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An organolithium reagent containing a 5,6-dihydro-1,4-dithiin moiety has been herein used as homologating agent to build up a fully protected divinylcarbinol by two different synthetic procedures, respectively, based on a step-by-step approach or a tandem process. The resulting molecule contains two double bonds masked by two dithiodimethylene bridges that can be stereoselectively removed to give a E,E- or Z,Z-configured divinylcarbinol. These products could then be conveniently functionalized, for example, with hydroxyl or amino functions, for the construction of the skeleton of more complex systems.

There are controversies regarding the impact of sex on mortality and postoperative complications in patients undergoing on-pump coronary artery bypass grafting (CABG), although some studies demonstrate comparable outcomes. This study sought to evaluate sex differences regarding risk factors associated with hospital mortality and postoperative clinical outcomes among patients undergoing isolated on-pump CABG. We conducted a retrospective observational cohort study of patients who underwent isolated on-pump CABG from January 1996 to January 2020. Patients were divided into two groups (male and female) and compared regarding preoperative characteristics, surgical technical variables, and in-hospital outcomes. All-cause mortality between groups was compared using logistic regression. Risk factors for mortality, along with their respective odds ratios (OR), were separately assessed using a logistic regression model with p-values for interaction. We analyzed 4,882 patients, of whom 31.6% were female. Women exhibited a higher prevalence of age >75 years (12.2% vs 8.3%, p

ABSTRACT Introduction: Due to Brazilian population aging, prevalence of aortic stenosis, and limited number of scores in literature, it is essential to develop risk scores adapted to our reality and created in the specific context of this disease. Methods: This is an observational historical cohort study with analysis of 802 aortic stenosis patients who underwent valve replacement at Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, from 1996 to 2018. With the aid of logistic regression, a weighted risk score was constructed based on the magnitude of the coeficients β of the logistic equation. Two performance statistics were obtained: area under the receiver operating characteristic curve and the chi-square (χ2) of Hosmer-Lemeshow goodness-of-fit with Pearson’s correlation coeficient between the observed events and predicted as a model calibration estimate. Results: The risk predictors that composed the score were valve replacement surgery combined with coronary artery bypass grafting, prior renal failure, New York Heart Association class III/IV heart failure, age > 70 years, and ejection fraction < 50%. The receiver operating characteristic curve area was 0.77 (95% confidence interval: 0.72-0.82); regarding the model calibration estimated between observed/predicted mortality, Hosmer-Lemeshow test χ2 = 3,70 (P=0.594) and Pearson’s coeficient r = 0.98 (P

Background Males have higher weight and length at birth than females. Aim To verify the influence of the Y chromosome and the action of intrauterine androgens on weight and length at birth of children with Disorders of Sex Development (DSD). Subjects and methods A cross-sectional and retrospective study. Patients with Turner syndrome (TS), complete (XX and XY), mixed (45,X/46,XY) and partial (XY) gonadal dysgenesis (GD), complete (CAIS) and partial (PAIS) androgen insensitivity syndromes and XX and XY congenital adrenal hyperplasia (CAH) were included. Weight and length at birth were evaluated. Results Weight and length at birth were lower in TS and mixed GD when compared to XY and XX DSD cases. In turn, patients with increased androgen action (117 cases) had higher weight and length at birth when compared to those with absent (108 cases) and decreased (68 cases) production/action. In birthweight, there was a negative influence of the 45,X/46,XY karyotype and a positive influence of increased androgen and gestational age. In birth length, there was a negative influence of the 45,X and 45,X/46,XY karyotypes and also a positive influence of increased androgen and gestational age. Conclusions The sex dimorphism of weight and length at birth could possibly be influenced by intrauterine androgenic action.

This Special Issue, “Molecules from Side Reactions II”, belongs to the section Organic Synthesis of the journal Molbank and was launched in 2021, after the first edition, “Molecules from Side Reactions” [...]

Three natural phenolic compounds are found to bind to an allosteric site in SARS-CoV-2 papain-like protease and exhibit antiviral activity in vitro, showing potential as starting scaffolds for drug design.

