The Dual Role of TRIM7 in Viral Infections.

The E3 ubiquitin ligase TRIM7 is known to have dual roles during viral infections. Like other TRIM proteins, TRIM7 can regulate the IFN pathway via the regulation of the cytosolic receptors RIG-I or MDA-5, which promote the production of type I interferons (IFN-I) and antiviral immune responses. Alternatively, under certain infectious conditions, TRIM7 can negatively regulate IFN-I signaling, resulting in increased virus replication. A growing body of evidence has also shown that TRIM7 can, in some cases, ubiquitinate viral proteins to promote viral replication and pathogenesis, while in other cases it can promote degradation of viral proteins through the proteasome, reducing virus infection. TRIM7 can also regulate the host inflammatory response and modulate the production of inflammatory cytokines, which can lead to detrimental inflammation. TRIM7 can also protect the host during infection by reducing cellular apoptosis. Here, we discuss the multiple functions of TRIM7 during viral infections and its potential as a therapeutic target.

Hidden Agony: Foot Pain Linked to Pet Hair Splinter.

Cutaneous pili migrans is a rare and interesting dermatological condition characterized by embedding a hair or its fragment in the epidermis or superficial dermis, sometimes leading to pain and a serpiginous rash. We present a 28-year-old male who came to the clinic concerned about the sudden onset of pain in his foot over 10 hours. Upon meticulous physical examination, we found a white hair embedded in the skin of the fifth toe of his left foot, which the patient immediately recognized as hair from his dog. Upon removal of the hair, the pain immediately resolved. We believe our case represents the first reported case in Panama, the second in Latin America, and the second associated with dog hair. We anticipate that more cases related to animal hairs will be reported in the coming years due to the increasing popularity of pets in this century.

Human-specific paralogs of SRGAP2 induce neotenic features of microglia structural and functional maturation.

Microglia play key roles in shaping synaptic connectivity during neural circuits development. Whether microglia display human-specific features of structural and functional maturation is currently unknown. We show that the ancestral gene SRGAP2A and its human-specific (HS) paralogs SRGAP2B/C are not only expressed in cortical neurons but are the only HS gene duplications expressed in human microglia. Here, using combination of xenotransplantation of human induced pluripotent stem cell (hiPSC)-derived microglia and mouse genetic models, we demonstrate that (1) HS SRGAP2B/C are necessary and sufficient to induce neotenic features of microglia structural and functional maturation in a cell-autonomous manner, and (2) induction of SRGAP2-dependent neotenic features of microglia maturation non-cell autonomously impacts synaptic development in cortical pyramidal neurons. Our results reveal that, during human brain evolution, human-specific genes SRGAP2B/C coordinated the emergence of neotenic features of synaptic development by acting as genetic modifiers of both neurons and microglia.

Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity.

Fasting is associated with improved outcomes in cancer. Here, we investigated the impact of fasting on natural killer (NK) cell anti-tumor immunity. Cyclic fasting improved immunity against solid and metastatic tumors in an NK cell-dependent manner. During fasting, NK cells underwent redistribution from peripheral tissues to the bone marrow (BM). In humans, fasting also reduced circulating NK cell numbers. NK cells in the spleen of fasted mice were metabolically rewired by elevated concentrations of fatty acids and glucocorticoids, augmenting fatty acid metabolism via increased expression of the enzyme CPT1A, and Cpt1a deletion impaired NK cell survival and function in this setting. In parallel, redistribution of NK cells to the BM during fasting required the trafficking mediators S1PR5 and CXCR4. These cells were primed by an increased pool of interleukin (IL)-12-expressing BM myeloid cells, which improved IFN-γ production. Our findings identify a link between dietary restriction and optimized innate immune responses, with the potential to enhance immunotherapy strategies.

Abdominal cocoon syndrome (sclerosing encapsulated peritonitis) causing small bowel occlusion in a patient with gastric bypass.

