Mapping of long interspersed element-1 (L1) insertions by TIPseq provides information about sub chromosomal genetic variation in human embryos.

PURPOSE: Retrotransposons play important roles during early development when they are transiently de-repressed during epigenetic reprogramming. Long interspersed element-1 (L1), the only autonomous retrotransposon in humans, comprises 17% of the human genome. We applied the Single Cell Transposon Insertion Profiling by Sequencing (scTIPseq) to characterize and map L1 insertions in human embryos. METHODS: Sixteen cryopreserved, genetically tested, human blastocysts, were accessed from consenting couples undergoing IVF at NYU Langone Fertility Center. Additionally, four trios (father, mother, and embryos) were also evaluated. scTIPseq was applied to map L1 insertions in all samples, using L1 locations reported in the 1000 Genomes as controls. RESULTS: Twenty-nine unknown and unique insertions were observed in the sixteen embryos. Most were intergenic; no insertions were located in exons or immediately upstream of genes. The location or number of unknown insertions did not differ between euploid and aneuploid embryos, suggesting they are not merely markers of aneuploidy. Rather, scTIPseq provides novel information about sub-chromosomal structural variation in human embryos. Trio analyses showed a parental origin of all L1 insertions in embryos. CONCLUSION: Several studies have measured L1 expression at different stages of development in mice, but this study for the first time reports unknown insertions in human embryos that were inherited from one parent, confirming no de novo L1 insertions occurred in parental germline or during embryogenesis. Since one-third of euploid embryo transfers fail, future studies would be useful for understanding whether these sub-chromosomal genetic variants or de novo L1 insertions affect embryo developmental potential.

Diagnosis support of major depressive disorder using event-related potentials during affective priming tasks.

Major Depressive Disorder (MDD) is a global problem. Currently, the most common diagnosis is based on criteria susceptible to the subjectivity of the patient and the clinician. A possible solution to this problem is to look for diagnostic biomarkers that can accurately and early detect this mental condition. Some researchers have focused on electroencephalogram (EEG) analysis to identify biomarkers. In this study we used a dataset composed of EEG recordings from 24 subjects with MDD and 29 healthy controls (HC), during the execution of affective priming tasks with three different emotional stimuli (images): fear, sadness, and happiness. We investigated abnormalities in depressed patients using a novel technique, by directly comparing Event-Related Potential (ERP) waveforms to find statistically significant differences between the MMD and HC groups. Compared to the control group (healthy subjects), we found out that for the emotions fear and happiness there is a decrease in cortical activity at temporal regions in MDD patients. Just the opposite, for the emotion sadness, an increase in MDD brain activity occurs in frontal and occipital regions. Our findings suggest that emotions regulate the attentional control of cognitive processing and are promising for clinical application in diagnosing patients with MDD more objectively.

CDH1 hypermethylation: a potential molecular pathway for invasiveness in glioblastoma.

Glioblastoma is the most aggressive central nervous system primary tumor. Prognosis is poor, mainly due to the malignant characteristics of the tumor, such as high cell proliferation and invasiveness. CDH1 hypermethylation is linked to the invasive potential in various cancer types, but its importance is still unknown in glioblastoma. In this context, the methylation status of CDH1 was analyzed using MSP-PCR (Methylation-specific Polymerase Chain Reaction) in glioblastoma (n = 34) and normal glial tissue samples (n = 11). CDH1 hypermethylation was found in 39.4% (13/34) of the tumor samples and none of the normal glial tissue, suggesting a relation between CDH1 hypermethylation and glioblastoma ( P = 0.0195). Finally, this study showed unprecedented information that could contribute to clarifying the molecular pathways involved in the invasiveness and aggressiveness of this type of cancer.