Intro: Mayaro virus (MAYV) is a neotropical, emerging, zoonotic mosquito-borne virus that causes an acute febrile illness similar to that produced by chikungunya virus (CHIKV), a close alphavirus relative. Emergence of MAYV is sporadic and involves spillover infections, but recent outbreaks indicate that it remains a public health concern for urban emergence. With the recent arrival of both ECSA and Asian lineage CHIKV strains in the Americas, it is critical to assess their ability to cross-protect against MAYV infection. We evaluated whether CHIKV- specific immunity derived from the 3 major lineages, ECSA, IOL and Asian/American, cross-protects against MAYV infection with major genotypes L and D. Methods: We used a type I interferon-defective C57BL/6J mouse model intradermally infected with CHIKV and, 3 months later, challenged with MAYV after treatment with an anti-Ifnar1 mAb to induce a virulent phenotype. Several indexes such as weight, signs of disease and footpad swelling were monitored up to 14 days post-infection. Viremia, neutralizing antibodies, cytokine production and T cell responses were evaluated. Findings: CHIKV immunity induced by all three lineages conferred strong and broad cross-protection against MAYV infection, reducing disease severity (weight loss, footpad swelling and clinical manifestations), viremia and proinflammatory chemokine/cytokine levels. The anti-CHIKV antibodies showed the ability cross- neutralize MAYV and mice previously exposed to CHIKV developed a different profile of adaptive immune cells, showing an increase of total CD3+ and CD8+ T cells, combined with a decrease in CD4+ populations. Conclusion: Our data suggest that cross-protection observed between CHIKV and MAYV is not lineage-dependent and is mediated by both humoral and cellular responses. These data indicate that preexisting immunity produced by different CHIKV strains may reduce the impact of secondary infection by MAYV as well as the risk of human-amplified MAYV transmission, which could lead to urban emergence.

Steroid 5α-reductase type 2 deficiency (5α-RD2) is an autosomal recessive disorder caused by mutations in the SRD5A2 gene. This condition is characterized by reduced enzymatic activity of the 5α-reductase type 2 enzyme. Individuals with mutations in the SRD5A2 gene may exhibit various symptoms of under-masculinization in 46, XY individuals. We conducted a comprehensive analysis of the SRD5A2 gene in a patient with disorder of sex development (DSD). We describe a patient with a homozygous Gly183Ser variant in the SRD5A2 gene. Their sibling also carries this variant in homozygosity, while both parents have it in a heterozygous state. The patient presents with predominantly female traits and was raised as a girl. Although the siblings exhibit distinct phenotypic characteristics, both have assumed a male gender identity. This study reveals different phenotypes for the two siblings, highlighting the complexity of establishing a genotype-phenotype correlation in the SRD5A2 gene. It is noteworthy that the Gly183Ser variant seems to be more prevalent among individuals of African descent, aligning with our patient's ethnic background. [ABSTRACT FROM AUTHOR]

Dengue is the most prevalent arboviral disease globally, with Brazil currently experiencing a significant rise in cases. Dengue virus (DENV) typically co‐circulates with other clinically and antigenically similar flaviviruses, such as Zika virus (ZIKV). The clinical diagnosis is difficult and accurate serological analysis represents an unmet challenge. Traditionally, serological analysis of DENV infection focuses on the acute phase via detection of NS1 or IgM. Developing IgG DENV‐specific assays has been defiant due to the co‐circulation of four antigenically distinct serotypes and a strong cross‐reactivity with other arboviruses, particularly with ZIKV. The goal of this study was to produce recombinant domain III of the Envelope (EDIII) proteins of each DENV serotype and ZIKV and evaluate the ability to detect specific IgG antibodies. The antigens were tested on the ELISA platform to measure DENV‐specific IgG in mice and patients infected with ZIKV and DENV. The assay differentiated serotype‐specific IgG responses in susceptible mice (AG129) experimentally infected with DENV or ZIKV. In addition, the test demonstrated a robust performance achieving 87.8% sensitivity and 91.4% specificity when tested against 648 well‐characterized sera collected from humans infected with DENV and/or ZIKV. The test was further applied to serum samples collected from 318 healthy individuals from an endemic region in Northwest/Central Brazil, without a previous diagnosis of DENV, and revealed that 65% of the samples reacted with at least one DENV serotype antigen, including 123 monotypic samples (88 for DENV‐1) and 90 samples reacting with multiple antigens. Collectively, these results indicate that the IgG DENV‐EDIII ELISA is a valuable tool for assessing the serological status of populations in endemic areas, particularly in regions where other flaviviruses, particularly ZIKV, co‐circulate and offer support to establish public health policies against the disease. [ABSTRACT FROM AUTHOR]

