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3.
J Infect Dis ; 227(4): 522-527, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35199165

RESUMO

BACKGROUND: Previously, our group conducted the Herpevac Trial for Women, a randomized efficacy field trial of type 2 glycoprotein D (gD2) herpes simplex virus (HSV) vaccine adjuvanted with ASO4 in 8323 women. Study participants were selected to be seronegative for HSV-1 and HSV-2. We found that the vaccine was 82% protective against culture-positive HSV-1 genital disease but offered no significant protection against HSV-2 genital disease. Efficacy against HSV-1 was associated with higher levels of antibody to gD2 at enzyme-linked immunosorbent assay (ELISA). METHODS: To better understand the results of the efficacy study, we measured postvaccination concentrations of neutralizing antibody (nAb) to either HSV-1 and HSV-2 from HSV-infected study participants and matched uninfected controls. Statistical modeling was used to determine whether these responses were correlated with protection against HSV. RESULTS: nAbs to either HSV-1 or HSV-2 were correlated with ELISA binding antibodies to gD2. HSV-1 or HSV-2 nAb findings support the observation of protection by higher levels of antibody against HSV-1 infection, but the lack of protection against HSV-2 remains unexplained. CONCLUSIONS: The protection against HSV-1 infection observed in the Herpevac Trial for Women was associated with nAbs directed against the virus, although the power to assess this was lower in the nAb study compared with the ELISA results owing to smaller sample size. CLINICAL TRIALS REGISTRATION: NCT00057330.


Assuntos
Doenças Genitais , Herpes Genital , Herpes Simples , Herpesvirus Humano 1 , Doenças Urogenitais , Vacinas Virais , Feminino , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Herpes Genital/prevenção & controle , Herpes Simples/prevenção & controle , Herpesvirus Humano 2 , Proteínas do Envelope Viral
4.
Psicol. ciênc. prof ; 43: e264982, 2023.
Artigo em Português | LILACS, Index Psicologia - Periódicos | ID: biblio-1529201

RESUMO

A violência por parceiro íntimo (VPI) consiste em atos que ameacem causar ou efetivamente causem danos em um parceiro dentro de uma relação afetivo-sexual, independente da configuração ou tempo do relacionamento ou de haver coabitação ou não entre as partes. Nas relações homossexuais, a VPI é invisibilizada de diversas maneiras, mesmo sendo reconhecida como uma grave violação de direitos humanos. O estudo objetivou compreender os significados da VPI para um grupo de homens que se relacionam com homens (HRH). Participaram da pesquisa oito HRH, selecionados através da técnica "bola de neve", utilizada devido à sensibilidade do tema, considerando os estigmas de ser HRH. Os dados foram obtidos através de entrevista semiestruturada e foram analisados pela Análise Temática. Como resultados, foram construídas seis categorias: 1º) O armário; 2º) Homofobia 3º) Racismo, poder e vulnerabilidade a VPI; 4º) Sexualidade; 5º) Infidelidade; 6º) HIV, que discutem a interseccionalidade de diversas formas de opressão na produção de VPI entre HRH. Conclui-se que a VPI vivenciada por esse grupo é influenciada por diversos fatores que envolvem a interseccionalidade de vários marcadores sociais, como os estereótipos de masculinidade em relação a hipersexualização e infidelidade, a homofobia como fator direto do estresse minoritário, o racismo que hierarquiza os corpos e invisibiliza o afeto de homens negros, e o estigma de HIV no imaginário social.(AU)


Intimate partner violence (IPV) consists of acts that threaten to harm or actually harm to a partner within an affective-sexual relationship, regardless of the configuration or duration of the relationship or whether or not there is cohabitation between the parties. In homosexual relationships, IPV is made invisible in several ways, even though it is recognized as a serious violation of human rights. The study aimed to understand the meanings of IPV for a group of men in same sex relationships (MSSR). Eight MSSR participated in the research, selected by snowball sampling, used due to the topic's sensitivity, considering the stigmas involved in being MSSR. Data were constructed via semi-structured interviews and analyzed using Thematic Analysis. As a result, six categories were constructed: 1) The closet persons; 2) Homophobia; 3) Racism, power, and vulnerability to IPV; 4) Sexuality; 5) Infidelity; 6) HIV, which discuss the intersectionality of various forms of oppression in the production of IPV among MSSR. Thus, the IPV experienced by this group is influenced by several factors that involve the intersectionality between different social markers, such as stereotypes of masculinity in relation to hypersexualization and infidelity, homophobia as a direct factor of minority stress, the racism that hierarchizes bodies and makes the affection of Black men and the stigma of HIV invisible in the social imaginary.(AU)


