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1.
J Pediatr Endocrinol Metab ; 37(9): 811-819, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39099554

RESUMO

OBJECTIVES: To generate normative data and validate the recently developed, gender-neutral, External Genitalia Score (EGS) in Indian preterm and term neonates and children up to 2 years of age with normal and atypical genitalia. METHODS: This observational study included 1,040 neonates born between 28 and 42 weeks of gestation and 152 children between 1 and 24 months of age. In addition, 50 children with disorders of sex development (DSD) were also enrolled in the study. The Prader stage/external masculinization score (EMS) (as applicable), anogenital ratio (AGR) and EGS were assessed for all neonates and children with typical and atypical genitalia. RESULTS: Median EGS values in newborn males with typical genitalia were 9.5 at 28-31 weeks, 10.5 at 32-33 weeks, 11 at 34 weeks and 11.5 in males at 35-42 weeks of gestation. For all females with typical genitalia, the EGS was 0. EMS and EGS showed a positive correlation in males with typical genitalia (r=0.421, p=0.000**) and all children with DSD (r=0.857, p=0.000**). Mean AGR in males and females with typical genitalia and those with DSD were 0.52±0.07, 0.31±0.05 and 0.47±0.13, respectively. EGS correlated with AGR in all males with typical genitalia (r=0.107, p=0.008**), and in all children with DSD (r=0.473, p=0.001**). CONCLUSIONS: The EGS enables accurate, gender-neutral and comprehensive assessment of external genitalia in Indian neonates and children with typical and atypical genitalia/DSD. Evaluation for DSD is recommended in any child with EGS greater than 0 and ≤10th percentile for gestation or age (10.5 in a term neonate).


Assuntos
Transtornos do Desenvolvimento Sexual , Humanos , Masculino , Recém-Nascido , Feminino , Lactente , Índia , Transtornos do Desenvolvimento Sexual/diagnóstico , Pré-Escolar , Genitália , Idade Gestacional , Genitália Masculina/crescimento & desenvolvimento , Genitália Masculina/anatomia & histologia , Seguimentos , Valores de Referência , Recém-Nascido Prematuro , Prognóstico
2.
Front Cell Infect Microbiol ; 14: 1417276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975329

RESUMO

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common pelvic pain syndrome in males, seriously affecting patients' quality of life. For a long time, CP/CPPS has been considered a complex and variable disease, and its pathogenesis remains incompletely understood. Currently, CP/CPPS is believed to be a group of diseases characterized by pelvic pain or discomfort, urinary abnormalities, and other symptoms, each with its unique etiology, clinical characteristics, and outcomes, likely resulting from the action of pathogens or (and) certain non-infectious factors. Traditionally, CP/CPPS was thought to be unrelated to bacterial infections. However, in recent years, with the development of microbiology and the advancement of high-throughput sequencing technology, an increasing number of studies have suggested that microorganisms in the reproductive system may play an important role in the pathogenesis of CP/CPPS. The unique characteristics of CP/CPPS, such as its refractory nature and tendency to recur, may be closely related to the microbiota and their biological functions in the reproductive system. The relationship between CP/CPPS and reproductive system microorganisms is one of the current hot topics in microbiology and urology, receiving considerable attention from scholars in recent years and making a series of new advances. Through this review, we will comprehensively explore the relationship between CP/CPPS and reproductive system microorganisms, and look forward to future research directions, aiming to provide new ideas and methods for clinical diagnosis and treatment, thereby improving the treatment outcomes and quality of life of CP/CPPS patients.


Assuntos
Microbiota , Dor Pélvica , Prostatite , Prostatite/microbiologia , Humanos , Masculino , Dor Pélvica/microbiologia , Dor Pélvica/etiologia , Animais , Qualidade de Vida , Dor Crônica/microbiologia , Dor Crônica/etiologia , Genitália/microbiologia , Doença Crônica
3.
Reprod Toxicol ; 128: 108662, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38986849

