Preliminary outcomes of the Cervical Cancer Screening Program of Northern Portugal: A snapshot.

BACKGROUND: Cervical cancer screening remains an essential preventive tool worldwide. First line high-risk Human Papillomavirus (HrHPV) genotyping became gold standard for cervical cancer screening, and has been adopted by several countries, including Portugal. Herein, we aimed to assess the early outcomes of the regional Cervical Cancer Screening Program of Northern Portugal. METHODS: The analysis of a representative set of cases evaluated during a one-month period (January 2020), with adequate follow-up was performed. Descriptive analysis was performed. RESULTS: Overall, 7278 samples were received, of which 15.2% were HrHPV positive, most of these disclosing a negative result in subsequent liquid-based cytology. Nearly half of the HrHPV-positive women were referred to colposcopy. Within this group, HPV16/18+ cases depicted the higher frequency of high-grade squamous intraepithelial lesion (HSIL) or worse, compared with abnormal cytology or persistent HrHPV infection. Among women with non-HPV16/18 HrHPV infection and negative cytology, which are eligible for repeat sampling in one year, 65% were re-tested. Importantly, nearly half of these cleared HrHPV infection. Furthermore, referral to colposcopy due to HPV16/18 infection and/or abnormal cytology results were associated with > 40% risk for HSIL or worse lesion. CONCLUSIONS: Our study confirmed the reliability and effectiveness of first line HrHPV genotyping in the Cervical Cancer Screening Program of Northern Portugal. Nonetheless, it also raised concerns about excessive referral to colposcopy, with the inherent human and financial costs. Thus, further improvement and optimization are key to ensure the sustainability of the program.

The impact of COVID-19 on male reproductive health: a Systematic Review.

OBJECTIVE: This systematic literature review aims to assess the impact of COVID-19 on male fertility. DATA SOURCES: The study draws upon data extracted from PubMed, SciELO, and LILACS databases. STUDY SELECTION: The review incorporates cross-sectional studies, cohort studies, and clinical trials, encompassing investigations related to the subject matter. The studies included were published between June 2020 and March 2023, and encompassed content in English, Portuguese, and Spanish. Exclusion criteria encompassed review articles, case reports, abstracts, studies involving animal models, duplicate articles, and letters to the editor. DATA COLLECTION: Data extracted included the author's name and publication year, the number of patients studied, patient age, the presence of COVID-19 in semen, observed hormonal changes, and alterations in seminal quality. CONCLUSIONS: While hormonal changes and a decline in seminal quality were observed in COVID-19 patients, the virus itself was not detected in semen in the analyzed articles, which contradicts certain findings in the existing literature. It is essential to note that methodologies in the studies were diverse, and, due to the novelty of this infection, it is premature to definitively ascertain its long-term effects on male fertility or whether fertility can recover after a period of convalescence. This underscores the necessity for further research, utilizing more robust methodologies such as cohort studies.

Effects of major analgesics on male fertility: A systematic literature review.

OBJECTIVE: To verify, based on a systematic literature review, the effects of the main analgesics on male fertility. DATA SOURCES: The studies were analyzed from the PubMed, SciELO and LILACS databases. STUDY SELECTION: The articles selected for the present review included: cohort studies; cross-sectional studies, clinical trials; complete studies; studies with animal models that addressed the proposed theme and that were published within the stipulated period from March 1, 2013, to March 31, 2023, in English, Portuguese and Spanish. These would later have to go through inclusion stages such as framing the type of study and exclusion criteria. DATA COLLECTION: Author's name, year of publication, study population, number of patients, analgesic, administration time, dose, and effect. CONCLUSIONS: There are in vitro and in vivo studies that link paracetamol and ibuprofen to endocrine and seminal changes that are harmful to male fertility. However, more clinical research is needed to determine the doses and timing of administration that affect fertility. The effects of aspirin on male fertility are still unclear due to the lack of studies and consistent methodologies. There is not enough research on dipyrone and its relationship with male fertility, requiring more studies in this area.