La violencia de pareja (VP) consiste en actos que amenazan con causar o de hecho causan daño a una pareja dentro de una relación afectivo-sexual, independientemente de la configuración o duración de la relación o de si existe o no cohabitación entre las partes. En las relaciones homosexuales, la VP se invisibiliza de varias formas, a pesar de que se reconoce como una grave violación de los derechos humanos. Este estudio tuvo como objetivo comprender los significados de VP para un grupo de hombres que se relacionan con hombres (HRH). Ocho HRH participaron de la investigación, seleccionados mediante la técnica de "bola de nieve", utilizada debido a la sensibilidad del tema, considerando los estigmas de ser HRH. Los datos se construyeron mediante entrevistas semiestructuradas y se sometieron a análisis temático. Como resultado se construyeron seis categorías: 1.ª) El armario; 2.º) Homofobia; 3.º) Racismo, poder y vulnerabilidad a la VP; 4.º) Sexualidad; 5.º) Infidelidad; 6.ª) HIV; que discuten la interseccionalidad de diferentes formas de opresión en la producción de VP entre HRH. Se concluye que la VP vivida por este grupo está influida por varios factores que involucran la interseccionalidad entre distintos marcadores sociales, como los estereotipos de masculinidad en relación con la hipersexualización y la infidelidad, la homofobia como factor directo de estrés minoritario, el racismo que jerarquiza cuerpos e invisibiliza en el imaginario social el afecto de los hombres negros y el estigma del HIV en el imaginario social.(AU)


Assuntos
Humanos , Masculino , Poder Psicológico , Casamento , Masculinidade , Violência por Parceiro Íntimo , Angústia Psicológica , Homens , Transtornos Parafílicos , Preconceito , Atenção Primária à Saúde , Psicologia , Estupro , Rejeição em Psicologia , Autoimagem , Comportamento Sexual , Delitos Sexuais , Vergonha , Problemas Sociais , Maus-Tratos Conjugais , Conscientização , Terapêutica , Comportamento e Mecanismos Comportamentais , Família , Infecções Sexualmente Transmissíveis , Saúde Mental , Prevalência , Síndrome de Imunodeficiência Adquirida , Assédio Sexual , Preservativos , Entrevista , Violência Doméstica , Homossexualidade Masculina , Ameaças , Sexo Seguro , Comportamento Perigoso , Agressão , Grupos Raciais , Dependência Psicológica , Sexo sem Proteção , Diagnóstico , Alcoolismo , Literatura Erótica , Conflito Familiar , Relações Familiares , Medo , Prazer , Estigma Social , Saúde Sexual , Racismo , Sexismo , Marginalização Social , Comportamento Criminoso , Difamação , Opressão Social , Vulnerabilidade Sexual , Androcentrismo , Estereotipagem de Gênero , Constrangimento , Abuso Emocional , Equidade de Gênero , Doenças Genitais , Estrutura Familiar , Culpa , Manobra Psicológica , Homicídio , Hostilidade , Ciúme
5.
Br J Dermatol ; 187(6): 1050-1052, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35977429

RESUMO

We describe a case of genital ulcer and inguinal adenopathies that were attributable to monkeypox virus infection. We suggest clinicians adopt a low threshold for suspicion, particularly when evaluating genital ulcer disease.


