Periparturient blood T-lymphocyte PD-1 and CTLA-4 expression as potential predictors of new intramammary infections in dairy cows during early lactation (short communication).

BACKGROUND: The periparturient period in dairy cows is marked by immunosuppression which increases the likelihood of infectious disorders, particularly also mastitis. An in-depth understanding of peripartum leukocyte biology is vital for the implementation of highly successful post-partum disease prevention measures. Immune checkpoint molecules, such as programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are critical inhibitory receptors expressed on immune cells, particularly T cells, that drive immunosuppressive signaling pathways. However, the potential role of immune checkpoint molecules expression in T-cells on udder health has never been explored. Thus, the association between the occurrence of new postpartum intramammary infections (IMIs) and the expression of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) on blood T-cells during the peripartum period was investigated. RESULTS: In this study, the incidence of IMIs by any pathogen in early lactation was not associated with a higher expression of PD-1 and CTLA-4 in the periparturient period. However, the incidence of IMIs by major pathogens throughout the first month of lactation was significantly associated with higher expression of PD-1 at 14 days before calving (P = 0.03) and CTLA-4 at parturition (P = 0.03) by blood T-cells. Also, the expression of CTLA-4 at D0 (P = 0.012) by T-cells was associated with the occurrence of persistent IMIs during the first month of lactation. CONCLUSIONS: To our knowledge, this is the first report to investigate the expression of PD-1 and CTLA-4 by blood T-lymphocytes during the periparturient period in dairy cows and to explore their relationship with the incidence of new IMIs in the postpartum period. Thus, a comprehensive understanding of leukocyte biology during peripartum would appear to be a prerequisite for the identification of resilient dairy cows or targets innovative (immunological) non-antibiotic approaches in the transition period.

Advances in strawberry postharvest preservation and packaging: A comprehensive review.

Strawberries spoil rapidly after harvest due to factors such as the ripening process, weight loss, and, most importantly, microbial contamination. Traditionally, several methods are used to preserve strawberries after harvest and extend their shelf life, including thermal, plasma, radiation, chemical, and biological treatments. Although these methods are effective, they are a concern from the perspective of safety and consumer acceptance of the treated food. To address these issues, more advanced environment-friendly technologies have been developed over the past decades, including modified and controlled atmosphere packaging, active biopolymer-based packaging, or edible coating formulations. This method can not only significantly extend the shelf life of fruit but also solve safety concerns. Some studies have shown that combining two or more of these technologies can significantly extend the shelf life of strawberries, which could significantly contribute to expanding the global supply chain for delicious fruit. Despite the large number of studies underway in this field of research, no systematic review has been published discussing these advances. This review aims to cover important information about postharvest physiology, decay factors, and preservation methods of strawberry fruits. It is a pioneering work that integrates, relates, and discusses all information on the postharvest fate and handling of strawberries in one place. Additionally, commercially used techniques were discussed to provide insight into current developments in strawberry preservation and suggest future research directions in this field of study. This review aims to enrich the knowledge of academic and industrial researchers, scientists, and students on trends and developments in postharvest preservation and packaging of strawberry fruits.

Cytokine profiling in patients with hepatic glycogen storage disease: Are there clues for unsolved aspects?

INTRODUCTION: Hepatic Glycogen Storage Diseases (GSD) are rare genetic disorders in which the gluconeogenesis pathway is impaired. Cytokines control virtually every aspect of physiology and may help to elucidate some unsolved questions about phenotypes presented by GSD patients. METHODS: This was an exploratory study in which 27 GSD patients on treatment (Ia = 16, Ib = 06, III = 02, IXα = 03) and 24 healthy age- and sex-matched subjects had plasma samples tested for a panel of 20 cytokines (G-CSF,GM-CSF, IL-1α,IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17A, GRO, IP-10/CXCL10, MCP-1/CCL2, MIP-1α/CCL3, MIP-1ß/CCL4, MDC/CCL22, IFN-γ, TNF-α, TNF-ß, VEGF) through a multiplex kit and analyzed in comparison to controls and among patients, regarding to clinical features as anemia, hepatic adenocarcinoma and triglyceride levels. RESULTS: Patients (GSD-Ia/III/IX) presented reduced levels of IL-4 (p = 0.040), MIP-1α/CCL3 (p = 0.003), MDC/CCL22 (p < 0.001), TNF-ß (p = 0.045) and VEGF (p = 0.043) compared to controls. When different types of GSD were compared, G-CSF was higher in GSD-Ib than -Ia (p < 0.001) and than -III/IX (p = 0.033) patients; IL-10 was higher in GSD-Ib than in GSD-Ia patients (p = 0.019); and GSD-III/IX patients had increased levels of IP-10/CXCL10 than GSD-Ib patients (p = 0.019). When GSD-I patients were gathered into the same group and compared with GSD-III/IX patients, IP10/CXCL10 and MCP-1 were higher in the latter group (p = 0.005 and p = 0.013, respectively). GSD-I patients with anemia presented higher levels of IL-4 and MIP-1α in comparison with patients who had not. Triglyceride level was correlated with neutrophil count and MDC levels on GSD-Ia patients without HCA. CONCLUSION: Altogether, altered levels of cytokines in GSD-I patients reflect an imbalance in immunoregulation process. This study also indicates that neutrophils and some cytokines are affected by triglyceride levels, and future studies on the theme should consider this variable.