Comparison of 8-weeks of full versus split body resistance training on appetite and energy intake in non-obese untrained men.

To investigate the effects of 8-weeks of full versus split body resistance training (RT) on appetite and energy intake in non-obese untrained men. The participants were pair-matched based on their initial fat mass and then randomly allocated into one of two treatment groups: Full body (FB, n = 20), in which all muscle groups were trained in every session, or Split body (SB, n = 15), in which upper and lower muscle groups were trained alternated per session; both groups trained in non-consecutive days, three times per week with total number of sets performed equated between groups. Energy intake, body composition, and strength performance were evaluated at pre-training, and after 8-weeks of RT, as well as self-reported hunger, fullness, and desire to eat, that were assessed at fasted and feed states pre- and post-intervention. FB and SB resistance training increased fat-free mass (FFM) (p < 0.001); and FB induced greater maximal strength improvement (p = 0.027). At fasted state self-reported hunger increased, and fullness decreased, while in feed state desire to eat something fatty increased in both groups. Carbohydrate intake (p = 0.011) decreased in both groups. In conclusion, FB and SB training increased orexigenic drive (increasing hunger and decreasing fullness), however, total energy intake and fat mass did not change after 8-weeks of RT in non-obese untrained men.Registered under Brazilian Registry of Clinical Trials no. RBR-3wkcvyw.

The impact of thyroid disorders on the clinical outcome of assisted reproductive techniques: a systematic approach over the last 10 years.

OBJECTIVE: To verify from a systematic literature review the possible effects of thyroid diseases on assisted reproduction techniques. DATA SOURCES: The studies were analyzed from the PubMed, Cochrane Library, LILACS databases. SELECTION OF STUDIES: The articles selected for the review included: cross-sectional studies, cohort studies, and clinical trials that addressed the proposed theme and which were published within the period stipulated from January 1, 2012, to March 5, 2022, in English, Portuguese and Spanish. These would later have to go through stages of inclusion as a framework of the type of study and exclusion criteria that were review articles, case reports, abstracts, articles with animal models, and duplicate articles and letters to the editor. DATA COLLECTION: Author's name; Number of patients; Clinical outcome; Use of drugs; Control group (in case it had); Clinical outcome. DATA SYNTHESIS: In in vitro fertilization and intracytoplasmic sperm injection it was verified that thyroid diseases can lead to effects such as a reduction in the rate of recovered oocytes, a decrease in the number of embryos, lower pregnancy rates, and increased chances of congenital anomalies in these patients and a reduction in the rate of implantation. Levothyroxine can increase the number of cycle cancellations. CONCLUSIONS: Thyroid diseases may have deleterious effects on the clinical outcome of in vitro fertilization and intracytoplasmic sperm injection.

Vaginal microbioma and the presence of Lactobacillus spp. as interferences in female fertility: A review system.

The vaginal microbiome is dominated by Lactobacillus spp. and the depletion of these microorganisms have been associated with adverse conditions that can affect women's health. Disturbance of the vaginal niche with a non-lactobacillary microbiota is associated with susceptibility to some diseases, such as obstetric alterations and infertility, resulting in failure in natural pregnancies and increased demand for assisted reproduction treatments. The present study sought to understand the influence of Lactobacillus spp. and fertility female. A systematic search was performed in the following databases: PubMed, MEDLINE, SciELO and LILACS, using the keywords: "Microbiome"; "Lactobacillus" and "Female Infertility", published in the last five years. The search resulted in 92 articles; however, 38 articles were excluded due to duplicity, 23 articles were excluded in the selection title/abstract, leaving 31 articles for full reading. In the end, 18 articles were analyzed. The studies encompassed a total of 2,011 women, using 27 types of samples to verify the composition of the microbiome. The eighteen articles that reported the microbiome of fertile women were constituted by a dominance of Lactobacillus spp. who joined to positive predictive outcomes in reproduction, while infertile women showed a dysbiotic profile. Therefore, analyzing bacterial patterns would allow a personalized diagnosis, which could favor personalized therapy for prevention and treatment of certain diseases.