RESUMO

The Adverse Outcome Pathway (AOP) framework has gained widespread acceptance in toxicological disciplines as a tool for aiding chemical hazard assessment. Despite increased activity in AOP development, progress towards a high volume of fully endorsed AOPs has been slow, partly due to the challenging task of constructing complete AOPs according to the AOP Developer's Handbook. To facilitate greater uptake of new knowledge units onto the open-source AOP-wiki platform, a pragmatic approach was recently proposed. This approach involves considering Key Event Relationships (KERs) for individual development through systematic approaches, as they represent essential units of knowledge from which causality can be inferred; from low complexity test data to adverse outcomes in intact organisms. However, more broadly adopted harmonized methodologies for KER development would be desirable. Using the AOP Developer's Handbook as a guide, a KER linking 'decreased androgen receptor (AR) activity' with 'reduced anogenital distance (AGD)' was developed to demonstrate a methodology applicable for future developments of KERs requiring systematic literature retrieval approaches.


Assuntos
Rotas de Resultados Adversos , Receptores Androgênicos , Receptores Androgênicos/metabolismo , Humanos , Animais , Masculino , Feminino , Canal Anal/anatomia & histologia , Canal Anal/efeitos dos fármacos , Medição de Risco , Genitália/anatomia & histologia , Genitália/efeitos dos fármacos
4.
Birth Defects Res ; 116(6): e2347, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38822636

RESUMO

BACKGROUND: Measurement of rat anogenital distance (AGD) dates to at least 1912. Increased interest in endocrine disrupting chemicals and the use of AGD as a biomarker for fetal androgen effects have increased the number of studies with this endpoint in recent decades. A literature review revealed different landmarks, methods of measurement, and methods to adjust for body weight differences. AGD is often reported to hundredths of millimeters and as such, deserves precision in all these aspects. This paper presents recommendations for the measurement and analysis of rodent AGD. METHODS: Literature and regulatory guidance documents that mentioned or measured rodent AGD were reviewed. Four adjustment methods were evaluated using available online data from three rat studies each with two generations of offspring. RESULTS: Tabulation of studies reveals that species/stocks and time of data collection, but more importantly anatomical landmarks and methods of measurement have produced a variety of results which are difficult to compare. Not all studies have adjusted for test article effects on body weight (and thus size). The four adjustment methods were fairly comparable. CONCLUSION: Recommendations are as follows. A microscopic method should be used to measure AGD of late rodent fetuses and early postnatal pups. The caudal edge of the genital tubercle and the cranial edge of the anus are clear and identifiable landmarks. The simplest adjustment is to divide individual AGDs by the cube root of animals' body weight. These recommendations will help ensure data consistency and accuracy, and facilitate meaningful comparisons across laboratories and chemical classes.


Assuntos
Canal Anal , Animais , Ratos , Canal Anal/anatomia & histologia , Canal Anal/embriologia , Feminino , Masculino , Gravidez , Roedores/anatomia & histologia , Peso Corporal , Feto/anatomia & histologia , Genitália/anatomia & histologia , Genitália/embriologia
5.
J Plast Reconstr Aesthet Surg ; 95: 17-20, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38865839

RESUMO

INTRODUCTION: The epidemiology, care, and outcomes of perineal and genital burns (PG) in high-income countries have been previously described, but an analysis of this topic in LMICs has yet to be performed. We use the World Health Organization's Global Burn Registry to fill this gap. METHODS: The GBR was searched from inception to November 2023 to identify all burn patients, excluding cases from high-income countries. Demographics and mechanism of injury were retrieved. Primary outcomes were length of hospital stay (LOHS), surgical intervention, discharge with physical impairment, and mortality. A multivariate regression analysis was performed controlling for burnt total body surface area (TBSA), age, sex, inhalation injury, mechanism of burn and care center characteristics. RESULTS: Of 9041 patients identified, 1213 (13.4 %) had PG burns with 136 (1.6 %) isolated to the PG region. PG patients had higher TBSA (p < 0.001) and more inhalation injury (p < 0.001). They had better access to rehabilitation and lower access to theater space for burns (p < 0.001). Multivariable analysis showed that PG patients had longer LOHS (p = 0.001), greater mortality (p < 0.001), were less likely to undergo surgery (p = 0.01) or be discharged home with physical impairment (p = 0.03). CONCLUSION: Similarities and differences exist between high- and low/middle-income countries in terms of the patterns of injury, care, and recovery in patients with PG burns. The longer LOHS and higher mortality among PG patients, previously reported in high-income countries, are verified. This highlights the importance of greater vigilance when caring for such patients.


