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1.
Tumour Virus Res ; 18: 200288, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960143

RESUMEN

Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea. Methylation of EPB41L3 (1-6 CpG-sites), hTERT (1-10 CpG-sites) and FAM19A4 (1-5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously. In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity]. Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

2.
Nat Commun ; 15(1): 5629, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965223

RESUMEN

Mutations that decrease or increase the activity of the tyrosine phosphatase, SHP2 (encoded by PTPN11), promotes developmental disorders and several malignancies by varying phosphatase activity. We uncovered that SHP2 is a distinct class of an epigenetic enzyme; upon phosphorylation by the kinase ACK1/TNK2, pSHP2 was escorted by androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation of histones H3 at Tyr54) epigenetic marks to trigger a transcriptional program of AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, SHP2 knock-in mice, and ACK1 knockout mice presented dramatic increase in pY54-H3, leading to loss of AR transcriptome. In contrast, prostate tumors with high pSHP2 and pACK1 activity exhibited progressive downregulation of pY54-H3 levels and higher AR expression that correlated with disease severity. Overall, pSHP2/pY54-H3 signaling acts as a sentinel of AR homeostasis, explaining not only growth retardation, genital abnormalities and infertility among NSML patients, but also significant AR upregulation in prostate cancer patients.


Asunto(s)
Epigénesis Genética , Histonas , Homeostasis , Ratones Noqueados , Neoplasias de la Próstata , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Receptores Androgénicos , Animales , Humanos , Masculino , Ratones , Cromatina/metabolismo , Histonas/metabolismo , Síndrome de Noonan/genética , Síndrome de Noonan/metabolismo , Fosforilación , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Transducción de Señal
3.
BMJ Open Diabetes Res Care ; 12(4)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013632

RESUMEN

INTRODUCTION: The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort's parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes. RESEARCH DESIGN AND METHODS: Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D. The primary outcome was persistent islet autoimmunity, with children followed until a T1D diagnosis or 10 years of age. Demographic data were collected at enrollment. Lifestyle, clinical and anthropometric data were collected at each visit during pregnancy and clinical pregnancy and birth data were verified against medical case notes. Data were compared between mothers with and without T1D. HLA genotyping was performed on the ENDIA child and all available FDRs. RESULTS: The final cohort comprised 1473 infants born to 1214 gestational mothers across 1453 pregnancies, with 80% enrolled during pregnancy. The distribution of familial T1D probands was 62% maternal, 28% paternal and 11% sibling. The frequency of high-risk HLA genotypes was highest in T1D probands, followed by ENDIA infants, and lowest among unaffected family members. Mothers with T1D had higher rates of pregnancy complications and perinatal intervention, and larger babies of shorter gestation. Parent demographics were comparable to the Australian population for age, parity and obesity. A greater percentage of ENDIA parents were Australian born, lived in a major city and had higher socioeconomic advantage and education. CONCLUSIONS: This comprehensive profile provides the context for understanding ENDIA's scope, methodology, unique strengths and limitations. Now fully recruited, ENDIA will provide unique insights into the roles of early-life factors in the development of islet autoimmunity and T1D in the Australian environment. TRIAL REGISTRATION NUMBER: ACTRN12613000794707.


Asunto(s)
Autoinmunidad , Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/etiología , Femenino , Embarazo , Australia/epidemiología , Estudios Prospectivos , Masculino , Niño , Lactante , Recién Nacido , Factores de Riesgo , Adulto , Islotes Pancreáticos/inmunología , Estudios Longitudinales , Estudios de Seguimiento , Efectos Tardíos de la Exposición Prenatal/epidemiología , Preescolar , Padres , Genotipo , Antígenos HLA/genética
4.
bioRxiv ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39026781

