Evaluation of pathogenic variants detected in high homology regions of the PMS2 gene. How effective is long-range PCR?

Introduction: Lynch syndrome (LS) is an inherited cancer predisposition syndrome characterized by a high risk of colorectal and extracolonic tumors. Germline pathogenic variants (GPV) in the PMS2 gene are associated with <15% of all cases. The PMS2CL pseudogene presents high homology with PMS2, challenging molecular diagnosis by next-generation sequencing (NGS). Due to the high methodological complexity required to distinguish variants between PMS2 and PMS2CL, most laboratories do not clearly report the origin of this molecular finding. Objective: The aim of this study was to confirm the GPVs detected by NGS in regions of high homology segments of the PMS2 gene in a Brazilian sample. Methods: An orthogonal and gold standard long-range PCR (LR-PCR) methodology to separate variants detected in the PMS2 gene from those detected in the pseudogene. Results: A total of 74 samples with a PMS2 GPV detected by NGS in exons with high homology with PMS2CL pseudogene were evaluated. The most common was NM_000535.6:c.2182_2184delinsG, which was previously described as deleterious mutation in a study of African-American patients with LS and has been widely reported by laboratories as a pathogenic variant associated with the LS phenotype. Of all GPVs identified, only 6.8% were confirmed by LR-PCR. Conversely, more than 90% of GPV were not confirmed after LR-PCR, and the diagnosis of LS was ruled out by molecular mechanisms associated with PMS2. Conclusion: In conclusion, the use of LR-PCR was demonstrated to be a reliable approach for accurate molecular analysis of PMS2 variants in segments with high homology with PMS2CL. We highlight that our laboratory is a pioneer in routine diagnostic complementation of the PMS2 gene in Brazil, directly contributing to a more assertive molecular diagnosis and adequate genetic counseling for these patients and their families.

Long-term in situ Eulerian Sea surface temperature records along the Portuguese Coast.

Monitoring ocean surface temperature is critical to infer the variability of the upper layers of the ocean, from short temporal scales to climatic change scales. Analysis of the climatological trends and anomalies is fundamental to comprehend the long-term effects of climate change on marine ecosystems and coastal regions. The original data for the dataset presented was collected by the Portuguese Hydrographic Institute (Instituto Hidrográfico) using seven Ondograph and Meteo-oceanography buoys anchored offshore along the Portuguese coast to acquire ocean surface temperatures. The original raw data was pre-processed to provide averages over 3-hour periods and daily averages, and this cleaned data constitutes the provided dataset. The 3-hour temperature averages were obtained mainly between 2011 and 2015, and the daily temperature averages were obtained in intervals that vary with the considered buoy, having an average interval of 14 years per buoy. The data gathered provides a considerable temporal window, enabling the creation of data series and the implementation of data mining algorithms to develop decision support systems. Collecting data in situ makes it possible to validate simulated results obtained using approximation models. This allows for more accurate temperature readings and facilitates testing and correcting created models.

Lessons from the pandemic and the value of a structured system of ultrasonographic findings in the diagnosis of COVID-19 pulmonary manifestations.