A rare condition, sclerosing encapsulating peritonitis, is characterized by a fibrotic membrane forming over the bowels, leading to intestinal obstruction. In this case of a 56-year-old male patient with a history of laparoscopic gastric bypass, a computed tomography scan showed findings indicative of the condition. Extensive adhesiolysis was performed, and biopsies confirmed the presence of fusiform cells (D2-40 positive on immunochemistry) resembling fibroblasts, within dense collagenous peritoneal tissue sheets, typical of sclerosing encapsulating peritonitis. The prevalence of this condition is uncertain, and diagnosis typically requires a peritoneal biopsy due to the nonspecific clinical presentation.

La peritonitis esclerosante encapsulada es una condición rara caracterizada por una membrana fibrótica que se genera sobre las asas intestinales causando cuadros de oclusión intestinal. Se presenta el caso de un paciente varón de 56 años con antecedente de derivación gastroyeyunal por laparoscopia que presenta oclusión intestinal. Se realizó tomografía computada que evidenció sitio de transición previo al sitio de anastomosis. Se realizó de anastomosis extensa y toma de biopsias. Histológicamente se observó engrosamiento de la membrana peritoneal, células fusiformes (D2-40 positivo en inmunohistoquímica) similares a fibroblastos con láminas de colágeno peritoneal denso. La peritonitis esclerosante encapsulada es una patología de prevalencia desconocida. El cuadro clínico es inespecífico y el diagnóstico definitivo es por patología con biopsia peritoneal.

Surface-based morphometry of the corpus callosum in young children of ages 1-5.

The corpus callosum (CC) is a large white matter fiber bundle in the brain and is involved in various cognitive, sensory, and motor processes. While implicated in various developmental and psychiatric disorders, much is yet to be uncovered about the normal development of this structure, especially in young children. Additionally, while sexual dimorphism has been reported in prior literature, observations have not necessarily been consistent. In this study, we use morphometric measures including surface tensor-based morphometry (TBM) to investigate local changes in the shape of the CC in children between the ages of 12 and 60 months, in intervals of 12 months. We also analyze sex differences in each of these age groups. We observed larger significant clusters in the earlier ages between 12 v 24 m and between 48 v 60 m and localized differences in the anterior region of the body of the CC. Sex differences were most pronounced in the 12 m group. This study adds to the growing literature of work aiming to understand the developing brain and emphasizes the utility of surface TBM as a useful tool for analyzing regional differences in neuroanatomical morphometry.

The impact of comorbidity status in COVID-19 vaccines effectiveness before and after SARS-CoV-2 omicron variant in northeastern Mexico: a retrospective multi-hospital study.

Introduction: The end of the coronavirus disease 2019 (COVID-19) pandemic has been declared by the World Health Organization on May 5, 2023. Several vaccines were developed, and new data is being published about their effectiveness. However, the clinical trials for the vaccines were performed before the Omicron variant appeared and there are population groups where vaccine effectiveness still needs to be tested. The overarching goal of the present study was to analyze the effects of COVID-19 vaccination before and after the Omicron variant in patients considering comorbidities in a population from Nuevo Leon, Mexico. Methods: Epidemiological COVID-19 data from the Mexican Social Security Institute were collected from 67 hospitals located in northeastern Mexico, from July 2020 to May 2023, and a total of 669,393 cases were compiled, 255,819 reported a SARS-CoV-2 positive reverse transcription quantitative polymerase chain reaction (RT-qPCR) test or a positive COVID-19 antigen rapid test. Results: Before Omicron (BO, 2020-2021), after 14 days of two doses of COVID-19 vaccine, BNT162b2 and ChAdOx1 vaccines were effective against infection in non-comorbid and all comorbid subgroups, whereas after Omicron (AO, 2022- 2023) there was no significant effectiveness against infection with none of the vaccines. Regarding hospitalization BO, BNT162b2, ChAdOx1, CoronaVac and mRNA-1273 significantly protected non-comorbid patients whereas BNT162b2, ChAdOx1, and mRNA-1273, protected all comorbid subgroups against hospitalization. AO, BNT162b2, ChAdOx1, CoronaVac and mRNA-1273 were effective against hospitalization in non-comorbid patients whereas for most comorbid subgroups BNT162b2, ChAdOx1 and CoronaVac were effective against hospitalization. Non-comorbid patients were protected against death as an outcome of COVID-19 during the BO period with most vaccines whereas a reduction in effectiveness was observed AO with mRNA-1273 vaccines in patients with hypertension, and diabetes mellitus. Discussion: BO, COVID-19 vaccines were effective against infection, hospitalization, and death whereas AO, COVID-19 vaccines failed to protect the population from COVID-19 infection. A varying effectiveness against hospitalization and death is observed AO.