COVID-19 en sujetos de riesgo participantes en ensayos clínicos durante la pandemia en Argentina / COVID-19 in subjects at risk participating in clinical trials during the pandemic in Argentina

Resumen Introducción : Existe poca información sobre la pre sencia de COVID-19 en participantes de ensayos clínicos. El objetivo del estudio fue evaluar la tasa de infección acumulada por SARS-CoV-2 en esta población. Además, investigamos el riesgo, letalidad y mortalidad por CO VID-19. Métodos : Diseño observacional retrospectivo que incluyó adultos participantes en ensayos clínicos de intervención aprobados por nuestro comité de ética du rante los dos primeros años de la pandemia (31/3/2020 a 31/3/2022). Se excluyeron protocolos pediátricos, obser vacionales, de corta duración y con sujetos internados. Resultados : Se incluyeron 513 sujetos adultos que participaron en ensayos clínicos durante ese período de la pandemia por COVID-19. Los pacientes con CO VID-19 se caracterizaron por tener una edad de 59.7 ± 13.7 años (50% sexo femenino) y el 92% presentó riesgo incrementado de letalidad por COVID-19. La tasa acu mulada de COVID-19 fue de 9.74% (IC 95%: 7.32-12.64%) que se situó por debajo del 17% de la población de 60 a 69 años de la Argentina (p<0.0001). La tasa de letalidad por COVID-19 fue de 14% (IC 95%: 5.8-26.7), que se situó por encima del 2.45% de la población de 50 a 69 años de la Argentina (p<0.0001). Conclusión : La tasa de COVID-19 en los sujetos adultos participantes de ensayos clínicos estuvo por debajo de las cifras de la población argentina de simi lar edad. La tasa de letalidad estuvo por encima de las cifras poblacionales y se explica por el alto riesgo de esa población.

Abstract Introduction : There is little information on the pres ence of COVID-19 in clinical trial participants. The objec tive of the study was to evaluate the cumulative infec tion rate for SARS-CoV-2 in this population. Additionally, we investigated the risk, lethality, and mortality from COVID-19. Methods : The design was observational retrospective that included adult subjects participating in clinical intervention trials approved by our ethics committee during the first two years of the pandemic (March 31, 2020 to March 31, 2022). Pediatric, observational, short-term, and inpatient protocols were excluded. Results : We included 513 adult subjects who par ticipated in clinical trials during the first two years of the COVID-19 pandemic. Patients with COVID-19 were characterized as being 59.7 ± 13.7 years old (50% fe male), and 92% had an increased risk of fatality from COVID-19. The cumulative rate of COVID-19 was 9.74% (95% CI: 7.32-12.64%) and its confidence intervals were below 17% of the population aged 60 to 69 in Argentina (p<0.0001). The case fatality rate for COVID-19 was 14% (95% CI: 5.8%-26.7%) and its confidence intervals were above 2.45% of the population aged 50 to 69 in Argentina (p< 0.0001). Conclusion : The rate of COVID-19 in adult subjects participating in clinical trials was below the figures for the Argentine population of similar age. The fatality rate was above the population figures, and it is explained by the high risk of the population.

[COVID-19 in subjects at risk participating in clinical trials during the pandemic in Argentina]. / COVID-19 en sujetos de riesgo participantes en ensayos clínicos durante la pandemia en Argentina.

INTRODUCTION: There is little information on the presence of COVID-19 in clinical trial participants. The objective of the study was to evaluate the cumulative infection rate for SARS-CoV-2 in this population. Additionally, we investigated the risk, lethality, and mortality from COVID-19. METHODS: The design was observational retrospective that included adult subjects participating in clinical intervention trials approved by our ethics committee during the first two years of the pandemic (March 31, 2020 to March 31, 2022). Pediatric, observational, shortterm, and inpatient protocols were excluded. RESULTS: We included 513 adult subjects who participated in clinical trials during the first two years of the COVID-19 pandemic. Patients with COVID-19 were characterized as being 59.7 ± 13.7 years old (50% female), and 92% had an increased risk of fatality from COVID-19. The cumulative rate of COVID-19 was 9.74% (95% CI: 7.32-12.64%) and its confidence intervals were below 17% of the population aged 60 to 69 in Argentina (p< 0.0001). The case fatality rate for COVID-19 was 14% (95% CI: 5.8%-26.7%) and its confidence intervals were above 2.45% of the population aged 50 to 69 in Argentina (p< 0.0001). CONCLUSION: The rate of COVID-19 in adult subjects participating in clinical trials was below the figures for the Argentine population of similar age. The fatality rate was above the population figures, and it is explained by the high risk of the population.

