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1.
Am J Respir Cell Mol Biol ; 67(2): 188-200, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35608953

RESUMEN

We previously identified a novel molecular subtype of idiopathic pulmonary fibrosis (IPF) defined by increased expression of cilium-associated genes, airway mucin gene MUC5B, and KRT5 marker of basal cell airway progenitors. Here we show the association of MUC5B and cilia gene expression in human IPF airway epithelial cells, providing further rationale for examining the role of cilium genes in the pathogenesis of IPF. We demonstrate increased multiciliogenesis and changes in motile cilia structure of multiciliated cells both in IPF and bleomycin lung fibrosis models. Importantly, conditional deletion of a cilium gene, Ift88 (intraflagellar transport 88), in Krt5 basal cells reduces Krt5 pod formation and lung fibrosis, whereas no changes are observed in Ift88 conditional deletion in club cell progenitors. Our findings indicate that aberrant injury-activated primary ciliogenesis and Hedgehog signaling may play a causative role in Krt5 pod formation, which leads to aberrant multiciliogenesis and lung fibrosis. This implies that modulating cilium gene expression in Krt5 cell progenitors is a potential therapeutic target for IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática , Bleomicina/toxicidad , Cilios/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Fibrosis Pulmonar Idiopática/patología , Transducción de Señal
2.
J Cardiothorac Vasc Anesth ; 36(1): 76-83, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34462201

RESUMEN

OBJECTIVE: The authors explored the current practice of fellowship training in cardiothoracic and vascular anesthesia and surveyed the acceptability of potential solutions to mitigate the interrupted fellowship training during the severe acute respiratory syndrome coronavirus disease 2019 (COVID-19) pandemic. DESIGN: A prospective electronic questionnaire-based survey. SETTING: The survey was initiated by the Education Committee of the European Association of Cardiothoracic Anesthesiology and Intensive Care (EACTAIC). PARTICIPANTS: The study comprised EACTAIC fellows, EACTAIC, and non-EACTAIC subscribers to the EACTAIC newsletter and EACTAIC followers on different social media platforms. INTERVENTIONS: After obtaining the consent of participants, the authors assessed the perioperative management of COVID-19 patients, infrastructural aspects of the workplace, local routines for preoperative testing, the perceived availability of personal protective equipment (PPE), and the impact of COVID-19 on fellowship training. In addition, participants rated suggested solutions by the investigators to cope with the interruption of fellowship training, using a traffic light signal scale. MEASUREMENTS AND MAIN RESULTS: The authors collected 193 responses from 54 countries. Of the respondents, 82.4% reported cancelling or postponing elective cases during the first wave, 89.7% had provided care for COVID-19 patients, 75.1% reported staff in their center being reassigned to work in the intensive care unit (ICU), and 45% perceived a shortage of PPE at their centers. Most respondents reported the termination of local educational activities (79.6%) and fellowship assessments (51.5%) because of the pandemic (although 84% of them reported having time to participate in online teaching), and 83% reported a definitive psychological impact. More than 90% of the respondents chose green and/or yellow traffic lights to rate the importance of the suggested solutions to cope with the interrupted fellowship training during the pandemic. CONCLUSIONS: The COVID-19 pandemic led to the cancellation of elective cases, the deployment of anesthesiologists to ICUs, the involvement of anesthesiologists in perioperative care for COVID-19 patients, and the interruption of educational activities and trainees' assessments. There is some consensus on the suggested solutions for mitigation of the interruption in fellowship training.


