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Introduction: Severe asthma is characterized by frequent exacerbations, symptoms limiting daily activities and nocturnal symptoms. It requires the continuous use of medications, at high doses, and, sometimes, continuous use of oral corticosteroids, representing a significant burden to health system and society. This systematic review sought to address economic data related to severe asthma in Brazil., Method: In June 2014, electronic searches were conducted to identify relevant publications. Quality criteria were developed and applied to each selected study. In order to compare results across the selected studies, costs were refined to an annual basis, grouped according to the study perspective, inflated and converted to 2014 USD., Results: Cost analyses from the Brazilian public health system perspective were derived from two studies and showed an average annual hospital cost per patient of 135 USD and 733 USD, respectively. From the family perspective, average annual direct costs per patient varied from 764 USD to 929 USD., Conclusion: Hospitalizations and medications seem to be the most important resources funded by the Brazilian public health system and by patients and their families. Although further studies are necessary, as information on cost of this disease is scarce in Brazil, these findings suggest that there is a potential room for improving severe asthma care among Brazilian patients.

Multiple endocrine neoplasia type 2 (MEN 2) is a rare hereditary endocrine tumor syndrome caused by mutations in the rearranged during transfection (RET) gene. MEN 2 is divided into two main entities, MEN 2A and MEN 2B, both of which present with medullary thyroid cancer (MTC) in approximately 100% of cases and pheochromocytoma in 50% of cases. Specific RET mutations are associated with a risk of early onset of MTC, from 1 year of age (highest risk) to 5 years of age (high risk). This risk defines the optimal timing for thyroidectomy, ideally at an age when the disease has not spread. This is the most important genotype-phenotype correlation observed in MEN 2. Specific RET mutations also define the penetrance of pheochromocytoma. However, despite the presence of these highest/high-risk variants, some patients unexpectedly present with non-aggressive MTC or never present with pheochromocytoma, suggesting that factors other than the major RET variant may modify the natural history and genotype-phenotype correlations. Improving our understanding of the genotype-phenotype correlations would allow individualizing the management and follow-up of patients with MEN 2. The aim of this brief review is to discuss the main genotype-phenotype correlations in MEN 2 and the potential factors that might influence these correlations. [ABSTRACT FROM AUTHOR]

Background: RET polymorphisms have been involved in the clinical presentation and prognosis of multiple endocrine neoplasia type 2 (MEN2)-associated medullary thyroid carcinoma., Objective: To investigate the effect of RET variants on the penetrance of pheochromocytoma (PHEO) in MEN2 patients., Methods: The RET variants L769L, S836S, and G691S/S904S were evaluated in a cohort of 153 MEN2 patients attending a tertiary teaching hospital. A comparison of RET variant frequencies between patients with and without PHEO was performed. Kaplan-Meier curves and Cox regression analysis were used to estimate the effect of RET variants on the age-dependent penetrance., Results: A total of 48 (31.4%) patients presented with MEN2-associated PHEOs. The mean age at diagnosis was 35.5±13.4 years, 60.4% of patients were women, and 92.8% had RET mutations at codon 634. The frequencies of RET polymorphisms were as follows: 20.1% L769L, 4.75% S836S, and 17.3% S904S/G691S. We did not observe any association between the frequencies of L769L, S836S, or S904S/G691S variants and PHEO development (all P>0.05). However, individuals carrying two RET polymorphic alleles had an increased estimated risk of PHEO (2.63; 95% CI, 1.4-5.0; P=0.004) and were younger at diagnosis when compared with those with one or no polymorphism (29.6±6.3 and 39.3±14.4 years respectively; P=0.006). Accordingly, additional analysis using Cox proportional hazard models demonstrated that the presence of two RET variants was associated with an increased risk for early PHEO development (hazard ratio, 5.99 (95% CI, 2.24-16.03); P<0.001)., Conclusions: RET polymorphic alleles have an additive effect on the estimated risk of age-related PHEO penetrance in MEN2 patients., (© 2014 European Society of Endocrinology.)

Agaricus brasiliensis cultures quickly lose viability when stored at cool temperatures, even for a short period of time. We evaluated several low-cost preservation methods using varied substrates, preservation solutions, and storage temperatures. Agaricus brasiliensis was intolerant to freezing temperatures, making liquid nitrogen use and deep-freezing methods impossible for its preservation. The best preservation conditions for the A. brasiliensis CS1 strain tested in this study were obtained by using rice as substrate and water as preservation solution, with storage at room temperature or when using soil, mushroom cultivation compost, or rice and stored at 10 °C without preservation solution. Those cultures that were reactivated showed the same productivity attributes as the control. In addition, no effect on productivity or biological efficiency was observed through successive subculturing of the strain (CS1). Parboiled rice was successfully used for other A. brasiliensis strains (CS2, CS5, CS7, CS9, and CS10), and also for Pleurotus ostreatus, P. sajor-caju, and Lentinula edodes.