Implementing a structured COVID-19 lung ultrasound system, using COVID-RADS standardization. This case series exams revealed correlations between ultrasonographic and tomographic findings. Ventilatory assessments showed that higher categories required second-line oxygen. This replicable tool will aid in screening and predicting disease severity beyond the pandemic. OBJECTIVE: We aimed to share our experience in implementing a structured system for COVID-19 lung findings, elucidating key aspects of the lung ultrasound score to facilitate its standardized clinical use beyond the pandemic scenario. METHODS: Using a scoring system to classify the extent of lung involvement, we retrospectively analyzed the ultrasound reports performed in our institution according to COVID-RADS standardization. RESULTS: The study included 69 thoracic ultrasound exams, with 27 following the protocol. The majority of patients were female (52%), with ages ranging from 1 to 96 years and an average of 56 years. Classification according to COVID-RADS was as follows: 11.1% in category 0, 37% in category 1, 44.4% in category 2, and 7.4% in category 3. Ground-glass opacities on tomography correlated with higher COVID-RADS scores (categories 2 and 3) in 82% of cases. Ventilatory assessment revealed that 50% of cases in higher COVID-RADS categories (2 and 3) required second-line oxygen supplementation, while none of the cases in lower categories (0 and 1) utilized this support. CONCLUSION: Lung ultrasound has been widely utilized as a diagnostic tool owing to its availability and simplicity of application. In the context of the pandemic emergency, a pressing need for a focused and easily applicable assessment arose. The structured reporting system, incorporating ultrasound findings for stratification, demonstrated ease of replicability. This system stands as a crucial tool for screening, predicting severity, and aiding in medical decisions, even in a non-pandemic context. Lung ultrasound enables precise diagnosis and ongoing monitoring of the disease. Ultrasound is an effective tool for assessing pulmonary findings in COVID-19. Structured reports enhance communication and are easily reproducible.

Exploring the Ideal of Breast Beauty: A Morphometric Analysis Based on the Opinions of the Brazilian Population.

Background The quest to identify parameters deemed optimal for breast aesthetics holds paramount significance in both aesthetic and reconstructive surgery. The definition of ideal breast beauty, however, is subject to cultural variations and diverse standards, necessitating a detailed understanding. Objective This study delves into the perspectives of the Brazilian population regarding the aesthetics of the female breast. Methods A selection of images portraying variations in the distribution of upper and lower pole ratios across four distinct proportion models (35:65, 45:55, 50:50, and 55:45) was presented to participants. Through a meticulously crafted questionnaire administered via Google Forms, respondents were tasked with identifying the images they deemed most beautiful and attractive. Comprehensive demographic data of the study participants were gathered and subsequently correlated with their group-specific opinions. Results A total of 3744 questionnaire responses were collected 228 of which were from plastic surgeons/residents. The average age was 35 years, with 55.3% being women. Notably, breasts featuring a ratio of 45:55 emerged as the consensus choice for the epitome of beauty, garnering preference from 73% of the general population, 68% of women, 78% of men, and an equal 78% of plastic surgeons. This preference was consistent across all regions of the country. Conclusion Breasts with a ratio of 45:55 were universally deemed the most aesthetically pleasing. Similarly, breasts with a 50:50 ratio of breast tissue emerged as the next preferred choice. These insights contribute valuable perspectives on aesthetic considerations in breast surgery within the unique cultural context of Brazil.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mitochondrial dysfunction heightens the integrated stress response to drive ALS pathogenesis.

Vesicle-associated membrane protein-associated protein-B (VAPB) is an ER membrane bound protein. VAPB P56S causes a dominant, familial form of amyotrophic lateral sclerosis (ALS), however, the mechanism through which this mutation causes motor neuron (MN) disease remains unknown. Using inducible wild type (WT) and VAPB P56S expressing iPSC-derived MNs we show that VAPB P56S, but not WT, protein decreased neuronal firing and mitochondrial-ER contact (MERC) with an associated age-dependent decrease in mitochondrial membrane potential (MMP); all typical characteristics of MN-disease. We further show that VAPB P56S expressing iPSC-derived MNs have enhanced age-dependent sensitivity to ER stress. We identified elevated expression of the master regulator of the Integrated Stress Response (ISR) marker ATF4 and decreased protein synthesis in the VAPB P56S iPSC-derived MNs. Chemical inhibition of ISR with the compound, ISRIB, rescued all MN disease phenotype in VAPB P56S MNs. Thus, our results not only support ISR inhibition as a potential therapeutic target for ALS patients, but also provides evidence to pathogenesis.

Genital Self-Image and Body Dysmorphic Disorder Symptoms in Patients Undergoing Central Wedge vs. Linear Resection Labiaplasty: A Randomized Clinical Trial.