Asunto(s)
Anestesia , Anestesiología , COVID-19 , Electrónica , Becas , Humanos , Pandemias , Estudios Prospectivos , SARS-CoV-2 , Encuestas y Cuestionarios
3.
Alcohol Clin Exp Res ; 44(8): 1571-1584, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32524622

RESUMEN

BACKGROUND: Alcohol use disorders (AUDs) and cigarette smoking both increase risk for the development of community-acquired pneumonia (CAP), likely through adverse effects on proximal airway mucociliary clearance and pathogen recognition. Smoking-related alterations on airway gene expression are well described, but little is known about the impact of AUDs. We measured gene expression in human airway epithelial cells (AECs), hypothesizing that AUDs would be associated with novel differences in gene expression that could alter risk for CAP. METHODS: Bronchoscopy with airway brushings was performed in participants with AUDs and controls to obtain AECs. An AUD Identification Test was used to define AUD. RNA was extracted from AECs, and mRNA expression data were collected on an Agilent micro-array. Differential expression analyses were performed on the filtered and normalized data with correction for multiple testing. Enrichment analyses were performed using clusterProfiler. RESULTS: Expression data from 19 control and 18 AUD participants were evaluated. After adjustment for smoking, AUDs were associated with significant differential expression of 520 AEC genes, including genes for ribosomal proteins and genes involved in protein folding. Enrichment analyses indicated significant differential expression of 24 pathways in AUDs, including those implicated in protein targeting to membrane and viral gene expression. Smoking-associated AEC gene expression differences mirrored previous reports, but differed from those associated with AUDs. CONCLUSIONS: AUDs have a distinct impact on AEC gene expression that may influence proximal airway function independent of smoking. Alcohol-associated alterations may influence risk for CAP through modifying key mechanisms important in protecting proximal airway integrity.


Asunto(s)
Alcoholismo/genética , Células Epiteliales/metabolismo , Expresión Génica , ARN Mensajero/metabolismo , Mucosa Respiratoria/citología , Adulto , Alcoholismo/metabolismo , Broncoscopía , Estudios de Casos y Controles , Fumar Cigarrillos/genética , Fumar Cigarrillos/metabolismo , Infecciones Comunitarias Adquiridas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía , Factores de Riesgo , Transcriptoma
4.
Biopolymers ; 110(4): e23248, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30578630

RESUMEN

A desire to replicate the structural and functional complexity of proteins with structured, sequence-specific oligomers motivates study of the structural features of water-soluble peptoids (N-substituted glycine oligomers). Understanding the molecular-level details of peptoid self-assembly in water is essential to advance peptoids' application as novel materials. Peptoid 1, an amphiphilic, putatively helical peptoid previously studied in our laboratory, shows evidence of self-association in aqueous solution. In this work, we evaluate how changes to aqueous solution conditions influence the self-association of 1. We report that changes to pH influence the fluorescence and CD spectroscopic features as well as the peptoid's interaction with a solvatochromic fluorophore and its apparent size as estimated by size exclusion chromatography. Addition of guanidine hydrochloride and ammonium sulfate also modulate spectroscopic features of the peptoid, its interaction with a solvatochromic fluorophore, and its elution in size exclusion chromatography. These data suggest that the ordering of the self-assembly changes in response to pH and with solvent additives and is more ordered at higher pH and in the presence of guanidine hydrochloride. The deeper understanding of the self-association of 1 afforded by these studies informs the design of new stimuli-responsive peptoids with stable tertiary or quaternary structures.


Asunto(s)
Peptoides/química , Agua/química , Dicroismo Circular , Concentración de Iones de Hidrógeno , Solubilidad , Solventes/química , Espectrometría de Fluorescencia
5.
Cochrane Database Syst Rev ; 11: CD012745, 2019 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-31778223