Challenges and recommendations to increasing the use of exome sequencing and whole genome sequencing for diagnosing rare diseases in Brazil: an expert perspective.

Early diagnosis of genetic rare diseases is an unmet need in Brazil, where an estimated 10-13 million people live with these conditions. Increased use of chromosome microarray assays, exome sequencing, and whole genome sequencing as first-tier testing techniques in suitable indications can shorten the diagnostic odyssey, eliminate unnecessary tests, procedures, and treatments, and lower healthcare expenditures. A selected panel of Brazilian experts in fields related to rare diseases was provided with a series of relevant questions to address before a multi-day conference. Within this conference, each narrative was discussed and edited through numerous rounds of discussion until agreement was achieved. The widespread adoption of exome sequencing and whole genome sequencing in Brazil is limited by various factors: cost and lack of funding, reimbursement, awareness and education, specialist shortages, and policy issues. To reduce the burden of rare diseases and increase early diagnosis, the Brazilian healthcare authorities/government must address the barriers to equitable access to early diagnostic methods for these conditions. Recommendations are provided, including broadening approved testing indications, increasing awareness and education efforts, increasing specialist training opportunities, and ensuring sufficient funding for genetic testing.

Consecutive Liver and Bone Marrow Transplantation for Erythropoietic Protoporphyria: Case Report and Literature Review.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disease of heme biosynthesis resulting in the accumulation of protoporphyrin, characterized by liver failure in a minority of cases. Although liver transplant (LT) is the therapeutic strategy for advanced hepatic disease, it does not correct the primary defect, which leads to recurrence in liver graft. Thus, hematopoietic stem cell transplantation (HSCT) is an approach for treating EPP. METHODS: We aim to describe the first sequential LT and HSCT for EPP performed in Latin America, besides reviewing the present-day literature. RESULTS: The patient, a 13-year-old female with a history of photosensitivity, presented with symptoms of cholestatic and hepatopulmonary syndrome and was diagnosed with EPP. Liver biopsy demonstrated cirrhosis. She was submitted to a successful LT and showed improvement of respiratory symptoms. However, she had disease recurrence on the liver graft. She underwent a myeloablative HSCT using a matched unrelated donor, conditioning with BuCy (busulfan and cyclophosphamide), and GvHD (graft vs. host disease) prophylaxis with ATG (thymoglobulin), tacrolimus and methotrexate. Neutrophil engraftment occurred on D+18. She has presented mixed chimerism, but normalization of PP levels, being 300 days after HSCT, in good state of health and normal liver function. CONCLUSIONS: Consecutive LT and HSCT for EPP is a procedure that has been described in 10 cases in the literature and, even though these patients are a highly diversified population, studies have shown favorable results. This concept of treatment should be considered in patients with established liver disease.

Lactational exposure to venlafaxine provokes late repercussions on reproductive parameters in male rat offspring.

Exposure to selective serotonin reuptake inhibitors can affect hormone-dependent processes, such as the brain sexual differentiation. Because the use of these antidepressants cause concern during lactation, we evaluated the possible effects of venlafaxine on lactational exposure and its late repercussions on reproductive parameters in male rats. Lactating rats were exposed to venlafaxine (3.85, 7.7, or 15.4 mg/kg/body weight; gavage), from lactational day 1 to 20. Venlafaxine and O-desmethylvenlafaxine residues were found in all milk samples of dams treated, demonstrating the lactational transfer of this antidepressant to the offspring. Although the maternal behavior was normal, the dams presented an increase in urea and uric acid levels in the groups treated with 7.7 and 15.4, respectively, as well as a spleen weight increased in the 3.85 and 15.4 groups. The male offspring showed a decrease in play behavior parameters in the intermediate dose group. Sperm analysis indicated a reduction in sperm motility in all treated groups. The androgen receptor expression in the hypothalamus was decreased in the highest dose group, although the sexual behavior had not been affected. In conclusion, venlafaxine was transferred through breast milk and promoted changes in play behavior, sperm quality, and hypothalamic androgen receptor (AR) content, which may indicate an incomplete masculinization of the brain of male offspring.

