balance, suggesting that dysregulation of this mechanism may underlie some changes in energy homeostasis seen in females. : González-García et al. demonstrate that estradiol (E2) acts in a precise area of the hypothalamus, named the ventromedial nucleus (VMH), to regulate brown fat thermogenesis. The actions of E2 are mediated by modulation of hypothalamic ceramides and ER stress. Keywords: estradiol, hypothalamus, ceramides, endoplasmic reticulum stress, brown adipose tissue, thermogenesis