RESUMEN

BACKGROUND: In the absence of bleeding, plasma is commonly transfused to people prophylactically to prevent bleeding. In this context, it is transfused before operative or invasive procedures (such as liver biopsy or chest drainage tube insertion) in those considered at increased risk of bleeding, typically defined by abnormalities of laboratory tests of coagulation. As plasma contains procoagulant factors, plasma transfusion may reduce perioperative bleeding risk. This outcome has clinical importance given that perioperative bleeding and blood transfusion have been associated with increased morbidity and mortality. Plasma is expensive, and some countries have experienced issues with blood product shortages, donor pool reliability, and incomplete screening for transmissible infections. Thus, although the benefit of prophylactic plasma transfusion has not been well established, plasma transfusion does carry potentially life-threatening risks. OBJECTIVES: To determine the clinical effectiveness and safety of prophylactic plasma transfusion for people with coagulation test abnormalities (in the absence of inherited bleeding disorders or use of anticoagulant medication) requiring non-cardiac surgery or invasive procedures. SEARCH METHODS: We searched for randomised controlled trials (RCTs), without language or publication status restrictions in: Cochrane Central Register of Controlled Trials (CENTRAL; 2017 Issue 7); Ovid MEDLINE (from 1946); Ovid Embase (from 1974); Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCOHost) (from 1937); PubMed (e-publications and in-process citations ahead of print only); Transfusion Evidence Library (from 1950); Latin American Caribbean Health Sciences Literature (LILACS) (from 1982); Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (Thomson Reuters, from 1990); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Search Platform (ICTRP) to 28 January 2019. SELECTION CRITERIA: We included RCTs comparing: prophylactic plasma transfusion to placebo, intravenous fluid, or no intervention; prophylactic plasma transfusion to alternative pro-haemostatic agents; or different haemostatic thresholds for prophylactic plasma transfusion. We included participants of any age, and we excluded trials incorporating individuals with previous active bleeding, with inherited bleeding disorders, or taking anticoagulant medication before enrolment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five trials in this review, all were conducted in high-income countries. Three additional trials are ongoing. One trial compared fresh frozen plasma (FFP) transfusion with no transfusion given. One trial compared FFP or platelet transfusion or both with neither FFP nor platelet transfusion given. One trial compared FFP transfusion with administration of alternative pro-haemostatic agents (factors II, IX, and X followed by VII). One trial compared the use of different transfusion triggers using the international normalised ratio measurement. One trial compared the use of a thromboelastographic-guided transfusion trigger using standard laboratory measurements of coagulation. Four trials enrolled only adults, whereas the fifth trial did not specify participant age. Four trials included only minor procedures that could be performed by the bedside. Only one trial included some participants undergoing major surgical operations. Two trials included only participants in intensive care. Two trials included only participants with liver disease. Three trials did not recruit sufficient participants to meet their pre-calculated sample size. Overall, the quality of evidence was low to very low across different outcomes according to GRADE methodology, due to risk of bias, indirectness, and imprecision. One trial was stopped after recruiting two participants, therefore this review's findings are based on the remaining four trials (234 participants). When plasma transfusion was compared with no transfusion given, we are very uncertain whether there was a difference in 30-day mortality (1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; risk ratio (RR) 0.38, 95% confidence interval (CI) 0.13 to 1.10; very low-quality evidence). We are very uncertain whether there was a difference in major bleeding within 24 hours (1 trial comparing FFP transfusion vs no transfusion, 76 participants; RR 0.33, 95% CI 0.01 to 7.93; very low-quality evidence; 1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; RR 1.59, 95% CI 0.28 to 8.93; very low-quality evidence). We are very uncertain whether there was a difference in the number of blood product transfusions per person (1 trial, 76 participants; study authors reported no difference; very low-quality evidence) or in the number of people requiring transfusion (1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; study authors reported no blood transfusion given; very low-quality evidence) or in the risk of transfusion-related adverse events (acute lung injury) (1 trial, 76 participants; study authors reported no difference; very low-quality evidence). When plasma transfusion was compared with other pro-haemostatic agents, we are very uncertain whether there was a difference in major bleeding (1 trial; 21 participants; no events; very low-quality evidence) or in transfusion-related adverse events (febrile or allergic reactions) (1 trial, 21 participants; RR 9.82, 95% CI 0.59 to 162.24; very low-quality evidence). When different triggers for FFP transfusion were compared, the number of people requiring transfusion may have been reduced (for overall blood products) when a thromboelastographic-guided transfusion trigger was compared with standard laboratory tests (1 trial, 60 participants; RR 0.18, 95% CI 0.08 to 0.39; low-quality evidence). We are very uncertain whether there was a difference in major bleeding (1 trial, 60 participants; RR 0.33, 95% CI 0.01 to 7.87; very low-quality evidence) or in transfusion-related adverse events (allergic reactions) (1 trial; 60 participants; RR 0.33, 95% CI 0.01 to 7.87; very low-quality evidence). Only one trial reported 30-day mortality. No trials reported procedure-related harmful events (excluding bleeding) or quality of life. AUTHORS' CONCLUSIONS: Review findings show uncertainty for the utility and safety of prophylactic FFP use. This is due to predominantly very low-quality evidence that is available for its use over a range of clinically important outcomes, together with lack of confidence in the wider applicability of study findings, given the paucity or absence of study data in settings such as major body cavity surgery, extensive soft tissue surgery, orthopaedic surgery, or neurosurgery. Therefore, from the limited RCT evidence, we can neither support nor oppose the use of prophylactic FFP in clinical practice.