RESUMEN

Background: In 2019, the Open Pediatric Brain Tumor Atlas (OpenPBTA) was created as a global, collaborative open-science initiative to genomically characterize 1,074 pediatric brain tumors and 22 patient-derived cell lines. Here, we extend the OpenPBTA to create the Open Pediatric Cancer (OpenPedCan) Project, a harmonized open-source multi-omic dataset from 6,112 pediatric cancer patients with 7,096 tumor events across more than 100 histologies. Combined with RNA-Seq from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA), OpenPedCan contains nearly 48,000 total biospecimens (24,002 tumor and 23,893 normal specimens). Findings: We utilized Gabriella Miller Kids First (GMKF) workflows to harmonize WGS, WXS, RNA-seq, and Targeted Sequencing datasets to include somatic SNVs, InDels, CNVs, SVs, RNA expression, fusions, and splice variants. We integrated summarized CPTAC whole cell proteomics and phospho-proteomics data, miRNA-Seq data, and have developed a methylation array harmonization workflow to include m-values, beta-vales, and copy number calls. OpenPedCan contains reproducible, dockerized workflows in GitHub, CAVATICA, and Amazon Web Services (AWS) to deliver harmonized and processed data from over 60 scalable modules which can be leveraged both locally and on AWS. The processed data are released in a versioned manner and accessible through CAVATICA or AWS S3 download (from GitHub), and queryable through PedcBioPortal and the NCI's pediatric Molecular Targets Platform. Notably, we have expanded PBTA molecular subtyping to include methylation information to align with the WHO 2021 Central Nervous System Tumor classifications, allowing us to create research- grade integrated diagnoses for these tumors. Conclusions: OpenPedCan data and its reproducible analysis module framework are openly available and can be utilized and/or adapted by researchers to accelerate discovery, validation, and clinical translation.

5.
Ann Fam Med ; 22(4): 333-335, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39038978

RESUMEN

PURPOSE: This study marks the 50th anniversary of NAPCRG (formerly the North American Primary Care Research Group) by examining social connections among members. METHODS: This descriptive social network analysis was conducted via the Program to Analyze, Record, and Track Networks to Enhance Relationships (PARTNER) survey tool. RESULTS: Responses from 906 participants resulted in 1,721 individuals with 5,196 partner relationships. Most relationships (60%) were characterized as having an integrated level of collaboration. Many relationships led to a research paper (58%) or a grant (34%). CONCLUSIONS: This social network analysis of NAPCRG members' relationships described over 5,000 relationships, many producing publications, grants, and perceived advancements in primary care.


Asunto(s)
Atención Primaria de Salud , Humanos , Apoyo Social , Red Social , Masculino , Femenino , Conducta Cooperativa , Análisis de Redes Sociales , Investigación sobre Servicios de Salud , Encuestas y Cuestionarios
6.
J Exp Bot ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058302

RESUMEN

The four carbon non-proteinogenic amino acid γ-aminobutyric acid (GABA) accumulates to high levels in plants in response to various abiotic and biotic stress stimuli, and plays a role in C:N balance, signaling and as a transport regulator. Expression in Xenopus oocytes and voltage-clamping allowed characterizing Arabidopsis GAT2 (At5g41800) as low affinity GABA transporter with a K0.5GABA~8 mM. L-alanine and butylamine represented additional substrates. GABA-induced currents were strongly dependent on the membrane potential, reaching highest affinity and highest transport rates at strongly negative membrane potentials. Mutation of Ser17, previously reported to be phosphorylated in planta, did not result in altered affinity. In short term stress experiment, AtGAT2 mRNA levels were upregulated at low water potential and under osmotic stress (polyethylene glycol, mannitol). Furthermore, AtGAT2 promoter activity was detected in vascular tissues, in maturating pollen, and the phloem unloading region of young seeds. Even though this suggested a role of AtGAT2 in long distance transport and loading of sink organs, under the conditions tested neither AtGAT2 overexpressing plants nor atgat2 or atgat1 T-DNA insertion lines, or atgat1 atgat2 double knockout mutants differed from wild type plants in growth on GABA, in amino acid levels or resistance to salt and osmotic stress.

7.
J Chem Phys ; 161(4)2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39056388

RESUMEN

Double ionization spectra of isothiocyanic acid (HNCS) have been measured using multi-electron and multi-ion coincidence techniques combined with high-level theoretical calculations. The adiabatic double ionization energy of HNCS is found at 27.1 ± 0.1 eV and is associated with the formation of the X 3A″ ground state of HNCS2+. The characteristics of different dissociation channels are examined and compared to the results of electronic structure calculations obtained by systematically elongating the three bonds H-NCS, HN-CS, and HNC-S. For instance, the adiabatic double ionization energy of the NCS fragment is deduced to be 30.95 ± 0.5 eV. In addition, the C+ and NS+ dissociation channels are of particular interest, possibly indicating the involvement of a structural rearrangement process upon doubly ionizing HNCS.

