Vaginal hysterectomy for the treatment of low-risk endometrial cancer: Surgical technique, costs, and perioperative and oncologic results.

OBJECTIVES: This study aimed to describe an operative technique for vaginal hysterectomy (VH) and assess the costs, perioperative, and oncological outcomes for this procedure when used in the treatment of patients with low-risk endometrial cancer (LREC). METHODS: A retrospective analysis of medical records was conducted on patients who underwent VH to treat precursor and invasive endometrial lesions between April 2019 and November 2021 at a single center in São Paulo, Brazil. RESULTS: Thirty-four patients met the inclusion criteria. The mean patient age was 61.9 years, and the mean body mass index (BMI) was 34. Obese patients (BMI ≥ 30) accounted for 77% of the sample. Preoperative functional capacity measures were Eastern Cooperative Oncology Group (ECOG) 0-1 and ECOG-2 for 91% and 9% of the patients, respectively. The mean operative time and length of hospital stay were 109 min and 1.2 days, respectively. Four patients had a conversion of the surgical route to laparotomy. No major intraoperative complications were observed. Patients who underwent surgical conversion had a greater uterine volume (227 versus 107 mL, p = 0.006) and longer operative time (177 versus 96 min, p = 0.001). The total cost associated with VH was, on average, US$ 2058.77 (R$ 10,925.91), representing 47% of the cost associated with non-vaginal routes. Twenty-eight patients received a definitive diagnosis of endometrial carcinoma; of these, three received adjuvant radiotherapy. The mean follow-up period was 34.6 months for the patients diagnosed with cancer. One case of disease recurrence occurred 16.6 months after surgery, with one death at 28.6 months of follow-up. CONCLUSIONS: These findings suggest that VH could be a feasible and cost-effective alternative for selected patients with LREC in low-resource settings.

Repeated pulmonary exposures to zinc ions enhance inflammatory responses to subsequent metal exposures.

AIM OF STUDY: Metal contaminants contribute to adverse human health effects via acute and chronic exposures. Acute metal exposures followed by prolonged secondary metal exposures may elicit exaggerated inflammatory responses in certain individuals. The aim of this study is to determine whether repeated pulmonary exposures to zinc chloride (ZnCl2) alter subsequent responses to zinc or cerium exposures. MATERIALS AND METHODS: Rats were intratracheally (IT) instilled with physiologic saline (n = 24) or 0.05 mg/kg ZnCl2 (n = 16) twice weekly for 4 weeks. Four days after last dosing, the saline group was divided into three subgroups, each IT-instilled with either saline, ZnCl2 or CeCl3 (both at 0.1 mg/kg). The ZnCl2 pre-instilled rats were divided into two subgroups, each instilled with 0.1 mg/kg ZnCl2 or CeCl3. Biomarkers of lung injury/inflammation were assessed in bronchoalveolar lavage (BAL) fluid collected 24 hours later. Oxidative stress was evaluated as total and reduced glutathione in BAL. RESULTS: Increases in inflammatory cells, LDH, albumin, leptin, MCP-1, IP-10, fractalkine, TNFα and RANTES were observed in rats instilled with multiple PBS and then with 0.1 mg/kg ZnCl2 and CeCl3. However, rats pre-exposed repeatedly to 0.05 mg/kg ZnCl2 and then challenged with 0.1 mg/kg ZnCl2 or CeCl3 showed even more eosinophils, lymphocytes, and increased concentrations of hemoglobin and MIP-1α. Significant reduction in GSH/GSSG ratios in BAL in response to all ZnCl2 or CeCl3 exposures indicated oxidative stress. CONCLUSION: Previous exposure to zinc ions increases responsiveness to subsequent exposures to zinc and cerium ions. These findings suggest enhanced sensitization possibly due to a reduction in antioxidant defenses.

Beneficial effects of N-acetylcysteine on hepatic oxidative stress in streptozotocin-induced diabetic rats.