Introducción: Existe poca información sobre la presencia de COVID-19 en participantes de ensayos clínicos. El objetivo del estudio fue evaluar la tasa de infección acumulada por SARS-CoV-2 en esta población. Además, investigamos el riesgo, letalidad y mortalidad por COVID-19. Métodos: Diseño observacional retrospectivo que incluyó adultos participantes en ensayos clínicos de intervención aprobados por nuestro comité de ética durante los dos primeros años de la pandemia (31/3/2020 a 31/3/2022). Se excluyeron protocolos pediátricos, observacionales, de corta duración y con sujetos internados. Resultados: Se incluyeron 513 sujetos adultos que participaron en ensayos clínicos durante ese período de la pandemia por COVID-19. Los pacientes con COVID-19 se caracterizaron por tener una edad de 59.7 ± 13.7 años (50% sexo femenino) y el 92% presentó riesgo incrementado de letalidad por COVID-19. La tasa acumulada de COVID-19 fue de 9.74% (IC 95%: 7.32-12.64%) que se situó por debajo del 17% de la población de 60 a 69 años de la Argentina (p<0.0001). La tasa de letalidad por COVID-19 fue de 14% (IC 95%: 5.8-26.7), que se situó por encima del 2.45% de la población de 50 a 69 años de la Argentina (p<0.0001). Conclusión: La tasa de COVID-19 en los sujetos adultos participantes de ensayos clínicos estuvo por debajo de las cifras de la población argentina de similar edad. La tasa de letalidad estuvo por encima de las cifras poblacionales y se explica por el alto riesgo de esa población.

COVID-19 and Nutrition: Focus on Chronic Kidney Disease.

Some chronic diseases, including chronic kidney disease (CKD), may be associated with poor outcomes, including a high rate of hospitalization and death after COVID-19 infection. In addition to the vaccination program, diet intervention is essential for boosting immunity and preventing complications. A healthy diet containing bioactive compounds may help mitigate inflammatory responses and oxidative stress caused by COVID-19. In this review, we discuss dietary interventions for mitigating COVID-19 complications, including in persons with CKD, which can worsen COVID-19 symptoms and its clinical outcomes, while diet may help patients with CKD to resist the ravages of COVID-19 by improving the immune system, modulating gut dysbiosis, mitigating COVID-19 complications, and reducing hospitalization and mortality. The concept of food as medicine, also known as culinary medicine, for patients with CKD can be extrapolated to COVID-19 infection because healthy foods and nutraceuticals have the potential to exert an important antiviral, anti-inflammatory, and antioxidant role.

Antiulcer mechanisms of the hydroalcoholic extract from Aztec marigolds' medicinal and edible flowers (Tagetes erecta L.).

The antiulcer mechanisms of the dry extract of T. erecta flowers (DETe) were studied here. The acute ulcers induced by acidified ethanol or indomethacin were reproduced in mice pretreated with DETe (3 - 300 mg/kg). The antiulcer activity of DETe was also verified in mice pretreated with NEM, L-NAME, indomethacin, or yohimbine. The antisecretory effect of DETe was verified in rats, and its anti-Helicobacter pylori activity was determined in vitro. DETe (300 mg/kg, p.o) reduced the ethanol- or indomethacin-induced ulcer by 49 and 93%, respectively. The pre-treatment with L-NAME, NEM or yohimbine abolished the gastroprotective effect of DETe. However, DETe did not change the volume, acidity, or peptic activity in rats and did not affect H. pylori. This study expands knowledge about the antiulcerogenic potential of DETe, evidencing the role of nitric oxide, non-protein sulfhydryl groups, α2 adrenergic receptors, and prostaglandins, but not antisecretory or anti-H. pylori properties.

The effect of rim-off deep lateral orbital decompression on the lateral rectus shape and oculomotor balance.

PURPOSE: The purpose of the study was to measure the effect of rim-off deep lateral decompression for Graves orbitopathy on the lateral rectus muscle path and oculomotor balance. METHODS: Retrospective analysis of the medical records and pre- and postoperative computed tomography scans of 34 orbits of 23 patients who underwent deep lateral decompression alone. The oculomotor balance of these 23 patients was measured with the alternate cover test and prisms before and after surgery. Bezier functions were used to measure the postoperative path of the lateral rectus in all decompressed orbits. RESULTS: Deep lateral decompression induced a curvilinear deformation of the lateral rectus. There was no significant correlation between the position of the point of maximum muscle displacement and the size of the residual lateral wall. The changes in the lateral rectus path had no adverse effects on the oculomotor balance of the patients. CONCLUSIONS: The location of the curvilinear deformation of the lateral rectus does not depend on the residual segment of the lateral wall. The changes of the lateral rectus path have no deleterious effect on the oculomotor balance.