Objective: RET single nucleotide polymorphisms (SNPs) have been implicated in the pathogenesis and progression of medullary thyroid carcinoma (MTC). Here, we investigated the influence of multiple RET variants (G691S, L769L, S836S, and S904S) on the risk of MTC and tumor behavior., Design and Methods: One hundred and seven MTC patients and 308 cancer-unaffected control individuals were included. SNPs were analyzed using Custom TaqMan Genotyping Assays. Haplotypes based on the combination of allelic variants were inferred using a Bayesian statistical method., Results: The minor allele frequencies in MTC patients were as follows: L769L: 28.0%, S836S: 8.9%, and G691S/S904S: 22.2%. The RET L769L and S836S SNPs were associated with increased risk of MTC (odds ratio (OR)=1.95, 95% CI: 1.2-3.1, P=0.005 and OR=2.29, 95% CI: 1.2-4.5, P=0.017 respectively). The adjusted OR for individuals harboring haplotypes with three or more polymorphic alleles was 3.79 (95% CI: 1.5-9.5; P=0.004), indicating an additive effect of these variants on the risk for MTC. Among MTC patients, no significant associations were observed between RET variants and age of diagnosis or tumor size but serum calcitonin levels increased according to the number of risk alleles (P=0.003). Remarkably, patients carrying haplotypes with three or four risk alleles had increased risk for lymph node and distant metastases at diagnosis (OR=5.84, 95% CI: 1.1-31.2, P=0.039). Further analysis using Kaplan-Meier model demonstrated that metastatic disease occurred earlier in individuals harboring multiple risk alleles., Conclusion: Our results demonstrated an additive effect of RET polymorphic alleles on the estimated risk of developing aggressive MTC.

Background: Morbidly obese patients develop more atelectasis during general anesthesia than non-obese ones, and these atelectasis persist for 24 hours after the end of the surgical procedure., Objectives: This study evaluated the effect of noninvasive ventilation with two pressure levels (BiPAP) in the pulmonary function, incidence of immediate postoperative pulmonary complications and the development of anastomotic dehiscence in morbid obese patients submitted to gastrojejunal derivation in Roux-en-Y (RYGB)., Methods: It was an analytical and clinical study involving patients who were submitted to RYGB, had a body mass index (BMI) of at least 35 kg/cm², and were randomly chosen to receive BiPAP (experimental group) or standard oxygen therapy (control group), in the first four hours of the post-operation period. Patients with chronic or acute pulmonary disease were not included, and neither were the ones who needed invasive mechanical ventilation by the end of the surgery. Vital capacity, maximal inspiratory and expiratory pressure, and arterial blood gases were measured in the preoperative and in the first postoperative. Chest X-ray was performed in the third postoperative., Results: Eighteen patients were chosen for the study: ten received BiPAP and eight received standard oxygen therapy. The study group had better partial oxygen pressure and lower maximal expiratory pressure levels in the postoperative state than the control group. Anastomotic dehiscence was not observed in any group. There was no significant difference between the control group and the study group relating to the loss of vital capacity, maximal inspiratory pressure in the postoperative period or the incidence of atelectasis., Conclusion: The BiPAP in the postoperative period of gastroplasty was useful to improve oxygenation and did not increase the incidence of anastomotic dehiscence.

Background: One of the main challenges for clinical research in dengue is the low validity of clinical diagnosis., Objective: To analyze clinical and laboratory data as predicitve factors of dengue diagnosis at Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, during the 2001-2002 dengue outbreak in Rio de Janeiro., Methods: Cross sectional study comparing clinical laboratory data collected from the National Information System for Compulsory Notification Diseases (SINAN) in two serologically confirmed groups: dengue D (N = 453) and non-dengue ND (N = 80)., Results: Fever, exanthema, itching, mean platelet count < 150,000, WBC count < 4,000 and absence of vomiting and of abdominal pain help to distinguish D from ND groups. When considered individually, these signs and symptoms enhance diagnostic sensitivity and, when used in combination, improve specificity., Conclusion: A combination of symptoms not necessarily considered indicative of dengue diagnosis could improve surveillance and medical decision-making in simple clinical settings.

The research landscape on cognitive computing algorithms, such as Genetic Algorithms (GA), in Cancer/Tumor and Oncological (CTO) research from 2003 to 2022 was examined using Scopus-indexed publications. Bibliometric analysis was employed to assess social networks and thematic areas of GACTO research. The analysis revealed that researchers published 114 articles and 92 conference papers, representing 55.34% and 44.66% of the total publications (TP=206), respectively. Of these, 129 publications were open access, distributed across Gold, Hybrid Gold, Bronze, and Green mediums. Researchers showed a preference for articles over conference papers. Stakeholder analysis highlighted a robust number of active authors, affiliations, and countries involved in GACTO research. Top performers included Zuherman Rustam (TP=5), Universitas Indonesia (TP=6), and India. Productivity was attributed to the availability of resources such as financial support, with top funders being Universitas Indonesia, the National Natural Science Foundation of China, and Brazil's Conselho Nacional de Desenvolvimento Científico e Tecnológico. Social network analysis indicated a low rate of co-authorship at 18.18%, suggesting limited collaboration at the author level. However, at the national level, collaborative links were stronger, with the largest cluster comprising India, Iran, and the United States, and the smallest including Turkey and the United Kingdom. This reflects better access to resources, funding, and infrastructure at the national level. Hotspot analysis identified three major keywords: genetic algorithms, diseases, and feature extraction. Cluster analysis revealed three focus areas: Precision Health Analytics, Genomic Cancer Profiling, and Integrated AI Diagnosis. In conclusion, the GACTO research landscape actively engages in socially impactful and scientific themes, utilizing computational tools to address challenges posed by cancer and other oncological diseases. [ABSTRACT FROM AUTHOR]

