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Aims: Pulsed field ablation (PFA) is described as non-thermal, but data from oncology and cardiology show thermal effects occur. The specific waveform parameters influencing thermal energy development during PFA are unclear. The aim of this study is to numerically evaluate the thermal effects of PFA on myocardial and oesophageal tissue at various peak voltage conditions., Methods and Results: A three-dimensional computer model of the left atrium quantified thermal effects from PFA at peak voltages of 1, 1.5, and 2 kV. Energy was applied using a bipolar configuration with far-field and symmetry boundaries set as electrically insulating. A monophasic waveform with a 100 μs pulse width and a 1 s gap between pulses was applied for a total of 50 pulses, mimicking clinical conditions. Minimal temperature rise in the oesophagus was observed with 1 kV pulses (214.5 J). At 1.5 and 2 kV (570.3 and 1.23 kJ), temperatures reached 46.3°C and >62°C, respectively, after a single pulse train. These findings suggest that repeated applications could lead to even higher temperatures, especially if good tissue contact is obtained. These results align with data from other medical fields using pulsed field treatments., Conclusion: Thermal effects from PFA depend on the total energy deposited, with peak voltage being a significant factor. Current commercially available PFA systems have the potential to induce collateral thermal injury with repeated applications of pulsed field energy. This highlights the need for careful monitoring and adjustment of PFA parameters in clinical settings., Competing Interests: Conflict of interest: M.M.-M.: employment with Insilico STEM; T.G.-B.: employment with Insilico STEM; E.K.: consulting for Haemonetics; S.R.M.: ownership of Field Medical, consulting for Atraverse; L.J.O.: none; A.G.-S.: none., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Forty-two 4-phenylthiazole analogs, organized in two libraries 4a-u and 6a-u, were prepared and biologically evaluated in human fatty acid amide hydrolase (FAAH), and human, rat and mouse soluble epoxide hydrolase (sEH) inhibition assays. This structure-activity relationship (SAR) study explores the impact of electronic and steric changes on the molecule's potency and binding affinity to better understand the structural features important for dual sEH/FAAH inhibition which will guide the development of novel treatments for pain and inflammation. Our SAR revealed that electron-donating groups on the aromatic ring of the 4-phenylthiazole moiety are particularly well tolerated by both enzymes when placed at the ortho, meta and para positions; however, the overall 3D shape of the molecule is very important for the potent FAAH inhibition, suggesting more restricted size of the FAAH binding pocket compared to sEH binding pocket. Two selected dual inhibitors, 4p and 4s, were tested in the rat liver microsomes stability assays and evaluated in vivo in the formalin test. Systemic administration of 4p and 4s via intraperitoneal injection decreased nociceptive behavior (i.e., licking of the injected paw) in male rats, and this effect was dose-dependent for both compounds. Two doses, 1 and 3 mg/kg of 4p, decreased nociceptive behavior to a similar extent to that of 30 mg/kg ketoprofen, a traditional nonsteroidal anti-inflammatory drug. However, only 3 mg/kg of 4s decreased nociceptive behavior compared to vehicle-treated animals, and this effect was comparable to ketoprofen-treated animals. Taken together, these findings reveal the antinociceptive potential of 4-phenylthiazole-based dual FAAH and sEH inhibitors and suggest pharmacodynamic differences within this class of inhibitors despite similar potencies in vitro., 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 © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Defining the trajectory of cells during differentiation and disease is key for uncovering the mechanisms driving cell fate and identity. However, trajectories of human cells remain largely unexplored due to the challenges of studying them with human samples. In this study, we investigate the proteome trajectory of iPSCs differentiation to hepatic stellate cells (diHSCs) and identify RORA as a key transcription factor governing the metabolic reprogramming of HSCs necessary for diHSCs' commitment, identity, and activation. Using RORA deficient iPSCs and pharmacologic interventions, we show that RORA is required for early differentiation and prevents diHSCs activation by reducing the high energetic state of the cells. While RORA knockout mice have enhanced fibrosis, RORA agonists rescue multi-organ fibrosis in in vivo models. Notably, RORA expression correlates negatively with liver fibrosis and HSCs activation markers in patients with liver disease. This study reveals that RORA regulates cell metabolic plasticity, important for mesoderm differentiation, pericyte quiescence, and fibrosis, influencing cell commitment and disease., Competing Interests: Competing interests: M.C. and P.S-B. have a patent (EP2016/079464) regarding the hepatic stellate cell differentiation. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Neltuma spp. are an important resource in arid and semiarid ecosystems of the country and serve, among other purposes, as an economic source of food for livestock. By analyzing the bromatological composition and in vitro fermentation of pods in three regions of the state of Zacatecas, Mexico, the viability as a food alternative in sheep is sought. Twenty-seven pod samples were collected from nine points in each region of the state. The samples were obtained when the pods were in the immature stage. The bromatological analysis of the pods was conducted and mathematical equations were used to calculate the megacalories per kilogram provided by these fruits. Statistical analysis was performed using Spearman's correlation coefficient. Bromatological analysis showed that crude protein averaged 20.86 ± 1.37% in the central region, while non-fiber carbohydrates averaged 26.78 ± 1.32% in the southern region. Neltuma spp. pods demonstrate potential as an alternative feed for sheep, provided that an adequate diet is formulated, since they present acceptable levels of protein, carbohydrates and fiber. It is recommended to consider the state of maturity of the pods when incorporating them into the diet of sheep.

Context: Genetic tests are part of the routine clinical approach to syndromic and nonsyndromic phenotypes of neuroendocrine neoplasms (NENs). Current data on phenotype-genotype associations in NENs, however, do not accurately represent all populations., Objective: To describe the frequency, inventory, and clinical associations of germline defects associated with multiple types of NENs in a Mexican cohort., Methods: Blood DNA from Mexican adults with NENs was analyzed with a 53-gene NGS panel developed ad hoc (n=90) or Sanger sequencing (n=2). Single nucleotide variants, indels and structural variants were identified, classified, and subjected to orthogonal confirmation. When possible, tumor samples and blood DNA from additional family members were tested using Sanger sequencing., Results: Ninety-two probands (70.7% women, 51.5% sporadic) were included; sixteen carried pathogenic or likely pathogenic (P/LP) variants and were significantly younger at disease onset, compared with the rest (29.6±10,7 vs. 40 [21.5-51.5] years, P=0.0384). Likely driving variants were identified in three-quarters of Von Hippel Lindau syndrome cases, one-third of multiple endocrine neoplasia type 1 (MEN1), one-quarter of early-onset acromegaly/gigantism, and individual cases of Cushing's disease, MEN2A, and medullary thyroid carcinoma. One patient with clinical MEN1 associated with an SDHA variant and one with a pituitary tumor and neurofibromatosis type 1 were also identified. Probands with familial disease were more likely to carry P/LP variants, compared with sporadic cases (26.7 vs 8.5%, P=0.0282)., Conclusion: P/LP variants were identified in 17.4% of individuals with NENs. Our research provides a view of the landscape of NEN drivers in a population not previously characterized., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.)