Prevalence, Risk Factors and Diagnosis of Helminths in Thoroughbred Horses Kept at Training Centers in Rio de Janeiro, Brazil.

The aims of this study were to determine the prevalence of helminths in Thoroughbred horses in Rio de Janeiro; make correlations with risk factors for these infections; and compare the efficiency of three floatation solutions applied in the quantitative Mini-FLOTAC technique. Fecal samples from 520 horses were collected from six training centers between 2019 and 2021. These were subjected to the Mini-FLOTAC technique using three solutions: NaCl (density = 1.200 g/mL), ZnSO4 (1.350 g/mL) and ZnSO4 (1.200 g/mL); and also to qualitative techniques. Information on the horses' sex and age of horses was retrieved from the studbook; data on management from a questionnaire. The overall prevalence of intestinal parasites was 71.9%, with significant differences between training centers (P ≤ .05). On farm C, 87.7% of the samples presented strongylids and 38.7% had Parascaris spp., with the highest egg counts per gram of feces (EPG), of 358.33 and 40.41 respectively. Horses less than 3 years of age were about eight times more likely to be parasitized by strongylids and eleven times more likely to have EPG ≥500. The NaCl solution used in Mini-FLOTAC enabled recovery of the greatest number of samples with high EPG and reached the highest sensitivity values in the diagnosis when compared to the other solutions. Moreover, in the diagnoses, the levels of agreement between the results from the solutions used in Mini-FLOTAC were substantial. However, in estimating the EPG, full agreement between the results from the solutions used in Mini-FLOTAC was not obtained.

Myositis Ossificans of the Breast Mimicking Breast Cancer: A Case Report.

Myositis ossificans (MO) is an uncommon tumor characterized by a rapidly growing mass following a history of local trauma. Few cases of MO affecting the breast have been reported, and some were misdiagnosed as primary osteosarcoma of the breast or metaplastic breast carcinoma. The following case report presents a patient with a growing breast lump whose core biopsy result was suspicious for breast cancer. MO was diagnosed after analysis of the mastectomy specimen. This case highlights the importance of MO as a differential diagnosis of a growing soft-tissue mass after trauma to avoid unnecessary overtreatment. Keywords: Myositis Ossificans, Osteosarcoma, Breast Cancer, Mastectomy, Heterotopic Ossification © RSNA, 2023.

A pilot study of LINE-1 copy number and telomere length with aging in human sperm.

PURPOSE: Unlike other cells in the body, in sperm, telomere length (TL) increases with age. TL can regulate nearby genes, and the subtelomeric region is rich in retrotransposons. We hypothesized that age-related telomere lengthening in sperm might suppress Long Interspersed Element 1 (LINE-1/L1), the only competent retrotransposon in humans. METHODS: We measured L1 copy number (L1-CN) and sperm telomere length (STL) from young and older men to evaluate the relationship between age, TL and L1-CN. We also evaluated L1-CN and TL in individual sperm to determine whether these variables influence sperm morphology. STL was assayed by Multiplex quantitative polymerase chain reaction method (mmqPCR) and L1-CN by Quantitative polymerase chain reaction (qPCR). RESULTS: We found that STL increased, and L1-CN decreased significantly with paternal age. STL in normal single sperm was significantly higher than in abnormal sperm. L1-CN did not differ between normal and abnormal sperm. Furthermore, morphologically normal sperm have longer telomeres than abnormal sperm. CONCLUSIONS: Elongation of telomeres in the male germline could repress retrotransposition, which tends to increase with cellular aging. More studies in larger cohorts across a wide age span are needed to confirm our conclusions and explore their biological and clinical significance.

Transposon insertion profiling by sequencing (TIPseq) identifies novel LINE-1 insertions in human sperm.