Objective: Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominantly inherited tumour syndrome and primary hyperparathyroidism (pHPT) is one of the major components of MEN2A. Our study evaluated the features of MEN2A-related hyperparathyroidism Material and Methods: Records of 49 patients with MEN2A followed up at Istanbul Faculty of Medicine were retrospectively reviewed. Results: This study included 25 females and 24 males, and 55% of the patients had RET 634 variants. The median follow-up duration was 12 years. Medullary thyroid cancer (MTC) was present in 44 patients, and the mean age at diagnosis was 30.8±14 years. Pheochromocytoma was detected in 61% of patients, and the mean age at diagnosis was 36.4±12.6 years. Twelve patients (F/M=1) had pHPT, and the mean age at diagnosis was 40±15.7 years. The frequency of pHPT was 6% in the ATA moderate-risk category and 33.3% in the high-risk category (RET 634 variants). pHPT developed in 3 of 4 patients carrying the RET C634R variant. The most common symptoms were nephrolithiasis and osteoporosis, and 67% of patients had normocalcemic pHPT. Selective surgery was performed in 9 patients and subtotal parathyroidectomy in 1 patient. The median follow-up duration after the diagnosis of pHPT was 10.5 years, and persistent disease developed in 1 patient. Recurrent hyperparathyroidism occurred in 1 patient 12 years after the first operation. Five patients developed permanent hypoparathyroidism. Conclusion: The RET mutation at codon 634 is associated with a high frequency of pHPT, usually accompanied by normocalcemia or, less frequently, mild hypercalcemia. [ABSTRACT FROM AUTHOR]

The Abbott Determine Rapid Syphilis TP assay is a treponemal test that can be used in resource-poor settings that lack laboratory facilities. However, this test has not been extensively evaluated. We measured its sensitivity and specificity by using stored serum specimens (n = 567) from all persons who tested Treponema pallidum hemagglutination assay (TPHA) positive (n = 250) or TPHA indeterminate (n = 17) in the year 2001 and the first 300 patients in 2001 who tested TPHA negative at the Evandro Chagas Research Institute in Rio de Janeiro, Brazil. This rapid assay was independently interpreted by three different observers. With TPHA results as the reference, sensitivity ranged between readers from 95.6 to 98.4% and specificity ranged from 97.3 to 95.7%. There was little interreader variability in the interpretation of results, with approximately 98% agreement for all reader combinations. Of samples from persons with human immunodeficiency virus (HIV) infection (n = 198), sensitivity was 96.9 to 99.2% and it was 94.4 to 96.3% among HIV-negative persons (n = 127). Specificity was 92.4 to 95.5% among HIV-positive persons and 97.2 to 100% among HIV-negative persons. We found this test to have high sensitivity and specificity and little interreader variability, indicating that it may be easily used in resource-poor settings without laboratory facilities. Further studies are needed using this test on whole blood and under the clinical conditions for which it is intended.

We report a case of Miller Fisher syndrome and bilateral demyelinating optic neuropathy suggesting the possible involvement of central nervous system in this syndrome. The optic neuritis was confirmed by visual evoked potential.

Surface temperature can be used as a tool for calculating sensible heat transfer. However, it needs to be associated with air temperature to identify the direction of heat flow (gain or loss). This study quantified sensible heat transfer in Japanese quail as a function of operative temperature. The meteorological variables were air temperature, relative humidity, and black globe temperature. Quail surface temperature was measured on 50 adult Coturnix coturnix japonica individuals 270 days old during 8 days by using a thermographic camera. The data were analyzed by the least-squares method to assess the effects of sex (male and female), period of the day (morning and afternoon), and body region (head, body, and feet). Quail surface temperature was strongly correlated with operative temperature. The total sensible heat flow was 64.02 W m -2 . The morning period had a mean operative temperature of 22.48 °C, providing a higher gradient between air and quail temperature and thereby producing a higher heat flow (82.19 W m -2 ). In the afternoon, the heat transfer was lower (45.70 W m -2 ) because the operative temperature was higher (30.84 °C). Comparison between sexes showed that heat transfer was higher in females (67.37 W m -2 ) than in males (60.53 W m -2 ). The head served as an important thermal window, with a heat transfer of 78.24 W m -2 , whereas the body and feet had a transfer of 56.80 W m -2 . Heat transfer by sensible mechanisms was quantified in Japanese quail. Heat transfer depended greatly on ambient temperature. When the operative temperature was below 28 °C, sensible mechanisms were efficient in dissipating heat to the environment. When the ambient temperature exceeded 29 °C, quail could not effectively dissipate heat to the environment through sensible mechanisms. At 30 °C and above, heat loss shifted to heat gain, causing thermal stress in Japanese quail., (© 2023. The Author(s) under exclusive licence to International Society of Biometeorology.)