The use of medicinal plants represents an alternative method for bacterial control due to their chemical compositions. This study's objective was to determine the inhibitory capacity of Larrea tridentata extracts against microbial strains of clinical interest. Four extracts were prepared, their phytochemical profiles were determined, and their antioxidant capacities were quantified. Additionally, the minimum concentrations of hemolysis were determined using human blood erythrocytes. For the extracts' growth inhibitory capacity, six bacterial and two fungal strains were evaluated using the disk diffusion test. Commercial medications specific for each strain were used as controls. The ethanolic extracts registered the greatest diversity of metabolites related to antibacterial activity. The inhibitory activities of the ethanolic extract and the Cedax ® control were similar for Enterococcus faecalis . A principal component analysis was performed with X 2 and ANOVA tests to identify the relationships and the effects of the extracts on bacterial inhibition, obtaining p > 0.05 with a confidence level of 95%. This research highlights the potential of L. tridentata extracts as an alternative treatment and to mitigate the growing problem of resistance to traditional antibiotics.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome. Currently, there is no preventative treatment or cure. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium aims to identify modulators of brain injury and adverse neurodevelopmental outcomes for Zika and other prenatal viral infections., Methods: The Consortium pools information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic repository, which is being mined for modifiers of virally induced brain injury. Partners include Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), Zika Instituto Fernandes Figueira (Brazil), the Centers for Disease Control and Prevention, and the National Institutes of Health., Results: We have enrolled 4102 mothers and 3877 infants with 3063 biological samples and clinical data covering over 80 phenotypic fields and 5000 variables. Thus far, we have performed whole exome sequencing on 1226 participants., Conclusion: Here, we present the Consortium's formation and overarching study design., Impact: The PING Consortium brings together investigators and institutions to determine the causes of virally induced brain injury and neurological deficits. The clinical and genomic repository, with data from over 8000 patients, will serve as a foundation for a variety of basic and clinical studies., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent statement: Samples and associated data collected through the Prenatal Infection and Neurodevelopmental Genetics Consortium were IRB approved by participating institutions and by Children’s National Hospital (IRB reference number 8259). Any changes to the protocol or materials are submitted for approval by the IRB/CEP before being implemented, through amendments to the project. The research team notifies the IRB/CEP of deviations from the protocol or any adverse events that might be related to the present study. Brazilian studies were also approved by CONEP (approval numbers of the original related projects: CAAEs: 61936216.9.0000.5404; 56673616.3.2002.5440; 61936216.9.0000.5404). The researchers ensured that this study was conducted in full compliance with the principles set out in the Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects in Research by the US National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research (18 April 1979) and encoded in 45 CFR Section 46 or the ICH E6; 62 Federal Regulations 25691 (1997). The Investigators’ institution must maintain an up-to-date, federal-level policy (FWA) issued by the Office of Human Protection in Research for US government-funded research. Both multi-center and site-specific IRB approvals were obtained in one of in two ways. A majority of the studies obtained informed consent for genetic testing prospectively. In some cases, informed consent was obtained retrospectively., (© 2025. The Author(s).)

Background: A novel rigidizing overtube (ROT) was developed to facilitate endoscopic removal of complex gastrointestinal polyps. We aimed to prospectively evaluate the efficacy and safety of the device in the management of large gastrointestinal polyps., Methods: A prospective, single-center study, conducted between May 2021 and April 2023, enrolled patients undergoing endoscopic resection of colon/duodenal polyps ≥25 mm. Primary outcomes were safety, technical success, and clinical success defined as the ability of ROT to facilitate endoscopic polyp removal without changing the initial resection method., Results: 97 patients (98 polyps), with a mean polyp size of 33.2 mm (median 31.1), were evaluated. Technical and clinical success rates were 100% and 84%, respectively. Ileocecal valve location was the only predictor of clinical failure (P = 0.02). The mean time to reach the lesion was 7.2 minutes (95%CI 5-8), with overall resection and procedure times of 53.6 minutes (95%CI 48-61) and 88.9 minutes (95%CI 79-95), respectively. No device-related adverse events occurred. Lower technical (67%) and clinical (67%) success rates were seen for duodenal polyps (n = 6)., Conclusion: The novel ROT was safe, with high technical and clinical success during resection of complex colon polyps. Future studies will determine timing of implementation during routine endoscopic resection., Competing Interests: S. Jawaid is a consultant for ConMed, Boston Scientific Corp., Creo Medical, and Lumendi. T. Keihanian is a consultant for Neptune Medical, ConMed, and Lumendi. M. Othman is a consultant for Olympus, Boston Scientific Corp., AbbVie, ConMed, Creo Medical, Lumendi, and Apollo. A.F. Aboelezz, G. Daba, M. Khalaf, F. Ayoub, N, Zabad, and M. Mercado declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Proactive esophageal cooling reduces injury during radiofrequency (RF) ablation of the left atrium (LA) for the treatment of atrial fibrillation (AF). New catheters are capable of higher wattage settings up to 90 W (very high-power short duration, vHPSD) for 4 s. Varying power and duration, however, does not eliminate the risk of thermal injury. Furthermore, alternative energy sources such as pulsed field ablation (PFA) also exhibit thermal effects, with clinical data showing esophageal temperatures up to 40.3°C. The ensoETM esophageal cooling device (Attune Medical, now a part of Haemonetics, Boston, MA, U.S.A.) is commercially available and FDA-cleared to reduce thermal injury to the esophagus during RF ablation for AF and is recommended in the 2024 expert consensus statement on catheter and surgical ablation of AF., Areas Covered: This review summarizes growing evidence of esophageal cooling during high power RF ablation for AF treatment, including data relating to procedural efficacy, safety, and efficiency, and techniques to enhance operator success while providing directions for further research., Expert Opinion: Proactive esophageal cooling reduces injury to the esophagus during high power RF ablation, and utilizing this approach may result in increased success in first-pass isolation, procedural efficiency, and long-term efficacy.