Asunto(s)
Anticoagulantes/uso terapéutico , Transfusión de Componentes Sanguíneos/métodos , Hemorragia/prevención & control , Procedimientos Quirúrgicos Operativos , Anticoagulantes/efectos adversos , Hemostáticos/uso terapéutico , Humanos , Plasma , Cuidados Preoperatorios , Ensayos Clínicos Controlados Aleatorios como Asunto , Tromboelastografía
6.
Cochrane Database Syst Rev ; 2017(8)2017 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-29151811

RESUMEN

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the clinical effectiveness and safety of prophylactic plasma transfusion for people with confirmed or presumed coagulopathy requiring non-cardiac surgery.

7.
J Immunol ; 192(12): 5687-94, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24813204

RESUMEN

CD4(+) Th2 development is regulated by the zinc finger transcription factor GATA3. Once induced by acute priming signals, such as IL-4, GATA3 poises the Th2 cytokine locus for rapid activation and establishes a positive-feedback loop that maintains elevated GATA3 expression. Type I IFN (IFN-α/ß) inhibits Th2 cells by blocking the expression of GATA3 during Th2 development and in fully committed Th2 cells. In this study, we uncovered a unique mechanism by which IFN-α/ß signaling represses the GATA3 gene in human Th2 cells. IFN-α/ß suppressed expression of GATA3 mRNA that was transcribed from an alternative distal upstream exon (1A). This suppression was not mediated through DNA methylation, but rather by histone modifications localized to a conserved noncoding sequence (CNS-1) upstream of exon 1A. IFN-α/ß treatment led to a closed conformation of CNS-1, as assessed by DNase I hypersensitivity, along with enhanced accumulation of H3K27me3 mark at this CNS region, which correlated with increased density of total nucleosomes at this putative enhancer. Consequently, accessibility of CNS-1 to GATA3 DNA binding activity was reduced in response to IFN-α/ß signaling, even in the presence of IL-4. Thus, IFN-α/ß disrupts the GATA3-autoactivation loop and promotes epigenetic silencing of a Th2-specific regulatory region within the GATA3 gene.


Asunto(s)
Metilación de ADN/inmunología , Elementos de Facilitación Genéticos/inmunología , Factor de Transcripción GATA3/inmunología , Interferón-alfa/inmunología , Transducción de Señal/inmunología , Células Th2/inmunología , Transcripción Genética/inmunología , Adulto , Metilación de ADN/genética , Exones/inmunología , Femenino , Factor de Transcripción GATA3/genética , Humanos , Interferón-alfa/genética , Interferón beta/genética , Interferón beta/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Masculino , Transducción de Señal/genética , Células Th2/citología , Transcripción Genética/genética
9.
Clin J Pain ; 40(4): 221-229, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38229502