PURPOSE: Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. Retrotransposons may perturb gene integrity or alter gene expression by altering regulatory regions in the genome. The germline employs a number of mechanisms, including cytosine methylation, to repress retrotransposon transcription throughout most of life. Demethylation during germ cell and early embryo development de-represses retrotransposons. Intriguingly, de novo genetic variation appearing in sperm has been implicated in a number of disorders in offspring, including autism spectrum disorder, schizophrenia, and bipolar disorder. We hypothesize that human sperm exhibit de novo retrotransposition and employ a new sequencing method, single cell transposon insertion profiling by sequencing (scTIPseq) to map them in small amounts of human sperm. METHODS: Cross-sectional case-control study of sperm samples (n=10 men; ages 32-55 years old) from consenting men undergoing IVF at NYU Langone Fertility Center. scTIPseq identified novel LINE-1 insertions in individual sperm and TIPseqHunter, a custom bioinformatics pipeline, compared the architecture of sperm LINE-1 to known LINE-1 insertions from the European database of Human specific LINE-1 (L1Hs) retrotransposon insertions (euL1db). RESULTS: scTIPseq identified 17 novel insertions in sperm. New insertions were mainly intergenic or intronic. Only one sample did not exhibit new insertions. The location or number of novel insertions did not differ by paternal age. CONCLUSION: This study for the first time reports novel LINE-1 insertions in human sperm, demonstrating the feasibility of scTIPseq, and identifies new contributors to genetic diversity in the human germ line.

Obesity and survival in a national cohort of incident hemodialysis patients: An analysis of the Brazilian Dialysis Registry.

INTRODUCTION: A phenomenon called the "obesity paradox" has consistently been reported in several cohorts of patients on chronic hemodialysis. In this setting, a higher body mass index (BMI) is paradoxically associated with better survival. This study aimed to evaluate the effect of BMI on mortality in patients undergoing chronic hemodialysis using the Brazilian Dialysis Registry. METHODS: This was a retrospective national cohort study with data on incident hemodialysis patients collected between January 2011 to December 2018. Those aged <18 or > 80 years were excluded from the study. The variables studied were the clinical and laboratory data regularly collected at the dialysis units. The variable of primary interest was BMI, represented as the median of the entire dialysis treatment and stratified into four ranges according to the World Health Organization (WHO) classification. The primary outcome was death within 4 years. Cox proportional hazards regression analysis was used to test associations with mortality. FINDINGS: The analyzed sample consisted of 5489 patients from 73 centers in five regions of the country. Of these, 5.9% were underweight, 48.3% were of normal weight, 31.0% were overweight, and 14.7% were obese. The 4-year survival rates in these BMI ranges were 58%, 70%, 75%, and 80%, respectively. The probability of survival for each BMI extract was significantly different from that in the normal-weight range (p < 0.05). In the fully adjusted Cox proportional hazard regression model, BMI > 24.9 kg/m2 remained an independent protective factor for mortality (HR: 0.76, 95% CI: 0.62-0.95, p = 0.016). DISCUSSION: In Brazil, being overweight and obese are protective factors for survival in the chronic hemodialysis population.

Brazilian Dialysis Survey 2021 / Censo Brasileiro de Diálise 2021

ABSTRACT Introduction: The Brazilian Dialysis Survey (BDS) is an important source of national data about people on chronic dialysis that contributes to the formulation of health policies regarding kidney failure. Objective: To report the 2021 epidemiological data from the BDS of the Brazilian Society of Nephrology (BSN). Methods: A survey was carried out in Brazilian chronic dialysis centers using an online questionnaire covering clinical and epidemiological aspects of patients in chronic dialysis, data on dialysis therapy, characteristics of dialysis centers, and the impact of the COVID-19 pandemic of 2021. Results: Thirty percent (n = 252) of the centers answered the questionnaire. In July 2021, the estimated total number of patients on dialysis was 148,363. The estimated prevalence and incidence rates of patients per million population (pmp) were 696 and 224, respectively. Of the prevalent patients, 94.2% were on hemodialysis (HD) (1.8% of these on hemodiafiltration), and 5.8% on peritoneal dialysis (PD); 21% were on the transplant waiting list. The incidence rate of confirmed COVID-19 between January and July 2021 was 1,236/10,000 dialysis patients, and the case-fatality rate reached 25.5%. Up to July 2021, 88.6% of patients had received at least one dose of the anti-SARS-CoV-2 vaccine. The estimated overall and COVID-19 crude annual mortality rates were 22.3% and 5.3%, respectively. Conclusion: The absolute number and the prevalence rate of patients on chronic dialysis continue to increase. Most dialysis patients were vaccinated against COVID-19 during the year. The COVID-19 pandemic was associated to the overall mortality rate.

