Search

Luca Giannella,1 Giovanni Delli Carpini,1 Jacopo Di Giuseppe,1 Giorgio Bogani,2 Barbara Gardella,3 Ermelinda Monti,4 Carlo Antonio Liverani,4 Alessandro Ghelardi,5 Salvatore Insinga,1 Michele Montanari,1 Francesco Raspagliesi,2 Arsenio Spinillo,3 Paolo Vercellini,4 Elena Roncella,4 Andrea Ciavattini1 1Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Ancona, Italy; 2Gynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy; 3Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy; 4Gynaecology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy; 5Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, Massa, ItalyCorrespondence: Andrea CiavattiniWoman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, via Filippo Corridoni, 16, Ancona, 60123, ItalyTel +390715962172Fax +3907136576Email ciavattini.a@libero.itAim: In the post-vaccination era, the starting age and time intervals of cervical screening could change (older age and longer screening intervals). This scenario may be achieved by significantly reducing human papillomavirus (HPV) 16/18 prevalence (genotypes included in the current vaccines). In this regard, assessing the trend over time of these HPV infections in high-grade cervical lesions can provide information on the objective. The present study aimed to evaluate the trend of HPV 16/18 over the years 2007– 2018 in women with cervical intraepithelial neoplasia (CIN) grade 3.Methods: This is a retrospective multi-institutional study including HPV genotyped and unvaccinated women under 30 with CIN3. The sample was divided into the following periods: 2007– 2010, 2011– 2014, 2015– 2018. HPV genotypes were grouped in genotypes 16/18, genotypes 31/33/35/52/58/67 (genetically related to HPV16), genotypes 39/45/59/68/70 (genetically related to HPV18), genotypes 31/33/45/52/58 (high-risk types included in the nonavalent vaccine), possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85), low-risk HPV (genotypes 6/11/40/42/43/44/54/55/61). The trend between periods and HPV genotypes was measured using the Cochran–Armitage test for trend.Results: The final analysis included 474 participants. HPV 16/18 prevalence decreased significantly over the years (77.8% vs 68.9% vs 66.0%, respectively, Ptrend=0.027). Possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85) showed a significant negative prevalence trend over time (4.9% vs 1.1% vs 1.3%, respectively, Ptrend=0.046). Finally, there was a significant positive trend over the years for high-risk HPV genotypes 31/33/45/52/58 in women under 25 (9.9% vs 17.0% vs 24.0%, respectively, Ptrend=0.048).Conclusion: The prevalence of CIN3 lesions related to HPV 16/18 genotypes decreased over time from 2007 to 2018. These data highlight a herd effect of the HPV vaccine. However, fifteen years after HPV vaccine introduction, we are still a long way from herd immunity. The increase in high-risk types 31/33/45/52/58 will need to be reassessed when the nonavalent vaccine impact will be more reliable.Keywords: cervical cancer, cervical intraepithelial neoplasia, cervical cancer screening program, HPV vaccine, HPV-16/18

Objective: Obesity is associated with increased thyroid-stimulating hormone (TSH) in non-pregnant subjects, but this phenomenon has not been fully characterized during pregnancy. Our aim was to evaluate the impact of BMI on first-trimester TSH in a wide cohort of pregnant women with negative anti-thyroperoxidase antibodies (AbTPO) and its implications on uterine artery pulsatility index (UtA-PI), a marker of early placentation. Methods: The study included 2268 AbTPO-negative pregnant women at their first antenatal visit. Anamnestic data, BMI, TSH, anti-nuclear antibody (ANA) and extractable nuclear antigen (ENA) positivity and mean UtA-PI were collected. Results: A total of 1693 women had normal weight, 435 were overweight and 140 were obese. Maternal age, ANA/ENA positivity, history of autoimmune diseases and familiar history of thyroid diseases were similar in the three groups. TSH was significantly higher in obese women (1.8 (IQR: 1.4–2.4) mU/L) when compared to normal weight (1.6 (IQR: 1.2–2.2) mU/L) and overweight (median: 1.6 (IQR: 1.2–2.2) mU/L) ones (P < 0.001). BMI was significantly related with the risk of having a TSH level ≥4 mU/L at logistic regression, independently from non-thyroid autoimmunity, smoking or familiar predisposition for thyroid diseases (OR: 1.125, 95% CI: 1.080–1.172, P < 0.001). A restricted cubic splines regression showed a non-linear relationship between BMI and TSH. Women with a TSH ≥4 mU/L had a higher UtA-PI, independently from BMI. Conclusion: Overweight/obesity is significantly related with TSH serum levels in AbTPO-negative pregnant women, independently from the other risk factors for hypothyroidism during pregnancy. The increase of TSH levels could be clinically relevant, as suggested by its association with abnormal UtA-PI, a surrogate marker of abnormal placentation.