The recently emerged SARS-CoV-2 Omicron sublineages, including the BA.2-derived XBB.1.5 (Kraken), XBB.1.16 (Arcturus), and EG.5.1 (Eris), have accumulated several spike mutations that may increase immune escape, affecting vaccine effectiveness. Older adults are an understudied group at significantly increased risk of severe COVID-19. Here we report the neutralizing activities of 177 sera samples from 59 older adults, aged 62–97 years, 1 and 4 months after vaccination with a 4th dose of ChAdOx1-S (Oxford/AstraZeneca) and 3 months after a 5th dose of Comirnaty Bivalent Original/Omicron BA.4/BA.5 vaccine (Pfizer-BioNTech). The ChAdOx1-S vaccination-induced antibodies neutralized efficiently the ancestral D614G and BA.4/5 variants, but to a much lesser extent the XBB.1.5, XBB.1.16, and EG.5.1 variants. The results showed similar neutralization titers between XBB.1.16 and EG.5.1 and were lower compared to XBB.1.5. Sera from the same individuals boosted with the bivalent mRNA vaccine contained higher neutralizing antibody titers, providing a better cross-protection against Omicron XBB.1.5, XBB.1.16 and EG.5.1 variants. Previous history of infection during the epidemiological waves of BA.1/BA.2 and BA.4/BA.5, poorly enhanced neutralization activity of serum samples against XBBs and EG.5.1 variants. Our data highlight the continued immune evasion of recent Omicron subvariants and support the booster administration of BA.4/5 bivalent vaccine, as a continuous strategy of updating future vaccine booster doses to match newly emerged SARS-CoV-2 variants.

Antibiotic resistance has become more and more widespread over the recent decades, becoming a major global health problem and causing colistin to be increasingly used as an antibiotic of last resort. Acinetobacter baumannii, an opportunistic pathogen that has rapidly evolved into a superbug exhibiting multidrug-resistant phenotypes, is responsible for a large number of hospital infection outbreaks. With the intensive use of colistin, A. baumannii resistance to colistin has been found to increase significantly. In previous work, we identified a deflazacort derivative, PYED-1 (pregnadiene-11-hydroxy-16,17-epoxy-3,20-dione-1), which exhibits either direct-acting or synergistic activity against Gram-positive and Gram-negative species and Candida spp., including A. baumannii. The aim of this study was to evaluate the antibacterial activity of PYED-1 in combination with colistin against both A. baumannii planktonic and sessile cells. Furthermore, the cytotoxicity of PYED-1 with and without colistin was assessed. Our results show that PYED-1 and colistin can act synergistically to produce a strong antimicrobial effect against multidrug-resistant populations of A. baumannii. Interestingly, our data reveal that PYED-1 is able to restore the efficacy of colistin against all colistin-resistant A. baumannii isolates. This drug combination could achieve a much stronger antimicrobial effect than colistin while using a much smaller dosage of the drugs, additionally eliminating the toxicity and resistance issues associated with the use of colistin.

IntroductionConsidering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information.MethodsWe used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. ResultsWe found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity.DiscussionThis peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.