Background: Distinguishing serous cystadenoma, a benign pancreatic cyst, from potentially malignant mucinous pancreatic cystic lesions carries significant clinical and prognostic implications; and while endoscopic ultrasound-guided fine needle aspiration is the standard diagnostic tool, its low diagnostic yield often results in additional workup., Objective: This study evaluates diagnostic yield of fine needle biopsy (FNB) on lesions suggestive of serous cystadenoma on endoscopic ultrasound., Methods: Patients with microcystic EUS appearance were identified through retrospective chart review in two institutions. Prior cross sectional imaging diagnosis was also obtained. All microcystic lesions with classic "honeycomb" appearance for serous cystadenoma on EUS were targeted for FNB and their pathology evaluated. Patients were identified through database search from 2015 to 2022 and procedure information was obtained through a retrospective chart review from two large academic centers., Results: Thirty-one patients with suspected serous cystadenoma who underwent EUS-FNB were included. EUS FNB was successful in obtaining diagnosis in 96.8% of patients. Serous cystadenoma was diagnosed via EUS FNB in 27 of 31 patients (87.1%). Of the remaining four patients, there was one invasive pancreatic ductal adenocarcinoma, one pancreatic neuroendocrine tumor, one intraductal papillary mucinous neoplasm, and one nondiagnostic sample., Conclusion: EUS-FNB sampling for histopathology is a safe and accurate diagnostic tool for pancreatic serous cystadenoma. When microcytic lesions are found on endoscopic ultrasound, our study results suggest that fine needle biopsy for histopathology should be considered as the initial diagnostic evaluation tool given the demonstrated improved diagnostic yield for serous cystadenoma., Competing Interests: Conflicts of Interest, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Neutralizing antibody (nAb) responses against SARS-CoV-2 variants after inactivated virus vaccine (CoronaVac) in kidney transplant recipients (KTRs) with or without SARS-CoV-2 infection history remains unclear. We aimed to evaluate the neutralizing antibody responses against emerging SARS-CoV-2 variants after two doses of CoronaVac in these patients. 22.2% of participants had hybrid immunity. Anti-spike IgG antibodies were evidenced in 44% of the patients. nAbs against B.1.111, Mu, and Omicron were detected in 28.5%, 17.9%, and 21.4% of naïve KTRs, respectively. Furthermore, nearly 100% of KTRs with hybrid immunity had nAbs against the variants evaluated. Thus, a significant proportion of infection-naïve KTRs had no detectable nAb titers against Mu and Omicron variants after two doses of the CoronaVac vaccine. However, the nAb titers were significantly higher in patients with hybrid immunity, and it was no association between the immunosuppressive regimen and the seropositivity rate of anti-SARS-CoV-2 neutralizing antibodies. Therefore, hybrid KTRs are protected against COVID-19 by emerging variants able to escape from vaccine-elicited nAbs such as Mu and Omicron., Competing Interests: Declarations. Ethical approval: This study was performed following the ethical standards of the Declaration of Helsinki 1964 on research ethics 2013 and resolution 8430 from the Health Ministry of Colombia. All subjects enrolled in this research responded voluntarily to an informed consent formulary previously approved by the Institutional Ethics Committee of the Instituto Nacional de Salud (CEMIN 010–2020, and CEMIN 019/2021). Informed consent: Written informed consents were obtained from the patients for the collection and publication of clinical data. Competing interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Prolactin (PRL) is a polypeptide hormone produced by the lactotrope cells of the anterior pituitary gland. Among its myriads of biological functions, PRL is the main regulator of mammary gland growth and development, as well as of the production and secretion of milk. Hyperprolactinemia represents a frequent consultation cause in medical practice. Nevertheless, elevations in serum PRL are not always pathological. Drug induced hyperprolactinemia is the most common cause, mainly by antipsychotics, followed by other causes such as pituitary neuroendocrine tumors, physiologic conditions, and systemic diseases such as chronic kidney disease and hypothyroidism. When evaluating a patient with hyperprolactinemia it is of utmost importance to consider the diverse etiologies of this condition in order to avoid unnecessary diagnostic workup and treatment. Regarding reproductive health, hyperprolactinemia is a well-documented cause of infertility, as approximately 15-20% of women undergoing infertility evaluation have hyperprolactinemia, which causes secondary amenorrhea, and other menstrual irregularities. Similarly, in men it is a cause of hypogonadism., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

This study explored the manifestations of intersectional structural stigma and stigma-reducing strategies in the context of health among a diverse group of persons experiencing homelessness in the southwest United States. Purposive sampling was used to recruit youth (ages 12-17), young adults (ages 18-24), adults (ages 25 years old or older), women with children, veterans, and males over 60 years old who self-identified as homeless. Grounded theory was applied, and thematic analysis was conducted using data collected from seven focus groups ( n = 76 participants). A model of intersectional stigma was adapted from the Health Stigma and Discrimination Framework. This adaptation depicts pathways for addressing intersectional stigmatization experienced by individuals with multiple intersecting identities across the interpersonal, organization, and community levels not explicitly addressed in the Health Stigma and Discrimination Framework. At the interpersonal level, participants indicated they experienced stigmatizing behaviors and practices by service providers due primarily to their identities related to economic or unhoused statuses, gender, age, and mental health. Facilitators of intersectional stigma were identified through organization practices and processes. Multiple stigmatized identities due to social beliefs also facilitated stigmatization at the community level. Health outcomes influenced by stigmatization were also identified. Despite the stigmatization they experienced, participants discussed stigma-reducing strategies related to community assets, medical care, and destigmatizing practices by service providers., Competing Interests: Declaration of Conflicting InterestsThe author(s) have no conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSCs) and immune cells, among others. MSC have been isolated from different tumors and they favor tumor cell growth; however, their role in pituitary tumors (PTs) remains unknown., Objective: Herein we report the presence of MSCs in 2 adrenocorticotropin (ACTH)-secreting PTs causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF), and 2 nontumoral pituitary glands (MS)., Methods: We have analyzed the transcriptomic profiles by RNA sequencing and compared MSCs in terms of their immunosuppressive effects against lymphoid T-cell and macrophage populations by means of cocultures and flow cytometry., Results: Our transcriptomic analysis revealed molecular differences between MSCs derived from nontumoral pituitaries and MSCs derived from PTs. Two distinct subpopulations of MSC emerged: one displaying immunosuppressive properties and the other with increased proproliferative capabilities, regardless of their origin. MSCs derived from ACTH- and nonfunctioning PTs, but not those derived from nontumoral glands, significantly inhibited the proliferation of activated T cells, favored the generation of regulatory T cells, and promoted M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony-stimulating factor (M-CSF) and interleukin-10. Importantly, MSC derived from ACTH-PTs showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors., Conclusion: This study demonstrates the presence of at least 2 MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSCs may have important implications in PT growth., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Ammonia is a pathogenic factor implicated in the progression of metabolic-associated steatotic liver disease (MASLD). The contribution of the glutaminase 1 (GLS) isoform, an enzyme converting glutamine to glutamate and ammonia, to hepatic ammonia build-up and the mechanisms underlying its upregulation in metabolic-associated steatohepatitis (MASH) remain elusive., Methods: Multiplex transcriptomics and targeted metabolomics analysis of liver biopsies in dietary mouse models representing the whole spectra of MASLD were carried out to characterize the relevance of hepatic GLS during disease pathological progression. In addition, the acute effect of liver-specific GLS inhibition in hepatic ammonia content was evaluated in cultured hepatocytes and in in vivo mouse models of diet-induced MASLD. Finally, the regulatory mechanisms of hepatic GLS overexpression related to the lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4) axis were explored in the context of MASH., Results: In mouse models of diet-induced MASLD, we found that augmented liver GLS expression is closely associated with the build-up of hepatic ammonia as the disease progresses from steatosis to steatohepatitis. Importantly, the acute silencing/pharmacological inhibition of GLS diminishes the ammonia burden in cultured primary mouse hepatocytes undergoing dedifferentiation, in steatotic hepatocytes, and in a mouse model of diet-induced steatohepatitis, irrespective of changes in ureagenesis and gut permeability. Under these conditions, GLS upregulation in the liver correlates positively with the hepatic expression of TLR4 that recognizes LPS. In agreement, the pharmacological inhibition of TLR4 reduces GLS and hepatic ammonia content in LPS-stimulated mouse hepatocytes and hyperammonemia animal models of endotoxemia., Conclusions: Overall, our results suggest that the LPS/TLR4 axis regulates hepatic GLS expression promoting liver ammonia build-up as steatotic liver disease progresses to steatohepatitis., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET., (© 2024. The Author(s).)