RESUMO Introdução: O Censo Brasileiro de Diálise (CBD) constitui importante fonte de dados nacionais sobre pessoas em diálise crônica que contribui para a formulação de políticas de saúde. Objetivo: Relatar dados epidemiológicos de 2021 do CBD da Sociedade Brasileira de Nefrologia (SBN). Métodos: Realizou-se pesquisa em centros brasileiros de diálise crônica utilizando questionário online abrangendo aspectos clínicos e epidemiológicos de pacientes em diálise crônica, dados sobre terapia dialítica, características dos centros de diálise e o impacto da pandemia COVID-19 em 2021. Resultados: Trinta por cento (n = 252) dos centros responderam ao questionário. Em Julho de 2021, o número total estimado de pacientes em diálise foi 148.363. As taxas estimadas de prevalência e incidência de pacientes por milhão da população (pmp) foram 696 e 224, respectivamente. Dos pacientes prevalentes, 94,2% estavam em hemodiálise (HD) (1,8% destes em hemodiafiltração), e 5,8% em diálise peritoneal (DP); 21% estavam na lista de espera para transplante. A taxa de incidência de COVID-19 confirmada entre Janeiro e Julho de 2021 foi 1.236/10.000 pacientes em diálise, e a taxa de letalidade atingiu 25,5%. Até Julho de 2021, 88,6% dos pacientes haviam recebido pelo menos uma dose da vacina anti-SARS-CoV-2. As taxas estimadas de mortalidade bruta anual geral e por COVID-19 foram de 22,3% e 5,3%, respectivamente. Conclusão: O número absoluto e a taxa de prevalência de pacientes em diálise crônica continuam aumentando. A maioria dos pacientes em diálise foram vacinados contra COVID-19 durante o ano. A pandemia COVID-19 contribuiu com a taxa de mortalidade geral.

The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.

The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.

Systemic immune mediators reflect tumour-infiltrating lymphocyte intensity and predict therapeutic response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer (BC). Neoadjuvant chemotherapy has proven efficacy in its treatment, and a pathological complete response (pCR) to therapy is predictive of improved long-term survival. The immune response is key to successful neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumour-infiltrating lymphocytes (TILs) in pre-treated tumour tissue samples and the likelihood of achieving pCR. Here we studied systemic immune mediators from volunteer TNBC patients before undergoing neoadjuvant chemotherapy to determine the systemic response association with TIL intensity, treatment response and survival. Patients were classified into pCR responder or non-responder at time of surgery. We found higher levels of immune mediators before treatment began in patients that went on to be pCR responders versus non-pCR, with area under the curve (AUC) values of 0.64-0.80. We also observed a positive correlation between inflammatory systemic immune mediators and the percentage of TILs in pCR responder patients. Combining TILs and systemic immune mediator levels provided stronger AUC values (range of 0.72-0.82). Last, performing a progression-free survival analysis with several of the systemic cytokines that predict pCR, segregated the patients into long- and short-survival groups based on high and low production of the cytokines, respectively. Our study demonstrates that circulating cytokines, before treatment begins, predict pCR in TNBC patients treated with neoadjuvant chemotherapy. Moreover, they may act as a surrogate marker of high TILs or together with TILs to better predict pCR and survival.

Brazilian Dialysis Survey 2021.