BACKGROUND: Labiaplasty, a surgical procedure designed to address labia minora hypertrophy, has been closely linked to the improvement of genital self-image and the alleviation of symptoms related to body dysmorphic disorder. Brazil stands as the global leader in the prevalence of labiaplasty procedures. OBJECTIVE: This study aimed to assess alterations in genital self-image and symptoms of body dysmorphic disorder in individuals with labia minora hypertrophy who underwent either wedge or trim labiaplasty. METHODS: A total of 48 adult women undergoing labiaplasty were enrolled in this randomized clinical trial with two parallel groups. Allocation ratio was 1:1. The Study Group (SG) underwent wedge labiaplasty, while the Control Group (CG) underwent trim labiaplasty. Genital self-image and symptoms of body dysmorphic disorder were assessed both preoperatively and six months postoperatively, using validated tools. RESULTS: After a six-month intervention period, a statistically significant improvement in genital self-image was observed (p<0.001), alongside a marked decrease in the score of symptoms related to body dysmorphic disorder (p<0.001). There were no significant differences in outcomes between the groups. Furthermore, no statistically significant associations were noted between complications and the specific technique employed. CONCLUSION: The study findings underscore the noteworthy improvement in genital self-image and a concurrent reduction in symptoms of body dysmorphic disorder, evident in both the wedge and linear labiaplasty groups at the six-month postoperative assessments. These results suggest that the choice of surgical technique does not significantly impact these outcomes.

Fisheries Inspection in Portuguese Waters from 2015 to 2023.

As a coastal state, Portugal must ensure active surveillance over its maritime area, ensuring its proper control and inspection. One of the most critical inspection activities is the fishery inspection. To protect biodiversity, we must ensure that all the ships comply with the existing safety regulations and respect the current fishing quotas. This georeferenced dataset describes the fisheries inspections done in Portuguese waters between 2015 and 2023. Since we are dealing with occurrences that may have originated some legal process to the ship's owner, we have ensured data anonymization by pre-processing the dataset to maintain its accuracy while guaranteeing no unique identifiers exist. All the pre-processing performed to ensure data consistency and accuracy is described in detail to allow a quick analysis and implementation of new algorithms. The data containing the results of these inspections can be easily analyzed to implement data mining algorithms that can efficiently retrieve more knowledge and, e.g., suggest new areas of actuation or new strategies.

Is it possible to estimate the number of patients with COVID-19 admitted to intensive care units and general wards using clinical and telemedicine data?

BACKGROUND: Gabaldi et al. utilized telemedicine data, web search trends, hospitalized patient characteristics, and resource usage data to estimate bed occupancy during the COVID-19 pandemic. The results showcase the potential of data-driven strategies to enhance resource allocation decisions for an effective pandemic response. OBJECTIVE: To develop and validate predictive models to estimate the number of COVID-19 patients hospitalized in the intensive care units and general wards of a private not-for-profit hospital in São Paulo, Brazil. METHODS: Two main models were developed. The first model calculated hospital occupation as the difference between predicted COVID-19 patient admissions, transfers between departments, and discharges, estimating admissions based on their weekly moving averages, segmented by general wards and intensive care units. Patient discharge predictions were based on a length of stay predictive model, assessing the clinical characteristics of patients hospitalized with COVID-19, including age group and usage of mechanical ventilation devices. The second model estimated hospital occupation based on the correlation with the number of telemedicine visits by patients diagnosed with COVID-19, utilizing correlational analysis to define the lag that maximized the correlation between the studied series. Both models were monitored for 365 days, from May 20th, 2021, to May 20th, 2022. RESULTS: The first model predicted the number of hospitalized patients by department within an interval of up to 14 days. The second model estimated the total number of hospitalized patients for the following 8 days, considering calls attended by Hospital Israelita Albert Einstein's telemedicine department. Considering the average daily predicted values for the intensive care unit and general ward across a forecast horizon of 8 days, as limited by the second model, the first and second models obtained R² values of 0.900 and 0.996, respectively and mean absolute errors of 8.885 and 2.524 beds, respectively. The performances of both models were monitored using the mean error, mean absolute error, and root mean squared error as a function of the forecast horizon in days. CONCLUSION: The model based on telemedicine use was the most accurate in the current analysis and was used to estimate COVID-19 hospital occupancy 8 days in advance, validating predictions of this nature in similar clinical contexts. The results encourage the expansion of this method to other pathologies, aiming to guarantee the standards of hospital care and conscious consumption of resources. BACKGROUND: Developed models to forecast bed occupancy for up to 14 days and monitored errors for 365 days. BACKGROUND: Telemedicine calls from COVID-19 patients correlated with the number of patients hospitalized in the next 8 days.