Introduction: Deployment-limiting medical conditions (DLMCs) such as debilitating injuries and conditions may interfere with the ability of military service members (SMs) to deploy. SMs in the United States (U.S.) Department of the Navy (DoN) with DLMCs who are not deployable should be placed in the medically restricted status of limited duty (LIMDU) or referred to the Physical Evaluation Board (PEB) for Service retention determination. It is critical to identify SMs correctly and promptly with DLMCs and predict their return-to-duty (RTD) to ensure the combat readiness of the U.S. Military. In this study, an algorithmic approach was developed to identify DoN SMs with previously unidentified DLMCs and predict whether SMs on LIMDU will be able to RTD., Materials and Methods: Five years of historical data (2016-2022) were obtained from inpatient and outpatient datasets across direct and purchased care from the Military Health System (MHS) Data Repository (MDR). Key fields included International Classification of Diseases diagnosis and procedure codes, Current Procedure Terminology codes, prescription medications, and demographics information such as age, rank, gender, and service. The data consisted of 44,580,668 medical encounters across 1,065,224 SMs. To identify SMs with unidentified DLMCs, we developed an ensemble model combining outputs from multiple machine learning (ML) algorithms. When the ML ensemble model predicted a SM to have high risk scores, despite appearing healthy on administrative reports, their case was reviewed by expert clinicians to investigate for previously unidentified DLMCs; and such feedback served to validate the developed algorithms. In addition, leveraging 1,735,422 encounters (60,433 SMs) from LIMDU periods, we developed four separate ML models to estimate RTD probabilities for SMs after each medical encounter and predict the final LIMDU outcome., Results: The ensemble model had 0.91 area under the receiver operating characteristic curve (AUROC). Out of 236 (round one) and 314 (round two) SMs reviewed by clinicians, 127 (54%) and 208 (66%) SMs were identified with a previously unidentified or undocumented DLMC, respectively. Regarding predicting RTD for SMs placed on LIMDU, the best performing ML model achieved 0.76 AUROC, 68% sensitivity, and 71% specificity., Conclusion: Our research highlighted potential benefits of using predictive analytics in a medical assessment to identify SMs with DLMCs and to predict RTD outcomes once placed on LIMDU. This capability is being deployed for real-time clinical decision support to enhance health care provider's deployability assessment capability, improve accuracy of the DLMC population, and enhance combat readiness of the U.S Military., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Competing Interests: S. Jawaid is a consultant for ConMed, Boston Scientific Corp., Creo Medical, and Lumendi. T. Keihanian is a consultant for Neptune Medical, ConMed, and Lumendi. M. Othman is a consultant for Olympus, Boston Scientific Corp., AbbVie, ConMed, Creo Medical, Lumendi, and Apollo. A.F. Aboelezz, G. Daba, M. Khalaf, F. Ayoub, N, Zabad, and M. Mercado declare that they have no conflict of interest.

This study aimed to understand vaccine hesitancy and confidence toward the COVID-19 vaccines among Latino adults in Arizona. Latinos ( n = 71) aged 18 years or older who resided in Arizona participated in 14 focus groups between February and June 2021. Theoretical thematic analysis was used to examine drivers of these two behaviors, namely, vaccine hesitancy and confidence toward the COVID-19 vaccines, using the COM-B model, comprising capability, opportunity, and motivation factors that generate a behavior. Vaccine hesitancy stemmed from the need for vaccine information (capability factor) and fear of the vaccines, religious beliefs, and perceived barriers stemming from government mistrust (motivation factors). Vaccine confidence arose from trust in science and doctors (capability factor), and a fear of getting sick, protection against COVID-19, getting vaccinated as a civic duty, and a desire to return to normal life (motivation factors). The influence of opportunity factors, such as having access to vaccinations, were not discussed as contributing to vaccine confidence or hesitancy. As predicted by the COM-B model, factors reflecting capabilities and motivations contributed to vaccine hesitancy and confidence, all of which need to be considered in public health messaging. These factors can be targeted to facilitate efforts to promote vaccine uptake and reduce the spread of COVID-19., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Drug-induced liver injury (DILI) is a significant cause of acute liver failure (ALF) and liver transplantation in the Western world. Acetaminophen (APAP) overdose is a main contributor of DILI, leading to hepatocyte cell death through necrosis. Here, we identified that neddylation, an essential post-translational modification involved in the mitochondria function, was upregulated in liver biopsies from patients with APAP-induced liver injury (AILI) and in mice treated with an APAP overdose. MLN4924, an inhibitor of the neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8)-activating enzyme (NAE-1), ameliorated necrosis and boosted liver regeneration in AILI. To understand how neddylation interferes in AILI, whole-body biotinylated NEDD8 ( bio NEDD8) and ubiquitin ( bio UB) transgenic mice were investigated under APAP overdose with and without MLN4924. The cytidine diphosphate diacylglycerol (CDP-DAG) synthase TAM41, responsible for producing cardiolipin essential for mitochondrial activity, was found modulated under AILI and restored its levels by inhibiting neddylation. Understanding this ubiquitin-like crosstalk in AILI is essential for developing promising targeted inhibitors for DILI treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Zika virus (ZIKV) infection in pregnancy is associated with severe abnormalities of the brain and eye and other adverse outcomes. Zika en Embarazadas y Niños was a prospective cohort study conducted in multiple Colombian cities that enrolled pregnant women in their first trimester. Specimens collected from pregnant women (n = 1,519) during February 2017-September 2018 and their infants (n = 1,080) during June 2017-March 2019 were tested for prenatal ZIKV infection by nucleic acid amplification tests or IgM antibody testing. Zika virus infection in pregnancy was present in 3.2% of pregnant women (incidence rate [IR] per 1,000 person-months = 5.9, 95% CI: 4.3-7.8). Presumptive ZIKV infection was present in 0.8% of infants (IR = 1.6, 95% CI: 0.7-2.9). Five percent of infants with prenatal ZIKV exposure or infection presented with Zika-associated abnormalities; 4.7% were small for gestational age. Understanding the risk of ZIKV infection during pregnancy and associated adverse outcomes can help inform counseling efforts.