RESUMEN

OBJECTIVES: Endometriosis, a painful chronic gynecologic condition, contributes to disruptions in multiple areas of life for both those affected and their partner. Pain catastrophizing has been associated with worse pain outcomes and quality of life for women with endometriosis and with more cognitive load for partners. Examining both partners' pain catastrophizing dyadically with our variables of interest will enhance understanding of its associations with the distressing nature of experiencing and responding to pain during sex for couples with endometriosis. METHODS: Persons with endometriosis experiencing pain during sex and their partners (n=52 couples; 104 individuals) completed online self-report measures of pain catastrophizing, depressive symptoms, sexual satisfaction, and partner responses to pain. Persons with endometriosis reported on pain during sexual activity. Analyses were guided by the Actor-Partner Interdependence Model. RESULTS: Persons with endometriosis' pain catastrophizing was associated with their higher pain intensity and unpleasantness during sex. When persons with endometriosis reported more pain catastrophizing, they were less sexually satisfied and reported their partners responded more negatively to their pain. When partners reported higher catastrophizing, they were more depressed and responded more negatively to the pain. DISCUSSION: Consistent with the Communal Coping Model of pain catastrophizing, although meant to elicit support from the environment, the often-deleterious cognitive process of magnifying, ruminating, and feeling helpless about one's pain (or one's partner's pain) is associated with poorer outcomes for the individual with pain and their romantic partner. Implications for pain management include the relevance of involving the partner and attending to the pain cognitions of both members of the couple.


Asunto(s)
Endometriosis , Parejas Sexuales , Humanos , Femenino , Parejas Sexuales/psicología , Endometriosis/complicaciones , Calidad de Vida , Conducta Sexual/psicología , Dolor , Catastrofización , Encuestas y Cuestionarios , Satisfacción Personal
10.
J Sex Res ; : 1-12, 2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37343014

RESUMEN

Endometriosis is a chronic pain condition characterized by the growth of endometrial-like tissue outside of the uterus. Affected individuals and their partners report consequences to sexual functioning, sexual satisfaction, and relationship quality. Previous studies in clinical and non-clinical samples have found that sexual motivation can support or detract from sexual functioning; however, similar investigations are lacking among couples with endometriosis. Informed by self-determination theory, associations between autonomous and controlled sexual motivations with sexual functioning, sexual satisfaction, and relationship satisfaction for persons with endometriosis and their partners, and pain in persons with endometriosis were investigated. Couples (n = 54) completed measures of sexual motivation, sexual functioning, sexual satisfaction, relationship satisfaction, and pain. When persons with endometriosis reported greater autonomous sexual motivation, they were more sexually and relationally satisfied. When persons with endometriosis reported higher controlled sexual motivation, their pain was more unpleasant, and they and their partners were less sexually satisfied. Finally, when partners reported greater controlled sexual motivation, both members of the couple reported significantly lower sexual functioning. While controlled sexual motivation may hinder sexual and relational well-being in couples with endometriosis, autonomous sexual motivation may support them. The findings may inform interventions to promote sexual and relational health in couples with endometriosis.

11.
J Immunol ; 185(2): 813-7, 2010 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-20554961

RESUMEN

T helper 2 cells regulate inflammatory responses to helminth infections while also mediating pathological processes of asthma and allergy. IL-4 promotes Th2 development by inducing the expression of the GATA3 transcription factor, and the Th2 phenotype is stabilized by a GATA3-dependent autoregulatory loop. In this study, we found that type I IFN (IFN-alpha/beta) blocked human Th2 development and inhibited cytokine secretion from committed Th2 cells. This negative regulatory pathway was operative in human but not mouse CD4(+) T cells and was selective to type I IFN, as neither IFN-gamma nor IL-12 mediated such inhibition. IFN-alpha/beta blocked Th2 cytokine secretion through the inhibition of GATA3 during Th2 development and in fully committed Th2 cells. Ectopic expression of GATA3 via retrovirus did not overcome IFN-alpha/beta-mediated inhibition of Th2 commitment. Thus, we demonstrate a novel role for IFN-alpha/beta in blocking Th2 cells, suggesting its potential as a promising therapy for atopy and asthma.