INTRODUCTION: The Brazilian Dialysis Survey (BDS) is an important source of national data about people on chronic dialysis that contributes to the formulation of health policies regarding kidney failure. OBJECTIVE: To report the 2021 epidemiological data from the BDS of the Brazilian Society of Nephrology (BSN). METHODS: A survey was carried out in Brazilian chronic dialysis centers using an online questionnaire covering clinical and epidemiological aspects of patients in chronic dialysis, data on dialysis therapy, characteristics of dialysis centers, and the impact of the COVID-19 pandemic of 2021. RESULTS: Thirty percent (n = 252) of the centers answered the questionnaire. In July 2021, the estimated total number of patients on dialysis was 148,363. The estimated prevalence and incidence rates of patients per million population (pmp) were 696 and 224, respectively. Of the prevalent patients, 94.2% were on hemodialysis (HD) (1.8% of these on hemodiafiltration), and 5.8% on peritoneal dialysis (PD); 21% were on the transplant waiting list. The incidence rate of confirmed COVID-19 between January and July 2021 was 1,236/10,000 dialysis patients, and the case-fatality rate reached 25.5%. Up to July 2021, 88.6% of patients had received at least one dose of the anti-SARS-CoV-2 vaccine. The estimated overall and COVID-19 crude annual mortality rates were 22.3% and 5.3%, respectively. CONCLUSION: The absolute number and the prevalence rate of patients on chronic dialysis continue to increase. Most dialysis patients were vaccinated against COVID-19 during the year. The COVID-19 pandemic was associated to the overall mortality rate.

Telomere fusions as a signal of term placental aging? A pilot study.

Lay summary: The placenta plays an essential role at the beginning of life, nourishing and supporting the fetus, but its life span is limited. In late pregnancy, the placenta develops signs of aging, including inflammation and impaired function, which may complicate pregnancy. Placentas also show another sign of aging - cells with extra or missing chromosomes. Chromosomally abnormal cells could gather in the placenta if they get stranded there and/or if the cells do not separate normally. Chromosome separation goes wrong in aging cells when the DNA sequences, which protect the ends of the chromosomes, erode. When chromosomes lose their protective caps, they fuse which leads to abnormal numbers of chromosomes. In this pilot study, for the first time, we found fusions between the caps in a human placenta when it reaches full term. More studies are needed to decide whether this has an influence on how the placenta works and outcomes of pregnancy.

Ganglio centinela positivo en melanoma: factores predictivos y resultados del vaciamiento ganglionar / Positive sentinel lymph node in melanoma: predictive factors and results of completion lymph node dissection

RESUMEN Antecedentes: la biopsia del ganglio centinela (GC) es la técnica aceptada para determinar el pronóstico en estadios iniciales de melanoma cutáneo. La ventaja del vaciamiento ganglionar (VG) cuando el GC resulta positivo ha sido recientemente cuestionada. Objetivo: describir los porcentajes y factores asociados a metástasis en el GC, y en los ganglios no centinela (GnC) en los VG de pacientes con GC positivo. Material y métodos: se llevó a cabo un estudio retrospectivo de los registros clínicos y patológicos de 139 pacientes operados por melanoma cutáneo entre enero de 2012 y diciembre de 2019. Resultados: a 96 (69%) pacientes se les realizó biopsia de GC. El promedio de edad fue 61,7 años ± 17,5 (19-93); 53 (55,2%) fueron hombres. La lesión primaria estuvo ubicada en: extremidades 47 (49%), tronco 39 (40,6%), cabeza y cuello 10 (10,4%). El promedio de espesor de Breslow fue 5,01 mm (1,05- 50 mm) y se encontró ulceración en 35 casos (36,4%). El GC fue identificado en todas las oportunidades y en 39 (40,6%) fue positivo. Hubo asociación con el espesor ≥ 3 mm (p = 0,000017) y con la ulceración (p = 0,0011). A los pacientes con GC positivo se les efectuó el VG del territorio afectado: 23 axilar, 10 inguinal y 6 cervical. Veintitrés (59%) presentaron metástasis en GnC. Se asoció con el espesor (p = 0,022) y la ulceración (p = 0,019). Conclusión: existió un alto porcentaje de GnC positivos en la población estudiada, vinculado al espesor y la ulceración. Estas características, así como la dificultad de un estricto seguimiento, inducen a no abandonar el VG en pacientes con GC positivo.