Diabetes is one of the leading diseases worldwide and, thus, finding new therapeutic alternatives is essential. The development of non-alcoholic fatty liver disease is a notable diabetic complication. Therefore, antioxidant therapy became a leading topic in the world of diabetes research. The objective of this present study was to evaluate the effects of antioxidant N-acetylcysteine (NAC) administration on serum biochemical parameters and oxidative stress parameters in hepatic tissue of the diabetic rats. Thirty-two animals were divided in 4 groups (n = 8): G1, normal rats; G2, normal rats + NAC; G3, diabetic rats; and G4, diabetic rats + NAC. Diabetes was induced in diabetic groups through streptozotocin. NAC administration was effective in improving hyperglycemia and hypoinsulinemia, as well as reducing serum alanine-aminotransferase and urea, hepatic triglycerides accumulation, and oxidative stress biomarkers in the diabetic liver, as well as improving the activity of hepatic antioxidant enzymes. This effect was likely due to NAC's ability of restoring intracellular glutathione, an important compound for the antioxidant defense, as well as due to NAC's direct antioxidant properties. Thus, NAC administration was useful for reducing hepatic oxidative stress and decreased the deposit of triacylglycerols, minimizing diabetic hepatic damage, making it a promising therapeutic adjuvant in the future.

Frequency of Oral Lesions, Olfactory, and Gustatory Disorders and Xerostomia in Patients with COVID-19.

COVID-19, a respiratory illness with a global impact on millions, has recently been linked to manifestations affecting various bodily systems, including the oral cavity. Studies highlight oral issues, like ulcers, blisters, and white patches, alongside olfactory and gustatory dysfunction, influencing an individual's quality of life. In this context, our study aimed to assess the frequency of oral lesions, olfactory and gustatory disorders, and xerostomia resulting from COVID-19. An observational study was conducted with 414 patients to evaluate the frequency of oral symptoms resulting from COVID-19. Patients were diagnosed with mild symptoms and evaluated through clinical examination of the oral cavity and a questionnaire to assess functional alterations. The findings showed that 139 out of 414 patients presented clinical manifestations, with oral lesions being the most prevalent (19.1%), followed by gustatory disorders (18.1%), xerostomia (14.2%), and olfactory dysfunction (14%). The most prevalent oral lesions were ulcerations (n = 51), candidiasis (n = 8), and erythema or red plaques (n = 7). Unfortunately, 50 (12.1%) patients died during this study. Therefore, oral lesions, olfactory and gustatory dysfunctions, and xerostomia are common symptoms associated with COVID-19.

IL17A and IL17RA gene polymorphisms in Fanconi anemia.

Fanconi anemia is a rare autosomal recessive disease. In this disease, cytokine pathways can induce the bone marrow failure that is observed in individuals with Fanconi anemia. Interleukin IL-17 exhibits a protective effect in organisms because it induces neutrophil recruitment and shows a pathological role in several models of autoimmune diseases, periodontal disease, cancer, allograft rejection, and graft versus host disease. Polymorphisms in the IL17A and IL17RA genes were evaluated from DNA in saliva, comparing individuals with or without Fanconi anemia, using models of genotypic transmission (additive, dominant, and recessive). Polymorphisms in the IL17A and IL17RA genes (rs2241044 [C allele], rs879577 [C allele], rs9606615 [T allele], and rs2241043 [C allele]) were risk factors for developing Fanconi anemia. We also performed an analysis of gene markers with clinical variables in the Fanconi group. Polymorphisms in the IL17A gene (rs3819025 [A allele] and rs2275913 [G allele], respectively) were associated with an age of less than 20 years (p = 0.026; RP 0.65) and the female sex (p = 0.043; RP 0.88). The IL17RA gene was also associated with age and the presence of leukoplakia (a potentially malignant oral disorder). An age of less than 20 years was associated with rs917864 (T allele; p = 0.036; RP 0.67). The presence of leukoplakia was associated with rs17606615 (T allele; p = 0.042; RP 0.47). To our knowledge, this is the first study that associates IL17A and IL17RA gene polymorphisms with Fanconi anemia and examines rs2241044 polymorphisms in scientific literature thus far.