Side-scan sonar imaging data of underwater vehicles for mine detection.

Unmanned vehicles have become increasingly popular in the underwater domain in the last decade, as they provide better operation reliability by minimizing human involvement in most tasks. Perception of the environment is crucial for safety and other tasks, such as guidance and trajectory control, mainly when operating underwater. Mine detection is one of the riskiest operations since it involves systems that can easily damage vehicles and endanger human lives if manned. Automating mine detection from side-scan sonar images enhances safety while reducing false negatives. The collected dataset contains 1170 real sonar images taken between 2010 and 2021 using a Teledyne Marine Gavia Autonomous Underwater Vehicle (AUV), which includes enough information to classify its content objects as NOn-Mine-like BOttom Objects (NOMBO) and MIne-Like COntacts (MILCO). The dataset is annotated and can be quickly deployed for object detection, classification, or image segmentation tasks. Collecting a dataset of this type requires a significant amount of time and cost, which increases its rarity and relevance to research and industrial development.

Is it possible to estimate the number of patients with COVID-19 admitted to intensive care units and general wards using clinical and telemedicine data?

ABSTRACT Objective: To develop and validate predictive models to estimate the number of COVID-19 patients hospitalized in the intensive care units and general wards of a private not-for-profit hospital in São Paulo, Brazil. Methods: Two main models were developed. The first model calculated hospital occupation as the difference between predicted COVID-19 patient admissions, transfers between departments, and discharges, estimating admissions based on their weekly moving averages, segmented by general wards and intensive care units. Patient discharge predictions were based on a length of stay predictive model, assessing the clinical characteristics of patients hospitalized with COVID-19, including age group and usage of mechanical ventilation devices. The second model estimated hospital occupation based on the correlation with the number of telemedicine visits by patients diagnosed with COVID-19, utilizing correlational analysis to define the lag that maximized the correlation between the studied series. Both models were monitored for 365 days, from May 20th, 2021, to May 20th, 2022. Results: The first model predicted the number of hospitalized patients by department within an interval of up to 14 days. The second model estimated the total number of hospitalized patients for the following 8 days, considering calls attended by Hospital Israelita Albert Einstein's telemedicine department. Considering the average daily predicted values for the intensive care unit and general ward across a forecast horizon of 8 days, as limited by the second model, the first and second models obtained R² values of 0.900 and 0.996, respectively and mean absolute errors of 8.885 and 2.524 beds, respectively. The performances of both models were monitored using the mean error, mean absolute error, and root mean squared error as a function of the forecast horizon in days. Conclusion: The model based on telemedicine use was the most accurate in the current analysis and was used to estimate COVID-19 hospital occupancy 8 days in advance, validating predictions of this nature in similar clinical contexts. The results encourage the expansion of this method to other pathologies, aiming to guarantee the standards of hospital care and conscious consumption of resources.