Short tandem repeat analysis: a practical tool to identify specimen mix-ups in the pathology laboratory.

Despite all precautions in pathology laboratories, contaminations and specimen mix-ups still occur and can negatively impact both patients and institutions. We present two cases in which short tandem repeat (STR) analysis was used to assert the correct identity of specimens. The first patient had a biopsy diagnosis of triple negative invasive carcinoma of no special type of the breast. Sample mix-up with another biopsy was suspected, because in her post-chemotherapy mastectomy specimen, a hormone receptor-positive lobular carcinoma was diagnosed. STR analysis displayed a complete common loci profile of the patient's biopsy and mastectomy, supporting that no mix-up occurred. The second patient underwent hysterectomy due to cervix squamous cell carcinoma. A fragment of adenocarcinoma was identified and confirmed by STR profile to be a contaminant. STR analysis is a fast, easy-to-perform, and widely available technique which can clarify contaminations and specimen mix-ups in pathology laboratories.

Impact of cervicovaginal microbiome on the risk of cervical abnormalities development.

The vaginal microbiome has emerged as potentially influencing the natural history of Human Papillomavirus (HPV) infections and their clinical impact. We aimed to characterize the vaginal microbiome in samples from 807 high-risk HPVs (Hr-HPV) positive women with a mean age of 41.45 ± 10.79 years who participated in the Regional Cervical Cancer Screening Program from the Northern Region of Portugal. Microbiome analysis was performed with commercial kits for the detection of 21 microorganisms. The most frequent microorganisms were Ureaplasma parvum (52.5%), Gardnerella vaginalis (GV) (34.5%), Atopobium vaginae (AV) (32.6%), Lacto (30.7%), and Mycoplasma hominis (MH) (23.5%). The distribution according to age reveals that MH, Mega1, GV, BVab2, AV, and Mob were more prevalent in women older than 41 years of age (p < 0.050), while Lacto is significantly decreased in this group (23.5% vs. 39.4%, p < 0.001; RR = 0.47). The risk analysis showed that Hr-HPV-16/-18 and Hr-HPV-9val genotypes are associated with an increased risk of developing cervical abnormalities, while Lacto (p < 0.001; odd ratio [OR] = 0.33), GV (p = 0.0111; OR = 0.41), AV (p = 0.033; OR = 0.53) and Mob (p = 0.022; OR = 0.29) are associated with protection. Similar results were found for the risk of development atypical squamous cells cannot exclude HSIL/high-grade squamous intraepithelial lesion. Overall, the multivariate analysis confirmed that lactobacillus and bacteria associated with bacterial vaginosis (GV, AV, and Mob) are associated with protection against the development of cervical abnormalities. This study provides important data to be included in the future management of risk stratification for Hr-HPV-positive women.

Microbiota and seminal quality: A systematic review.

The microbiota is composed of numerous resident microorganisms, which contribute to the health and illness of the individual. When the microbiota is in dysbiosis, it can cause some pathological processes and in men it can be correlated with male infertility, so the present study does a systematic review, identifying whether there is a correlation between the microbiota and seminal quality. We analyzed 7 papers published in PubMed, Medline and the Cochrane library databases, in English and published between 2012 and 2022. In men with normal semen parameters, a higher prevalence of Lactobacillus. There was a higher prevalence of Prevotella in patients who had some seminal alteration. We conclude that the microbiota is correlated with seminal quality, since the decrease in Lactobacillus and the increase in other species is seen in infertile men.

Impact of sperm DNA fragmentation on the clinical outcome of assisted reproduction techniques: a systematic review of the last five years.