Assuntos
Queimaduras , Países em Desenvolvimento , Tempo de Internação , Períneo , Sistema de Registros , Humanos , Queimaduras/epidemiologia , Queimaduras/terapia , Masculino , Feminino , Adulto , Períneo/lesões , Períneo/cirurgia , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Genitália/lesões , Adulto Jovem , Adolescente , Saúde Global , Criança
7.
Invertebr Syst ; 382024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38744499

RESUMO

Mastigusa is a genus of small palearctic spiders that has recently been moved to the family Cybaeidae after the first inclusion of the genus in a phylogenetic matrix. Three species are currently recognised: M. arietina , M. lucifuga and M. macrophthalma . The status and delimitation, though, has always been problematic due to inconsistency in the characters used to discriminate between these, leading to great confusion in identity and distribution. We present a detailed morphological redescription of the genus and a taxonomic revision of the included species by the combined use of morphological data and molecular species-delimitation techniques based on the mitochondrial COI gene. The status of the three currently described species has been reevaluated and Mastigusa diversa was revalidated based on material from the Iberian Peninsula, North Africa and the United Kingdom. The distribution of Mastigusa species is updated based on novel taxonomic considerations, and comments on the natural history and ecological differences observed in the species are provided. ZooBank: urn:lsid:zoobank.org:pub:AAD3FAED-440F-4295-B458-455B1D913F81.


Assuntos
Filogenia , Aranhas , Animais , Feminino , Masculino , Complexo IV da Cadeia de Transporte de Elétrons/genética , Genitália/anatomia & histologia , Aranhas/classificação , Aranhas/anatomia & histologia , Aranhas/genética
8.
Micron ; 183: 103660, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38820862

RESUMO

Tardigrades are invertebrates known to science for over 250 years. Although the ability of some species of tardigrades to form cysts has been reported, little is known about the encystment and internal organisation of the cysts. During cyst formation, contraction of the body affects the internal organs' morphology. The organs are compressed and have a compact appearance. The organisation of the digestive system, associated structures, and the reproductive system are analysed in cysts on indefinite and well-defined encystment periods - up to eleven months. The digestive system of encysted animals was organised into three main parts - a foregut, a midgut, and a hindgut. The presence of digestive system-associated structures, such as buccal glands or muscles, was noted and described. The excretory organs, called Malpighian tubules, open into the zone between the midgut and the hindgut. Furthermore, the oviduct opens into the hindgut. The first analysis of the reproductive system of cysts at the ultrastructural level is presented here, revealing interesting and undescribed aspects related to the physiology. Besides the anatomical and histological examination, the morphology and changes that occur during cyst formation are described.


Assuntos
Sistema Digestório , Tardígrados , Animais , Tardígrados/fisiologia , Sistema Digestório/ultraestrutura , Sistema Digestório/anatomia & histologia , Genitália/anatomia & histologia , Genitália/ultraestrutura , Água Doce , Microscopia Eletrônica de Transmissão , Feminino
9.
Int J Mol Sci ; 25(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38612936

RESUMO

Male infertility is a significant factor in approximately half of all infertility cases and is marked by a decreased sperm count and motility. A decreased sperm count is caused by not only a decreased production of sperm but also decreased numbers successfully passing through the male reproductive tract. Smooth muscle movement may play an important role in sperm transport in the male reproductive tract; thus, understanding the mechanism of this movement is necessary to elucidate the cause of sperm transport disorder. Recent studies have highlighted the presence of platelet-derived growth factor receptor α (PDGFRα)-positive interstitial cells (PICs) in various smooth muscle organs. Although research is ongoing, PICs in the male reproductive tract may be involved in the regulation of smooth muscle movement, as they are in other smooth muscle organs. This review summarizes the findings to date on PICs in male reproductive organs. Further exploration of the structural, functional, and molecular characteristics of PICs could provide valuable insights into the pathogenesis of male infertility and potentially lead to new therapeutic approaches.