Premature Death, Suicide, and Nonlethal Intentional Self-Harm After Psychiatric Discharge.

Importance: There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization. Objective: To compare rates of premature death, suicide, and nonlethal intentional self-harm after psychiatric discharge with rates in the general population and investigate associations of these outcomes with relevant variables associated with the index psychiatric hospitalization. Design, Setting, and Participants: This retrospective cohort study included all residents from Catalonia, Spain (7.6 million population), who had psychiatric hospitalizations between January 1, 2014, and December 31, 2018, and were older than 10 years at the index (first) hospitalization. Follow-up was until December 31, 2019. Statistical analysis was performed from December 1, 2022, through April 11, 2024. Exposures: Socioeconomic status, psychiatric diagnoses, duration of index hospitalization, and number of previous psychiatric hospitalizations. Main Outcomes and Measures: Postdischarge premature death (ie, all-cause death before age 70 years) and suicide (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code range X60-X84), identified using mortality data, and postdischarge nonlethal intentional self-harm, identified using electronic health record and self-harm case register data. Standardized mortality ratios (SMRs) compared rates of premature death and suicide between the cohort and the general population. Fully adjusted, multivariable, cause-specific Cox proportional hazards regression models for the 3 outcomes were fitted. Results: A total of 49 108 patients discharged from psychiatric hospitalization were included (25 833 males [52.6%]; mean [SD] age at discharge, 44.2 [18.2] years). During follow-up, 2260 patients (4.6%) died prematurely, 437 (0.9%) died by suicide, and 4752 (9.7%) had an episode of nonlethal intentional self-harm. The overall SMR for premature death was 7.5 (95% CI, 7.2-7.9). For suicide, SMR was 32.9 (95% CI, 29.9-36.0) overall and was especially high among females (47.6 [95% CI, 40.2-54.9]). In fully adjusted sex-stratified hazard models, postdischarge premature death was associated with cognitive disorders (adjusted hazard ratio [AHR], 2.89 [95% CI, 2.24-3.74] for females; 2.59 [95% CI, 2.17-3.08] for males) and alcohol-related disorders (AHR, 1.41 [95% CI, 1.18-1.70] for females; 1.22 [95% CI, 1.09-1.37] for males). Postdischarge suicide was associated with postdischarge intentional self-harm (AHR, 2.83 [95% CI, 1.97-4.05] for females; 3.29 [95% CI, 2.47-4.40] for males), with depressive disorders (AHR, 2.13 [95% CI, 1.52-2.97]) and adjustment disorders (AHR, 1.94 [95% CI, 1.32-2.83]) among males, and with bipolar disorder among females (AHR, 1.94 [95% CI, 1.21-3.09]). Postdischarge intentional self-harm was associated with index admissions for intentional self-harm (AHR, 1.95 [95% CI, 1.73-2.21] for females; 2.62 [95% CI, 2.20-3.13] for males) as well as for adjustment disorders (AHR, 1.48 [95% CI, 1.33-1.65] for females; 1.99 [95% CI, 1.74-2.27] for males), anxiety disorders (AHR, 1.24 [95% CI, 1.10-1.39] for females; 1.36 [95% CI, 1.18-1.58] for males), depressive disorders (AHR, 1.54 [95% CI, 1.40-1.69] for females; 1.80 [95% CI, 1.58-2.04] for males), and personality disorders (AHR, 1.59 [95% CI, 1.46-1.73] for females; 1.43 [95% CI, 1.28-1.60] for males). Conclusions and Relevance: In this cohort study of patients discharged from psychiatric hospitalization, risk for premature death and suicide was significantly higher compared with the general population, suggesting individuals discharged from psychiatric inpatient care are a vulnerable population for premature death and suicidal behavior.