Sperm banking for male cancer patients: social and semen profiles.

PURPOSE: Report the characteristics of cryopreserved semen from a cohort of male cancer patients, attitudes towards cryopreservation and outcomes of semen samples based on a 12-year cryopreservation program. MATERIAL AND METHODS: Data from 98 male cancer patients whose sperm samples were banked were evaluated. Demographic parameters, semen characteristics, destination of sperm banked samples and questionnaires answered by the patients regarding cryopreservation time were evaluated. RESULTS: The cancer diagnoses were testicle (56.1%), prostate (15.3%), Hodgkin's lymphomas (9.2%), non-Hodgkin's lymphomas (7.1%), leukemia (3.1%) and other malignancies (9.2%). The patients with testicular cancer presented lower sperm concentration (p < 0.001); however, there were no differences with the percentage of normozoospermic patients among cancer type groups (p = 0.185). A shorter time between cancer diagnosis and sperm banking was observed for testicular and prostate cancer patients (p < 0.001). Most of the patients (89.5%) favored sperm banking as a fertility preservation method. CONCLUSIONS: Although less than 20% of banked sperm samples were disposed of, the majority of patients related sperm banking with safe for fertility preservation. Our results show that all male cancer patients of reproductive age facing cancer treatment could be offered sperm banking.

Fate of Barium Sulfate Nanoparticles Deposited in the Lungs of Rats.

We have shown that barium [from BaSO4 nanoparticles (NPs)] was cleared from the lungs faster than other poorly soluble NPs and translocated mostly to bone. We now studied barium biokinetics in rats during Study 1: two-year inhalation exposure to 50 mg/m3 BaSO4 NP aerosols, and Study 2: single intratracheal (IT) instillation of increasing doses of BaSO4 NPs or BaCl2. Study 1 showed that lung barium content measured by inductively coupled plasma mass spectrometry increased during 360 days of BaSO4 NP aerosol exposures. An equilibrium was established from that time until 2 years. Barium concentrations in BaSO4-exposed animals were in the order (lungs > lymph nodes > hard bone > bone marrow > liver). In Study 2, there was an increase in lung barium post-IT instillation of BaSO4 NPs while barium from BaCl2 was mostly cleared by day 28. Transmission electron microscopy showed intact BaSO4 NPs in alveolar macrophages and type II epithelial cells, and in tracheobronchial lymph nodes. Using stimulated Raman scattering microscopy, specific BaSO4 Raman spectra were detected in BaSO4 NP-instilled lungs and not in other organs. Thus, we posit that barium from BaSO4 NPs translocates from the lungs mainly after dissolution. Barium ions are then incorporated mostly into the bone and other organs.

Behavioral adjustment to asymmetric reward availability among children with and without ADHD: effects of past and current reinforcement contingencies.

Altered reinforcement sensitivity is hypothesized to underlie symptoms of attention deficit hyperactivity disorder (ADHD). Here we evaluate the behavioral sensitivity of Brazilian children with and without ADHD to a change in reward availability. Forty typically developing children and 32 diagnosed with DSM-IV ADHD completed a signal-detection task in which correct discriminations between two stimuli were associated with different frequencies of reinforcement. The response alternative associated with the higher rate of reinforcement switched, without warning, after 30 rewards were delivered. The task continued until another 30 rewards were delivered. Both groups of children developed a response bias toward the initially more frequently reinforced alternative. This effect was larger in the control group. The response allocation of the two groups changed following the shift in reward availability. Over time the ADHD group developed a significant response bias toward the now more frequently reinforced alternative. In contrast, the bias of the control group stayed near zero after an initial decline following the contingency change. The overall shift in bias was similar for the two groups. The behavior of both groups of children was sensitive to the asymmetric reward distribution and to the change in reward availability. Subtle group differences in response patterns emerged, possibly reflecting differences in the time frame of reward effects and sensitivity to reward exposure.