In this philosophical exploration, we investigate the concept of robotic moral environment interaction. The common view understands moral interaction to occur between agents endowed with ethical and interactive capacities. However, recent developments in moral philosophy argue that moral interaction also occurs in relation to the environment. Here conditions and situations of the environment contribute to human moral cognition and the formation of our moral experiences. Based on this philosophical position, we imagine robots interacting as moral environments—a novel conceptualization of human–robot moral interaction with an inherent capacity for moral augmentation. To explicate this idea, we first define moral environments as moral systems providing moral affordances. We then intuit and explicate two constitutive conditions of moral environments: the environment's moral ambiance and its moral atmosphere and compare them with real-life cases of moral environments—the moral landmarks. Based on these explications, we construct several explanatory cases to illustrate robots interacting as moral environments. Lastly, we set to evaluate the ethical challenges and wider social ramifications of using moral environment robots in the public space. [ABSTRACT FROM AUTHOR]

Abstract, author, keywords, institution, and cited literature, and used CiteSpace (version 6.1.R3) to visualize the data through the knowledge map, burst keyword analysis, cluster analysis, and collaborative network analysis. Results: A total of 979 articles and reviews were retrieved. Regarding productivity, the top 2 countries were the United States (n =239) and Japan (n =236). Hidetaka Wakabayashi (n =26) was one of the most prolific writers. The first paper in the frequency ranking of references cited was a white paper: European Society for Swallowing Disorders and European Union Geriatric Medicine Society white paper: oropharyngeal dysphagia as a geriatric syndrome (n =53). "Prevalence" (n =173), "risk factor" (n =119), and "aspiration pneumonia" (n =108) were the most frequently occurring keywords (excluding defining nouns). The study identified reliability, tongue pressure, home discharge, and swallowing function as research hotspots from 2020 to 2022. Conclusion: Prevalence, risk factors, and pneumonia are significant areas of study. Tongue pressure and sarcopenia are research hotspots and potential targets. In the future, research on dysphagia needs to refine strategies for prevention and control, as well as provide tertiary preventative services. [ABSTRACT FROM AUTHOR]

Smallholder farmers, crucial to global food security, face challenges in sustainable integration into agricultural innovation due to inherent flaws in existing finance models. This research addresses the conspicuous gap in comprehensive reviews on sustainable finance in agriculture through a bibliometric approach. Financial constraints, limited market access, and climate vulnerability plague smallholder farmers, hindering the long-term sustainability of current financial models. This study aims to systematically map the scholarly landscape of sustainable finance models for smallholder farmers, focusing on the adoption of agricultural innovations. A critical knowledge gap exists regarding bibliometric patterns and trends in the adoption of agricultural innovations by smallholder farmers. The study utilizes the RAPID framework for a streamlined and evidence-based bibliometric review, employing RStudio and the bibliometrix-package. The analysis aims to recognize, assess, purge, investigate, and document key themes and emerging patterns in the literature. Noteworthy trends from bibliometric reviews indicate a rise in bibliometric approaches, with VOSviewer as a prevalent tool. This research contributes methodologically by advocating for Scopus as the primary database. The study's significance lies in informing policy, practice, and research initiatives supporting smallholder farmers. By revealing bibliometric patterns, this study aims to guide the design of innovative and context-specific financial instruments, fostering a more sustainable and inclusive agricultural landscape. In conclusion, this research endeavors to bridge the knowledge gap and provide novel insights at the intersection of sustainable finance and agricultural innovation adoption. The anticipated outcomes will inform the development of tailored financial models, advancing the resilience and productivity of smallholder farmers globally. [ABSTRACT FROM AUTHOR]

Copyright of Enfermagem em Foco is the property of Conselho Federal de Enfermagem and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The finance and natural resources revenue nexus play a critical role in an economy. The recent development and significant increase in academic literature regarding the resource-finance nexus are the primary motivations for conducting this study. This study aims to conduct a bibliometric analysis of 363 documents published between 1976 and 2021 collected from the Scopus database. The results have been demonstrated via graphs, tables, knowledge maps about the past trends, growth, and prospects using co-occurrence, co-authorship, and co-citation analysis via the VOSviewer tool. This study has identified prolific authors, journals, countries, academic institutions, and future pathways. The findings indicate that China has the highest share of publications (88, 24.2%), followed by Pakistan (58, 15.9%) and Turkey (37, 10.2%). The most productive academic institution is the Beijing Institute of Technology in China (13, 3.6%). This study proposes new avenues for further research concerning the resource-finance nexus, such as ecological footprint, sustainability, fiscal decentralization, green investment, energy prices, environmental quality, technological innovation, financial resource curse (especially the stock market resource curse), human capital, and renewable energy in policy development and sustainability towards the achievement of the SDGs. [ABSTRACT FROM AUTHOR]

Background: This case report provides detailed experiences of a patient with Multiple Endocrine Neoplasia type 2A (MEN-2A) who underwent surgery for pheochromocytoma and medullary thyroid cancer (MTC). Case Report: A 58-year-old male patient with resistant hypertension, despite triple anti-hypertensive drug therapy, was diagnosed with pheochromocytoma after investigation into the underlying etiology. Although the adrenalectomy performed was unilateral rather than bilateral, and there were no signs of Cushing's syndrome or adrenal insufficiency before the operation, temporary adrenal insufficiency developed after the excision of the large adrenal mass. Additionally, the biochemical diagnosis of MTC was primarily established using a calcium stimulation test (CST) rather than basal calcitonin levels. Conclusion: In cases where unilateral adrenalectomy is performed for a large adrenal mass, postoperative hypotension resistant to conservative therapy should raise suspicion of adrenal insufficiency. Furthermore, when basal calcitonin levels fall within the gray zone, a CST may be necessary for the diagnosis of MTC. [ABSTRACT FROM AUTHOR]