Assuntos
Infertilidade Masculina , Sêmen , Masculino , Humanos , Espermatozoides , Genitália , Receptores do Fator de Crescimento Derivado de Plaquetas
10.
Front Endocrinol (Lausanne) ; 15: 1365602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645429

RESUMO

The 25 kDa-sized protein Lipocalin 2 (LCN2) was originally isolated from human neutrophil granulocytes more than 30 years ago. LCN2 is an emerging player in innate immune defense, as it reduces bacterial growth due to its ability to sequester iron-containing bacterial siderophores. On the other hand, LCN2 also serves as a transporter for various hydrophobic substances due to its ß-barrel shaped structure. Over the years, LCN2 has been detected in many other cell types including epithelial cells, astrocytes, and hepatocytes. Studies have clearly shown that aberrant expression of LCN2 is associated with a variety of disorders and malignancies, including several diseases of the reproductive system. Furthermore, LCN2 was proposed as a non-invasive prognostic and/or diagnostic biomarker in this context. Although several studies have shed light on the role of LCN2 in various disorders of the female and male reproductive systems, including tumorigenesis, a comprehensive understanding of the physiological function of LCN2 in the reproductive tract is still lacking. However, there is evidence that LCN2 is directly related to fertility, as global depletion of Lcn2 in mice has a negative effect on their pregnancy rate. Since LCN2 expression can be regulated by steroid hormones, it is not surprising that its expression fluctuates greatly during remodeling processes in the female reproductive tract, especially in the uterus. Well-founded details about the expression and regulation of LCN2 in a healthy reproductive state and also about possible changes during reproductive aging could contribute to a better understanding of LCN2 as a target in various diseases. Therefore, the present review summarizes current knowledge about LCN2 in the reproductive system, including studies in rodents and humans, and discusses changes in LCN2 expression during pathological events. The limited data suggest that LCN2 is expressed and regulated differently in healthy male and female reproductive organs.


Assuntos
Lipocalina-2 , Humanos , Lipocalina-2/metabolismo , Lipocalina-2/genética , Animais , Feminino , Masculino , Reprodução/fisiologia , Genitália/metabolismo
11.
Int J Mol Sci ; 25(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38612451

RESUMO

Reproduction is the important process of transmitting one's genetic information to the next generation [...].


Assuntos
Células Germinativas , Neoplasias , Genitália , Reprodução , Biologia
12.
PLoS One ; 19(4): e0300276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38557670

RESUMO

Experimental evolution (EE) is a powerful research framework for gaining insights into many biological questions, including the evolution of reproductive systems. We designed a long-term and highly replicated EE project using the nematode C. elegans, with the main aim of investigating the impact of reproductive system on adaptation and diversification under environmental challenge. From the laboratory-adapted strain N2, we derived isogenic lines and introgressed the fog-2(q71) mutation, which changes the reproductive system from nearly exclusive selfing to obligatory outcrossing, independently into 3 of them. This way, we obtained 3 pairs of isogenic ancestral populations differing in reproductive system; from these, we derived replicate EE populations and let them evolve in either novel (increased temperature) or control conditions for over 100 generations. Subsequently, fitness of both EE and ancestral populations was assayed under the increased temperature conditions. Importantly, each population was assayed in 2-4 independent blocks, allowing us to gain insight into the reproducibility of fitness scores. We expected to find upward fitness divergence, compared to ancestors, in populations which had evolved in this treatment, particularly in the outcrossing ones due to the benefits of genetic shuffling. However, our data did not support these predictions. The first major finding was very strong effect of replicate block on populations' fitness scores. This indicates that despite standardization procedures, some important environmental effects were varying among blocks, and possibly compounded by epigenetic inheritance. Our second key finding was that patterns of EE populations' divergence from ancestors differed among the ancestral isolines, suggesting that research conclusions derived for any particular genetic background should never be generalized without sampling a wider set of backgrounds. Overall, our results support the calls to pay more attention to biological variability when designing studies and interpreting their results, and to avoid over-generalizations of outcomes obtained for specific genetic and/or environmental conditions.