8.
Transplantation ; 108(8): 1669-1680, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39012953

RESUMEN

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS: A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS: The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS: The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.


Asunto(s)
Consenso , Preservación de Órganos , Perfusión , Humanos , Perfusión/normas , Perfusión/métodos , Preservación de Órganos/normas , Preservación de Órganos/métodos , Donantes de Tejidos/provisión & distribución , Trasplante de Órganos/normas , Trasplante de Órganos/métodos , Selección de Donante/normas , Obtención de Tejidos y Órganos/normas , Obtención de Tejidos y Órganos/métodos
9.
Cell Rep ; 43(7): 114502, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39002130

RESUMEN

Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, exclusive to Nairoviridae, is a target of protective antibodies and is a key antigen in preclinical vaccine candidates. Here, we isolate 188 GP38-specific antibodies from human survivors of infection. Competition experiments show that these antibodies bind across 5 distinct antigenic sites, encompassing 11 overlapping regions. Additionally, we show structures of GP38 bound with 9 of these antibodies targeting different antigenic sites. Although these GP38-specific antibodies are non-neutralizing, several display protective efficacy equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and may inform the development of broadly effective CCHFV antibody therapeutics.


Asunto(s)
Anticuerpos Antivirales , Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Humanos , Animales , Fiebre Hemorrágica de Crimea/inmunología , Virus de la Fiebre Hemorrágica de Crimea-Congo/inmunología , Anticuerpos Antivirales/inmunología , Ratones , Sobrevivientes , Anticuerpos Neutralizantes/inmunología , Femenino , Glicoproteínas/inmunología , Epítopos/inmunología
10.
J Investig Med High Impact Case Rep ; 12: 23247096241264635, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39051436

RESUMEN

This case series explores the association between tirzepatide-assisted weight loss and the development of foot drop due to peroneal nerve neuropathy, a phenomenon known as slimmer's paralysis. Two cases are presented of patients who experienced rapid weight loss after initiation of tirzepatide therapy and within 6 to 8 months developed bilateral foot drop. As providers, we have more medications than ever to assist patients in their weight loss journeys, but both of these cases are reminders of the risks of rapid weight loss and the need to monitor therapy closely for patients on tirzepatide and similar medications.


Asunto(s)
Neuropatías Peroneas , Pérdida de Peso , Humanos , Neuropatías Peroneas/etiología , Neuropatías Peroneas/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Trastornos Neurológicos de la Marcha/etiología , Masculino , Adulto , Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/administración & dosificación
11.
J Psychiatr Pract ; 30(4): 247-248, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39058522
12.
J Neurosurg Pediatr ; : 1-12, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39029127

RESUMEN

OBJECTIVE: Cerebral revascularization surgery (CRS) has been used to prevent stroke in children with sickle cell disease (SCD) and cerebral vasculopathy (e.g., moyamoya syndrome). While results suggest that it may be an effective treatment, surgical indications have not been well defined. This study sought to determine indications for offering revascularization surgery in centers with established sickle cell programs in the US. METHODS: Three sequential surveys utilizing the Delphi methodology were administered to neurosurgeons participating in the Stroke in Sickle Cell Revascularization Surgery study. Respondents were presented with clinical scenarios of patients with SCD and varying degrees of ischemic presentation and vasculopathy, and the group's agreement to offer surgical revascularization was measured. Consensus was defined as ≥ 75% similar responses. RESULTS: The response rate to all 3 surveys was 100%. Seventeen neurosurgeons from 16 different centers participated. The presence of moyamoya collaterals (MMCs) and arterial stenosis matching an ischemic distribution yielded the strongest recommendations to offer surgery. There was consensus to offer revascularization in the presence of MMCs and at least 50% arterial stenosis matching an ischemic distribution. In contrast, there was no consensus to offer revascularization with 50%-70% stenosis not matching an ischemic presentation in the absence of MMCs. The presence of the ivy sign in the distribution of the stenotic artery also contributed to the consensus to offer surgery in certain scenarios. CONCLUSIONS: There were several clinical scenarios that attained consensus to offer surgery; the strongest was moderate to severe arterial stenosis that matched the distribution of ischemic presentation in the presence of MMCs. Radiological findings of decreased cerebral flow or perfusion also facilitated attaining consensus to offer surgery. The findings of this study reflect expert opinion about questions that deserve prospective clinical research. Determination of indications for CRS can guide clinical practice and aid the design of prospective studies.