Providing accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis of the infection and the associated risk. The 2015-17 Zika virus epidemic overwhelmingly affected women in countries with limited access to safe abortion. Understanding women's perspectives on risk communication during pregnancy in the context of an emerging pathogen can help inform risk communication in response to future outbreaks that affect fetal or child development. We conducted a cross-sectional qualitative interview study with 73 women from 7 locations in Brazil, Colombia, and Puerto Rico to understand women's experiences of Zika virus (ZIKV) test and outcome-related communication during the ZIKV pandemic. We used thematic analysis to analyze the in-depth interviews. Participants in Brazil and Colombia reported that the healthcare system's lack of preparation and organization in communicating ZIKV test results and associated adverse outcomes led to their feeling abandoned and alone in confronting the challenges of a ZIKV-affected pregnancy. In contrast, participants in Puerto Rico reported that the regular testing schedules and clear, well-planned communication between the care team and between providers and pregnant women helped them to feel they could prepare for a ZIKV-affected pregnancy. Communication of the risk associated with an emerging pathogen suspected to affect pregnancy and developmental outcomes is a fraught issue. Public health authorities and healthcare providers should work together in the interpandemic period to understand families' preferences for risk communication during pregnancy in the presence of uncertainty and develop a community-informed plan for risk communication., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Montoya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pituitary apoplexy (PA) is a clinical syndrome resulting from a hemorrhagic infarction of the pituitary gland. It is characterized by the sudden onset of visual disturbances, nausea, vomiting, headache and occasionally, signs of meningeal irritation and an altered mental status. The exact pathogenesis of PA remains to be elucidated, although tumor overgrowth of its blood supply remains the most popular theory. Main risk factors for the development of PA include systemic, iatrogenic, and external factors as well as the presence of an underlying pituitary tumor. The diagnostic approach of PA includes both neuroimaging and evaluation of pituitary secretory function. PA is a potentially life-threatening condition which should be managed with hemodynamic stabilization, correction of electrolyte abnormalities and replacement of hormonal deficiencies. PA treatment should be individualized based on the severity of the clinical picture which may vary widely. Treatment options include conservative management with periodic follow-up or neurosurgical intervention, which should be decided by a multidisciplinary team. We conducted a systematic review of the literature to unveil the frequency of PA predisposing factors, clinical and biochemical presentations, management strategies and outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Discordant outcomes among dizygotic twins could be explained by genetic susceptibly or protection. Among several well-recognized threats to the developing brain, Zika is a mosquito-borne, positive-stranded RNA virus that was originally isolated in Uganda and spread to cause epidemics in Africa, Asia, and the Americas. In the Americas, the virus caused congenital Zika syndrome and a multitude of neurodevelopmental disorders. As of now, there is no preventative treatment or cure for the adverse outcomes caused by prenatal Zika infection. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium was initiated in 2016 to identify factors modulating prenatal brain injury and postnatal neurodevelopmental outcomes for Zika and other prenatal viral infections., Methods: The Consortium has pooled information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic data repository. This repository is being mined to search for modifiers of virally induced brain injury and developmental outcomes. Multilateral partnerships include commitments with Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), and Zika Instituto Fernandes Figueira (Brazil), in addition to the Centers for Disease Control and Prevention and the National Institutes of Health., Discussion: Our goal in bringing together these sets of patient data was to test the hypothesis that personal and populational genetic differences affect the severity of brain injury after a prenatal viral infection and modify neurodevelopmental outcomes. We have enrolled 4,102 mothers and 3,877 infants with 3,063 biological samples and clinical data covering over 80 phenotypic fields and 5,000 variables. There were several notable challenges in bringing together cohorts enrolled in different studies, including variability in the timepoints evaluated and the collected clinical data and biospecimens. Thus far, we have performed whole exome sequencing on 1,226 participants. Here, we present the Consortium's formation and the overarching study design. We began our investigation with prenatal Zika infection with the goal of applying this knowledge to other prenatal infections and exposures that can affect brain development.

GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest in the making of this article. None of the authors have any financial or personal relationships with individuals or organizations that could potentially bias the results or interpretation of this review., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Migration research poses several unique challenges and opportunities. Conducting ethical global health practice, especially when studying migrant mental health, is of particular concern. This article explores seven challenges and lessons learned in our mixed-methods study conducted to assess the impact of the migration experience on Haitian migrants' mental health in Santiago, Chile. The primary challenges were recruiting in a highly mobile population, building trust and community participation, overcoming language barriers, safety considerations during the Covid-19 pandemic, mitigating potential negative impacts of research on the community, providing psychological support, and finding meaningful ways to benefit the community. We propose moving toward a better and more ethical migrant research practice by ensuring language accessibility, hiring community members for the study team, working with local institutions and nongovernmental organizations, and maintaining sustainable connections., (© 2024 by The Hastings Center. All rights reserved.)

Pituitary neuroendocrine tumors (PitNET) are known to be variably infiltrated by different immune cells. Nonetheless, their role in pituitary oncogenesis has only begun to be unveiled. The immune microenvironment could determine the biological and clinical behavior of a neoplasm and may have prognostic implications. To evaluate the expression of immune-related genes and to correlate such expression with the presence of infiltrating immune cells in forty-two PitNETs of different lineages, we performed whole transcriptome analysis and RT-qPCR. Deconvolution analysis was carried out to infer the immune cell types present in each tumor and the presence of immune cells was confirmed by immunofluorescence. We found characteristic expression profiles of immune-related genes including those encoding interleukins and chemokines for each tumor lineage. Genes such as IL4-I1 , IL-36A , TIRAP , IL-17REL , and CCL5 were upregulated in all PitNETS, whereas IL34 , IL20RA , and IL-2RB characterize the NR5A1- , TBX19 -, and POU1F1 -derived tumors, respectively. Transcriptome deconvolution analysis showed that M2 macrophages, CD4+ T cells, CD8+ T cells, NK cells, and neutrophils can potentially infiltrate PitNET. Furthermore, CD4+ and CD8+ T cells and NK cells infiltration was validated by immunofluorescence. Expression of CCL18, IL-5RA , and HLA-B as well as macrophage tumor infiltration could identify patients who can potentially benefit from treatment with immune checkpoint inhibitors.

Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.