Assuntos
Doenças Genitais , Herpes Genital , Úlcera Péptica , Doenças Urogenitais , Humanos , Úlcera/diagnóstico , Diagnóstico Diferencial , Genitália
8.
J Immunother Cancer ; 10(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101944

RESUMO

Cemiplimab is a highly potent, hinge-stabilized human IgG4 monoclonal antibody (mAb) targeting programmed cell death 1 (PD-1) receptor approved for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (SCC) who are not candidates for curative surgery or curative radiation. Recently, the phase 3 trial EMPOWER-Cervical 1 has investigated cemiplimab in patients with recurrent/metastatic cervical cancer. At interim analysis, overall survival (OS), progression free survival (PFS) and objective response rate (ORR) in overall and SCC populations favored cemiplimab over single agent chemotherapy. Cervical SCCs are the first for incidence among Human Papilloma Virus (HPV) related neoplasms and are highly correlated (about 95%) with the viral infection. Similarly, penile and vulvar SCC may develop on chronic HPV infections or on dermatological chronic conditions (ie, lichen). The molecular and viral similarities between external genital SCC and SCC originating from the cervical epithelium could be the rationale for using cemiplimab to treat locally advanced or metastatic penile and vulvar SCC as well. Some retrospective data have shown that cemiplimab may provide objective response and clinical benefit to some patients with penile or vulvar SCC and is overall safe to utilize in this population. Given the complexity of the immune activation and the considerable variability in tumor biology across patients and tumor types, the identification of biomarkers to warrant patient selection needs to be further explored. Ongoing clinical trials will hopefully shed light on the treatment paradigm of these rare tumors too, with special regard to the ideal combination and sequencing of immunotherapeutic strategies.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Genitais/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Doenças Raras/tratamento farmacológico , Humanos
9.
Arch Soc Esp Oftalmol (Engl Ed) ; 97(1): 17-27, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35027140

RESUMO

The objective of this work was to collect updated information on Treponema pallidum, Chlamydia trachomatis and Neisseria gonorrhoeae, causing sexually transmitted infections (STIs) and etiological agents of eye infections, to provide relevant information on this public health problem. For this, a bibliographic review was carried out using different electronic databases such as: PubMed central, google academic, Lilacs, Scopus, Science Direct and Scielo, between March 2009 and August 2019. According to the WHO, more than a million people a day contract a sexually transmitted infection. For T. pallidum, a global prevalence of 0.5% is estimated for both men and women. It is a causative agent of syphilis and ocular syphilis, which manifests as uveitis. Overall, a prevalence of 2.8% in men and 3.8% in women for C. trachomatis is estimated. It is associated with oculo-genital disease, which includes STIs, inclusion conjunctivitis in adults and neonatal ophthalmia. Among its complications is trachoma, which is the leading cause of infectious blindness worldwide. Regarding N. gonorrhoeae, it has a global selection of 0.9% and 0.7% in women and men, respectively. It manifests with gonococcal conjunctivitis and neonatal ophthalmia. We can conclude that the information that relates T. pallidum, C. trachomatis and N. gonorrhoeae with their ocular compromise problems is insufficient, and even more so if we seek to find them related to each other, which makes it difficult to access data of clinical utility for visual health.


Assuntos
Infecções por Chlamydia , Infecções Oculares Bacterianas , Doenças Genitais , Gonorreia , Adulto , Chlamydia trachomatis , Feminino , Gonorreia/epidemiologia , Humanos , Recém-Nascido , Masculino
10.
Pharmacol Res Perspect ; 10(1): e00910, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35005849

RESUMO

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are antidiabetic drugs with associated safety concerns regarding the risk of genital and urinary tract infections. This study assessed the risk of genital and urinary tract infections associated with prescription of SGLT-2 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM) compared to dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylurea (SU), and thiazolidinedione (TZD). We conducted a retrospective cohort study using the NHIS-National Health Insurance-Database in Korea from 2014 to 2017. Patients aged ≥19 years and those diagnosed with T2DM prior to drug prescription were enrolled. The outcomes were genital and urinary tract infections. Analysis was performed using Cox's proportional hazard model following 1:1 propensity score matching to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Among the 107 131 patients included in the study, a total of 7738, 7145, and 2175 patients were assigned to the DPP-4 inhibitors, SU, and TZD comparator groups, using the propensity score (PS) of each comparator based on 7741 people in the assessed drug SGLT-2 inhibitor group. SGLT-2 inhibitors were associated with a higher risk of genital infections than DPP-4 inhibitors (HR: 2.39, 95% CI: 2.07-2.76), SU (HR: 3.23, 95% CI: 2.73-3.81), and TZD (HR: 3.23, 95% CI: 2.35-4.44), as an add-on therapy to metformin. Similar results were observed for the risk of urinary tract infections. In conclusion, SGLT-2 inhibitors are significantly associated with a higher risk of genital and urinary tract infections compared to DPP-4 inhibitors, SU, and TZD.