Rare cutaneous adverse reactions associated with GLP-1 agonists: a review of the published literature.

Glucagon-like-peptide-1 (GLP-1) agonists are an emerging class of medications used to manage type 2 diabetes mellitus (T2DM) and weight loss, with demonstrated efficacy in reducing hemoglobin A1c levels, body mass index, and adverse cardiovascular events. While previous studies have reviewed notable cutaneous adverse effects with other antidiabetic medications, little is known about GLP-1 agonist-induced cutaneous reactions. Nevertheless, rare but significant cutaneous adverse reactions have been reported, including but not limited to dermal hypersensitivity reactions, eosinophilic panniculitis, bullous pemphigoid, and morbilliform drug eruptions. As GLP-1 induced cutaneous reactions are diverse, diagnosis requires clinical suspicion, thorough history-taking, and supportive histopathological findings when available. Management involves cessation of the offending agent with a tailored regimen to address inflammatory and/or immunogenic etiologies as well as irritative symptoms. This review aims to consolidate available information from case reports and case series regarding rare skin-related adverse outcomes due to GLP-1 use, aiming to provide a comprehensive overview of the presentation, pathogenesis, and management for dermatologists and other clinicians.

Patient Satisfaction and Willingness to Continue with Telemental Health Care During and After the Early Period of SARS-CoV-2 Pandemic: A User Survey.

Objective: The SARS-CoV-2 pandemic and related lockdown periods generated an increase in the use of virtual care for mental health (MH). This study aimed to assess patient satisfaction with Telemental Health services (TMH) during first lockdown and factors related to their willingness to continue using this service. Methods: We conducted a cross-sectional survey of 364 MH outpatients from 9 centers in the Barcelona region (Spain), who received TMH between April 20 and May 22, 2020. We assessed sociodemographic and clinical characteristics, prior experience, and familiarity with technologies and satisfaction with TMH. Willingness to receive TMH after the lockdown was measured separately for telephone and videoconferencing. We performed descriptive statistics and bivariate and multivariate regression models to predict TMH willingness. Results: From 450 patients contacted, 364 were interviewed. Satisfaction with TMH was high (mean 9.24, standard deviation 0.07); 2.47% preferred only TMH visits after lockdown, 23.08% preferred mostly TMH visits, 50.82% accepted some TMH visits, and 23.63% would prefer in-person consultations. Female patients and those having received TMH during lockdown showed higher odds of willingness to receive TMH in the future, while patients unfamiliar with technologies showed lower odds. Concerning TMH through telephone, willingness was more likely in patients living with more persons. Videoconferencing willingness was more likely for people living with depression. Conclusions: TMH was well accepted during the first lockdown and patients were willing to maintain it after lockdown. Low familiarity with new technologies is an important barrier to TMH willingness, which needs to be addressed for appropriate implementation going forward.

Evaluation of adherence to antipsychotics: A real-world data study using four different dosing assumptions.