OBJECTIVE: To elucidate through a systematic literature review the impact sperm DNA fragmentation has on embryos from assisted reproduction techniques. DATA SOURCE: Studies from the "PubMed", "Embase", and "BVS" databases were analyzed. STUDIES SELECTION: The articles selected in the review included: cohort and case-control studies that addressed the proposed theme, published between January 1, 2017, and January 31, 2022, in English, Portuguese, and Spanish. As inclusion criteria: cohort and case-control articles. As exclusion criteria: articles outside the scope of the research, review articles, case reports, articles using animal models, abstracts, letters to the editor, and articles found duplicates in the databases. DATA COLLECTION: Number of couples or cycles; age (men/women); collection type; DNA damage (%); assisted reproduction activity and techniques. DATA SYNTHESIS: In in vitro fertilization, a reduction in fertilization rate, blastocyst rate, and embryo quality was observed. In addition to implantation and increased abortion rates in patients with high sperm DNA fragmentation. High rates of sperm DNA fragmentation in intracytoplasmic sperm injection led to reduced blastocyst production rate, embryo quality, implantation, and live birth rate, and in intrauterine insemination, a reduction in pregnancy rate. CONCLUSION: Sperm DNA fragmentation was a potential limiting factor for assisted reproduction techniques.

Impact of high-risk Human Papillomavirus genotyping in cervical disease in the Northern region of Portugal: Real-world data from regional cervical cancer screening program.

Cervical cancer prevention is based on primary prevention with vaccines against Human Papillomavirus (HPV) and secondary prevention by screening with High-Risk-HPV (Hr-HPV) detection. Since 2017, cervical cancer screening in women aged 25-60 years has been performed in Portugal using Hr-HPV detection, followed by cytology in Hr-HPV-positive cases. Herein we report the prevalence of Hr-HPV genotypes and cytological abnormalities among 462 401 women (mean age: 43.73 ± 10.79; median age: 45; range: 24-66 years) that participated in the Regional Cervical Cancer Screening Program of the Northern Region of Portugal, performed between August 2016 and December 2021. Overall, we describe a prevalence rate of 12.50% for Hr-HPV varying from 20.76% at age 25% to 8.32% at age 64. The five most common Hr-HPV genotypes identified were HPV-68 (16.09%), HPV-31 (15.30%), HPV-51 (12.96%), HPV-16 (11.06%), and HPV-39 (11.01%). The prevalence of Hr-HPV included in the nonavalent vaccine (HPV-9valent) was 55.00% ranging from 47.78% to 59.18% across different age groups. Considering positive Hr-HPV cases, 65.68% had a Negative for Intraepithelial Lesion or Malignancy (NILM) cytology, 20.83% atypical squamous cells of undetermined significance (ASC-US), 8.85% Low-Grade Squamous Intraepithelial Lesion (LSIL), 1.65% High-Grade Squamous Intraepithelial Lesion (HSIL), 2.85% ASC-H, 0.09% Atypical Glandular Cells, 0.02% Adenocarcinomas, and 0.02% Squamous Cell Carcinoma (SCC). Our analysis revealed that HPV-9val genotypes were responsible for 52.13% NILM, 59.21% ASC-US, 55.06% LSIL, 90.14% HSIL, 83.50% ASC-H, and 100.00% SCC. Furthermore, multiple Hr-HPV infections (risk ratio [RR] = 1.46; 95% confidence interval [CI] 1.34-1.58), HPV-16/18 (RR = 5.16; 95% CI 4.75-5.93), or HPV-9val genotypes (RR = 5.23; 95% CI 4.68-5.85) were associated with a significant risk of developing > HSIL (p < 0.001). To date, this is the largest study on Hr-HPV genotyping in cervical cancer screening that includes data from a complete cycle of the screening program. Our findings suggest a high prevalence of HPV-9valent genotypes and a significant association with an increased risk of developing > HSIL. This constitutes important data for health authorities, which may help define the future of vaccination and cervical cancer screening strategies.

Evaluation of the Implementation and Diagnostic Accuracy of the Paris Classification for Reporting Urinary Cytology in Voided Urine Specimens: A Cyto-Histological Correlation Study in a Cancer Center.