Assuntos
Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Quimioterapia Combinada , Feminino , Doenças Genitais/epidemiologia , Doenças Genitais/etiologia , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Adulto Jovem
11.
Clin Microbiol Infect ; 28(2): 299.e1-299.e8, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34126230

RESUMO

OBJECTIVES: Little is known about asymptomatic norovirus infection and its risk factors in healthy adults. This study investigated detection of norovirus in stool and its associated factors among asymptomatic healthy adults in a high-income country. METHODS: This prospective cross-sectional study-conducted between February 2016 and January 2017 at a teaching hospital in Japan-included apparently healthy adults aged ≥18 years who underwent voluntary health check-ups. Our primary outcome was detection of norovirus in stool specimens confirmed by real-time RT-PCR. We evaluated descriptive statistics and associated factors, including demographics, social habits, and clinical parameters. RESULTS: Among 15 532 participants, 4536 (29.2%, mean age 58.0 (standard deviation 11.8) years, male 44.6%) were enrolled, and 112 (2.5%, GI 57, GII 54, GI + GII 1) were norovirus-positive. Monthly prevalence rates of the GI norovirus were consistent throughout the year, while those of GII were high in May. Participants aged <40 and ≥ 80 years had higher rates of GII norovirus detection. Participants who occasionally consume alcohol, especially wine (odds ratio (OR) 0.17, 95% confidence interval (CI) 0.04-0.68), had lower norovirus detection rates than abstainers. Participants with untreated dyslipidaemia and a low high-density lipoprotein (HDL) cholesterol level had higher detection rates than those with treated dyslipidaemia (OR 1.48, 95%CI 1.07-2.05) and a normal HDL cholesterol level (OR 2.60, 95%CI 1.46-4.61). Some gastrointestinal and female genital diseases were associated with norovirus detection. CONCLUSIONS: The norovirus detection rate in asymptomatic adults was 2.5%. Participants with specific lifestyles or medical histories may have higher risks of asymptomatic norovirus infection.


Assuntos
Infecções por Caliciviridae , Norovirus , Idoso , Infecções Assintomáticas , Infecções por Caliciviridae/diagnóstico , Infecções por Caliciviridae/epidemiologia , Estudos Transversais , Fezes , Feminino , Gastroenteropatias , Doenças Genitais , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Norovirus/isolamento & purificação , Estudos Prospectivos
12.
J Diabetes Investig ; 13(3): 478-488, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34610204