Copyright of Revista Baiana de Enfermagem is the property of Universidade Federal da Bahia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Respiration rate (RR) is a proficient indicator to measure the health status of cattle. The common method of measurement is to count the number of respiratory cycles each minute based on flank movements. However, there is no consistent method of execution. In previous studies, various methods have been described, including counting flank movements for 15 s, 30 s or 60 s as well as stopping the time for 5 or 10 breaths. We assume that the accuracy of the aforementioned methods differs. Therefore, we compared their precision with an RR sensor, which was used as the reference method in this study. Five scientists from the fields of agricultural science and veterinary medicine quantified the flank movement according to each of the five methods mentioned above. The results showed that with an average RR of 30 breaths per minute (bpm), all methods showed a high correlation to the values of the RR sensor. However, counting breaths for 60 s had the highest level of conformity with the RR sensor (Lin's concordance correlation coefficient: 0.96) regardless of the level of RR. With rising RR, the inaccuracy increased significantly for the other four investigated methods, especially when counting 5 and 10 breaths. Therefore, we would recommend that counting for 60 s should be used as the standard method for future studies due to its high precision regardless of the level of RR. [ABSTRACT FROM AUTHOR]

Background A syphilis outbreak among Australian Aboriginal and Torres Strait Islander people (respectfully referred to as Aboriginal) has resulted in almost 4000 notifications by 2020, with several congenital syphilis cases and infant deaths. Outbreak control efforts became coordinated under a National enhanced test and treat response in 2017. We evaluated the impact of these efforts and of expansion of testing interventions on syphilis prevalence. Methods We developed an individual-based mathematical model of infectious syphilis transmission among young heterosexual Aboriginal people aged 15–34 years living in and moving between regional and remote areas, and we assessed the impact of existing and hypothetical outbreak control responses on syphilis prevalence. Results The increased testing coverage achieved through the response (from 18% to 39% over 2011–2020) could stabilize the epidemic from 2021. To return to pre-outbreak prevalence (<0.24%) by 2025, testing coverage must reach 60%. The addition of annual community-wide screening, where 30% of youth in communities are tested over 6 weeks, would reduce prevalence to the pre-outbreak level within 4 years. If testing coverage had been scaled-up to 60% at the start of outbreak in mid-2011, the outbreak would have been mitigated. Conclusions Our results suggest that to control the syphilis outbreak, the response needs to be delivered to enable the maximum coverage of testing to be reached in the shortest time to reduce the prevalence to pre-outbreak levels. Reduction could be hastened with community-wide screening at similar time periods across all communities together with increases in annual testing coverage. [ABSTRACT FROM AUTHOR]

Copyright of Enfermagem em Foco is the property of Conselho Federal de Enfermagem and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Enfermagem em Foco is the property of Conselho Federal de Enfermagem and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Enfermería Global is the property of Servicio de Publicaciones de la Universidad de Murcia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Germline RET mutations and variants are involved in development of multiple endocrine neoplasia type 2 (MEN2). The present study investigated a spectrum of RET variants, analyzed genotype-phenotype relationships, and evaluated their effect on the MEN2 phenotype in Han Chinese patients.Methods: Targeted sequencing detected germline RET variants in 697 individuals, including 245 MEN2, 120 sporadic medullary thyroid cancer (MTC), and 15 pheochromocytoma (PHEO) patients and their 493 relatives. In silico analyses and classifications following ACMG-2015 were performed. Demographic, clinical variant types, and endocrine neoplasia molecular diagnosis records were also analyzed.Results: Nineteen different RET mutations (18 point and 1 del/ins mutations) in 214 patients with MEN2A (97.7%) or MEN2B (2.3%) were found, of which exon 11/10 mutations accounted for 79% (169/214). Nineteen compound mutations were found in 31 patients with MEN2A. Twenty-three variants (18 single and 5 double base substitution/compound variants) non-classification were also found. Of these, 17 (3 of pathogenic, 10 of uncertain significance, 2 of likely benign and 2 as benign) were found in 31 patients with MTC/PHEO. The remaining 6 variants (4 of uncertain significance and 2 of likely benign) found in 8 carriers had no evidence of MEN2. The entire cohort showed MEN2A-related PHEO, all occurring in exons 11/10, particularly at C634. Kaplan-Meier curves showed age-dependent penetration rates of MTC and PHEO, and occurrence rates of PHEO in patients with exon 11 mutations were all higher than those within exon 10; these bilateral PHEO were always associated with exon 11 mutations (all P < 0.05). While patient offspring had PHEO, parents with MEN2A had none, the frequency was approximately 10%. Interestingly, at least 6.8% of families were adoptive. Also, 3 non-hotspot RET variants (R114H, T278N, and D489N) appeared with high frequency. Conversely, polymorphism S836S was absent.Conclusions: These data are largely consistent with current evidence-based recommendations in the clinical practice guidelines. Diversity of RET variants or carriers may involve a different natural disease course. Further large-scale targeted sequencing studies will serve as an accurate and cost-effective approach to investigating MEN2 genotype-phenotype correlations for discovery of rare or unknown variants of RET. [ABSTRACT FROM AUTHOR]