O conhecimento matemático de crianças sobre a divisão foi investigado a partir de dois aspectos: desempenho em problemas de divisão e as concepções sobre a divisão. Oitenta crianças (5-9 anos) foram solicitadas a resolver dois tipos de problemas de divisão(um de partição e outro por quotas) e, em uma entrevista clínica, eram solicitadas a responder a pergunta 'O que é dividir?'. Cada criança foi classificada em um grupo de desempenho em função do número de acertos nos problemas. Diferentes tipos de definições foram identificados, os quais variavam desde definições sem um significado matemático até definições que expressavam um significado matemático exclusivamente associado à divisão. Os dados mostraram haver uma relação entre desempenho e as definições sobre a divisão, e que as crianças atribuem um significado matemático à divisão antes de adotarem procedimentos apropriados na resolução dos problemas. Os resultados inserem-se em um quadro teórico de desenvolvimento que analisa as relações entre conhecimento procedural e conhecimento explicitado lingüisticamente.

BackgroundThis study aimed to evaluate the prevalence of multiple high-risk (HR) human papillomavirus (HPV) infections in women with human immunodeficiency virus (HIV) compared to negative controls. This study also aimed to assess the impact of multiple HR-HPVs on the risk of high-grade squamous cervical lesions (HSILs) among women with HIV.MethodsWe performed a systematic search of PubMed/Medline, Scopus, Cochrane databases, and ClinicalTrials.gov from 1 January 2004 to 30 June 2023, including screenings and clinical studies evaluating the rates and role of multiple HPV infections in squamous intraepithelial lesions (SILs). Three reviewers independently screened the abstracts of the selected studies and extracted data from full-text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method.ResultsForty-seven studies meet definitive inclusion criteria. The quality of the observations was considered low in 26 of the included studies and moderate in 21 of the included studies. In comparative screening studies, the pooled prevalence of multiple HR-HPV was 39.1% (95% CI = 33.7–44.7) among women with (n = 1734) and 21.6% (95% CI = 17.3–26.1) in those without HIV infection (n = 912) (OR = 2.33, 95% CI = 1.83–2.97, I2 = 2.8%). The pooled ORs of HR-HPV multiple infections were similar in African (OR = 2.72, 95% CI = 1.89–3.9) and non-African countries (OR = 2.1, 95% CI = 1.46–3, p for difference = 0.96). Among women with HIV, the risk of HSIL diagnosed either by cytology or histology was higher among those with overall (OR = 2.62, 95% CI = 1.62–4.23) and HR multiple infections than those with single HPV infection (OR = 1.93, 95% CI = 1.51–2.46). Among women with HIV, the excess rates of multiple HPV infections and the excess risk of associated HSIL were consistent across studies including both HIV-naïve subjects and those on antiretroviral therapy, as well as in studies with different rates of immunocompromised women. When study quality (low vs. moderate) was used as a moderator, the results were unchanged.ConclusionMultiple HR-HPV infections are common among women living with HIV and are associated with an increased prevalence of HSIL. These associations were also confirmed in studies with high rates of antiretroviral therapy and low rates of immunocompromise.Systematic Review Registration: PROSPERO [registration number: CRD42023433022].

Diferentes tarefas são adotadas para avaliar habilidades de compreensão de textos, sendo cada uma delas considerada como o instrumento que melhor retrata esta habilidade. Entretanto, é possível supor que um único instrumento não revele todos os mecanismos envolvidos na compreensão, e que tarefas distintas possam avaliar diferentes mecanismos cognitivos e lingüísticos. Esta possibilidade foi investigada em duas tarefas apresentadas a crianças de 4 e 6 anos: reprodução de uma história ouvida; e perguntas inferenciais sobre a mesma história. Na análise das reproduções considerou-se a fidelidade ao texto ouvido e a integração dos enunciados. As respostas às perguntas foram analisadas em função do grau de precisão apresentado. Verificou-se uma progressão com a idade e dificuldades de compreensão relacionadas a determinadas partes do texto. Identificou-se, ainda, aspectos específicos relacionados às características das tarefas e ao gênero de texto adotado. Enfatiza-se a importância de tais aspectos específicos no processo de compreensão.