Background and Objectives: Laser ablation is increasingly used to treat atrial fibrillation (AF). However, atrioesophageal injury remains a potentially serious complication. While proactive esophageal cooling (PEC) reduces esophageal injury during radiofrequency ablation, the effects of PEC during laser ablation have not previously been determined. We aimed to evaluate the protective effects of PEC during laser ablation of AF by means of a theoretical study based on computer modeling., Methods: Three-dimensional mathematical models were built for 20 different cases including a fragment of atrial wall (myocardium), epicardial fat (adipose tissue), connective tissue, and esophageal wall. The esophagus was considered with and without PEC. Laser-tissue interaction was modeled using Beer-Lambert's law, Pennes' Bioheat equation was used to compute the resultant heating, and the Arrhenius equation was used to estimate the fraction of tissue damage (FOD), assuming a threshold of 63% to assess induced necrosis. We modeled laser irradiation power of 8.5 W over 20 s. Thermal simulations extended up to 250 s to account for thermal latency., Results: PEC significantly altered the temperature distribution around the cooling device, resulting in lower temperatures (around 22°C less in the esophagus and 9°C in the atrial wall) compared to the case without PEC. This thermal reduction translated into the absence of transmural lesions in the esophagus. The esophagus was thermally damaged only in the cases without PEC and with a distance equal to or shorter than 3.5 mm between the esophagus and endocardium (inner boundary of the atrial wall). Furthermore, PEC demonstrated minimal impact on the lesion created across the atrial wall, either in terms of maximum temperature or FOD., Conclusions: PEC reduces the potential for esophageal injury without degrading the intended cardiac lesions for a variety of different tissue thicknesses. Thermal latency may influence lesion formation during laser ablation and may play a part in any collateral damage., (© 2024 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

Objectives: The purpose of this study was to describe the theoretical and procedural framework of a novel intervention, Respiratory Lung Volume Training (RLVT), and to implement a standardized treatment taxonomy to operationalize the RLVT treatment paradigm., Study Design: This study involved a prospective design with a consensus treatment classification process., Methods: The RLVT paradigm was developed based on biomechanical constructs governing the interactions of the respiratory and phonatory systems in voice production and principles of motor learning theory. In RLVT, higher levels of lung volume (LV) during speech are trained using multiple speech breathing strategies while providing real-time visual biofeedback with superimposed guidelines for desired LV initiation and termination levels. For people with primary muscle tension dysphonia (MTD), RLVT can capitalize on nonmuscular respiratory forces to increase efficiency of voice production with reduced speaking effort. To define and operationalize the treatment components of RLVT, six investigators with training in RLVT used the Rehabilitation Treatment Specification System to delineate the treatment targets, mechanisms of action, ingredients and dosing through a multistage, consensus decision-making process., Results: The finalized taxonomy for RLVT included four treatment targets, with three addressing the area of Respiratory Function and one addressing Somatosensory Function. For each treatment target, three categories of ingredients were defined: (1) provide opportunities to practice breathing during voicing/speech, (2) provide feedback, and (3) provide volition ingredients. Within each ingredient category, three to seven specific ingredients were ultimately defined to further operationalize RLVT., Conclusions: The RLVT paradigm is a theoretically driven approach for optimizing speech breathing patterns to increase efficient voice production in people with primary MTD. By applying a standardized, systematic treatment taxonomy system to specify the components of RLVT, future researchers and clinicians can implement RLVT with improved fidelity and consistency to optimize treatment outcomes., 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 Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Approaches to safety culture assessment may have many limits if supported exclusively by quantitative methods. Based on this, a research team developed a quantitative-qualitative approach to assess the maturity of the safety culture on an oil platform. To that end, the team sought to develop and test a method consisting of an initial ethnographic phase followed by four other distinct phases: definition of homogeneous groups; production of customized questionnaires; quantitative evaluation; and qualitative assessment. The results show the emergence of trends, from pre-defined themes in safety culture to specific levels of maturity for each of the homogeneous groups. At the same time, it was perceived that the maturity level of the groups is defined from the daily work practices developed by each one of them. This experience allowed us to propose a framework for assessing the maturity levels of safety culture for the oil and gas industry.

5'-end modifications play key roles in determining RNA fates. Phospho-methylation is a noncanonical cap occurring on either 5'-PPP or 5'-P ends. We used ChemRAP, in which affinity purification of cellular proteins with chemically synthesized modified RNAs is coupled to quantitative proteomics, to identify 5'-Pme "readers". We show that 5'-Pme is directly recognized by EPRS, the central subunit of the multisynthetase complex (MSC), through its linker domain, which has previously been involved in key noncanonical EPRS and MSC functions. We further determine that the 5'-Pme writer BCDIN3D regulates the binding of EPRS to specific mRNAs, either at coding regions rich in MSC codons, or around start codons. In the case of LRPPRC (leucine-rich pentatricopeptide repeat containing), a nuclear-encoded mitochondrial protein associated with the French Canadian Leigh syndrome, BCDIN3D deficiency abolishes binding of EPRS around its mRNA start codon, increases its translation but ultimately results in LRPPRC mislocalization. Overall, our results suggest that BCDIN3D may regulate the translation of specific mRNA via RNA-5'-Pme., (© 2024. The Author(s).)

Background: The SARS-CoV-2 pandemic resulted in shortages of supplies, which limited the use of extracorporeal membrane oxygenation (ECMO) support. As a contingency strategy, polypropylene (PP) oxygenation membranes were used. This study describes the clinical outcomes in patients on ECMO with PP compared to poly-methylpentene (PMP) oxygenation membranes., Methods: Retrospective cohort of patients in ECMO support admitted between 2020 and 2021., Results: A total of 152 patients with ECMO support were included, 71.05% were men with an average age of 42 (SD 9.91) years. Veno-venous configuration was performed in 75.6% of cases. The PP oxygenation membranes required more changes 22 (63.1%), than the PMP Sorin® 24 (32,8%) and Euroset® 15 (31,9%) (p.0.022). The main indication for membrane change was low oxygen transfer for PP at 56.2%, Sorin® at 50%, and Euroset® at 14.8%. Renal replacement therapy was the most frequent complication with PP membrane in 22 patients (68.7%) Sorin® 25 patients (34.2%), and Euroset® 15 patients (31.9%) (p 0.001) without statistically significant differences in mortality., Conclusion: PP oxygenation membranes was a useful and feasible strategy. It allowed a greater disponibility of ECMO support for critically ill in a situation of great adversity during the SARS-CoV-2 pandemic., (© 2024. The Author(s).)

Background: Latino caregivers caring for children under 5 years old who are under resourced, and underserved may be most vulnerable for experiencing mental health problems. Furthermore, Latino families with young children-during the COVID-19 pandemic-were at particular risk for multiple and concurrent stressors and acute adversities., Objectives: The Family Wellbeing Program (FWP) was designed to strengthen Latino caregivers' mental health and mental well-being, and facilitate their access to mental health supports and service providers., Methods: Using the principles of community-based participatory research, a university research team and staff from a federally qualified health care center co-developed and implemented the FWP. Pre- and post-implementation focus groups with six staff were conducted and data analysis was guided by the RE-AIM framework., Results: Staff identified implementation challenges related to the pandemic and socioenvironmental factors affecting the reach and participation of Latino families. Staff perceived the program improved caregivers' help-seeking behaviors, yet suggestions for improving the FWP for Latino caregivers were noted. Staff also discussed implementation strategies to sustain future programming., Conclusions: Implementation strategies along the RE-AIM dimensions were identified to improve the participation of Latino caregivers in future adaptations of the FWP. The implications of this work could show promise for sustaining programs designed to address disparities in mental health among Latino caregivers.