Assessment of the relationship between the MLST genetic diversity of Listeria monocytogenes and growth under selective and non-selective conditions.

Listeria monocytogenes can grow under stressful conditions and contaminate various food categories. Progresss in DNA sequencing-based identification methods, such as multi-locus sequence typing (MLST) now allow for more accurate characterization of pathogens. L. monocytogenes MLST genetic diversity is reflected by the different prevalence of the "clonal complexes" (CCs) in foods or infections. Better understanding of the growth potentials of L. monocytogenes is essential for quantitative risk assessment and efficient detection across CCs genetic diversity. Using optical density measurements taken with an automated spectrophotometer, we compared the maximal growth rate and lag phase of 39 strains from 13 different CCs and various food origins, in 3 broths mimicking stresful food conditions (8 °C, aw 0.95 and pH5) and in ISO Standard enrichment broths (Half Fraser and Fraser). This is important as growth could influence risk through pathogen multiplication in food. Besides, enrichment problems could lead to a lack of detection of some CCs. Despite small differences highlighting natural intraspecific variability, our results show that growth performances of L. monocytogenes strains under the conditions tested in selective and non-selective broth do not appear to be strongly correlated to CCs and cannot explain higher CC "virulence" or prevalence.

Applications of Electronic Nose, Electronic Eye and Electronic Tongue in Quality, Safety and Shelf Life of Meat and Meat Products: A Review.

The quality and shelf life of meat and meat products are key factors that are usually evaluated by complex and laborious protocols and intricate sensory methods. Devices with attractive characteristics (fast reading, portability, and relatively low operational costs) that facilitate the measurement of meat and meat products characteristics are of great value. This review aims to provide an overview of the fundamentals of electronic nose (E-nose), eye (E-eye), and tongue (E-tongue), data preprocessing, chemometrics, the application in the evaluation of quality and shelf life of meat and meat products, and advantages and disadvantages related to these electronic systems. E-nose is the most versatile technology among all three electronic systems and comprises applications to distinguish the application of different preservation methods (chilling vs. frozen, for instance), processing conditions (especially temperature and time), detect adulteration (meat from different species), and the monitoring of shelf life. Emerging applications include the detection of pathogenic microorganisms using E-nose. E-tongue is another relevant technology to determine adulteration, processing conditions, and to monitor shelf life. Finally, E-eye has been providing accurate measuring of color evaluation and grade marbling levels in fresh meat. However, advances are necessary to obtain information that are more related to industrial conditions. Advances to include industrial scenarios (cut sorting in continuous processing, for instance) are of great value.

Resveratrol-Loaded Attalea funifera Oil Organogel Nanoparticles: A Potential Nanocarrier against A375 Human Melanoma Cells.

This study aimed to evaluate Attalea funifera seed oil with or without resveratrol entrapped in organogel nanoparticles in vitro against A375 human melanoma tumor cells. Organogel nanoparticles with seed oil (SON) or with resveratrol entrapped in the seed oil (RSON) formed functional organogel nanoparticles that showed a particle size <100 nm, polydispersity index <0.3, negative zeta potential, and maintenance of electrical conductivity. The resveratrol entrapment efficiency in RSON was 99 ± 1%. The seed oil and SON showed no cytotoxicity against human non-tumor cells or tumor cells. Resveratrol at 50 µg/mL was cytotoxic for non-tumor cells, and was cytotoxic for tumor cells at 25 µg/mL. Resveratrol entrapped in RSON showed a decrease in cytotoxicity against non-tumor cells and cytotoxic against tumor cells at 50 µg/mL. Thus, SON is a potential new platform for the delivery of resveratrol with selective cytotoxic activity in the treatment of melanoma.

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire.

PURPOSE: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib.

Antitumoral effect of novel synthetic 8-hydroxy-2-((4-nitrophenyl)thio)naphthalene-1,4-dione (CNN16) via ROS-mediated DNA damage, apoptosis and anti-migratory effect in colon cancer cell line.