Lessons from the pandemic and the value of a structured system of ultrasonographic findings in the diagnosis of COVID-19 pulmonary manifestations

ABSTRACT Objective We aimed to share our experience in implementing a structured system for COVID-19 lung findings, elucidating key aspects of the lung ultrasound score to facilitate its standardized clinical use beyond the pandemic scenario. Methods Using a scoring system to classify the extent of lung involvement, we retrospectively analyzed the ultrasound reports performed in our institution according to COVID-RADS standardization. Results The study included 69 thoracic ultrasound exams, with 27 following the protocol. The majority of patients were female (52%), with ages ranging from 1 to 96 years and an average of 56 years. Classification according to COVID-RADS was as follows: 11.1% in category 0, 37% in category 1, 44.4% in category 2, and 7.4% in category 3. Ground-glass opacities on tomography correlated with higher COVID-RADS scores (categories 2 and 3) in 82% of cases. Ventilatory assessment revealed that 50% of cases in higher COVID-RADS categories (2 and 3) required second-line oxygen supplementation, while none of the cases in lower categories (0 and 1) utilized this support. Conclusion Lung ultrasound has been widely utilized as a diagnostic tool owing to its availability and simplicity of application. In the context of the pandemic emergency, a pressing need for a focused and easily applicable assessment arose. The structured reporting system, incorporating ultrasound findings for stratification, demonstrated ease of replicability. This system stands as a crucial tool for screening, predicting severity, and aiding in medical decisions, even in a non-pandemic context.

Georeferenced dataset of maritime piracy in the Gulf of Guinea from 2010 to 2021.

Piracy has been a global concern and a threat to the safety of people performing maritime trade around the globe. Since ancient times maritime piracy has been a common practice that, unfortunately, has not ended in the current days. A georeferenced dataset providing the position, meteorologic conditions, and a description of the occurrence can provide essential information for analyzing this global phenomenon. The dataset focuses on the Gulf of Guinea (GoG) as an area dominated by corruption and weak supervision capacity by the local authorities. The time interval considered in this paper is between 2010 and 2021. Using this simple dataset, it is possible to analyze attributes such as when the piracy occurred or if the illegal activity involved deaths or kidnapping. The accuracy of the data was guaranteed by cross-referencing data sources, so we have 595 pirate attacks accurately described. This dataset can easily be used for data mining, allowing further analysis of the patterns and trends of pirate attacks in the GoG over time.

Post-transplant diabetes mellitus: Findings in nutritional status and body composition.

INTRODUCTION: Weight gain and changes in body composition are associated with the onset of diabetes after kidney transplantation, and detailing these changes can help prevent this situation. The study aimed to assess the prevalence of diabetes mellitus after kidney transplantation and changes in the nutritional status and body composition in patients with diabetes one year from surgery. MATERIALS AND METHODS: This survey was a single-center, prospective cohort study. Twenty-nine patients over 18 years old who underwent isolated kidney transplantation, without diabetes, were included and followed up for one year. At hospital discharge after transplantation and one year later, anthropometric (weight, height and abdominal circumference), body composition (electrical bioimpedance), routine biochemical and dietary intake assessments were performed. RESULTS: Most of the patients were male (75%), and the mean age was 48.0±11.8 years old. In the first-year post-surgery 27.6% of patients had DM and the diagnosis was made, on average, 4 months after transplantation. The group with diabetes had, from the beginning to the end of the study, greater weight and body fat, especially abdominal fat. The non-diabetic group, after one year, showed an increase in phase angle, body weight and body masses, more pronounced of fat-free mass, when compared with fat mass gain. CONCLUSIONS: Both groups showed weight gain, but in the non-diabetic group these changes can be interpreted as an improvement in the nutritional profile. Metabolic abnormalities associated with immunosuppression and eating habits, combination that maintains increased the risk for diabetes for long time, keeping this group with priority in nutritional care.

Cost-effectiveness of a second opinion program on spine surgeries: an economic analysis.