RESUMO

AIMS/INTRODUCTION: To evaluate the effectiveness and safety of the novel sodium-glucose cotransporter inhibitor, ertugliflozin, compared with a placebo or other antihyperglycemic agents for type 2 diabetes patients. MATERIALS AND METHODS: We carried out a meta-analysis of randomized controlled trials to assess the benefits and harms of ertugliflozin. Online database searches were carried out in PubMed, EMBASE, WEB OF SCIENCE and Cochrane from inception up to 11 March 2021. Our end-points were glycated hemoglobin, fasting plasma glucose and bodyweight. We analyzed the results using a random effects model, computed weighted mean differences and risk ratios. RESULT: A total of 10 randomized controlled trials with 13,223 patients met the inclusion criteria. Compared with a placebo, the weighted mean differences in glycated hemoglobin were -0.77% (95% confidence interval [CI] -0.86 to -0.68%) for ertugliflozin 5 mg, and -0.82% (95% CI -1.01 to -0.63%) for ertugliflozin 15 mg. Ertugliflozin 5 mg daily was also associated with bodyweight loss (weighted mean difference -1.87 kg, 95% CI -2.12 to -1.6). When compared with a placebo, ertugliflozin significantly reduced fasting plasma glucose by -1.62 mmol/L (weighted mean difference, 95% CI -1.82 to -1.42 for 5 mg ertugliflozin). Yet, we observed a rising risk for genital mycotic infections (risk ratio 4.34, 95% CI 2.78-6.76). The results were similar for the 15 mg ertugliflozin group. CONCLUSION: Ertugliflozin effectively reduces glycated hemoglobin levels and provides extra clinical benefits including bodyweight and fasting plasma glucose. Common adverse effects, including genital mycotic infections and so on, were reviewed.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doenças Genitais/epidemiologia , Doenças Genitais/microbiologia , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Micoses/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
13.
Curr Protoc ; 1(12): e332, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34936238

RESUMO

This article describes procedures for two preclinical animal models for genital herpes infection. The guinea pig model shares many features of genital herpes in humans, including a natural route of inoculation, self-limiting primary vulvovaginitis, spontaneous recurrences, symptomatic and subclinical shedding of HSV-2, and latent infection of the associated sensory ganglia (lumbosacral dorsal root ganglia, DRG). Many humoral and cytokine responses to HSV-2 infection in the guinea pig have been characterized; however, due to the limited availability of immunological reagents, assessments of cellular immune responses are lacking. In contrast, the mouse model has been important in assessing cellular immune responses to herpes infection. Both the mouse and guinea pig models have been extremely useful for evaluating preventative and immunotherapeutic approaches for controlling HSV infection and recurrent disease. In this article, we describe procedures for infecting guinea pigs and mice with HSV-2, scoring subsequent genital disease, and measuring replicating virus to confirm infection. We also provide detailed protocols for dissecting and isolating DRG (the site of HSV-2 latency), quantifying HSV-2 genomic copies in DRG, and assessing symptomatic and subclinical shedding of HSV-2 in the vagina. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Primary and recurrent genital herpes infection in the guinea pig model Support Protocol 1: Blood collection via lateral saphenous vein or by cardiac puncture after euthanasia Support Protocol 2: Dissection and isolation of dorsal root ganglia from guinea pigs Support Protocol 3: PCR amplification and quantification of HSV-2 genomic DNA from samples Basic Protocol 2: Primary genital herpes infection in the mouse model Alternate Protocol: Flank infection with HSV-2 in the mouse model Support Protocol 4: Dissection and isolation of mouse dorsal root ganglia.


Assuntos
Doenças Genitais , Herpes Genital , Animais , Modelos Animais de Doenças , Feminino , Cobaias , Herpesvirus Humano 2 , Imunidade Celular , Camundongos
14.
J Reprod Immunol ; 148: 103384, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34583090

RESUMO

Over the past two decades, nanotechnology has been involved in an array of applications in various fields, including diagnostic kits, disease treatment, drug manufacturing, drug delivery, and gene therapy. But concerns about the toxicity of nanoparticles have greatly hindered their use; also, due to their increasing use in various industries, all members of society are exposed to the toxicity of these nanoparticles. Nanoparticles have a negative impact on various organs, including the reproductive system. They also can induce abortion in women, reduce fetal growth and development, and can damage the reproductive system and sperm morphology in men. In some cases, it has been observed that despite the modification of nanoparticles in composition, concentration, and method of administration, there is still damage to the reproductive organs. Therefore, understanding how nanoparticles affect the reproductive system is of very importance. In several studies, the nanoparticle toxicity effect on the genital organs has been investigated at the clinical and molecular levels using the in vivo and in vitro models. This study reviews these investigations and provides important data on the toxicity, hazards, and safety of nanoparticles in the reproductive system to facilitate the optimal use of nanoparticles in the industry.