The Zika virus (ZIKV) epidemic had a sanitary, psychosocial, and economic impact on individuals of reproductive age. The primary concern revolved around infection during pregnancy due to possible vertical transmission and its association with adverse fetal and infant outcomes, known as Congenital Zika Syndrome (CZS). This qualitative study employs phenomenology and grounded theory. This study includes interviews with 98 women, some pregnant during the ZIKV epidemic in Brazil, Colombia, and Puerto Rico, who had children with CZS or without diagnosed neurological impairment. Additionally, the study included a group of women who were pregnant during the COVID-19 pandemic in these same countries. In both groups, interviewees had varying levels of knowledge about ZIKV. The study found that messages conveyed through the media tended to be alarmist, in contrast to the information provided by healthcare professionals, which was considered more trustworthy. Pregnant women during the ZIKV epidemic reported receiving their ZIKV and CSZ infection diagnoses late, either during or after childbirth. The study underscores the needs of pregnant women in high-risk scenarios, the importance of health education processes, and the necessity to reinforce communication and continuing education.

Pituitary tumors (PT) are highly heterogeneous neoplasms, comprising functioning and nonfunctioning lesions. Functioning PT include prolactinomas, causing amenorrhea-galactorrhea in women and sexual dysfunction in men; GH-secreting adenomas causing acromegaly-gigantism; ACTH-secreting corticotrophinomas causing Cushing disease (CD); and the rare TSH-secreting thyrotrophinomas that result in central hyperthyroidism. Nonfunctioning PT do not result in a hormonal hypersecretion syndrome and most of them are of gonadotrope differentiation; other non-functioning PT include null cell adenomas and silent ACTH-, GH- and PRL-adenomas. Less than 5% of PT occur in a familial or syndromic context whereby germline mutations of specific genes account for their molecular pathogenesis. In contrast, the more common sporadic PT do not result from a single molecular abnormality but rather emerge from several oncogenic events that culminate in an increased proliferation of pituitary cells, and in the case of functioning tumors, in a non-regulated hormonal hypersecretion. In recent years, important advances in the understanding of the molecular pathogenesis of PT have been made, including the genomic, transcriptomic, epigenetic, and proteomic characterization of these neoplasms. In this review, we summarize the available molecular information pertaining the oncogenesis of PT., Competing Interests: Conflicts of Interest There is no conflict of interest that could be perceived to affect the impartiality of the reported research., (Copyright © 2023. Published by Elsevier Inc.)

Background: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline., Methods: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue., Findings: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection., Interpretation: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups., Funding: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: We present a series that describes the presenting features and clinical outcomes in patients with CSDH treated with a standardised technique and an open-drain placement., Methods: We reviewed the medical records of 155 consecutive patients at a single centre who underwent CSDH evacuation by placing burr holes, accompanied by intraoperative irrigation and a subdural Penrose drain between 2014 and 2018., Results: The mean age was 65.9 years, 81.9% were males. The most common clinical characteristics were an altered mental state (21.9%) and headache (12.9%). It was necessary to perform a second surgical intervention due to the evidence in the postoperative tomography of a residual hematoma in 10.3% of the cases; there were 2 cases of recurrence in 6 months (1.3%). Pneumonia (6.5%) and seizures (5.8%) were the most frequent medical complications. Intracranial infections accounted for 1.9%, and the mortality rate was 6.4% of cases., Conclusions: We provided our experience with a low-cost and less-commonly used technique in the management of CSDH. This technique showed similar recurrence, mortality and intracranial infection rates to those reported in the literature for closed drainage systems. Additional studies will be required to assess this technique.