INTRODUCTION: The Paris classification highlights the need to focus on accurately identifying high-grade urothelial carcinoma (HGUC). Herein, we aimed to assess the overall implementation and diagnostic performance of the Paris classification for reporting urinary cytology in a cancer center. METHODS: All urinary cytology reports from July 2018 to December 2019 were collected (n = 1,240). Only voided urine samples were included (n = 1,180). Risk of high-grade malignancy (ROHM) was calculated for each Paris category. The diagnostic performance of urinary cytology was assessed, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. RESULTS: The distribution of categories was: 0.3% unsatisfactory, 90.5% negative for HGUC, 5.6% atypical urothelial cells (AUC), 1.6% suspicious for HGUC, 1.9% HGUC, and 0.1% other malignancies. No diagnosis of low-grade urothelial neoplasia was given. The ROHM was 21.4% for negative for HGUC, 66.7% for AUC, 91.7% for suspicious for HGUC, and 100% for HGUC. When using suspicious for HGUC as a cutoff, the diagnostic performance of urinary cytology in identifying HGUC histology was 46% sensitivity, 98% specificity, 96% PPV, 68% NPV, and 74% accuracy. CONCLUSION: Specificity of urinary cytology was very high (with only 1 false-positive result), which is important since this will trigger a clinical intervention. The ROHM for each category was in accordance with literature, except for AUC where ROHM was slightly higher (66.7%). This may be explained by the study population characteristics (cancer center; many patients treated with intravesical therapies; lack of clinical annotation for patients referred from outside institutions).

New paradigm of human papillomavirus infection.

Laryngotracheobronchial papillomatosis is a rare dis- ease, with few reported cases. Histologically has been report- ed has a benign proliferation of the epithelium, limited to the larynx but it may occasionally become aggressive and result in persistent and recurrent involvement of the tracheobronchial tree, extending in more severe cases to the lungs.

ENDOBRONCHIAL TUBERCULOSIS.

Videobronchofibroscopy of a Chinese 74-year-old woman showing abundant whitish plaques in the vocal cords with antraconic lesions extending throughout the tracheal pathway and bronchial trees, predominantly in the upper left lobe, compatible with Endobronchial My- cobacterium tuberculosis. The evolution and prognosis varies, from complete resolution to severe endobronchial stenosis.

Non-invasive preimplantation genetic testing: a literature review.

Non-invasive preimplantation genetic testing emerged from the discovery of embryonic DNA in spent embryo culture medium. Considering that such methodology would be an important advance in assisted reproduction, this study aimed to evaluate the current scientific evidence, based on the reliability of non-invasive chromosome screening, through a literature review. We analyzed 14 original research papers in PubMed and SciELO, in English and Portuguese, published between 2016 and 2021 related to the topic. The agreement rate for ploidy compared to the traditional method ranged from 3.5% - 93.8% raising the discussion about the possible causes of this large variation, which may be due to the day of collection, spent culture media contamination, amplification methodology or the cytogenetic method used by each author. We concluded that the non-invasive test has many advantages over the traditional method, but that clinical replacement is not yet possible, and further studies are needed in order to have an accurate clinical test with the non-invasive methodology.

Brain-Derived Neurotrophic Factor and Psychophysiological Response in Youth Badminton Athletes During the Season.

PURPOSE: To analyze peripheral brain-derived neurotrophic factor (BDNF) levels and psychophysiological parameters in youth badminton athletes during the season and to determine the relationship between variables. METHODS: Fourteen young badminton athletes were assessed over the season (preseason, middle season, and final season). Serum BDNF (sBDNF) was determined during the preseason and final season. Sleep time, total physical activity, and time in vigorous activity were measured using an accelerometer. The fat-free mass, skeletal muscle mass, fat mass, handgrip strength, cardiorespiratory fitness (VO2max), and dietary intake were evaluated during the season. The Stroop Color and Word Test was employed to assess cognitive tasks. To evaluate the mood, the Brunel Mood Scale was used. RESULTS: There  were lower sBDNF levels (-16.3% [46.8%]; P = .007) and sleep time (final season = 5.7 [1.1] vs preseason = 6.6 [1.1] h·night-1, P = .043) during the end of the season. The total calories and carbohydrate intake decreased across the season (P < .05). Conversely, better cognitive function was found in the final season with respect to the preseason (P < .05). There were significant correlations between BDNF and VO2max only in the preseason (r = .61, P = .027), but no significant relationship was found among sBDNF and cognitive performance, sleep time, and percentage of won games. CONCLUSIONS: Youth badminton athletes decreased their sBDNF levels, sleep time, carbohydrate, and calorie intake across the season. The athletes improved in cognitive function; however, only the females improved in body composition, and the males improved their VO2max in the middle season. The sBDNF levels were positively correlated with the VO2max in the preseason, and no correlations were observed among the sBDNF and psychological parameters, sleep time, and sport performance during the season.