Assuntos
Doenças Genitais/etiologia , Genitália/fisiologia , Nanopartículas/efeitos adversos , Animais , Modelos Animais de Doenças , Feminino , Retardo do Crescimento Fetal , Humanos , Nanotecnologia , Gravidez
15.
Presse Med ; 50(3): 104075, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34562560

RESUMO

Generalized lipodystrophy (GL) syndromes are a group of rare heterogenous disorders, characterized by total subcutaneous fat loss. The frequency of GL is currently assessed as approximately 0,23 cases per million of the population, in Europe - as 0,96 cases per million of the population. They can be congenital (CGL) or acquired (AGL) depending on the etiology and the time of the onset of fat loss. Both CGL and AGL are often associated with different metabolic complications, such as hypertriglyceridemia, insulin resistance and lipoatrophic diabetes mellitus, metabolically associated FLD, arterial hypertension, proteinuria, reproductive system disorders. In this review we aimed to summarize the information on all forms of generalized lipodystrophy, especially the ones of genetic etiology, their clinical manifestations and complications, the perspectives for diagnostics, treatment and further research.


Assuntos
Lipodistrofia , Aciltransferases/genética , Idade de Início , Caveolina 1/genética , Proteínas de Ligação a DNA/genética , Diabetes Mellitus Lipoatrófica/complicações , Diagnóstico Diferencial , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Subunidades gama da Proteína de Ligação ao GTP/genética , Doenças Genitais/complicações , Humanos , Hipertensão/complicações , Hipertrigliceridemia/complicações , Resistência à Insulina , Lamina Tipo A/genética , Lipodistrofia/classificação , Lipodistrofia/diagnóstico , Lipodistrofia/etiologia , Lipodistrofia/genética , Lipodistrofia Generalizada Congênita/classificação , Lipodistrofia Generalizada Congênita/genética , Mandíbula/anormalidades , Proteínas de Membrana/genética , Metaloendopeptidases/genética , Mutação , Progéria/genética , Proteinúria/complicações , RNA Polimerase III/genética , Proteínas de Ligação a RNA/genética , Síndrome , Helicase da Síndrome de Werner/genética
16.
Regul Toxicol Pharmacol ; 125: 105004, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34256083

RESUMO

In 2017, the European Union (EU) Committee for Risk Assessment (RAC) recommended the classification of metallic cobalt (Co) as Category 1B with respect to its carcinogenic and reproductive hazard potential and Category 2 for mutagenicity but did not evaluate the relevance of these classifications for patients exposed to Co-containing alloys (CoCA) used in medical devices. CoCA are inherently different materials from Co metal from a toxicological perspective and thus require a separate assessment. CoCA are biocompatible materials with a unique combination of properties including strength, durability, and a long history of safe use that make them uniquely suited for use in a wide-range of medical devices. Assessments were performed on relevant preclinical and clinical carcinogenicity and reproductive toxicity data for Co and CoCA to meet the requirements under the EU Medical Device Regulation triggered by the ECHA re-classification (adopted in October 2019 under the 14th Adaptation to Technical Progress to CLP) and to address their relevance to patient safety. The objective of this review is to present an integrated overview of these assessments, a benefit-risk assessment and an examination of potential alternative materials. The data support the conclusion that the exposure to CoCA in medical devices via clinically relevant routes does not represent a hazard for carcinogenicity or reproductive toxicity. Additionally, the risk for the adverse effects that are known to occur with elevated Co concentrations (e.g., cardiomyopathy) are very low for CoCA implant devices (infrequent reports often reflecting a unique catastrophic failure event out of millions of patients) and negligible for CoCA non-implant devices (not measurable/no case reports). In conclusion, the favorable benefit-risk profile also in relation to possible alternatives presented herein strongly support continued use of CoCA in medical devices.