IL17A and IL17RA gene polymorphisms in Fanconi anemia

Abstract Fanconi anemia is a rare autosomal recessive disease. In this disease, cytokine pathways can induce the bone marrow failure that is observed in individuals with Fanconi anemia. Interleukin IL-17 exhibits a protective effect in organisms because it induces neutrophil recruitment and shows a pathological role in several models of autoimmune diseases, periodontal disease, cancer, allograft rejection, and graft versus host disease. Polymorphisms in the IL17A and IL17RA genes were evaluated from DNA in saliva, comparing individuals with or without Fanconi anemia, using models of genotypic transmission (additive, dominant, and recessive). Polymorphisms in the IL17A and IL17RA genes (rs2241044 [C allele], rs879577 [C allele], rs9606615 [T allele], and rs2241043 [C allele]) were risk factors for developing Fanconi anemia. We also performed an analysis of gene markers with clinical variables in the Fanconi group. Polymorphisms in the IL17A gene (rs3819025 [A allele] and rs2275913 [G allele], respectively) were associated with an age of less than 20 years (p = 0.026; RP 0.65) and the female sex (p = 0.043; RP 0.88). The IL17RA gene was also associated with age and the presence of leukoplakia (a potentially malignant oral disorder). An age of less than 20 years was associated with rs917864 (T allele; p = 0.036; RP 0.67). The presence of leukoplakia was associated with rs17606615 (T allele; p = 0.042; RP 0.47). To our knowledge, this is the first study that associates IL17A and IL17RA gene polymorphisms with Fanconi anemia and examines rs2241044 polymorphisms in scientific literature thus far.

Screening for Chemical Toxicity Using Cryopreserved Precision Cut Lung Slices.

To assess chemical toxicity, current high throughput screening (HTS) assays rely primarily on in vitro measurements using cultured cells. Responses frequently differ from in vivo results due to the lack of physical and humoral interactions provided by the extracellular matrix, cell-cell interactions, and other molecular components of the native organ. To more accurately reproduce organ complexity in HTS, we developed an organotypic assay using the cryopreserved precision cut lung slice (PCLS) from rats and mice. Compared to the never-frozen PCLS, their frozen-thawed counterpart slices showed viability or metabolic activity that is decreased to an extent comparable to that observed in other cryopreserved cells and tissues, but shows no differences in further changes in cell viability, mitochondrial integrity, and glutathione activity in response to the model toxin zinc chloride (ZnCl2). Notably, these measurements were successfully miniaturized so as to establish HTS capacity in a 96-well plate format. Finally, PCLS responses correlated with common markers of lung injury measured in lavage fluid from rats intratracheally instilled with ZnCl2. In summary, we establish that the cryopreserved PCLS is a feasible approach for HTS investigations in predictive toxicology.

Zona pellucida birefringence in in vivo and in vitro matured oocytes.

OBJECTIVE: To evaluate zona pellucida birefringence (ZPB) in immature and mature oocytes collected after controlled ovarian stimulation and to assess the influence of ZPB on oocyte development. DESIGN: Prospective study. SETTING(S): Private assisted reproduction centre. PATIENT(S): Thirty patients undergoing intracytoplasmic sperm injection. INTERVENTION(S): The ZPB of mature and immature oocytes was evaluated using a polarization imaging software module, and the oocytes were classified as high birefringence (HB) or low birefringence. MAIN OUTCOME MEASURE(S): The ZPB of in vivo and in vitro matured oocytes and its influence on spontaneous nuclear maturation in vitro, fertilization, and embryo quality. RESULT(S): The percentage of HB oocytes was higher in immature than in mature oocytes (40.1 vs. 23.6%). Among immature oocytes, an increased percentage of HB in prophase-I stage oocytes compared to metaphase I stage oocytes was also observed (50.7 vs. 25.0%). However, the percentage of HB oocytes did not change when comparing oocytes before and after in vitro maturation for both prophase I and metaphase I oocytes. No influence of ZPB was observed on the spontaneous in vitro maturation potential. Exclusively for metaphase II retrieved oocytes, a positive influence of ZPB on fertilization (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.27-2.49) and embryo quality (OR, 2.28; 95% CI, 1.04-4.99) was noted. CONCLUSION(S): ZPB may be a useful tool to predict embryo quality for metaphase-II oocytes. Moreover, the completion of nuclear changes in the production of metaphase-II oocytes in vitro may not reflect their molecular maturity.