Asunto(s)
Factor de Transcripción GATA3/metabolismo , Interferón-alfa/farmacología , Interferón beta/farmacología , Células Th2/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Factor de Transcripción GATA3/genética , Expresión Génica/efectos de los fármacos , Humanos , Interleucina-4/metabolismo , Ratones , Ratones Transgénicos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Th2/citología , Células Th2/metabolismo
12.
Immunology ; 132(4): 466-74, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21320124

RESUMEN

Type I interferon (IFN-α/ß) is comprised of a family of highly related molecules that exert potent antiviral activity by interfering with virus replication and spread. IFN-α/ß secretion is tightly regulated through pathogen sensing pathways that are operative in most somatic cells. However, specialized antigen-presenting plasmacytoid dendritic cells are uniquely equipped with the capacity to secrete extremely high levels of IFN-α/ß, suggesting a key role for this cytokine in priming adaptive T-cell responses. Recent studies in both mice and humans have demonstrated a role for IFN-α/ß in directly influencing the fate of both CD4(+) and CD8(+) T cells during the initial phases of antigen recognition. As such, IFN-α/ß, among other innate cytokines, is considered an important 'third signal' that shapes the effector and memory T-cell pool. Moreover, IFN-α/ß also serves as a counter-regulator of T helper type 2 and type 17 responses, which may be important in the treatment of atopy and autoimmunity, and in the development of novel vaccine adjuvants.


Asunto(s)
Células Dendríticas/inmunología , Interferón-alfa/inmunología , Interferón beta/inmunología , Linfocitos T/inmunología , Animales , Células Dendríticas/metabolismo , Humanos , Memoria Inmunológica/inmunología , Interferón-alfa/metabolismo , Interferón beta/metabolismo , Ratones , Modelos Inmunológicos , Linfocitos T/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo
13.
Int J Cancer ; 129(3): 553-64, 2011 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-21469138

RESUMEN

km23-1 is a dynein light chain that was identified as a TGFß receptor-interacting protein. To investigate whether km23-1 controls human ovarian carcinoma cell (HOCC) growth, we established a tet-off inducible expression system in SKOV-3 cells in which the expression of km23-1 is induced upon doxycycline removal. We found that forced expression of km23-1 inhibited both anchorage-dependent and anchorage-independent growth of SKOV-3 cells. More importantly, induction of km23-1 expression substantially reduced the tumorigenicity of SKOV-3 cells in a xenograft model in vivo. Fluorescence-activated cell sorting analysis of SKOV-3 and IGROV-1 HOCCs demonstrated that the cells were accumulating at G2/M. Phospho-MEK, phospho-ERK and cyclin B1 were elevated, as was the mitotic index, suggesting that km23-1 suppresses HOCCs growth by inducing a mitotic delay. Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells. Further, although the mitotic spindle assembly checkpoint protein BubR1 was present at the prometaphase kinetochore in Dox+/- cells, it was inappropriately retained at the metaphase kinetochore in Dox- cells. Thus, the mechanism by which high levels of km23-1 suppress ovarian carcinoma growth in vitro and inhibit ovary tumor formation in vivo appears to involve a BubR1-related mitotic delay.


Asunto(s)
Dineínas Citoplasmáticas/metabolismo , Dineínas/metabolismo , Neoplasias Ováricas/metabolismo , Prometafase , Animales , División Celular , Línea Celular Tumoral , Femenino , Humanos , Metafase , Ratones , Ratones Desnudos , Mitosis , Trasplante de Neoplasias , Neoplasias Ováricas/prevención & control , Trasplante Heterólogo , Regulación hacia Arriba
14.
Gut Microbes ; 13(1): 1997292, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34818131