Brazil has one of the fastest-growing COVID-19 epidemics worldwide. Non-pharmaceutical interventions (NPIs) have been adopted at the municipal level with asynchronous actions taken across 5,568 municipalities and the Federal District. This paper systematises the fragmented information on NPIs reporting on a novel dataset with survey responses from 4,027 mayors, covering 72.3% of all municipalities in the country. This dataset responds to the urgency to track and share findings on fragmented policies during the COVID-19 pandemic. Quantifying NPIs can help to assess the role of interventions in reducing transmission. We offer spatial and temporal details for a range of measures aimed at implementing social distancing and the dates when these measures were relaxed by local governments. Measurement(s) prevention and control intervention • SARS-CoV-2 non-pharmaceutical interventions Technology Type(s) Survey Sample Characteristic - Location Brazil Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13862108 [ABSTRACT FROM AUTHOR]

Dengue virus, the etiological agent of dengue fever (DF) occurs in four genetically distinct serotypes (DENV1-4), being transmitted by female Aedes mosquitoes. DF incidence is increasing in Brazil, following vector dispersal, proliferation and DENV serotypes introduction, co-circulation and substitution. Medium- and small-sized cities in Sao Paulo State, such as Marilia (Midwest region), have been affected by huge epidemics. To understand the evolution of DENV epidemics in medium-sized cities, in this study a historical data on DENV incidence (2000-2015) in Marilia, was evaluated. Previous studies disclosed regional and specific DF outcomes associated with 2007 outbreak in that city, when co-circulating DENV1 and DENV3 presented different hematological profiles. In this study, characteristics of 2007 DENV epidemics were compared to the epidemiological, hematological and demographic outlines of the major outbreak of DENV1 in Marilia in 2015. DENV1 genetic diversity was assessed through capsid and pre-membrane junction encoding gene (CprM) sequencing. The results revealed circulation of DENV1 serotype from 2007 to 2015, with epidemics occurring every three-years until 2013 and then, increasing yearly. There were significant differences in hematological profiles of DENV1 patients between 2015 and 2007. CprM showed DENV1 genetic variability in 2015, contrasting with the unique sequence pattern in 2007. These results reinforce the regional and temporal characteristics of DENV epidemics that need local public health research to improve care for people and to limit the spread of new serotypes/genotypes to uninfected areas. [ABSTRACT FROM AUTHOR]

After the groundbreaking works of Joseph Schumpeter, a burgeoning literature related to innovations emerged. As works in this tradition have progressed, the innovation literature has recognized that the keystone to stimulate innovation across all economies relies on Research and Development (R&D) activities. As well occur in all modern economies, innovation and R&D have drawn the attention of the academic literature and governments in Latin America and the Caribbean countries (LAC). However, the process of innovation and R&D investments in LAC have different signatures, which may result in a complex and fragmented literature. As a novelty, this research explains how innovation and R&D are fundamental in modern times and brings new systematic literature review of the state-of the-art in innovation and R&D in manufacturing industries across LAC. The results suggests that the LAC has great challenges and opportunities. The review demonstrates that after decades of investment, innovation and R&D gains prominence and firms invest more on these activities. However, the development and investment in these activities, especially considering the government support and firm cooperation are frustrating when compared to OECD countries and Asian Tigers' economies, and yet much remains to be done by the governments. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia type 2 (MEN2) is a rare hereditary syndrome due to mutations of the proto-oncogene REarranged during Transfection (RET), defined by the association of medullary thyroid carcinoma (MTC) in almost 100% cases, and pheochromocytoma in roughly 50% (primary hyperparathyroidism can be seen in 10–20% of patients with MEN2A). Early thyroidectomy and the efficacy of novel tyrosine kinase inhibitors modified the natural history of MTC, with possibilities of cure or long-term control. The second main compound, pheochromocytoma, is reported with a variable penetrance, from 10 to 80% cases, depending on the mutation of RET. Pheochromocytoma constitutes the main disease to screen in patients with RET mutations. Pheochromocytoma clinical and biochemical diagnosis, as well as the way to treat it are thus crucial. This review will thus focus on the epidemiological specificities of MEN2-related pheochromocytoma, the genotype/phenotype relationship, the modern imaging modalities necessary to confirm the diagnosis in this hereditary context, as well as the optimal management and the possibilities of adrenal sparing surgery. Additional information will include the natural history of MEN2B-pheochromocytoma, the rare cases of malignant pheochromocytoma, and the factors that could modify the penetrance between individuals carrying the same mutation, especially in the same family. [ABSTRACT FROM AUTHOR]