13.
Artículo en Inglés | MEDLINE | ID: mdl-39029637

RESUMEN

Primary graft dysfunction (PGD) is a complication of lung transplantation that continues to cause significant morbidity. The Th2 immune response has been shown to counteract tissue-damaging inflammation. We hypothesized that Th2 cytokines/chemokines in blood would be associated with protection from PGD. Utilizing pre-transplant sera from the multicenter Clinical Trials in Organ Transplantation (CTOT-20) study, we evaluated Th2 cytokines/chemokines in 211 patients. Increased concentrations of Th2 cytokines were associated with freedom from PGD, namely IL-4 (Odds Ratio (OR) 0.66 (95% CI 0.45-0.99), p=0.043), IL-9 (OR 0.68 (95% CI 0.49-0.94), p=0.019), IL-13 (OR 0.73 (95% CI 0.55-0.96), p=0.023), and IL-6 (OR 0.74 (95% CI 0.56-0.98), p=0.036). Multivariable regression performed for each cytokine including clinically relevant covariables confirmed these associations and additionally demonstrated association with IL-5 (OR 0.57 (95% CI 0.36-0.89), p=0.014) and IL-10 (OR 0.55 (95% CI 0.32-0.96), p=0.035). Higher levels of Th2 immune response prior to lung translant appear to have a protective effect against PGD, which parallels the Th2 role in resolving inflammation and tissue injury. Pre-transplant cytokine assessments could be utilized for recipient risk stratification.

14.
Methods Mol Biol ; 2823: 193-223, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39052222

RESUMEN

Archived tumor specimens are routinely preserved by formalin fixation and paraffin embedding. Despite the conventional wisdom that proteomics might be ineffective due to the cross-linking and pre-analytical variables, these samples have utility for both discovery and targeted proteomics. Building on this capability, proteomics approaches can be used to maximize our understanding of cancer biology and clinical relevance by studying preserved tumor tissues annotated with the patients' medical histories. Proteomics of formalin-fixed paraffin-embedded (FFPE) tissues also integrates with histological evaluation and molecular pathology strategies, so that additional collection of research biopsies or resected tumor aliquots is not needed. The acquisition of data from the same tumor sample also overcomes concerns about biological variation between samples due to intratumoral heterogeneity. However, the protein extraction and proteomics sample preparation from FFPE samples can be onerous, particularly for small (i.e., limited or precious) samples. Therefore, we provide a protocol for a recently introduced kit-based EasyPep method with benchmarking against a modified version of the well-established filter-aided sample preparation strategy using laser-capture microdissected lung adenocarcinoma tissues from a genetically engineered mouse model. This model system allows control over the tumor preparation and pre-analytical variables while also supporting the development of methods for spatial proteomics to examine intratumoral heterogeneity. Data are posted in ProteomeXchange (PXD045879).


Asunto(s)
Formaldehído , Adhesión en Parafina , Proteómica , Fijación del Tejido , Proteómica/métodos , Adhesión en Parafina/métodos , Fijación del Tejido/métodos , Formaldehído/química , Animales , Ratones , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Captura por Microdisección con Láser/métodos , Neoplasias/patología , Neoplasias/metabolismo , Neoplasias/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo
15.
Biology (Basel) ; 13(7)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39056733