A Protocol of Intradialytic Exercise for Improvements in Inflammatory Status, Body Composition, and Functional Capacity.

Skeletal muscle wasting has been well-documented among hemodialysis patients. This catabolic condition can be induced by numerous factors, including low-grade inflammation, and is associated with impairments in functional capacity and quality of life, as well as an increased mortality risk. We previously showed that 12 weeks of intradialytic resistance training increases lean mass, functional capacity, and the quality of life of hemodialysis patients. This chapter provides the details of a protocol of intradialytic exercise that leads to improvements in inflammatory status, body composition, and functional capacity.

No effect of intradialytic neuromuscular electrical stimulation on inflammation and quality of life: a randomized and parallel design clinical trial.

Neuromuscular electrical stimulation (NMES) elicits muscle contraction and has been shown to improvement of quality of life. However, if NMES improvement the quality of life and attenuate the inflammation is not fully understood. Therefore, our aim sought to assess the effects of short-term of intradialytic NMES on inflammation and quality of life in patients with chronic kidney disease patients undergoing hemodialysis. A randomized clinical trial conducted with parallel design enrolled adult hemodialysis patients three times a week during 1 month. Patients were randomly assigned to two groups (control group, n = 11; 4F/7 M) or (NMES group, n = 10; 4F/6 M). Pre-and post-intervention, was measured the high-sensitivity C reactive protein, interleukin-6, interleukin-10, and TNFα by the ELISA, and quality of life was applied using the SF-36. During each hemodialysis session, NMES was applied bilaterally at thigh and calves for 40 min. There was not change in cytokines (hs-CRP, IL-6, IL-10, and TNFα) concentrations time × group interaction. In addition, no difference was found in eight domains of quality of life. In addition, the groups did not differ for muscle strength and muscle mass. In conclusion, we found that intradialytic NMES did not change inflammation neither quality of life.

Performance of DNA methylation-based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study.

Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High-risk HPV (hr-HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage tests to reduce unnecessary colposcopy referrals and overdiagnosis/overtreatment are crucial. Hence, we aimed to validate a panel of DNA methylation-based markers as triage test for women hr-HPV+ in the population-based Regional Cervical Cancer Screening Program of Northern Portugal. Firstly, CADM1, MAL, FAM19A4 and hsa-miR124-2 promoter methylation levels were assessed by multiplex QMSP in a testing set of 402 FFPE tissue samples (159 normal samples and 243 cervical lesions, including 39 low-grade intraepithelial squamous lesions [LSIL], 59 high-grade intraepithelial squamous lesions [HSIL] and 145 cancerous lesions). Then, preliminary validation was performed in 125 hr-HPV+ cervical scrapes (including 59 normal samples, 30 LSIL, 34 HSIL and 2 cancerous lesions). Higher MALme , FAM19A4me and hsa-miR124-2me methylation levels were disclosed in histological HSIL or worse (HSIL+) in testing set. Individually, markers depicted over 86% specificity for HSIL+ detection. In validation set, all these genes significantly differed between histological HSIL+ and low-grade squamous intraepithelial lesions or less. In combination, these markers reached 74% specificity and 61% sensitivity for identification of histological HSIL+. We concluded that host gene methylation might constitute a useful referral triage tool of hr-HPV+ women enrolled in the Cervical Cancer Screening Program of Northern Portugal.