A. ACUTE HYPERCAPNIC RESPIRATORY FAILURE A1. Acute Exacerbation of COPD: Recommendations: NIV should be used in management of acute exacerbation of COPD in patients with acute or acute-on-chronic respiratory acidosis (pH = 7.25-7.35). (1A) NIV should be attempted in patients with acute exacerbation of COPD (pH <7.25 & PaCO2 ≥ 45) before initiating invasive mechanical ventilation (IMV) except in patients requiring immediate intubation. (2A). Lower the pH higher the chance of failure of NIV. (2B) NIV should not to be used routinely in normo- or mildly hyper-capneic patients with acute exacerbation of COPD, without acidosis (pH > 7.35). (2B) A2. NIV in ARF due to Chest wall deformities/ Neuromuscular diseases: Recommendations: NIV may be used in patients of ARF due to chest wall deformity/Neuromuscular diseases. (PaCO2 ≥ 45) (UPP) A3. NIV in ARF due to Obesity hypoventilation syndrome (OHS): Recommendations: NIV may be used in AHRF in OHS patients when they present with acute hypercapnic or acute on chronic respiratory failure (pH 45). (3B) NIV/CPAP may be used in obese, hypercapnic patients with OHS and/or right heart failure in the absence of acidosis. (UPP) B. NIV IN ACUTE HYPOXEMIC RESPIRATORY FAILURE: B1. NIV in Acute Cardiogenic Pulmonary Oedema: Recommendations: NIV is recommended in hospital patients with ARF, due to Cardiogenic pulmonary edema. (1A). NIV should be used in patients with acute heart failure/ cardiogenic pulmonary edema, right from emergency department itself. (1B) Both CPAP and BiPAP modes are safe and effective in patients with cardiogenic pulmonary edema. (1A). However, BPAP (NIV-PS) should be preferred in cardiogenic pulmonary edema with hypercapnia. (3A) B2. NIV in acute hypoxemic respiratory failure: Recommendations: NIV may be used over conventional oxygen therapy in mild early acute hypoxemic respiratory failure (P/F ratio <300 and >200 mmHg), under close supervision. (2B) We strongly recommend against a trial of NIV in patients with acute hypoxemic failure with P/F ratio <150. (2A) B3. NIV in ARF due to Chest Trauma: Recommendations: NIV may be used in traumatic flail chest along with adequate pain relief. (3B) B4. NIV in Immunocompromised Host: Recommendations: In Immunocompromised patients with early ARF, we may consider NIV over conventional oxygen. (2B). B5. NIV in Palliative Care: Recommendations: We strongly recommend use of NIV for reducing dyspnea in palliative care setting. (2A) B6. NIV in post-operative cases: Recommendations: NIV should be used in patients with post-operative acute respiratory failure. (2A) B6a. NIV in abdominal surgery: Recommendations: NIV may be used in patients with ARF following abdominal surgeries. (2A) B6b. NIV in bariatric surgery: Recommendations: NIV may be used in post-bariatric surgery patients with pre-existent OSA or OHS. (3A) B6c. NIV in Thoracic surgery: Recommendations: In cardiothoracic surgeries, use of NIV is recommended post operatively for acute respiratory failure to improve oxygenation and reduce chance of reintubation. (2A) NIV should not be used in patients undergoing esophageal surgery. (UPP) B6d. NIV in post lung transplant: Recommendations: NIV may be used for shortening weaning time and to avoid re-intubation following lung transplantation. (2B) B7. NIV during Procedures (ETI/Bronchoscopy/TEE/Endoscopy): Recommendations: NIV may be used for pre-oxygenation before intubation. (2B) NIV with appropriate interface may be used in patients of ARF during Bronchoscopy/Endoscopy to improve oxygenation. (3B) B8. NIV in Viral Pneumonitis ARDS: Recommendations: NIV cannot be considered as a treatment of choice for patients with acute respiratory failure with H1N1 pneumonia. However, it may be reasonable to use NIV in selected patients with single organ involvement, in a strictly controlled environment with close monitoring. (2B) B9. NIV and Acute exacerbation of Pulmonary Tuberculosis: Recommendations: Careful use of NIV in patients with acute Tuberculosis may be considered, with effective infection control precautions to prevent air-borne transmission. (3B) B10. NIV after planned extubation in high risk patients: Recommendation: We recommend that NIV may be used to wean high risk patients from invasive mechanical ventilation as it reduces re-intubation rate. (2B) B11. NIV for respiratory distress post extubation: Recommendations: We recommend that NIV therapy should not be used to manage respiratory distress post-extubation in high risk patients. (2B) C. APPLICATION OF NIV: Recommendation: Choice of mode should be mainly decided by factors like disease etiology and severity, the breathing effort by the patient and the operator familiarity and experience. (UPP) We suggest using flow trigger over pressure triggering in assisted modes, as it provides better patient ventilator synchrony. Especially in COPD patients, flow triggering has been found to benefit auto PEEP. (3B) D. MANAGEMENT OF PATIENT ON NIV: D1. Sedation: Recommendations: A non-pharmacological approach to calm the patient (Reassuring the patient, proper environment) should always be tried before administrating sedatives. (UPP) In patients on NIV, sedation may be used with extremely close monitoring and only in an ICU setting with lookout for signs of NIV failure. (UPP) E. EQUIPMENT: Recommendations: We recommend that portable bilevel ventilators or specifically designed ICU ventilators with non-invasive mode should be used for delivering Non--invasive ventilation in critically ill patients. (UPP) Both critical care ventilators with leak compensation and bi-level ventilators have been equally effective in decreasing the WOB, RR, and PaCO2. (3B) Currently, Oronasal mask is the most preferred interface for non-invasive ventilation for acute respiratory failure. (3B) F. WEANING: Recommendations: We recommend that weaning from NIV may be done by a standardized protocol driven approach of the unit. (2B) [ABSTRACT FROM AUTHOR]