Colorectal cancer (CRC) is estimated as the third most incident cancer and second in mortality worldwide. Moreover, CRC metastasis reduces patients' survival rates. Thus, the study and identification of new compounds with anticancer activity selectively to tumor cells are encouraged in the CRC treatment. Naphtoquinones are compounds with several pharmacologic activities, including antitumoral properties. Therefore, this study aimed to investigate the anticancer mechanism of synthetic 8-Hydroxy-2-(P-Nitrothiophenol)-1,4-Naphthoquinone (CNN16) in colon cancer cell line HCT-116. CNN16 showed an IC50 of 5.32 µM in HCT-116, and 9.36, 10.77, and 24.57 µM in the non-cancerous cells MRC-5, MNP-01, and PMBC, respectively, evaluated by the MTT assay. CNN16 showed an anticlonogenic effect in HCT-116 and induced cell fragmentation identified by flow cytometry analysis. Furthermore, we observed that CNN16 presented genotoxicity and induces reactive oxygen species (ROS) after 3 h of treatment visualized by alkaline comet assay and DCFH-DA dye fluorescence, respectively. Furthermore, CNN16 caused cellular membrane disruption, reduction in the mitochondrial membrane polarization, and the presence of apoptotic bodies and chromatin condensation was visualized by differential stained (HO/FD/PI) in fluorescent microscopy along with PARP1, TP53, BCL-2, and BAX analyzed by RT-qPCR. Results also evidenced inhibition in the migratory process analyzed by wound healing assay. Therefore, CNN16 can be considered as a potential new leader molecule for CRC treatment, although further studies are still necessary to comprehend the effects of CNN16 in in vivo models to evaluate the anti-migratory effect, and toxicology and assure compound safety and selectively.

Sanfilippo syndrome type B: Analysis of patients diagnosed by the MPS Brazil Network.

Mucopolysaccharidosis type IIIB is a rare autosomal recessive disorder characterized by deficiency of the enzyme N-acetyl-alpha-d-glucosaminidase (NAGLU), caused by biallelic pathogenic variants in the NAGLU gene, which leads to storage of heparan sulfate and a series of clinical consequences which hallmark is neurodegeneration. In this study clinical, epidemiological, and biochemical data were obtained from MPS IIIB patients diagnosed from 2004-2019 by the MPS Brazil Network ("Rede MPS Brasil"), which was created with the goal to provide an easily accessible and comprehensive investigation of all MPS types. One hundred and ten MPS IIIB patients were diagnosed during this period. Mean age at diagnosis was 10.9 years. Patients were from all over Brazil, with a few from abroad, with a possible cluster of MPS IIIB identified in Ecuador. All patients had increased urinary levels of glycosaminoglycans and low NAGLU activity in blood. Main clinical symptoms reported at diagnosis were coarse facies and neurocognitive regression. The most common variant was p.Leu496Pro (30% of alleles). MPS IIIB seems to be relatively frequent in Brazil, but patients are diagnosed later than in other countries, and reasons for that probably include the limited awareness about the disease by health professionals and the difficulties to access diagnostic tests, factors that the MPS Brazil Network is trying to mitigate.

Detection of Epstein-Barr virus in gastric adenocarcinoma: qPCR and FISH comparison.

EBV-associated gastric cancer accounts for about 10% of all gastric carcinomas worldwide. We aimed to verify the prevalence of EBV in gastric adenocarcinoma samples using FISH and qPCR and comparing the results obtained by both techniques. Gastric cancer samples from 191 cases were analyzed. The FISH assay was performed to detect small EBV RNAs (EBER1) and qPCR was performed to detect the EBV-EBNA-1 gene region. Cohen's kappa index and the chi-square test were used to compare the methodologies and investigate correlations with the clinical-pathological data of the gastric adenocarcinoma patients. Most of the patients were men, and the average age was 60 years. The intestinal subtype cancer presented more aggressive stages with 90% of patients having a reactive FISH for EBV (EBV+), although the virus infection frequency in epithelial gastric tissue was only 1%. No positive association with clinicopathological features and EBV+ was found by FISH. Using qPCR analysis, the percentage of positive samples was lower (52.4%), and a positive association was found in samples from older patients (> 60 years). Interestingly, 71 qPCR-negative cases were detected by FISH in the presence of non-epithelial cells and in 10 qPCR-positive cases with no evidence of EBV according to FISH. The concordance between the two techniques was low, with only 57.6%. FISH is more informative for associating the gastric carcinoma with EBV positivity in tumor/epithelial cells; however, qPCR can provide relevant information regarding the progression and characteristics of neoplasia.