ABSTRACT BACKGROUND: Knowledge of clinical and laboratory differences between chromosomal and undefined causes aids etiological research on non-obstructive azoospermia. OBJECTIVE: Compare clinical and laboratory differences between men with non-obstructive azoospermia due to chromosomal anomalies versus undefined causes DESIGN AND SETTING: A cross-sectional retrospective study conducted at a public university hospital in Campinas (Brazil) METHODS: All men aged 20–40 years with non-obstructive azoospermia were included in the analysis. RESULTS: The 107 cases included 14 with Klinefelter syndrome (KS) (13%), 1 with mosaic KS, 4 with sex development disorders (2 testicular XX, 1 NR5A1 gene mutation, and 1 mild androgen insensitivity syndrome) (4%), 9 with other non-obstructive azoospermia etiologies (8%), and 79 with undefined causes. The 22 chromosomal anomaly cases (14 KS, 1 mosaic KS, 2 testicular XX, 4 sex chromosome anomalies, and 1 autosomal anomaly) were compared with the 79 undefined cause cases. The KS group had lower average testicular volume, shorter penile length, and lower total testosterone levels but greater height, arm span, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and gynecomastia frequency (absent in the undefined group and affecting more than half of the KS group). Patients with testicular XX DSD had LH, FSH, and penile length data intermediate between the KS and undefined cause groups, testicular volume similar to the KS group, and other data similar to the undefined group. CONCLUSION: Clinical and laboratory data differentiate men with non-obstructive azoospermia and chromosomal anomalies, particularly KS and testicular XX, from those with undefined causes or other chromosomal anomalies.

Background APOL1 high-risk genotypes (HRG) are associated with increased risk of kidney disease in individuals of African ancestry. We analyzed the effects of APOL1 risk variants on an ethnically diverse Brazilian pediatric nephrotic syndrome (NS) cohort. Methods Multicenter study including 318 NS patients, categorized as progressors to advanced CKD [estimated glomerular filtration rate (eGFR)] < 30 mL/min/1.73 m.sup.2] and slow/non-progressors (eGFR 30 mL/min/1.73 m.sup.2 through the study). We employed Cox regression with progression time as the outcome and APOL1 genotype as the independent variable. We tested this association in the entire cohort and three subgroups; (1) focal segmental glomerulosclerosis (FSGS), (2) steroid-resistant NS (SRNS), and (3) those who underwent kidney biopsy. Results Nineteen patients (6%) had an HRG. Of these, 47% were self-reported White. Patients with HRG manifested NS at older ages and presented higher frequencies of FSGS and SRNS. HRG patients progressed to advanced CKD more often than low-risk-genotype (LRG) children in the whole NS cohort (p = 0.001) and the three subgroups. In SRNS and biopsied patients, a single risk variant was associated with trends of higher CKD progression risk. Conclusions Novel discoveries include a substantial prevalence of HRG among patients self-reported White, worse kidney outcomes in HRG versus LRG children in the FSGS subgroup, and a trend of higher CKD progression risk associated with a single risk variant in the SRNS cohort. These findings suggest APOL1-associated NS extends beyond patients self-reported non-White, the HRG effect is independent of FSGS, and a single risk variant may have a detrimental impact in children with NS., Author(s): Andreia Watanabe [sup.1] [sup.2] , Mara Sanches Guaragna [sup.3] , Vera Maria Santoro Belangero [sup.4] , Fernanda Maria Serafim Casimiro [sup.5] , João Bosco Pesquero [sup.5] , Luciana de [...]

Abstract The risk of contamination and dissemination by SARS-CoV-2 has a strong link with nasal, oral and pharyngeal cavities. Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients infected with SARS-CoV-2. The present two-arm study evaluated in vitro the antiviral activity and cytotoxicity of APD. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19. All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n = 20) or nonactive mouthwash (control group NAM/n = 21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge. Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS). The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death were also evaluated. The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity. Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM group (7 days) (p = 0.0314). Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM group needed ICU care, and 50% of this ICU subgroup passed way, p = 0.0207). This study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use of APD in a mouthwash as an adjuvant the hospital COVID-19 treatment presented no contraindication and reduced the hospital stay period. Trial registration: The clinical study was registered at REBEC—Brazilian Clinical Trial Register (RBR-58ftdj).

This article investigated whether the number of supervised students (masters and doctors/PhD) per professor impacts in the average number of periodic documents per student, and it evaluated the contributions to the production of scientific knowledge for the area of Science Education in the context of the Programa de Pós-Graduação em Educação em Ciências: Química da Vida e Saúde-PPGQVS (Universidade Federal do Rio Grande do Sul, Universidade Federal de Santa Maria, Universidade Federal do Rio Grande, and Universidade Federal do Pampa), from 2013 to 2019. The theoretical framework discusses the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Evaluation System in the area of Teaching and Education in Science in Brazil. It is a descriptive study, with a qualitative and quantitative approach, which uses mixed analysis techniques: bibliometrics and scientometrics indicators and Content Analysis (Bardin). Data collection took place on the Sucupira Platform and on the periodical’s website. As a results, it was identified that the average number of documents per student is not affected by the number of students who have their professor. The most researched topics were “Science Teaching” (26.0%), “Teacher Training” (24.3%) and “Educational Policies” (15.7%). Based on the training of masters and doctors along with the production and dissemination of scientific knowledge, the contribution of the PPGQVS to the area of Science Education in the country becomes evident.