[Safe gametes acquisition through association of seminal processing techniques with HIV serodiscordant couples]. / Obtenção de gametas seguros por meio de associação de técnicas de processamento seminal para casais sorodiscordantes para HIV.

PURPOSE: the propose of this study was to analyze the clinical and laboratorial parameters of patients submitted to human assisted reproduction techniques with association of sperm processing techniques, in order to remove virus particles from semen samples of couples in which men was infected by human immunodeficiency virus (HIV). METHODS: assessed were 11 intracytoplasmatic sperm injection (ICSI) cycles from couples whose men were HIV seropositive (HIV Group), and 35 cycles in which semen donors' samples were used in ICSI procedures (Control Group). Semen samples from Control Group were submitted to routine semen analysis, sperm wash and cryopreservation. The man from HIV Group received previous antibiotic therapy; the semen samples were analyzed routinely and prepared by sperm wash and density gradient method before cryopreservation. Those samples were evaluated to viral load and ICSI was performed when no HIV was detected. RESULTS: with regards to semen analysis, the groups were similar to sperm concentration and progressive motility. Nevertheless, the percentage of sperm with normal morphology were higher on Control Group (14.3%) than HIV (5.8%; p=0.002). On embryo parameters assessment, the normal fertilization (CT: 74.7% and HIV: 71.7; p=0.838, respectively) and good embryos rate (CT: 42.4% and HIV: 65.1%; p=0.312, respectively) were comparable. On the other hand, the Control Group presented better clinic results than HIV Group (ongoing pregnancy rate: 52.9% versus 12.5%; p=0.054, and implantation rate: 42.6 versus 10.4%; p=0.059, respectively), however the differences were not statistically significant. After delivery, no seroconversion was observed on mother and child. CONCLUSIONS: the association of sperm processing techniques in order to remove HIV from semen samples does not influence in laboratorial parameters of assisted reproduction techniques cycles. On the other hand, it has been demonstrated excellent results getting safety gametes to serodiscordant couples.

Sperm banking for male cancer patients: social and semen profiles

PURPOSE: Report the characteristics of cryopreserved semen from a cohort of male cancer patients, attitudes towards cryopreservation and outcomes of semen samples based on a 12-year cryopreservation program. MATERIAL AND METHODS: Data from 98 male cancer patients whose sperm samples were banked were evaluated. Demographic parameters, semen characteristics, destination of sperm banked samples and questionnaires answered by the patients regarding cryopreservation time were evaluated. RESULTS: The cancer diagnoses were testicle (56.1 percent), prostate (15.3 percent), Hodgkin’s lymphomas (9.2 percent), non-Hodgkin’s lymphomas (7.1 percent), leukemia (3.1 percent) and other malignancies (9.2 percent). The patients with testicular cancer presented lower sperm concentration (p < 0.001); however, there were no differences with the percentage of normozoospermic patients among cancer type groups (p = 0.185). A shorter time between cancer diagnosis and sperm banking was observed for testicular and prostate cancer patients (p < 0.001). Most of the patients (89.5 percent) favored sperm banking as a fertility preservation method. CONCLUSIONS: Although less than 20 percent of banked sperm samples were disposed of, the majority of patients related sperm banking with safe for fertility preservation. Our results show that all male cancer patients of reproductive age facing cancer treatment could be offered sperm banking.