Utilization of Agro-Industrial Residues in the Rearing and Nutritional Enrichment of Zophobas atratus Larvae: New Food Raw Materials.

Edible insects are a potential alternative food source of high feed conversion efficiency and protein content. Zophobas atratus is an edible insect that adapts to different diets, enabling sustainable rearing by adding value to by-products and agro-industrial residues. This study aimed to evaluate the performance and nutritional characterization of Zophobas atratus larvae fed with different proportions of grape residue. Physicochemical analysis of the diets and larvae (AOAC procedures), fatty acid profile (chromatographic techniques), metals and non-metals (inductively coupled plasma optical emission spectrometry), larval mass gain, feed conversion efficiency, and mortality rate were assessed. The replacement of 25% of the conventional diet with grape residue increased lipid, ash, and fiber contents and reduced protein, carbohydrates, and energy. It promoted greater mass gain, lower mortality rate, and reduced larval growth time by 51%. Among the replacements, 25% resulted in the second-highest content of calcium, sodium, magnesium, and zinc, and the lowest content of potassium and phosphorus in the larvae. The 100% replacement resulted in the highest amounts of C18:2n6 (27.8%), C18:3n3 (2.2%), and PUFA (30.0%). Replacing 25% of the conventional diet with grape residue is equivalent to the conventional diet in many aspects and improves several larvae performance indices and nutritional values.

Basidiocarp structures of Lentinus crinitus: an antimicrobial source against foodborne pathogens and food spoilage microorganisms.

Lentinus crinitus basidiocarps are an alternative to antimicrobials, but the stipe (24% basidiocarp) is discarded even with potential antimicrobial activity. This study evaluated the antimicrobial activity of L. crinitus basidiocarp pileus and stipe extracts against foodborne pathogens and food spoilage microorganisms. Basidiocarps of L. crinitus were grown in sugarcane bagasse and rice husks and the pileus and stipe methanolic extract was analyzed by broth microdilution method for antimicrobial activity against eight bacteria and eight fungi. The minimum bactericidal concentration values for pileus and stipe ranged from 0.40 to 0.50 mg mL- 1, for streptomycin from 0.10 to 0.50 mg mL- 1, and for ampicillin from 0.40 to 1.20 mg mL- 1. The minimum fungicidal concentration values for pileus and stipe ranged from 0.06 to 0.60 mg mL- 1, for bifonazole from 0.20 to 0.25 mg mL- 1, and for ketoconazole from 0.30 to 3.50 mg mL- 1. Extracts had bacteriostatic, bactericidal, fungistatic and fungicidal activity against all microorganisms, but with greater efficiency and specificity for some microorganisms. Both pileus and stipe are promising and sustainable alternatives for use in food, agricultural, and pharmaceutical industries.

Physicochemical composition, fatty acid profile and sensory attributes of meat (longissimus lumborum muscle) from Nellore and Nellore-cross bulls.

This study aimed to compare the physicochemical characteristics, fatty acid composition, and sensory attributes of the meat from three genetic groups: Nellore (Nell), ½ Nellore × ½ Angus (NeAn), and » Nellore × » Angus × ½ Senepol (NASe). Longissimus lumborum muscle from 30 slaughtered bulls with a body weight of 549 ± 32.5 kg was used. The water holding capacity was greater for the Nell and NeAn groups than for the NASe group. Meat samples from the NASe group exhibited a higher L* index than those from the NeAn group and lower a* and b* color indexes than those from the Nell group. The meat fatty acid profiles showed that the Nell group had higher concentrations of 12:0, 14:0, 18:1 t11, 14:1 c9, 16:1 c9, 18:1 c9, 18:1 c11, 18:2 c9, t11 (conjugated linoleic acid (CLA)), and 20:3 n-6 polyunsaturated fatty acid (PUFA) than the NeAn and NASe groups. The total saturated (ΣSFA), unsaturated (ΣUFA), and monounsaturated (ΣMUFA) fatty acid concentrations were higher and the ΣPUFA:ΣSFA ratio was lower in the Nell group than in the NeAn group. The Δ9-desaturase C16 activity was significantly higher in the Nell and NASe groups than in the NeAn group. The atherogenicity index (AI) tended to be lower in the crossbreeds than in the Nell breed. The NASe group presented meat with better tenderness, juiciness, and overall acceptance than the Nell and NeAn groups and was therefore the best genetic group for beef production of the tested groups.