Abstract Introduction: Stroke is a complication that causes considerable morbidity and mortality during the heart surgery postoperative period (incidence: 1.3 to 5%; mortality: 13 to 41%). Models for assessing the risk of stroke after heart surgery have been proposed, but most of them do not evaluate postoperative morbidity. The aim of this study was to develop a risk score for postoperative stroke in patients who undergo heart surgery with cardiopulmonary bypass. Methods: A cohort study was conducted with data from 4,862 patients who underwent surgery from 1996 to 2016. Logistic regression was used to assess relationships between risk factors and stroke. Data from 3,258 patients were used to construct the model. The model’s performance was then validated using data from the remainder of the patients (n=1,604). The model’s accuracy was tested using the area under the receiver operating characteristic (ROC) curve. Results: The prevalence of stroke during the postoperative period was 3% (n=149); 59% of the patients who exhibited this outcome were male, 51% were aged ≥ 66 years, and 31.5% of the patients died. The variables that remained as independent predictors of the outcome after multivariate analysis were advanced age, urgent/emergency surgery, peripheral arterial occlusive disease, history of cerebrovascular disease, and cardiopulmonary bypass time ≥ 110 minutes. The area under the ROC curve was 0.71 (95% confidence interval 0.66 - 0.75). Conclusion: We were able to develop a risk score for stroke after heart surgery. This score classifies patients as low, medium, high, or very high risk of a surgery-related stroke.

A notorious close connection between cinema and architecture exists, as between cinematography and literature, however we are convinced that architecture plays a central role in this context. These topics are easily identified in Alfred Hitchcock’s vast filmography, which shows that architecture is fundamental in order to create the atmosphere the director wishes to obtain to infuse further emotions to the story. Hitchcock through the editing, the shots and the course of actions provides the movie with what lacks in the conventional narrative of the novel the movie itself is taken. The director manages to enhance the audience’s emotions especially through the expressive help of the architectures that frame the story.

There are controversies regarding the impact of sex on mortality and postoperative complications in patients undergoing on-pump coronary artery bypass grafting (CABG), although some studies demonstrate comparable outcomes. This study sought to evaluate sex differences regarding risk factors associated with hospital mortality and postoperative clinical outcomes among patients undergoing isolated on-pump CABG. We conducted a retrospective observational cohort study of patients who underwent isolated on-pump CABG from January 1996 to January 2020. Patients were divided into two groups (male and female) and compared regarding preoperative characteristics, surgical technical variables, and in-hospital outcomes. All-cause mortality between groups was compared using logistic regression. Risk factors for mortality, along with their respective odds ratios (OR), were separately assessed using a logistic regression model with p-values for interaction. We analyzed 4,882 patients, of whom 31.6% were female. Women exhibited a higher prevalence of age >75 years (12.2% vs 8.3%, p<0.001), obesity (22.6% vs 11.5%, p<0.001), diabetes (41.6% vs 32.2%, p<0.001), hypertension (85.2% vs 73.5%, p<0.001), and NYHA functional classes 3 and 4 (16.2% vs 11.2%, p<0.001) compared to men. Use of the mammary artery for revascularization was less frequent among women (73.8% vs 79.9%, p<0.001), who also received fewer saphenous vein grafts (2.17 vs 2.27, p = 0.002). A history of previous or recent myocardial infarction (MI) had an impact on women's mortality, unlike in men (OR 1.61 vs 0.94, p = 0.014; OR 1.86 vs 0.99, p = 0.015, respectively). After adjusting for several risk factors, mortality was found to be comparable between men and women, with an OR of 1.20 (95% CI 0.94–1.53, p = 0.129). In conclusion, female patients undergoing isolated on-pump CABG presented with a higher number of comorbidities. Previous and recent MI were associated with higher mortality only in women. In this cohort analysis, female gender was not identified as an independent risk factor for outcome after CABG. [ABSTRACT FROM AUTHOR]