RESUMEN

Men who have sex with men (MSM), regardless of HIV infection status, have an intestinal microbiome that is compositionally distinct from men who have sex with women (MSW) and women. We recently showed HIV-negative MSM have elevated levels of intestinal CD4+ T cells expressing CCR5, a critical co-receptor for HIV. Whether elevated expression of CCR5 is driven by the altered gut microbiome composition in MSM has not been explored. Here we used in vitro stimulation of gut Lamina Propria Mononuclear Cells (LPMCs) with whole intact microbial cells isolated from stool to demonstrate that fecal bacterial communities (FBCs) from HIV-positive/negative MSM induced higher frequencies of CCR5+ CD4+ T cells compared to FBCs from HIV-negative MSW and women. To identify potential microbial drivers, we related the frequency of CCR5+ CD4+ T cells to the abundance of individual microbial taxa in rectal biopsy of HIV-positive/negative MSM and controls, and Holdemanella biformis was strongly associated with increased frequency of CCR5+ CD4+ T cells. We used in vitro stimulation of gut LPMCs with the type strain of H. biformis, a second strain of H.biformis and an isolate of the closely related Holdemanella porci , cultured from either a HIV-positive or a HIV-negative MSM stool. H. porci elevated the frequency of both CCR5+ CD4+ T cells and the ratio of TNF-α/IL-10 Genomic comparisons of the 3 Holdemanella isolates revealed unique cell wall and capsular components, which may be responsible for their differences in immunogenicity. These findings describe a novel mechanism potentially linking intestinal dysbiosis in MSM to HIV transmission and mucosal pathogenesis.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Firmicutes/inmunología , Microbioma Gastrointestinal/inmunología , Infecciones por VIH/microbiología , Homosexualidad Masculina , Mucosa Intestinal/inmunología , Receptores CCR5/metabolismo , Citocinas/metabolismo , Disbiosis/inmunología , Disbiosis/microbiología , Heces/microbiología , Femenino , Firmicutes/clasificación , Firmicutes/genética , Firmicutes/aislamiento & purificación , Genoma Bacteriano/genética , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Minorías Sexuales y de Género
15.
Front Chem ; 8: 260, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32391314

RESUMEN

Peptoids, N-substituted glycine oligomers, are a class of diverse and sequence-specific peptidomimetics with wide-ranging applications. Advancing the functional repertoire of peptoids to emulate native peptide and protein functions requires engineering peptoids that adopt regular secondary and tertiary structures. An understanding of how changes to peptoid sequence change structural features, particularly in water-soluble systems, is underdeveloped. To address this knowledge gap, five 15-residue water-soluble peptoids that include naphthalene-functionalized side chains were designed, prepared, and subjected to a structural study using a palette of techniques. Peptoid sequence designs were based on a putative amphiphilic helix peptoid bearing structure-promoting (S)-N-(1-naphthylethyl)glycine residues whose self-association in water has been studied previously. New peptoid variants reported here include sequence changes that influenced peptoid conformational flexibility, functional group patterning (amphiphilicity), and hydrophobicity. Peptoid structures were evaluated and compared using circular dichroism spectroscopy, fluorescence spectroscopy, and size exclusion chromatography. Spectral data confirmed that sequence changes alter peptoids' degree of assembly and the organization of self-assembled structures in aqueous solutions. Insights gained in these studies will inform the design of new water-soluble peptoids with regular structural features, including desirable higher-order (tertiary and quaternary) structural features.

16.
J Sex Med ; 6(3): 791-9, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19170862

RESUMEN

INTRODUCTION: The internal pelvic exam is a critical component of women's reproductive health care; however, it can be perceived as uncomfortable, embarrassing, and painful, which may lead some women to avoid this procedure. AIMS: The purpose of this study was to survey physicians with respect to their experiences with female patients who are difficult or impossible to examine gynecologically. METHODS: Six hundred and fifty-eight obstetrician-gynecologist and family physicians were sent a 15-item questionnaire by mail and 424 participants responded (64% response rate). The survey consisted of questions pertaining to demographic variables, professional training and practice information, the frequency with which they encounter female patients who are difficult or impossible to examine, and the strategies employed with and beliefs surrounding such patients. MAIN OUTCOME MEASURES: The main outcome measures were the frequency of patients who are difficult or impossible to examine, strategies used to manage such patients, and beliefs as to why these patients are difficult or impossible to examine. RESULTS: The results, based on a final sample size of 401, indicated that most respondents have had some experience with patients who are difficult or impossible to examine. In such cases, most physicians (87%) reported attempting to address their patients' lack of relaxation. The majority of physicians in this study believed that a previous negative experience with (87%), and heightened anxiety about (79%), the exam were to blame. Twelve percent of respondents specifically reported that a previous history of sexual abuse was an important factor. CONCLUSIONS: This study reinforces the importance of being aware of patient discomfort during pelvic exams and of developing strategies that fit the individual patient and her needs. Future research should examine women's perceptions of their reproductive care, particularly correlates of pain and anxiety during pelvic exams, prevalence of negative experiences, and doctor-patient interactions in this context.