Assuntos
Ligas/química , Cobalto/análise , Equipamentos e Provisões/normas , Doenças Genitais/epidemiologia , Neoplasias/epidemiologia , Carcinogênese , União Europeia , Humanos , Próteses e Implantes/normas , Medição de Risco , Aço/análise
17.
J Cutan Pathol ; 48(12): 1471-1479, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34159622

RESUMO

BACKGROUND: Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by gluteal/anogenital erythema and symmetric involvement of other intertriginous location(s) without systemic signs. Clinicopathologic characterization has been limited to case reports and small series. We describe 19 new cases and review the literature to better define the clinical and histopathologic spectrum of SDRIFE. METHODS: Pathology archives were searched for "SDRIFE" and "baboon syndrome." Cases meeting clinical criteria were included. Clinical and histopathologic features were recorded. Previous reports of SDRIFE with histopathologic descriptions were reviewed. RESULTS: Nineteen new cases were included, over half triggered by antibiotics. Six new causative medications were identified. Median onset was 7 days. Typical lesions were erythematous plaques or papules with or without scale. The most common histopathologic finding was superficial perivascular lymphocytic infiltrate followed by dermal eosinophils, spongiosis, and orthokeratosis. Basal vacuolization and apoptotic keratinocytes were less common. Interstitial histiocytes were present in almost half of our cases. Other findings included atypical lymphocytes and "flame figure." CONCLUSIONS: Appreciation of the range of inciting medications and clinicopathologic features in SDRIFE will improve recognition of this condition. Although many histopathologic features overlap with other common dermatitides, biopsy may assist in excluding key clinical mimics.


Assuntos
Erupção por Droga/patologia , Exantema/induzido quimicamente , Exantema/patologia , Intertrigo/induzido quimicamente , Intertrigo/patologia , Adulto , Idoso , Canal Anal/patologia , Nádegas/patologia , Erupção por Droga/etiologia , Eritema/induzido quimicamente , Eritema/patologia , Feminino , Doenças Genitais/patologia , Humanos , Masculino , Pessoa de Meia-Idade
18.
Infect Genet Evol ; 93: 104878, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33905885

RESUMO

Condyloma acuminatum, which is caused by low-risk human papillomavirus (lrHPV) infection, is one of the most common sexually transmitted diseases. Autophagy is thought to be associated with condyloma acuminatum, but how the autophagy process is regulated remains unclear. MicroRNAs (miRNAs) are important regulators of gene transcription that play a central role in many biological processes, including autophagy and viral infection. This study was designed to identify autophagy-related miRNAs and their targets in condyloma acuminatum and to validate their expression. The levels of the autophagy proteins microtubule-associated protein 1 light chain 3 (LC3) and P62/SQSTM1 (P62) were abnormally increased in the local lesion tissue of condyloma acuminatum patients compared with healthy controls. MiRNAs and their target mRNAs in condyloma acuminatum patients were analyzed by bioinformatics. Eighty-one differentially expressed miRNAs were identified, of which 56 were downregulated and 25 were upregulated. Two of the differentially expressed miRNAs associated with autophagy, miRNA-30a-5p and miRNA-514a-3p, were analyzed further, and their target genes were identified as autophagy-related protein (Atg) 5 and Atg12 and Atg3 and Atg12, respectively. The expression levels of miRNA-30a-5p and miRNA-514a-3p were decreased and those of Atg5, Atg12 and Atg3 were increased in condyloma acuminatum patients compared with healthy controls. In addition, miRNA-30a-5p and miRNA-514a-3p expression correlated with the proliferation index Ki-67 in condyloma acuminatum. Taken together, our results suggest that the changes in autophagy levels in patients with condyloma acuminatum may be related to the changes in miRNA-30a-5p and miRNA-514a-3p expression. This study provides a theoretical basis for identifying new mechanisms that link miRNAs, HPV infection and host autophagy in vivo.