Background:DHX37 is an autosomal gene responsible for encoding a helicase from the DExD/H-box family that plays an essential role in ribosome biogenesis. Variants in this gene were previously reported in two different phenotypes: neurodevelopmental disorders and disorders/differences of sex development (DSD). Particularly for the DSD group, variants were mainly reported associated with gonadal dysgenesis and testicular regression syndrome. Summary: Focusing specifically in the DSD group, we revised the 21 DHX37 variants described across a total of 55 cases published in the literature so far. We summarized the most important clinical and molecular features of all cases, trying to have a better comprehensiveness about this gene in the sexual development. Key Messages: The trick question regarding DHX37 is how a helicase involved in basic cell function could have a specific role in testis development. Little is known about the impact of DHX37 variants in DSD individuals. Nevertheless, current research strongly suggests that DHX37 is involved in the male sex development pathway, particularly in testis determination and maintenance. This is evidenced by the predominant assignment of affected individuals as males and the presence of Wolffian structures in most of the cases. Advancements in molecular techniques, such as the generation of induced pluripotent stem cells and the digenic inheritance for DHX37 cases, are also addressed in this paper. This represents the first comprehensive review of all DHX37 variants published in the literature to date. [ABSTRACT FROM AUTHOR]

An organolithium reagent containing a 5,6-dihydro-1,4-dithiin moiety has been herein used as homologating agent to build up a fully protected divinylcarbinol by two different synthetic procedures, respectively, based on a step-by-step approach or a tandem process. The resulting molecule contains two double bonds masked by two dithiodimethylene bridges that can be stereoselectively removed to give a E,E- or Z,Z-configured divinylcarbinol. These products could then be conveniently functionalized, for example, with hydroxyl or amino functions, for the construction of the skeleton of more complex systems. [ABSTRACT FROM AUTHOR]

The reagent system based on the combined use of Et3SiH/I2 acts as an efficient N-glycosidation promoter for the synthesis of natural and sugar-modified nucleosides. An analysis of reaction stereoselectivity in the absence of C2-positioned stereodirecting groups revealed high selectivity with six-membered substrates, depending on the nucleophilic character of the nucleobase or based on anomerization reactions. The synthetic utility of the Et3SiH/I2-mediated N-glycosidation reaction was highlighted by its use in the synthesis of the investigational drug apricitabine. [ABSTRACT FROM AUTHOR]

Reliable serological tests for the detection of SARS-CoV-2 antibodies among infected or vaccinated individuals are important for epidemiological and clinical studies. Low-cost approaches easily adaptable to high throughput screenings, such as Enzyme-Linked Immunosorbent Assays (ELISA) or electrochemiluminescence immunoassay (ECLIA), can be readily validated using different SARS-CoV-2 antigens. A total of 1,119 serum samples collected between March and July of 2020 from health employees and visitors to the University Hospital at the University of São Paulo were screened with the Elecsys® Anti-SARS-CoV-2 immunoassay (Elecsys) (Roche Diagnostics) and three in-house ELISAs that are based on different antigens: the Nucleoprotein (N-ELISA), the Receptor Binding Domain (RBD-ELISA), and a portion of the S1 protein (ΔS1-ELISA). Virus neutralization test (CPE-VNT) was used as the gold standard to validate the serological assays. We observed high sensitivity and specificity values with the Elecsys (96.92% and 98.78%, respectively) and N-ELISA (93.94% and 94.40%, respectively), compared with RBD-ELISA (90.91% sensitivity and 88.80% specificity) and the ΔS1-ELISA (77.27% sensitivity and 76% specificity). The Elecsys® proved to be a reliable SARS-CoV-2 serological test. Similarly, the recombinant SARS-CoV-2 N protein displayed good performance in the ELISA tests. The availability of reliable diagnostic tests is critical for the precise determination of infection rates, particularly in countries with high SARS-CoV-2 infection rates, such as Brazil. Collectively, our results indicate that the development and validation of new serological tests based on recombinant proteins may provide new alternatives for the SARS-CoV-2 diagnostic market.