Background & Aims: Current therapies for the treatment of alcohol-related liver disease (ALD) have proven largely ineffective. Patients relapse and the disease progresses even after liver transplantation. Altered epigenetic mechanisms are characteristic of alcohol metabolism given excessive acetate and NAD depletion and play an important role in liver injury. In this regard, novel therapeutic approaches based on epigenetic modulators are increasingly proposed. MicroRNAs, epigenetic modulators acting at the post-transcriptional level, appear to be promising new targets for the treatment of ALD., Methods: MiR-873-5p levels were measured in 23 liver tissue from Patients with ALD, and GNMT levels during ALD were confirmed using expression databases (transcriptome n = 62, proteome n = 68). High-resolution proteomics and metabolomics in mice following the Gao-binge model were used to investigate miR-873-5p expression in ALD. Hepatocytes exposed to 50 mM alcohol for 12 h were used to study toxicity. The effect of anti-miR-873-5p in the treatment outcomes of ALD was investigated., Results: The analysis of human and preclinical ALD samples revealed increased expression of miR-873-5p in the liver. Interestingly, there was an inverse correlation with NNMT, suggesting a novel mechanism for NAD depletion and aberrant acetylation during ALD progression. High-resolution proteomics and metabolomics identified miR-873-5p as a key regulator of NAD metabolism and SIRT1 deacetylase activity. Anti-miR-873-5p reduced NNMT activity, fuelled the NAD salvage pathway, restored the acetylome, and modulated the levels of NF-κB and FXR, two known SIRT1 substrates, thereby protecting the liver from apoptotic and inflammatory processes, and improving bile acid homeostasis., Conclusions: These data indicate that targeting miR-873-5p, a repressor of GNMT previously associated with NAFLD and acetaminophen-induced liver failure. is a novel and attractive approach to treating alcohol-induced hepatoxicity., Impact and Implications: The role of miR-873-5p has not been explicitly examined in the progression of ALD, a pathology with no therapeutic options. In this study, inhibiting miR-873-5p exerted hepatoprotective effects against ALD through rescued SIRT1 activity and consequently restored bile acid homeostasis and attenuated the inflammatory response. Targeting hepatic miR-873-5p may represent a novel therapeutic approach for the treatment of ALD., Competing Interests: MLMC advises for Mitotherapeutix LLC. All other authors have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Introduction: Despite the inherent heterogeneity of the information derived from national registries, they are a useful tool to investigate the epidemiological, clinical, biochemical and treatment outcome characteristics of low prevalence conditions such as acromegaly. Although the information provided by single-center experiences is more homogeneous, these studies usually comprise a limited number of patients and thus, frequently lack statistical power., Areas Covered: Registry-based Information regarding the epidemiology, clinical presentation, biochemical and imaging diagnosis, as well as therapeutic outcome and mortality in acromegaly is critically analyzed., Expert Opinion: By gathering data from multiple centers in a specific Country, these registries generate important insights into the real-life behavior of this condition, that should be considered, both, in international consensus meetings and in the design of local, Country-specific diagnostic and therapeutic strategies., (Copyright © 2023 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Background and study aims A novel electrosurgical generator unit (ESU), ConMed Beamer, was recently introduced to facilitate endoscopic submucosal dissection (ESD) by employing Automatic Cutting Effect (ACE) technology. Its use in submucosal endoscopy has yet to be investigated. The aim of this study was to evaluate the feasibility and safety of performing ESD and peroral endoscopic myotomy (POEM) using novel settings generated with ConMed Beamer ESU. Patients and methods This was a single-center prospective study of 59 consecutive patients undergoing ESD/POEM at a tertiary referral center. ESU settings were initially generated by testing in live animal models prior to first in-human study. The primary outcome was technical success. Secondary outcomes were procedure times, rate of en bloc/R0 resection, and rate of adverse events (AEs). Results A total of 44 patients (50 polyps) and 15 patients underwent ESD and POEM, respectively. En bloc resection, R0 resection, and curative resection rates were 90%, 77.1%, and 70.8%, respectively. Mean maximal length of the lesion was 3.07 cm ± 1.43 with an average dissection speed of 14.2 cm 2 /hr ± 11.1. Technical success was achieved in 100% of POEM patients. Mean time (minutes) to complete the POEM procedure was 50.1 min ± 12.4. Two major AEs occurred among all patients (3.4%). All intraprocedural bleeding events were controlled using the ConMed Beamer ESU. Conclusions ConMed Beamer ESU settings generated from this study were proven safe and effective in a prospective cohort of patients who underwent submucosal endoscopic procedures. This novel ESU can be added to the armamentarium of ESD capable generators., Competing Interests: Conflict of Interest Mohamed O. Othman: Mohamed O Othman is a consultant for Olympus, Boston Scientific Corporation, Abbvie, ConMed, Creo Medical, Lumendi, Nestle and Apollo. Mohamed O Othman received research grants from Lucid Diagnostics, AbbVie, ConMed, Olympus and Boston Scientific. Salmaan Jawaid: Salmaan Jawaid is a consultant for ConMed, Creo Medical, and Lumendi. Tara Keihanian: Tara Keihanian is a consultant for Lumendi and Neptune medical. Mai Khalaf, Margarita Riojas-Barrett, Wesam Abdeljaber, Michael Mercado & Noor Zabad have no conflicts of interest. This study was investigator-initiated study funded by ConMed. The funding body was not involved with the study design, execution or results. The funding body did not contribute to the drafting of this manuscript., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Racial/ethnic minority communities are underrepresented in research. Medical mistrust and mistreatment, discrimination, and a lack of diverse research workforce may influence recruitment and engagement. Engaging Latinx immigrants for research presents unique recruitment challenges, especially for biobehavioral research which is not well explored. The purpose of this paper is to examine the effect of targeted strategies for recruiting young adult, Latinx immigrants. Methods: Recruitment occurred from 2018 to 2019 in an ongoing, longitudinal, community-engaged research study examining risk and resilience factors for health outcomes in Latinx immigrants. Strategies included active recruitment (e.g., community-based events and public events) and passive recruitment (e.g., word-of-mouth and radio and flyer advertisements). Logistic regression analysis was conducted to examine the influence of type of recruitment on participant enrollment. Results: The study enrolled 391 participants of 701 interested individuals (55%). Greater odds of enrollment were among participants recruited through radio and flyer advertisements (adjusted odds ratio [AOR]=2.90, 95% CI [1.59, 5.27], p =.001), word-of-mouth (AOR=2.50, 95% CI [1.55, 4.03], p <.000), or community-based organization events (AOR=1.68, 95% CI [1.19, 2.38], p =.003). Conclusions: Passive recruitment strategies through trusted sources increased the odds of enrollment of Latinx immigrants in biobehavioral research. Future recruitment efforts should leverage trusted sources to disseminate recruitment materials addressing barriers to recruiting Latinx participants for research.

Acromegaly/giantism results from the chronic excess of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), in more than 96% of cases, due to a GH-secreting pituitary adenoma. Primary treatment of choice is transsphenoidal resection of the adenoma. More than 30% to 40% of operated cases require adjunctive forms of treatment, be it pharmacological or radiotherapeutical. The multimodal treatment of acromegaly has resulted in substantial improvements in the quality of life and life expectancy of these patients. We herein present the complex case of a patient with acromegaly due to a mammosomatotrope adenoma, with a germ-line AIP (aryl hydrocarbon receptor-interacting protein) mutation, who had a chronic and protracted course of more than 15 years during which he was treated with surgery, somatostatin receptor ligands, dopamine agonist, and the GH receptor antagonist pegvisomant. At one point, he was able to come off medications and was even found to be transiently GH-deficient, only to develop acromegaly again after a couple of years., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Adaptations to interventions for specific settings or communities are critical for facilitating successful implementation. The Dynamic Adaptation Process model was applied to systematically assess the adaptation process made to an in-person parenting intervention (FPNG+) prior to its implementation online. This qualitative case study design included meeting notes and interviews completed with project team members. Meeting notes were analyzed using content analysis. Semi-structured interviews regarding project team members' roles on FPNG+ and processes and activities they identified as critical for the adaptation of FPNG+ to an online intervention were analyzed using a deductive-inductive approach. In the formative phase, three primary processes were identified: information gathering to determine if the environment existed for the implementation of an online program; considerations to support the facilitation process of FPNG+ to an online environment, and decision-making to support modifications to FPNG+. The pre-implementation phase consisted of three processes: information shared by the instructional designer to facilitate the delivery of the FPNG+ content online; modifications made to the format of the intervention to meet the cultural needs of Hispanic families and address contextual issues; and iterative efforts to tailor the intervention by the project team. This study used implementation science to distinguish the dynamic processes that occurred across different systems and multiple levels in the project team's effort to modify FPNG+ to an online intervention. The contribution of this study underscores the importance of identifying the processes that facilitate the modifications made to an intervention and the capacity to implement the modified intervention with Hispanic families., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Over 20 years ago, Hanahan and Weinberg published a seminal review that addressed the biological processes that underly malignant transformation. This classical review, along with two revisions published in 2011 and 2022, has remain a classic of the oncology literature. Since many of the addressed biological processes may apply to non-malignant tumorigenesis, we evaluated to what extent these hallmarks pertain to the development of pituitary adenomas.Some of the biological processes analyzed in this review include genome instability generated by somatic USP8 and GNAS mutations in Cushing's diseases and acromegaly respectively; non-mutational epigenetic reprograming through changes in methylation; induction of angiogenesis through alterations of VEGF gene expression; promotion of proliferative signals mediated by EGFR; evasion of growth suppression by disrupting cyclin dependent kinase inhibitors; avoidance of immune destruction; and the promotion of inflammation mediated by alteration of gene expression of immune check points. We also elaborate further on the existence of oncogene induced senescence in pituitary tumors. We conclude that a better understanding of these processes can help us dilucidated why pituitary tumors are so resistant to malignant transformation and can potentially contribute to the development of novel anticancer treatments., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)