AIMS: This study aimed to assess the frequency of dosing inconsistencies in prescription data and the effect of four dosing assumption strategies on adherence estimates for antipsychotic treatment. METHODS: A retrospective cohort, which linked prescription and dispensing data of adult patients with ≥1 antipsychotic prescription between 2015-2016 and followed up until 2019, in Catalonia (Spain). Four strategies were proposed for selecting the recommended dosing in overlapping prescription periods for the same patient and antipsychotic drug: (i) the minimum dosing prescribed; (ii) the dose corresponding to the latest prescription issued; (iii) the highest dosing prescribed; and (iv) all doses included in the overlapped period. For each strategy, one treatment episode per patient was selected, and the Continuous Medication Availability measure was used to assess adherence. Descriptive statistics were used to describe results by strategy. RESULTS: Of the 277 324 prescriptions included, 76% overlapped with other prescriptions (40% with different recommended dosing instructions). The number and characteristics of patients and treatment episodes (18 292, 18 303, 18 339 and 18 536, respectively per strategy) were similar across strategies. Mean adherence was similar between strategies, ranging from 57 to 60%. However, the proportion of patients with adherence ≥90% was lower when selecting all doses (28%) compared with the other strategies (35%). CONCLUSION: Despite the high prevalence of overlapping prescriptions, the strategies proposed did not show a major effect on the adherence estimates for antipsychotic treatment. Taking into consideration the particularities of antipsychotic prescription practices, selecting the highest dose in the overlapped period seemed to provide a more accurate adherence estimate.

Ebola virus VP35 interacts non-covalently with ubiquitin chains to promote viral replication.

Ebolavirus (EBOV) belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans. EBOV replication requires the activity of the viral polymerase complex, which includes the cofactor and Interferon antagonist VP35. We previously showed that the covalent ubiquitination of VP35 promotes virus replication by regulating interactions with the polymerase complex. In addition, VP35 can also interact non-covalently with ubiquitin (Ub); however, the function of this interaction is unknown. Here, we report that VP35 interacts with free (unanchored) K63-linked polyUb chains. Ectopic expression of Isopeptidase T (USP5), which is known to degrade unanchored polyUb chains, reduced VP35 association with Ub and correlated with diminished polymerase activity in a minigenome assay. Using computational methods, we modeled the VP35-Ub non-covalent interacting complex, identified the VP35-Ub interacting surface, and tested mutations to validate the interface. Docking simulations identified chemical compounds that can block VP35-Ub interactions leading to reduced viral polymerase activity. Treatment with the compounds reduced replication of infectious EBOV in cells and in vivo in a mouse model. In conclusion, we identified a novel role of unanchored polyUb in regulating Ebola virus polymerase function and discovered compounds that have promising anti-Ebola virus activity.

A focused review of visible light therapies for vitiligo.

BACKGROUND: Vitiligo can be challenging to treat and exhibit an unpredictable clinical course. Phototherapy in the form of visible light can achieve both repigmentation and depigmentation outcomes in vitiligo, with minimal associated adverse events. This review focuses on the mechanistic understandings and clinical outcomes of visible light-based treatments for vitiligo. METHODS: Articles were retrieved from PubMed starting from May 1965 until August 2023, yielding 496 unique articles. We conducted title, abstract, and full-text screening to identify articles describing the use of visible light (380-750 nm), either as part of combination therapy or as monotherapy, for repigmentation or depigmentation treatment in vitiligo. RESULTS: Twenty-seven articles met inclusion criteria, offering preclinical and clinical data regarding the utilization of helium-neon laser (red light) and blue light-emitting diodes (LEDs) as methods of repigmentation therapy in vitiligo. Preclinical and clinical data on the utilization of Q-switched ruby laser (694 nm) and frequency-doubled (FD) Nd:YAG laser (532 nm) for vitiligo depigmentation therapy were also identified. CONCLUSION: While limited by small studies and a lack of standardized administration of phototherapy, the evidence for visible light's effectiveness in managing vitiligo is encouraging. Red light therapy using He-Ne lasers and blue light therapy via LEDs can stimulate repigmentation in patients with vitiligo with minimal adverse events. Q-switched ruby and FD Nd:YAG lasers provide viable, visible light depigmentation options, either alone or with topical agents. With limited clinical data, larger studies are needed to validate the efficacy of visible light therapy in treating vitiligo and to better understand its long-term outcomes.