BACKGROUND: In this study we proposed a new strategy to measure cost-effectiveness of second opinion program on spine surgery, using as measure of effectiveness the minimal important change (MIC) in the quality of life reported by patients, including the satisfaction questionnaire regarding the treatment and direct medical costs. METHODS: Retrospective analysis of patients with prior indication for spine surgery included in a second opinion program during May 2011 to May 2019. Treatment costs and outcomes were compared considering each patients' recommended treatment before and after the second opinion. Costs were measured under the perspective of the hospital, including hospital stay, surgical room, physician and staff fees and other costs related to hospitalization when surgery was performed and physiotherapy or injection costs when a conservative treatment was recommended. Reoperation costs were also included. For comparison analysis, we used data based on our clinical practice, using data from patients who underwent the same type of surgical procedure as recommended by the first referral. The measure of effectiveness was the percentage of patients who achieved the MIC in quality of life measured by the EQ-5D-3 L 2 years after starting treatment. An incremental cost-effectiveness ratio (ICER) was calculated. RESULTS: Based upon the assessment of 1,088 patients that completed the entire second opinion process, conservative management was recommended for 662 (60.8%) patients; 49 (4.5%) were recommended to injection and 377 (34.7%) to surgery. Complex spine surgery, as arthrodesis, was recommended by second opinion in only 3.7% of cases. The program resulted in financial savings of -$6,705 per patient associated with appropriate treatment indication, with an incremental effectiveness of 0.077 patients achieving MIC when compared to the first referral, resulting in an ICER of $-87,066 per additional patient achieving the MIC, ranging between $-273,016 and $-41,832. CONCLUSION: After 2 years of treatment, the second opinion program demonstrated the potential for cost-offsets associated with improved quality of life.

Congenital and acquired symmastia: a novel correction technique.

BACKGROUND: Symmastia, first defined by Spence in 1984, is a medical condition characterized by the convergence of breast tissues in the midline, resulting in the absence of adhesion between the skin and subcutaneous tissue over the presternal area. It can be either congenital or acquired. Currently, there is no universally accepted treatment for symmastia. This study presents a surgical approach, preoperative, and postoperative care for the correction of symmastia. METHODS: Between January 2014 and December 2020, a surgical technique was performed on 100 patients, including 59 with congenital symmastia and 41 with acquired symmastia. The technique involved creating a thin skin flap and attaching it to the sternum to reconstruct the intermammary V-shaped region. RESULTS: All patients in both groups underwent subglandular implant placement, with textured/polyurethane prostheses used in 97% of cases. Three cases did not use any implants. In the corrective surgery, patients received smaller, round implants, following the steps of the surgical approach devised by the author. The median satisfaction scores were high in both groups. CONCLUSION: The surgical approach described in this study is a safe, one-time procedure with a low risk of complications and high patient satisfaction. The technique is reproducible and provides consistent outcomes.

Impact of a quality programme on overindication of surgeries for endometriosis and cholecystectomies.

Approximately 45% of patients receive medical services with minimal or no benefit (low-value care). In addition to the increasing costs to the health system, performing invasive procedures without an indication poses a potentially preventable risk to patient safety. This study aimed to determine whether a managed quality improvement programme could prevent cholecystectomy and surgery for endometriosis treatment with minimal or no benefit to patients.This before-and-after study was conducted at a private hospital in São Paulo, Brazil, which has a main medical remuneration model of fee for service. All patients who underwent cholecystectomy or surgery for endometriosis between 1 August 2020 and 31 May 2021 were evaluated.The intervention consisted of allowing the performance of procedures that met previously defined criteria or for which the indications were validated by a board of experts.A total of 430 patients were included in this analysis. The programme prevented the unnecessary performance of 13% of cholecystectomies (p=0.0001) and 22.2% (p=0.0006) of surgeries for the treatment of endometriosis. This resulted in an estimated annual cost reduction to the health system of US$466 094.93.In a hospital with a private practice and fee-for-service medical remuneration, the definition of clear criteria for indicating surgery and the analysis of cases that did not meet these criteria by a board of reputable experts at the institution resulted in a statistically significant reduction in low-value cholecystectomies and endometriosis surgeries.