Objective: Steroid measurement is a challenge in pediatric endocrinology. Currently, liquid chromatography with tandem mass spectrometry (LC-MS/MS) is considered a gold standard for this purpose. The aim of this study was to co mpare both LC-MS/MS and immunoassay (IA) for androgens before and after human recom binant chorionic gonadotropin (rhCG) stimulus in children with 46,XY disorders o f sex development (DSD). Methods: Nineteen patients with 46,XY DSD were evaluated; all of them w ere prepubertal and non-gonadectomized. Testosterone, dihydrotestosterone (DHT), DHEA and androstenedione were measured by IA and LC-MS/MS before and 7 d ays after rhCG injection. The correlation between IA and LC-MS/MS was analyzed by the intraclass correlation coefficient (ICC) and Spearman’s rank correlation coe fficient (SCC). For concordance analysis the Passing and Bablok (PB) regression and the Bland and Altman (BA) method were used. Results: Testosterone showed excellent correlation (ICC = 0.960 and SCC = 0.964); DHT showed insignificant and moderate correlations as indicated by I CC (0.222) and SCC (0.631), respectively; DHEA showed moderate correlation (ICC = 0.585 and SCC = 0.716); and androstenedione had poor and moderate correlations in ICC ( 0.363) and SCC (0.735), respectively. Using the PB method, all hormones showed a linear correlation, but proportional and systematic concordance errors were detected fo r androstenedione, systematic errors for testosterone and no errors for DHEA and D HT. By the BA method, there was a trend of IA to overestimate testosterone and andros tenedione and underestimate DHEA and DHT when compared to LC-MS/MS. Conclusion: Traditional IA should be replaced by LC-MS/MS for the androgen s measurement in prepubertal children whenever is possible.

Abstract BACKGROUND: Because normal male sexual differentiation is more complex than normal female sexual differentiation, there are more cases of disorders of sex development (DSDs) with 46,XY karyotype that have unclear etiology. However, Leydig and Sertoli cell markers are rarely used in distinguishing such individuals. OBJECTIVES: To evaluate the function of Leydig and Sertoli cells in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion. STUDY DESIGN AND SETTING: Case-control study with 77 patients, including eight with partial androgen insensitivity syndrome, eight with 5α-reductase deficiency type 2 (5ARD2) and 19 with idiopathic 46,XY DSD, and 42 healthy controls, from the Interdisciplinary Study Group for Sex Determination and Differentiation (GIEDDS), at the State University of Campinas (UNICAMP), Campinas, Brazil. METHODS: Baseline levels of gonadotropins, anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), testosterone and dihydrotestosterone in cases, and AMH, inhibin B, and INSL3 levels in controls, were assessed. RESULTS: There was no significant difference in age between cases and controls (P = 0.595). AMH and inhibin B levels were significantly lower in cases than in controls (P = 0.031 and P < 0.001, respectively). INSL3 levels were significantly higher in cases than in controls (P = 0.003). Inhibin B levels were lower in 5ARD2 patients (P = 0.045) and idiopathic patients (P = 0.001), in separate comparisons with the controls. CONCLUSION: According to our findings, we can speculate that inhibin B levels may be used to differentiate among DSD cases.

Zika virus (ZIKV), a mosquito-borne pathogen, is an emerging arbovirus associated with sporadic symptomatic cases of great medical concern, particularly among pregnant women and newborns affected with neurological disorders. Serological diagnosis of ZIKV infection is still an unmet challenge due to the co-circulation of the dengue virus, which shares extensive sequence conservation of structural proteins leading to the generation of cross-reactive antibodies. In this study, we aimed to obtain tools for the development of improved serological tests for the detection of ZIKV infection. Polyclonal sera (pAb) and a monoclonal antibody (mAb 2F2) against a recombinant form of the ZIKV nonstructural protein 1 (NS1) allowed the identification of linear peptide epitopes of the NS1 protein. Based on these findings, six chemically synthesized peptides were tested both in dot blot and ELISA assays using convalescent sera collected from ZIKV-infected patients. Two of these peptides specifically detected the presence of ZIKV antibodies and proved to be candidates for the detection of ZIKV-infected subjects. The availability of these tools opens perspectives for the development of NS1-based serological tests with enhanced sensitivity regarding other flaviviruses.