Gastrointestinal Foreign Bodies: 14 Years of Experience in a University Clinic

Introduction: Ingesting foreign bodies is a common medical problem, especially in the emergency department. Some small studies describe experiences in this regard. Materials and methods: A descriptive retrospective study included patients with suspected ingestion of foreign bodies admitted to the gastroenterology and GI endoscopy service of the Clínica Universitaria Colombia between January 2007 and August 2020. Results: The age of occurrence of the event was 18 to 95 years, and the average age was 45 years. The foreign bodies ingested and found were variable. The most frequent was fish bones, representing 64.11% of the cases, followed by chicken bones and dietary impaction. Thirty-eight percent of patients required foreign body removal; the most frequently used tool was the foreign body forceps. The primary location was the esophagus in 12.53% of cases, followed by the cricopharynx in 11.18% and the hypopharynx in 10%. Conclusions: The Clínica Universitaria Colombia is a referral site for many gastroenterology emergencies due to its high technological level and extensive human resources. This paper probably describes the largest number of patients with this reason for consultation, which is why this retrospective descriptive study was designed. It shows the demographic characteristics, foreign body types, radiological and endoscopic findings, and associated complications, which help to provide a more accurate knowledge of this pathology.

Introducción: La ingesta de cuerpos extraños es un problema médico frecuente, especialmente en el servicio de urgencias. Existen algunos estudios pequeños que describen las experiencias al respecto. Materiales y métodos: Estudio descriptivo, retrospectivo, en el cual se incluyó a pacientes con sospecha de ingesta de cuerpos extraños, ingresados al servicio de gastroenterología y endoscopia digestiva de La Clínica Universitaria Colombia, entre enero de 2007 y agosto de 2020. Resultados: La edad de ocurrencia del evento se presentó en pacientes desde los 18 hasta los 95 años, y la edad promedio fue de 45 años. Los cuerpos extraños ingeridos y encontrados fueron variables; los más frecuentes fueron la ingesta de espinas de pescado, que representó el 64,11% de los casos, seguido por la ingesta de huesos de pollo y la impactación alimentaria. Un 38% de los pacientes requirieron la extracción de cuerpo extraño y la herramienta usada con mayor frecuencia fue la pinza de cuerpo extraño. La localización principal fue el esófago, en el 12,53% de los casos, seguido por la cricofaringe, en el 11,18%, y la hipofaringe, en el 10%. Conclusiones: La Clínica Universitaria Colombia es un sitio de referencia de una gran cantidad de urgencias en gastroenterología debido a su alto nivel tecnológico y al gran recurso humano que requieren. Este trabajo representa probablemente la cantidad más grande de pacientes con este motivo de consulta, razón por la que se diseñó este estudio descriptivo retrospectivo, que muestra las características demográficas, los tipos de cuerpo extraño, los hallazgos radiológicos y endoscópicos y las complicaciones asociadas, que son de utilidad para tener un conocimiento más real de esta patología.

Hospital Civil de Santiago de Cuba: una historia de cambios, dificultades y realizaciones / Civil Hospital of Santiago de Cuba: a history of changes, difficulties and realizations i: en

El Hospital Civil de Santiago de Cuba fue fundado en 1863 y, desde entonces, se ha mantenido prestando asistencia a pacientes de esta provincia y de toda la región oriental. En 1960 fue trasladado a su sede actual y se convirtió en pilar fundamental del inicio de la docencia médica superior para todo el oriente de Cuba. Es mencionado en varios textos desde el siglo XIX, mas se desconoce su creación y trayectoria. En ese sentido, luego de una revisión exhaustiva de documentos y periódicos de la época, se realizó el presente artículo con el objetivo de describir la evolución de este centro y los contextos históricos fundamentales.

The Civil Hospital of Santiago de Cuba was founded in 1863 and, since that time, it has given assistance to patients of this province and of all east region. In 1960 it was transferred to the current head office and became fundamental column in the beginning of higher medical teaching for the whole east of Cuba. It is mentioned in several texts from the XIX century, but its creation and trajectory is not known. In that sense, after an exhaustive review of documents and newspapers of that time, the present work was carried out aimed at describing the evolution of this center and the fundamental historical contexts.