Assuntos
Caenorhabditis elegans , Genitália , Animais , Caenorhabditis elegans/genética , Temperatura , Reprodutibilidade dos Testes , Patrimônio Genético , Evolução Biológica
13.
BMC Vet Res ; 20(1): 131, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566185

RESUMO

BACKGROUND: Bovine genital campylobacteriosis (BGC) is caused by Campylobacter fetus subsp. venerealis (Cfv) including its biovar intermedius (Cfvi). This sexually transmitted disease induces early reproductive failure causing considerable economic losses in the cattle industry. Using a collection of well-characterized isolates (n = 13), C. fetus field isolates (n = 64) and saprophytic isolates resembling Campylobacter (n = 75) obtained from smegma samples of breeding bulls, this study evaluated the concordance of the most used phenotypic (H2S production in cysteine medium and 1% glycine tolerance) and molecular (PCR) methods for the diagnosis of BGC and assessed possible cross-reactions in the molecular diagnostic methods. RESULTS: Characterization at the subspecies level (fetus vs. venerealis) of C. fetus isolated from bull preputial samples using phenotypic and molecular (PCR targeting nahE and ISCfe1) methods showed moderate concordance (κ = 0.462; CI: 0.256-0.669). No cross-reactions were observed with other saprophytic microaerophilic species or with other Campylobacter species that can be present in preputial samples. Whole genome sequencing (WGS) of discrepant isolates showed 100% agreement with PCR identification. For the differentiation of Cfv biovars, comparison of the H2S test (at 72 h and 5 days of incubation) and a PCR targeting the L-cysteine transporter genes showed higher concordance when H2S production was assessed after 5 days (72 h; κ = 0.553, 0.329-0.778 CI vs. 5 days; κ = 0.881, 0.631-1 CI), evidencing the efficacy of a longer incubation time. CONCLUSIONS: This study confirmed the limitations of biochemical tests to correctly identify C. fetus subspecies and biovars. However, in the case of biovars, when extended incubation times for the H2S test (5 days) were used, phenotypic identification results were significantly improved, although PCR-based methods produced more accurate results. Perfect agreement of WGS with the PCR results and absence of cross-reactions with non-C. fetus saprophytic bacteria from the smegma demonstrated the usefulness of these methods. Nevertheless, the identification of new C. fetus subspecies-specific genes would help to improve BGC diagnosis.


Assuntos
Infecções por Campylobacter , Doenças dos Bovinos , Bovinos , Animais , Masculino , Campylobacter fetus/genética , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/veterinária , Infecções por Campylobacter/microbiologia , Espanha , Sequenciamento Completo do Genoma/veterinária , Genitália , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/microbiologia
14.
BMC Pregnancy Childbirth ; 24(1): 233, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570745

RESUMO

BACKGROUND: The association of genital Mollicutes infection transition with adverse pregnancy outcomes was insignificant among general pregnant women, but there remains a paucity of evidence linking this relationship in gestational diabetes mellitus (GDM) women. The aim was to investigate the association between genital Mollicutes infection and transition and adverse pregnancy outcomes in GDM women, and to explore whether this association still exist when Mollicutes load varied. METHODS: We involved pregnant women who attended antenatal care in Chongqing, China. After inclusion and exclusion criteria, we conducted a single-center cohort study of 432 GDM women with pregnancy outcomes from January 1, 2018 to December 31, 2021. The main outcome was adverse pregnancy outcomes, including premature rupture of membrane (PROM), fetal distress, macrosomia and others. The exposure was Mollicutes infection, including Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) collected in both the second and the third trimesters, and testing with polymerase chain reaction method. The logistic regression models were used to estimate the relationship between Mollicutes infection and adverse pregnancy outcomes. RESULTS: Among 432 GDM women, 241 (55.79%) were infected with genital Mollicutes in either the second or third trimester of pregnancy. At the end of the pregnancy follow-up, 158 (36.57%) participants had adverse pregnancy outcomes, in which PROM, fetal distress and macrosomia were the most commonly observed adverse outcomes. Compared with the uninfected group, the Mollicutes (+/-) group showed no statistical significant increase in PROM (OR = 1.05, 95% CI:0.51 ∼ 2.08) and fetal distress (OR = 1.21, 95% CI: 0.31 ∼ 3.91). Among the 77 participants who were both Uu positive in the second and third trimesters, 38 participants presented a declined Uu load and 39 presented an increased Uu load. The Uu increased group had a 2.95 odds ratio (95% CI: 1.10~8.44) for adverse pregnancy outcomes. CONCLUSION: Mollicutes infection and transition during trimesters were not statistically associated with adverse pregnancy outcomes in GDM women. However, among those consistent infections, women with increasing Uu loads showed increased risks of adverse pregnancy outcomes. For GDM women with certain Mollicutes infection and colonization status, quantitative screening for vaginal infection at different weeks of pregnancy was recommended to provide personalized fertility treatment.