RESUMEN

Foreign body response (FBR) is a universal reaction to implanted biomaterial that can affect the function and longevity of the implant. A few studies have attempted to identify targets for treating FBR through the use of single-cell RNA sequencing (scRNA-seq), though the generalizability of these findings from an individual study may be limited. In our study, we perform a meta-analysis of scRNA-seq data from all available FBR mouse studies and integrate these data to identify gene signatures specific to FBR across different models and anatomic locations. We identify subclusters of fibroblasts and macrophages that emerge in response to foreign bodies and characterize their signaling pathways, gene ontology terms, and downstream mediators. The fibroblast subpopulations enriched in the setting of FBR demonstrated significant signaling interactions in the transforming growth factor-beta (TGF-ß) signaling pathway, with known pro-fibrotic mediators identified as top expressed genes in these FBR-derived fibroblasts. In contrast, FBR-enriched macrophage subclusters highly expressed pro-fibrotic and pro-inflammatory mediators downstream of tumor necrosis factor (TNF) signaling. Cell-cell interactions were additionally interrogated using CellChat, with identification of key signaling interactions enriched between fibroblasts and macrophages in FBR. By combining multiple FBR datasets, our meta-analysis study identifies common cell-specific gene signatures enriched in foreign body reactions, providing potential therapeutic targets for patients requiring medical implants across a myriad of devices and indications.

16.
Diabetes Res Clin Pract ; : 111791, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39059738

RESUMEN

AIM(S): To examine the association between non-exercise estimated cardiorespiratory fitness (eCRF) and incident type 2 diabetes. METHODS: In a sample of 13,616 men and women without diabetes at baseline, incidence of type 2 diabetes was determined as fasting plasma glucose level ≥ 7 mmol/l (126 mg/dL), self-reported type 2 diabetes, or insulin usage at follow-up. eCRF was calculated in metabolic equivalents (METs) at baseline using sex-specific algorithms, including physical activity, smoking status, age, body mass index, waist circumference, and resting heart rate. Cox regression models were performed, and reported as hazard ratios (HRs), 95 % confidence intervals (CIs), and p values. RESULTS: Each 1-MET unit increase in eCRF was associated with an 11 % lower risk of incident type 2 diabetes (p < 0.0001). Men in the upper and middle eCRF tertiles were at 46 % (95 % CI, 0.42-0.68) and 29 % (95 % CI, 0.57-0.88) lower risk of incident type 2 diabetes compared to the lower eCRF tertile (p < 0.0001). For women, there were no significant findings between eCRF tertiles and incident type 2 diabetes (p ≥ 0.11 for all). CONCLUSIONS: Higher eCRF was associated with a lower incidence of type 2 diabetes in men. Further research needs to examine the association between eCRF and type 2 diabetes in women.

17.
Elife ; 132024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037763

RESUMEN

HERV-K(HML-2), the youngest clade of human endogenous retroviruses (HERVs), includes many intact or nearly intact proviruses, but no replication competent HML-2 proviruses have been identified in humans. HML-2-related proviruses are present in other primates, including rhesus macaques, but the extent and timing of HML-2 activity in macaques remains unclear. We have identified 145 HML-2-like proviruses in rhesus macaques, including a clade of young, rhesus-specific insertions. Age estimates, intact ORFs, and insertional polymorphism of these insertions are consistent with recent or ongoing infectious activity in macaques. 106 of the proviruses form a clade characterized by an ~750 bp sequence between env and the 3' LTR, derived from an ancient recombination with a HERV-K(HML-8)-related virus. This clade is found in Old World monkeys (OWM), but not great apes, suggesting it originated after the ape/OWM split. We identified similar proviruses in white-cheeked gibbons; the gibbon insertions cluster within the OWM recombinant clade, suggesting interspecies transmission from OWM to gibbons. The LTRs of the youngest proviruses have deletions in U3, which disrupt the Rec Response Element (RcRE), required for nuclear export of unspliced viral RNA. We show that the HML-8 derived region functions as a Rec-independent constitutive transport element (CTE), indicating the ancestral Rec-RcRE export system was replaced by a CTE mechanism.

18.
Ann Plast Surg ; 93(2): 205-207, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39023409

RESUMEN

BACKGROUND: Mercury, an element with threats of severe toxic insult to humans and no biological function, has a surprisingly extensive record of human exposure. Regardless of hesitancies toward its harmfulness, it has been historically identified with an almost supernatural power to provide protection from evil and sickness, give good fortune, lend aid in athletic undertakings, or even allow one to achieve immortality. Mercury poisoning is an iatrogenic disease even today as people attempt to achieve these effects through volitional injections into their body by practitioners. Although an uncommon practice in the United States, awareness of patient presentation after volitional injections of elemental mercury is necessary for appropriate treatment of these patients. We aim to increase awareness of the cultural practice of subcutaneous injections of mercury, as it is uncommonly seen in the United States, to contribute a broader understanding to the patient's medical presentation and describe an approach and the impact of medical and surgical intervention. METHODS: In this report, we describe a rare case of elemental mercury poisoning secondary to volitional subcutaneous injection to the arm. Initial management of care through chelation therapy and monitoring of renal and serum mercury levels in addition to symptoms of systemic spread was overseen by an internal medicine physician and poison control. Surgical intervention via full-thickness excision of the visible mercury to the right arm followed by local flap and skin grafting reconstruction was performed. CONCLUSIONS: Mercury poisoning from intentional subcutaneous administration is an uncommon patient presentation in the United States; however, knowledge of management of this rare condition is important for effective management of iatrogenic mercury toxicity.