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Medullary thyroid carcinoma (MTC) is a rare type of tumor that originates from thyroid C cells and accounts for 2-4% of all malignant thyroid neoplasm s. MTC may occur sporadically or be inherited, as part of the MEN 2 syndrome. Ge rmline mutations of the RET (REarranged during Transfection) proto-oncogene cause hereditary cancer, whereas somatic RET mutations and, less frequently, RAS mutations have been described in sporadic MTC samples. Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC. Nevertheless, despite recent advances, the management of advanced, progressive MTC remains challenging. The multikinase inhibitors (MKI), vandetanib and cabozantinib, were approved for the treatment of progressive or symptomatic MTC, and several other compounds have exhibited variable efficacy. Although these drugs have been shown to improve progression-free survival, no MKI has been shown to increase the overall survival. As these drugs are nonselective, significant off-target toxicities may occur, limiting achievement of the required TK-specific inhibition. Recently, next-generation small-molecule TKI has been developed. These TKI are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. Here, we summarize the curre nt understanding of the intracellular signaling pathways involved in MTC pathogenesis as well as the therapeutic approaches and challenges for the management of advanced MTC, focusing on targeted molecular therapies. [ABSTRACT FROM AUTHOR]

Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm. [ABSTRACT FROM AUTHOR]

The focus of precision cancer medicine is the use of patient genetic signatures to predict disease occurrence and course and tailor approaches to individualized treatment to improve patient outcomes. The rearranged during transfection (RET) receptor tyrosine kinase represents a paradigm for the power of personalized cancer management to change cancer impact and improve quality of life. Oncogenic activation of RET occurs through several mechanisms including activating mutations and increased or aberrant expression. Activating RET mutations found in the inherited cancer syndrome multiple endocrine neoplasia 2 permit early diagnosis, predict disease course and guide disease management to optimize patient survival. Rearrangements of RET found in thyroid and lung tumors provide insights on potential disease aggressiveness and offer opportunities for RET-targeted therapy. Aberrant RET expression in a subset of cases is associated with tumor dissemination, resistance to therapies and/or poorer prognosis in multiple cancers. The potential of RET targeting through repurposing of small-molecule multikinase inhibitors, selective RET inhibitors or other novel approaches provides exciting opportunities to individualize therapies across multiple pathologies where RET oncogenicity contributes to cancer outcomes. [ABSTRACT FROM AUTHOR]

Background: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. Objective: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. Methods: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. Results: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m2, prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. Conclusion: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases. [ABSTRACT FROM AUTHOR]

The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies not only between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which suggests the involvement of additional modulators of the disease. However, genetic factors responsible for this heterogeneity of the MTC clinical course still remain unknown. The aim of this study was to determine if polymorphic variants or specific haplotypes of the RET gene may modify the MTC clinical course. We genotyped the following loci: c.73+9277T>C, c.135G>A, c.1296A>G, c.2071G>A, c.2307T>C, c.2508C>T and c.2712C>G in 142 MTC patients and controls. We demonstrated considerable differences in the genotypes distribution within c.73+9277T>C, c.135G>A and c.2307T>C loci. Our results show that the c.73+9277T variant associated with a decreased activity of the MCS+9.7 RET enhancer is rare in hereditary MTC patients with primary hyperparathyroidism, and thus, may influence the MTC clinical picture. The decreased activity of the RET promoter enhancer reduces RET expression level and may counterbalance the activating mutation in this gene. Frequent co-occurrence of the c.73+9277T allele with p.E768D, p.Y791F, p.V804M or p.R844Q RET mutations may be associated with their attenuation and milder clinical picture of the disease. Haplotypes analysis showed that C-G-A-G-T-(C)-C (c.73+9277T>C - c.135G>A - c.1296A>G - c.2071G>A - c.2307T>G - (c.2508C>T) - c.2712C>G) alleles combination predisposes to pheochromocytomas and primary hyperparathyroidism. We consider that RET haplotypes defining may become an auxiliary diagnostic tool in MTC patients. [ABSTRACT FROM AUTHOR]

Over the last years, the knowledge of MEN2 and non-MEN2 familial forms of pheochromocytoma (PHEO) has increased. In MEN2, PHEO is the second most frequent disease: the penetrance and age at diagnosis depend on the mutation of RET. Given the prevalence of bilateral PHEO (50% by age 50), adrenal sparing surgery, aimed at sparing a part of the adrenal cortex to avoid adrenal insufficiency, should be systematically considered in patients with bilateral PHEO. Non-MEN2 familial forms of PHEO now include more than 20 genes: however, only small phenotypic series have been reported, suggesting that phenotypic features of isolated hereditary PHEO must be better explored, and follow-up series are needed to better understand the outcome of patients carrying mutations of these genes. The first part of this review will mainly focus on these points. In the second part, a focus will be given on MEN2 and non-MEN2 familial forms of hyperparathyroidism (HPTH). Again, the management of MEN2 HPTH should be aimed at curing the disease while preserving an optimal quality of life by a tailored parathyroidectomy. The phenotypes and outcome of MEN1-, MEN4- and HRPT2- related HPTH are briefly described, with a focus on the most recent literature data and is compared with familial hypocalciuric hypercalcemia. [ABSTRACT FROM AUTHOR]