Background: Controversial evidence suggests a potential association between female genital mutilation (FGM/C) and adverse obstetric outcomes, with type III FGM/C (infibulation) carrying the greatest risk. The aim of this systematic review and meta-analysis was to assess current rate of adverse obstetric outcomes in women with type III female genital mutilation and cutting (FGM/C; infibulation) delivering across different settings worldwide. Methods: We searched PubMed, Scopus, Embase, and ClinicalTrials.gov databases from inception to Jan 1, 2023. Studies were selected if they included the main outcome of postpartum haemorrhage (PPH) or secondary outcomes, which included major conditions affecting maternal-neonatal health during labour and delivery. DerSimonian-Laird random effects meta-analysis including pooled effect estimates with corresponding 95 % confidence intervals was performed. Heterogeneity was assessed using the I2 statistic. Meta regression for relevant covariates was performed when data on relevant confounders were available. The Newcastle-Ottawa scale (NOS) was used to assess quality of observational studies. The level of evidence was assessed with the GRADE method. Results: 14 observational studies including 15,320 type III FGM/C women and 59,347 controls were eligible. The risk for postpartum haemorrhage was significantly increased in type III FGM/C, in the main analysis (OR 1.83, 95 % CI 1.03 to 3.24, I2 = 93 %), in pooling of data adjusted for confounders (aOR 1.76, CI 1.42 to 2.17, I2 = 0 %), and in sensitivity analysis of higher quality studies with NOS≥7 (OR 2.76, CI 1.38 to 5.51, I2 = 95 %). Meta-regression showed that nulliparity was significantly and positively associated with postpartum haemorrhage. Similarly, analysis of data adjusted for confounders showed an increased risk of episiotomy in type III FGM/C (aOR 1.56, CI 1.03 to 2.35, I2 = 52 %). Sensitivity analysis of studies with NOS≥7 revealed a significant increase for episiotomy (OR 7.53, CI 1.19 to 47.54, I2 = 96 %), perineal tears (OR 4.24, CI 1.09 to 16.46, I2 = 66 %), prolonged second stage of labour (OR 5.19, 95 % CI 1.00 to 26.85, I2 = 66 %), and Apgar score less than 7 (OR 4.19, CI 1.64 to 10.70, I2 = 0 %). No difference was found regarding obstetric anal sphincter injuries and mode of delivery in these women. Deinfibulation achieved similar obstetric and neonatal outcomes to women who never had type III FGM. The overall quality of the studies was adequate (median NOS score: 7; IQR: 6–8), the level of evidence, according to the GRADE assessment, was low. Conclusions: These results consistently show an increased risk of adverse obstetric outcomes in women with FGM/C type III. Infibulation substantially increases the risk for PPH, particularly in nulliparae. Systematic Review registration: PROSPERO CRD42023421993.

Objetivo: descrever a elaboração de uma cartilha informativa para familiares e cuidadores de crianças que vivem Transtorno do Espectro Autista. Método:pesquisa metodológica, realizada entre setembro de 2019 a julho de 2022 no sul do Brasil. Resultados: a elaboração envolveu a etapa teórica, validação de conteúdo e construção da cartilha denominada “Crianças autistas**: cartilha para familiares e cuidadores”.Composta com seis capítulos: características do transtorno, comportamento da criança, direitos, futuro da criança com autismo e compartilhando experiências e visões. O conteúdo foi validado e para a construção da cartilha foram investigadas as preferências de dispositivos tecnológicos e layout de recursos informativos pelos familiares; após, o protótipo da cartilha passou por teste de usabilidade e navegação, hospedada no Articulate Storyline Software e está disponível para o público-alvo. Considerações finais:o processo de elaboração de recursos educativos para familiares pode auxiliar outros pesquisadores com interesse na área.