Assuntos
Autofagia/genética , Condiloma Acuminado/fisiopatologia , Doenças Genitais/fisiopatologia , MicroRNAs/metabolismo , Infecções por Papillomavirus/fisiopatologia , Adulto , Condiloma Acuminado/virologia , Regulação para Baixo , Feminino , Doenças Genitais/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Infecções por Papillomavirus/virologia , Adulto Jovem
19.
J Diabetes Investig ; 12(4): 546-556, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33245620

RESUMO

AIMS/INTRODUCTION: Several clinical trials reported the effects of sodium-glucose cotransporter (SGLT) inhibitors in type 1 diabetes patients. This meta-analysis aimed to assess the efficacy and safety of SGLT inhibitors in type 1 diabetes patients. MATERIALS AND METHODS: Relevant studies were identified in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases through 1 April 2020. Differences were expressed as the 95% confidence interval (CI) or weighted mean difference (WMD) for continuous outcomes, and risk ratio (RR) for discontinuous outcomes. RESULTS: A total of 13 RCTs with 7,962 cases were included. SGLT inhibitors reduced the fasting plasma glucose level (WMD -1.320 mmol/L, 95% CI -1.609 to -1.031, P < 0.001), glycated hemoglobin level (WMD -0.386%, 95% CI -0.431 to -0.342, P < 0.001) and daily total insulin dose (WMD -5.403, 95% CI -7.218 to -3.859, P < 0.001). However, higher risks of diabetic ketoacidosis (RR 5.042, 95% CI 3.160-8.046, P < 0.001), urinary tract infections (RR 1.259, 95% CI 1.034-1.533,P = 0.022) and genital infections (RR 2.995, 95% CI 1.953-4.594, P < 0.001) were associated with SGLT inhibitors, but SGLT inhibitors did not increase the hypoglycemia risk (RR 0.980, 95% CI 0.840-1.144,P = 0.799). In subgroup analysis, with a significant reduction of fasting plasma glucose, glycated hemoglobin and daily insulin doses, SGLT1/2 inhibitor did not increase genitourinary tract infections compared with a placebo. CONCLUSIONS: SGLT2 and SGLT1/2 inhibitors can improve glycemic control in patients with type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Quimioterapia Combinada , Doenças Genitais/induzido quimicamente , Controle Glicêmico , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Urinárias/induzido quimicamente
20.
Pediatr Res ; 90(3): 678-683, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33070163

RESUMO

BACKGROUND: Preterm birth (PTB) is the leading cause of perinatal morbimortality worldwide. Genetic and environmental factors could raise PTB risk. The aim of this study was to analyze the contribution of the statistical interaction between genes and vaginal-urinary tract infections (VI-UTI) to the risk of PTB by clinical subtype. METHODS: Twenty-four SNPs were genotyped in 18 candidate genes from 352 fetal triads and 106 maternal triads. Statistical interactions were evaluated with conditional logistic regression models based on genotypic transmission/disequilibrium test. RESULTS: In PTB-idiopathic subtype mothers exposed to UTI, fetal SNPs rs11686474 (FSHR), rs4458044 (CRHR1, allele G), rs883319 (KCNN3), and maternal SNP rs1882435 (COL4A3) showed a nominal significant increment in prematurity risk. In preterm premature rupture of membranes (PPROM), fetal SNP rs2277698 (TIMP2) showed a nominal significant risk increment. In mothers exposed to VI, fetal SNP rs5742612 (IGF1) in PTB-PPROM and maternal SNP rs4458044 (CRHR1, allele C) in spontaneous PTB showed nominal significant increment in prematurity risk. CONCLUSIONS: Certain maternal and fetal genes linked to infectious/inflammatory and hormonal regulation processes increase prematurity risk according to clinical subtype when mothers are exposed to UTI or VI. These findings may help in the understanding of PTB etiology and PTB prevention. IMPACT: Preterm birth is a major cause of perinatal morbimortality worldwide and its etiology remains unknown. This work provides evidence on the statistical interaction of six genes with gestational vaginal or urinary infections leading to the occurrence of preterm births. Statistical interactions vary according to infection type, genotype (maternal and fetal), and clinical subtype of prematurity. Certain maternal and fetal genetic variants of genes linked to infectious/inflammatory and hormonal regulation processes would increase the risk of prematurity according to clinical subtype and infection type. Our findings may help in the study of etiology of preterm birth and its prevention.


Assuntos
Interação Gene-Ambiente , Doenças Genitais/epidemiologia , Nascimento Prematuro , Infecções Urinárias/epidemiologia , Doenças Genitais/genética , Humanos , Recém-Nascido , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Infecções Urinárias/genética
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