Assuntos
Diabetes Gestacional , Tenericutes , Gravidez , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Diabetes Gestacional/diagnóstico , Terceiro Trimestre da Gravidez , Macrossomia Fetal/etiologia , Estudos de Coortes , Estudos Prospectivos , Sofrimento Fetal , Aumento de Peso , Genitália
15.
BMC Infect Dis ; 24(1): 405, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622501

RESUMO

BACKGROUND: Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. METHODS: Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. RESULTS: High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219-39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p < 0.001). C. trachomatis DNA, but not pgp3 antibody, was significantly associated with CIN (OR = 4.087, 95% CI = 2.284-7.315, p < 0.001). CONCLUSION: Our results revealed a high prevalence, particularly seroprevalence, of C. trachomatis among women with infertility. Furthermore, we found an association between C. trachomatis omp1 sense mutations and CIN. Therefore, C. trachomatis serves as a risk factor for CIN.


Assuntos
Infecções por Chlamydia , Infertilidade , Humanos , Feminino , Chlamydia trachomatis/genética , Estudos Soroepidemiológicos , Infertilidade/epidemiologia , Infertilidade/complicações , Infecções por Chlamydia/diagnóstico , DNA , Genitália
17.
BMC Vet Res ; 20(1): 144, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641595

RESUMO

BACKGROUND: Bovine Genital Campylobacteriosis (BGC), a worldwide distributed venereal disease caused by Campylobacter fetus subsp. venerealis (Cfv), has a relevant negative economic impact in cattle herds. The control of BGC is hampered by the inexistence of globally available effective vaccines. The present in silico study aimed to develop a multi-epitope vaccine candidate against Cfv through reverse vaccinology. RESULTS: The analysis of Cfv strain NCTC 10354 proteome allowed the identification of 9 proteins suitable for vaccine development. From these, an outer membrane protein, OmpA, and a flagellar protein, FliK, were selected for prediction of B-cell and T-cell epitopes. The top-ranked epitopes conservancy was assessed in 31 Cfv strains. The selected epitopes were integrated to form a multi-epitope fragment of 241 amino acids, which included 2 epitopes from OmpA and 13 epitopes from FliK linked by GPGPG linkers and connected to the cholera toxin subunit B by an EAAAK linker. The vaccine candidate was predicted to be antigenic, non-toxic, non-allergenic, and soluble upon overexpression. The protein structure was predicted and optimized, and the sequence was successfully cloned in silico into a plasmid vector. Additionally, immunological simulations demonstrated the vaccine candidate's ability to stimulate an immune response. CONCLUSIONS: This study developed a novel vaccine candidate suitable for further in vitro and in vivo experimental validation, which may become a useful tool for the control of BGC.


Assuntos
Infecções por Campylobacter , Doenças dos Bovinos , Vacinas , Animais , Bovinos , Infecções por Campylobacter/prevenção & controle , Infecções por Campylobacter/veterinária , Vacinologia , Epitopos de Linfócito T/química , Genitália , Biologia Computacional , Doenças dos Bovinos/prevenção & controle
18.
Lymphat Res Biol ; 22(2): 138-146, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563697