In the setting of infectious diseases, antibodies show different functions beyond neutralizing activity. In this study, we investigated the activation of NK cells in vitro in the presence of human cytomegalovirus (HCMV)-specific antibodies and their potential role in the control of HCMV infection through antibody-dependent cell cytotoxicity (ADCC). Retinal pigmented epithelial cells (ARPE-19) infected with the HCMV strain VR1814 were co-cultured with cytokine-activated peripheral blood mononuclear cells (PBMCs) in the presence of sera collected from 23 HCMV-seropositive and 9 HCMV-seronegative donors. Moreover, 13 pregnant women sampled 3 and 6 months after HCMV primary infection and 13 pregnant women with pre-conception immunity were tested and compared. We determined the percentage of activated NK cells via the analysis of CD107a expression as a marker of degranulation. Significantly higher levels of NK-cell activation were observed using 1/100 and 1/10 dilutions of sera from HCMV-seropositive individuals, and when cells were infected for 96 and 120 h, suggesting that NK cells are activated by antibodies directed against late antigens. In the absence of serum NK cells, activation was negligible. In seropositive subjects, the median percentages of CD107a-positive NK cells in the presence of autologous serum and pooled HCMV-positive serum were similar (14.03% [range 0.00–33.56] and 12.42% [range 1.01–46.00], respectively), while NK-cell activation was negligible using an HCMV-negative serum pool. In HCMV-seronegative subjects, the median percentage of activated NK cells was 0.90% [range 0.00–3.92] with autologous serum and 2.07% [0.00–5.76] in the presence of the HCMV-negative serum pool, while it was 8.97% [0.00–26.49] with the pool of HCMV-positive sera. NK-cell activation using hyperimmune globulin is comparable to what is obtained using autologous serum. Sera from subjects at 3 and 6 months post primary infection showed a lower capacity of NK-cell activation than sera from subjects with past infection (p < 0.001). NK activation against HCMV-infected epithelial cells is dependent on the presence of HCMV-specific antibodies. This serum activity increases with time after the onset of HCMV infection. The protective role of NK-cell activation by HCMV-specific serum antibodies should be verified in clinical settings.

Noncommunicable diseases (NCDs) are the main cause of death globally (70%) and in the Region of the Americas (80%), and poor diets are a leading driver of NCDs. In response, the Pan American Health Organization (PAHO)/World Health Organization (WHO) introduced a set of evidence-based regulatory measures to help countries improve diets through the reduced consumption of processed and ultra-processed foods. This paper aims to describe the needs of and propose actions for key actors to advance these measures. A workshop was designed to assess member states’ regulatory capacity. A thematic analysis was conducted to analyze regional needs, successes and challenges. Thereafter, the Government Capacity-Building Framework for the prevention and control of NCDs was used to examine findings. The findings were organized in two sets: (i) PAHO/WHO actions to support member states and (ii) key actors’ actions to advance regulatory policies. The results show notable regulatory progress across the Region of the Americas. However, progress differs between countries, with opportunities to strengthen measures in most countries, mainly in conflict of interest management. The results identified important actions to strengthen the regulatory capacity of PAHO/WHO member states. To maximize momentum for these actions, timelines must be identified, and political commitment can be boosted by applying human rights-based and food system-wide approaches.

Background/Objectives: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections. The HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection in pregnancy. In this study, the antigen-specific T-cell response against different HCMV proteins (IE-1, pp65, gB, gHgLpUL128L) was investigated in pregnant women with primary infection and in control subjects with remote infection to identify possible components of a vaccine. Methods: Blood samples from 35 pregnant women with HCMV primary infection and 30 HCMV-seropositive healthy adult subjects with remote infection were tested. The antigen-specific T-cell response was measured using cytokine intracellular staining after stimulation with IE-1, pp65, gB and gHgLpUL128L peptides pool. Results: The pp65-specific CD4+ T-cell response was higher in pregnant women with HCMV primary infection at the late time point and in control subjects with remote infection, while the pregnant women at the early time point showed a higher gB-specific CD8+ T-cell response. Regarding the CD4+ and CD8+ T-cell phenotypes, we observed that HCMV-specific CD4+ and CD8+ T cells expressing CD45RA+ remained constant in pregnant women with primary infection at the early and late time points and in subjects with remote infection, while HCMV-specific CD4+ and CD8+ T cells expressing IL-7R+ or producing IL-2 were higher in control subjects with remote infection than in pregnant women with HCMV primary infection. Conclusions: The T-cell response was higher against gB in the early phase of infection and against pp65 in the late phase. Therefore, these proteins should be taken into consideration as candidates for a vaccine. [ABSTRACT FROM AUTHOR]