ABSTRACT Background: Sentinel lymph node (SLN) biopsy is the technique accepted to determine the prognosis of early cutaneous melanomas. The advantage of lymph node dissection (LND) when SLN biopsy is positive has recently been questioned. Objective: The aim of this study is to describe the percentages and factors associated with SLN and non-sentinel node (NSN) metastases in LNDs of SLN-positive patients. Material and methods: The clinical records and pathology reports of 139 patients undergoing surgery for cutaneous melanoma between January 2012 and December 2019 were retrospectively reviewed. Results: Ninety-six (69%) patients underwent SLN biopsy. Mean age was 61.7 ± 17.5 years (19-93) and 53 (55.2%) were men. The primary lesion was located in the extremities in 47 (49%) cases, in the trunk in 39 (40.6%), and in the head and neck in 10 (10.4%). Mean Breslow thickness was 5.01 mm (1.05-50 mm) and ulceration was found in 35 cases (36.4%). The SLN was identified in all the cases and was positive in 39 (40.6%). There was an association with thickness ≥ 3 mm (p = 0.000017) and ulceration (p = 0.0011). Those patients with positive SLN biopsy underwent LND of the territory involved: axillary in 23, inguinal in 10 and cervical in 6. Twenty-three (59%) presented NSLN metastases and were associated with thickness (p = 0.022) and ulceration (p = 0.019). Conclusion: There was a high percentage of positive NSLN in the population studied which was associated with thickness and ulceration. These characteristics and the difficulty to achieve strict follow-up are the reasons for completion LND in SLN-positive patients.

Brazilian Dialysis Survey 2020 / Censo Brasileiro de Diálise 2020

Abstract Introduction: National data on chronic dialysis treatment are essential to support the development of health policies aimed at improving the treatment for thousands of people. Objective: To report epidemiological data from the 2020 Brazilian Dialysis Survey, sponsored by the Brazilian Society of Nephrology. Methods: A survey was carried out in Brazilian chronic dialysis centers using an online questionnaire for the year, covering clinical and epidemiological aspects of patients in a chronic dialysis program, data on dialysis therapy, characteristics of dialysis units and the impact of the COVID-19 pandemic. Results: 235 (28%) of the centers responded to the questionnaire. In July 2020, the estimated total number of patients on dialysis was 144,779. The estimated prevalence and incidence rates of patients per million population (pmp) were 684 and 209, respectively. Of the prevalent patients, 92.6% were on hemodialysis (HD) and 7.4% were on peritoneal dialysis (PD); 23% were on the transplant waiting list. A central venous catheter was used by a quarter of patients on HD. The incidence rate of confirmed COVID-19 between February and July 2020 was 684/10,000 dialysis patients, and the lethality rate was 25.7%. The estimated overall mortality and COVID-19 crude annual mortality rates were 24.5 and 4.2%, respectively. Conclusion: The absolute number of patients on chronic dialysis and prevalence rate continued to increase. The low use of PD as dialysis therapy was maintained and the use of long-term catheters for HD increased. The COVID-19 pandemic contributed to the increase in the overall mortality rate.

Resumo Introdução: Dados nacionais sobre tratamento dialítico crônico são essenciais para apoiar o desenvolvimento de políticas de saúde destinadas a melhorar o tratamento de milhares de pessoas. Objetivo: Relatar dados epidemiológicos do Censo Brasileiro de Diálise 2020, patrocinado pela Sociedade Brasileira de Nefrologia. Métodos: Realizou-se pesquisa em centros brasileiros de diálise crônica utilizando questionário online relativo ao ano, abrangendo aspectos clínicos e epidemiológicos de pacientes em programa de diálise crônica, dados sobre terapia dialítica, características das unidades de diálise e impacto da pandemia COVID-19. Resultados: 235 (28%) centros responderam ao questionário. Em julho de 2020, o número total estimado de pacientes em diálise foi 144.779. As taxas estimadas de prevalência e incidência de pacientes por milhão da população (pmp) foram 684 e 209, respectivamente. Dos pacientes prevalentes, 92,6% estavam em hemodiálise (HD) e 7,4% em diálise peritoneal (DP); 23% estavam na lista de espera para transplante. Cateter venoso central foi utilizado por um quarto dos pacientes em HD. A taxa de incidência de COVID-19 confirmada entre fevereiro e julho de 2020 foi 684/10.000 pacientes em diálise, a taxa de letalidade foi 25,7%. As taxas estimadas de mortalidade geral e mortalidade bruta anual por COVID-19 foram 24,5 e 4,2%, respectivamente. Conclusão: O número absoluto de pacientes em diálise crônica e a taxa de prevalência continuaram a aumentar. O baixo uso de DP como terapia de diálise foi mantido e o uso de cateteres de longa permanência para HD aumentou. A pandemia COVID-19 contribuiu para o aumento da taxa de mortalidade geral.