Asunto(s)
Trastornos de Ansiedad/psicología , Ginecología/métodos , Ginecología/estadística & datos numéricos , Relaciones Médico-Paciente , Relajación , Femenino , Genitales Femeninos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Dolor/fisiopatología , Encuestas y Cuestionarios
17.
J Perinat Educ ; 28(1): 43-50, 2019 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31086474

RESUMEN

Studies reveal that prenatal health-care providers and educators often refrain from discussing sexuality with their patients. The present study explored the relationship between sexuality and pregnancy by considering whether the way in which women view themselves sexually is associated with their experience of pregnancy. Findings revealed that a positive sexual self was significantly related to a positive experience of pregnancy and that particular experiences of pregnancy were more significantly related to how women viewed themselves sexually than others. The findings encourage further discussion regarding the role that comprehensive sex education and training of prenatal health-care providers might play in ultimately establishing open, honest, and nonjudgmental discussions about sexuality between providers and their pregnant patients and partners.

18.
Mitochondrial DNA ; 26(5): 672-3, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-24148019

RESUMEN

The Canada goose (Branta canadensis) entire mitochondrial genome of a bird from Western Pennsylvania has 16,760 bp (GenBank accession number NC 007011) and has been analyzed for gene locations, length, start codon and stop codons. This genome from a bird harvested during the non-migratory season is the REFSEQ and the haplotype is designated GCC-A. There are two rRNAs, 22 tRNAs, 13 protein-coding regions, and 1 displacement loop region. The base composition of mtDNA was A (30.2%), G (15.1%), C (32.1%), and T (22.6%), so the percentage of A and T (52.8%) was slightly higher than G and C. All genes except ND6 and eight tRNA genes (Gln, Ala, Asn, Cys, Tyr, Ser, Pro and Glu) are encoded on the heavy strand. The gene arrangement is the same as most birds and differs from mammals by an inversion of the mtDNA at the connection between the D-loop and the ND5 junctions.


Asunto(s)
Gansos/genética , Genoma Mitocondrial , Mitocondrias/genética , Animales , Composición de Base , Orden Génico
19.
J Homosex ; 42(3): 1-20, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12066985

RESUMEN

The present study attempts to determine how men who have sex with men (MSM) identify in terms of their sexual orientation. The sexual identity of MSM has important implications for the spread of HIV. The literature suggests that gay or bisexual identifying MSM are more likely to practice safer sex than heterosexually-identified MSM. A significant number of the MSM in public settings, such as parks, are believed to be heterosexual identifying. MSM in bathhouses are presumed to be gay or bisexual identifying. Parks have been the focus of safer sex outreach efforts targeted towards heterosexually-identified MSM. Sexual orientation self-identification was ascertained from park and bathhouse users via one-on-one interactions with outreach workers from 1996 to 1998. Chi-square analysis revealed no significant difference in the expressed sexual orientation of bath and park users, with both populations consisting mostly of gay-identified men. Heterosexually-identified MSM are not found in significant numbers in public settings. The current micro educational approach used to target these men may not be cost-effective. Alternative strategies are discussed.


Asunto(s)
Delitos Sexuales/psicología , Conducta Sexual/psicología , Adulto , Bisexualidad/psicología , Canadá , Heterosexualidad/psicología , Homosexualidad Masculina/psicología , Humanos , Masculino , Autoimagen
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