Asunto(s)
Enfermedad Iatrogénica , Intoxicación por Mercurio , Humanos , Intoxicación por Mercurio/cirugía , Inyecciones Subcutáneas , Brazo/cirugía , Femenino , Masculino , Adulto , Trasplante de Piel/métodos , Colgajos Quirúrgicos
19.
Am J Transplant ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39025302

RESUMEN

Mycoplasma hominis and Ureaplasma species are urogenital mollicutes that can cause serious donor-derived infections in lung transplant recipients. Best practices for mollicute screening remain unknown. We conducted a single center prospective study analyzing lung transplants performed from 10/5/20 - 9/5/21 whereby donor and recipient bronchoalveolar lavage (BAL) samples obtained at time of transplant underwent mollicute screening via culture and polymerase chain reaction (PCR). Of 115 total lung transplants performed, 99 (86%) donors underwent combined mollicute BAL culture and PCR testing. The study cohort included these 99 donors and their matched recipients. In total, 18 (18%) of 99 donors screened positive via culture or PCR. Among recipients, 92 (93%) of 99 had perioperative BAL screening performed, and only 3 (3%) had positive results. After transplant, 9 (9%) recipients developed mollicute infection. Sensitivity of donor screening in predicting recipient mollicute infection was 67% (6/9) via culture and 56% (5/9) via PCR. Positive predictive value (PPV) for donor culture was 75% (6/8), compared to 33% (5/15) for PCR. Donor screening via culture predicted all serious recipient mollicute infections and had better PPV than PCR; however, neither screening test predicted all mollicute infections. Independent of screening results, clinicians should remain suspicious for post-transplant mollicute infection.

20.
J Surg Educ ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39025720

RESUMEN

OBJECTIVE: Obtaining surgical informed consent (SIC) is a critical skill most residents are expected to learn "on-the-job." This study sought to quantify the effect of 1 year of clinical experience on performance obtaining SIC in the absence of formal informed consent education. DESIGN: In this case-control cohort study, PGY1 and PGY2 surgical residents in an academic program were surveyed regarding their experiences and confidence in obtaining SIC; then assessed obtaining informed consent for a right hemicolectomy from a standardized patient. SETTING: Single academic general surgery residency program in Buffalo, NY. PARTICIPANTS: Ten PGY1 and eight PGY2 general surgery residents were included in the study, after excluding residents with additional years of training. RESULTS: PGY2 residents had significantly more experience obtaining SIC compared to PGY1 residents (median response: ">50" vs "between 6 and 15," p = 0.001), however there was no difference in self-reported confidence in ability obtaining SIC (mean 3.2/5 in PGY1 vs 3.4/5 in PGY2, p = 0.61), self-reported knowledge of SIC (mean 3.1/5 in PGY1 vs 3.6/5 in PGY2, p = 0.15), performance on a test regarding SIC (mean score 9.0/20, SD 3.9 for PGY1 vs mean score 9.6/20, SD 3.5, t = 0.387, p = 0.739) or performance during a standardized patient interview (mean 11.2/20, SD 2.78 for PGY1 vs mean 11.4/20, SD 1.51 for PGY2, p = 0.87). In the interviews all residents addressed general risks (bleeding/infection), however both groups performed worse in addressing procedure-specific risks including anastomotic leak as risk for hemicolectomy. CONCLUSIONS: A year of clinical training between PGY1 to PGY2 did not improve performance in obtaining surgical informed consent when lacking formal education, despite self-confidence in their ability. A curriculum covering the content, delivery and assessment of informed consent should be initiated for residents upon arrival to surgical training.

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