RESUMO

Purpose: Genital lymphedema is a chronic debilitating condition associated with highly impaired health-related quality of life (QoL). This prospective multicenter study evaluated the use of a new compressive garment in patients with secondary and primary genital lymphedema. Methods: Thirty-two patients prospectively enrolled were advised to wear the compressive garment for 12 weeks (day and night). The primary endpoint was change in patient-reported QoL at 12 weeks via the patient global impression of change (PGI-C) instrument. Secondary outcomes included change in other QoL measures at 12 weeks (visual analog scale, Lymphedema Quality of Life Inventory [LyQLI], and EQ-5D questionnaires), lymphedema severity (genital lymphedema score [GLS]), and physician assessment (Clinical Global Impression-Improvement [CGI-I]). Safety and tolerability were also assessed. Results: After 12 weeks, improvement was reported in 78.6% of patients (PGI-C). Physician assessment (CGI-I) indicated clinical improvement in 82.8% of patients. Patient assessment of lymphedema symptoms showed a significant decrease in discomfort (p = 0.02) and swelling (p = 0.01). Significant declines in the mean global GLS (p < 0.0001), and in the proportion of patients reporting heaviness, tightness, swelling, or urinary dysfunction (p < 0.05 for all), were also observed. LyQLI scores decreased (indicating improved QoL) in each of the physical, psychosocial (p = 0.05), and practical domains. The compressive garment was well tolerated with high compliance, and adverse events (due to swelling or discomfort) led to permanent discontinuation in only three patients. Conclusion: The use of a new genital compression garment over 12 weeks improves the QoL and clinical measures in patients with genital lymphedema (ClinicalTrials.gov ID: NCT04602559; Registration: October 20, 2020).


Assuntos
Linfedema , Qualidade de Vida , Humanos , Vestuário , Genitália , Estudos Prospectivos
19.
Am J Med Genet A ; 194(9): e63587, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38687163

RESUMO

Genital anomalies have been reported with VACTERL association but not considered a core feature. Acute and chronic complications stemming from unrecognized genital anomalies have been reported in adolescents and young adults with VACTERL association. We sought to determine the frequency and severity of genital anomalies in VACTERL patients and identify which core features were more frequently associated with genital anomalies. A retrospective chart review from January 2010 to October 2021 identified 211 patients with two or more core VACTERL features, 34% of whom had a genital anomaly. The majority of genital anomalies (83% of those in males and 90% in females) were classified as functionally significant (requiring surgical intervention or causing functional impairment). The frequency of genital anomalies in the VACTERL cohort was higher if anorectal malformations or renal anomalies were present in both males and females and if vertebral anomalies were present in females. Due to their functional significance, genital anomalies should be assessed in all patients with two or more core features of VACTERL association, especially in those with anorectal or renal anomalies. Most genital anomalies in males will be detected on physical examination but additional investigation is often needed to detect genital anomalies in females. The timing and type of investigation are subjects for future study.


Assuntos
Canal Anal , Esôfago , Cardiopatias Congênitas , Rim , Deformidades Congênitas dos Membros , Coluna Vertebral , Traqueia , Humanos , Masculino , Feminino , Canal Anal/anormalidades , Canal Anal/patologia , Deformidades Congênitas dos Membros/patologia , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/epidemiologia , Esôfago/anormalidades , Esôfago/patologia , Coluna Vertebral/anormalidades , Coluna Vertebral/patologia , Traqueia/anormalidades , Traqueia/patologia , Adolescente , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/diagnóstico , Rim/anormalidades , Rim/patologia , Adulto , Estudos Retrospectivos , Criança , Adulto Jovem , Pré-Escolar , Anormalidades Urogenitais/epidemiologia , Anormalidades Urogenitais/genética , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/patologia , Lactente , Malformações Anorretais/epidemiologia , Malformações Anorretais/genética , Malformações Anorretais/diagnóstico , Malformações Anorretais/patologia , Genitália/anormalidades , Genitália/patologia
20.
Lancet Glob Health ; 12(4): e641-e651, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38485431

RESUMO

BACKGROUND: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. METHODS: In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. FINDINGS: Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. INTERPRETATION: Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome. FUNDING: UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; UK Medical Research Council; the Wellcome Trust; the Australian National Health and Medical Research Council; and Swiss National Science Foundation.


Assuntos
Nascimento Prematuro , Infecções Urinárias , Vaginose Bacteriana , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer , Chlamydia trachomatis , Estudos Cross-Over , Genitália , Neisseria gonorrhoeae , Papua Nova Guiné/epidemiologia , Testes Imediatos , Nascimento Prematuro/prevenção & controle , Vaginose Bacteriana/diagnóstico , Vaginose Bacteriana/tratamento farmacológico , Adolescente , Adulto Jovem , Adulto
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