Obtenção de gametas seguros por meio de associação de técnicas de processamento seminal para casais sorodiscordantes para HIV / Safe gametes acquisition through association of seminal processing techniques with HIV serodiscordant couples

OBJETIVO: o objetivo deste estudo foi avaliar os parâmetros laboratoriais e clínicos de pacientes submetidos à reprodução humana assistida, associando técnicas de processamento seminal para eliminação de partículas virais da amostra de sêmen em casais nos quais o homem é infectado pelo vírus da imunodeficiência humana adquirida (HIV). MÉTODOS: foram avaliados 11 ciclos de injeção intracitoplasmática de espermatozóide (ICSI) realizados em casais nos quais os homens eram infectados pelo HIV (Grupo HIV), e 35 ciclos de ICSI nos quais se utilizaram espermatozóides doados (Grupo Controle). As amostras de sêmen dos doadores foram submetidas à análise seminal completa, processamento seminal (lavagem) e criopreservação. Os homens do Grupo HIV receberam antibioticoterapia prévia e realizou-se análise seminal, lavagem e gradiente descontínuo de densidade antes da criopreservação. As amostras foram avaliadas para carga viral e a ICSI foi realizada quando não houve detecção do HIV. RESULTADOS: quanto aos resultados da análise seminal, os grupos se mostraram comparáveis em relação à concentração e motilidade progressiva dos espermatozóides. Entretanto, a porcentagem de espermatozóides morfologicamente normais foi maior no Grupo Controle (14,3 por cento) comparado ao HIV (5,8 por cento; p=0,002). Na avaliação dos parâmetros embrionários, as taxas de fertilização normal (Controle: 74,7 por cento e HIV: 71,7; p=0,838) e de bons embriões (Controle: 42,4 por cento e HIV: 65,1 por cento; p=0,312) foram semelhantes. Por outro lado, o Grupo Controle apresentou melhores resultados clínicos que o HIV (gestação continuada: 52,9 e 12,5 por cento; p=0,054; implantação: 42,6 e 10,4 por cento; p=0,059, respectivamente), apesar de as diferenças não serem estatisticamente significantes. Após o nascimento, não houve soroconversão das mães e das crianças nascidas. CONCLUSÕES: a associação de técnicas de processamento seminal para eliminação do HIV de amostras...

PURPOSE: the propose of this study was to analyze the clinical and laboratorial parameters of patients submitted to human assisted reproduction techniques with association of sperm processing techniques, in order to remove virus particles from semen samples of couples in which men was infected by human immunodeficiency virus (HIV). METHODS: it was assessed 11 intracytoplasmatic sperm injection (ICSI) cycles from couples whose men were HIV seropositive (HIV Group), and 35 cycles in which semen donors' samples were used in ICSI procedures (Control Group). Semen samples from Control Group were submitted to routine semen analysis, sperm wash and cryopreservation. The man from HIV Group received previous antibiotic therapy; the semen samples were analyzed routinely and prepared by sperm wash and density gradient method before cryopreservation. Those samples were evaluated to viral load and ICSI was performed when no HIV was detected. RESULTS: regards to semen analysis the groups were similar to sperm concentration and progressive motility. Nevertheless, the percentage of sperm with normal morphology were higher on Control Group (14.3 percent) than HIV (5.8 percent; p=0.002). On embryo parameters assessment, the normal fertilization (CT: 74.7 percent and HIV: 71.7; p=0.838, respectively) and good embryos rate (CT: 42.4 percent and HIV: 65.1 percent; p=0.312, respectively) were comparable. On the other hand, the Control Group presented better clinic results than HIV Group (ongoing pregnancy rate: 52.9 percent versus 12.5 percent; p=0.054, and implantation rate: 42.6 versus 10.4 percent; p=0.059, respectively), however the differences were not statistically significant. After delivery, no seroconversion was observed on mother and child. CONCLUSIONS: the association of sperm processing techniques in order to remove HIV from semen samples does not influence in laboratorial parameters of assisted reproduction techniques cycles. On the other hand, ...