Intelligent pH-sensing film based on jaboticaba peels extract incorporated on a biopolymeric matrix.

Food spoilage is associated with pH change. Thus, the aim of this study was to develop a pH-sensing film based on the addition of anthocyanin extracted from jaboticaba peel to a biopolymeric matrix. UV-Vis spectroscopy analysis of the anthocyanin extract was performed to detect the color change in a broad pH range (1-11). Also, the thermal properties, morphology, moisture content (MC), water solubility (WS), water vapor permeability (WVP) and release test results were examined. The applicability of the pH-sensing film as intelligent packaging was tested by monitoring milk spoilage. Results showed that the film developed has satisfactory thermal stability up to 200 °C. Also, the MC and WVP properties of the film were reduced when the anthocyanin extract was present, 11.5% and 6.5 × 10-10 g H2O Pa- 1 s-1 m-1, respectively, while the WS showed an increase (54.33%). Release tests showed remarkable performance in simulated alcoholic and fatty aqueous foods. The food application test demonstrated the potential use of the anthocyanin-based film as a food quality indicator due to film visual color change ( Δ E >10, after 8 days of milk spoilage monitoring).

SARS-CoV-2 pandemic in the Brazilian community of rare diseases: A patient reported survey.

The COVID-19 pandemic has led to a reorganization of health systems to prioritize the fight against the virus. The adoption of social distancing interfered with the flow of existing policies, and may thus negatively affect the most vulnerable groups, such as the rare disease community. Aimming at characterizing the perception of the impact of COVID-19 on the health care of the Brazilian rare disease community, an online questionnaire addressed to patients with rare diseases and their caregivers was disseminated in the Brazilian territory between June 1st to July 5th, 2020. The questions dealt with the sanitary measures adopted; access to medical services; and mental suffering during the pandemic. The survey was answered by 1,466 participants (<18 yo = 53.3%) representing 192 rare diseases. Regarding physical distancing, 1,372 (93.6%) participants did not leave their residence, or did so only when essential; 1,321 (90.1%) always wore masks when leaving home. 1,042 (71.1%) and 995 (67.9%) participants, respectively, referred medical genetics appointments and rehabilitation therapies were postponed/canceled. Telemedicine was experienced by 1,026 (70%), and 68.3% agreed this is a good strategy for health care. Patients with Inborn Errors of Metabolism (IEM, n = 624, 42.5%) appear to have more access to information and ability to overcome difficulties, and feel less threatened, lonely and depressed than the non-IEM group (p < .05). There was an increment of the rare disease patients' vulnerability in the pandemic scenario. The cooperation of patients/caregivers along with adaptation of the health system is crucial and may be so even post-pandemic.

Genotype-phenotype studies in a large cohort of Brazilian patients with Hunter syndrome.

Mucopolysaccharidosis type II (MPS II) is an X-linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate-2-sulfatase and consequent widespread storage of glycosaminoglycans, leading to several clinical consequences, with progressive manifestations which most times includes cognitive decline. MPS II has wide allelic and clinical heterogeneity and a complex genotype-phenotype correlation. We evaluated data from 501 Brazilian patients diagnosed with MPS II from 1982 to 2020. We genotyped 280 of these patients (55.9%), which were assigned to 206 different families. Point mutations were present in 70% of our patients, being missense variants the most frequent. We correlated the IDS pathogenic variants identified with the phenotype (neuronophatic or non-neuronopathic). Except for two half-brothers, there was no discordance in the genotype-phenotype correlation among family members, nor among MPS II patients from different families with the same single base-pair substitution variant. Mothers were carriers in 82.0% of the cases. This comprehensive study of the molecular profile of the MPS II cases in Brazil sheds light on the genotype-phenotype correlation and helps the better understanding of the disease and the prediction of its clinical course, enabling the provision of a more refined genetic counseling to the affected families.

Experience of Sexuality in Women with Gynecological Cancer: Meta-Synthesis of Qualitative Studies.

Gynecological cancers have an impact on women's psychosexual health in which results vary from adjuvant cancer therapy, such as loss of pleasure, to anxious symptoms. This study aimed to present a meta-synthesis of qualitative primary studies on the sexual experience of women with gynecological cancer. The SPIDER tool and the PRISMA guidelines were used to recover evidence from the databases Web of Science, SCOPUS, PubMed/MedLine, CINAHL, PsycINFO and LILACS. Twenty articles were included. The thematic synthesis showed that alterations in sexual functions can be mitigated by direct involvement and dialogue with a sexual partner and the resignification of sexual intimacy.