The Prevalence and Prognostic Implications of BRAF K601E Mutations in Thyroid Neoplasms: A Systematic Review and Meta-Analysis.

BACKGROUND: Activating mutations in the BRAF oncogene occur in 45% of papillary thyroid carcinomas (PTCs). Though less studied, K601E may identify a clinically distinct subset of thyroid neoplasms. METHODS: A bioinformatics assessment was conducted using the COSMIC database and in silico data analysis. A systematic search was conducted through August 2024 to identify studies reporting BRAF mutation in thyroid neoplasms. Pooled prevalence, histopathological subtype distribution, extrathyroidal extension, lymph node metastasis, recurrence, and survival were extracted/analyzed from 32 studies (13 191 patients). RESULTS: In the COSMIC database, BRAF K601E was found in various tissue types but mainly in the thyroid. In silico data analysis revealed a structural and functional basis for differences between K601E and V600E. Upon systematic review, the BRAF K601E mutation was identified in 2.8% of PTCs compared to 22% with V600E. The stratified analysis revealed geographical differences, with higher rates in Italy (5.23%) and the United States of America (3.31%). The K601E mutant was enriched for follicular-patterned variants like NIFTP (11.2% of cases). Meta-analysis demonstrated significantly reduced extrathyroidal extension for K601E versus V600E mutants (RR = 0.22, 95% CI = 0.10-0.50, p = 0.0003). CONCLUSION: K601E-mutated neoplasms could be a unique clinicopathological entity associated with low-risk histology and reduced extrathyroidal extension, consistent with a more indolent course than V600E mutants. Although detecting K601E may potentially guide conservative management, further prospective studies are needed.

Feedback Versus Compliments Versus Both in Suturing and Knot Tying Simulation: A Randomized Controlled Trial.

INTRODUCTION: Suturing is an expected skill for students graduating from health professions programs. Previous studies investigated student experience with teaching sessions utilizing constructive feedback versus compliments but did not investigate the combination of both. METHODS: In this parallel, randomized controlled trial, participants were divided into three groups: feedback (F), compliments (C), or feedback and compliments (FC). Participants received standardized instruction on simple interrupted suturing and two-handed knot-tying, and were videotaped performing this skill before and after the intervention. Performance was evaluated using a validated Objective Structured Assessment of Technical Skills (OSATS) instrument. Participants completed a preintervention and postintervention survey rating their task enjoyment and self-assessment of performance. Analysis was performed to determine differences between and within the groups using Kruskal-Wallis, Wilcoxon rank-sum, and Mann-Whitney U tests. RESULTS: A total of 31 students participated: 11 in C, 10 in F, and 10 in FC. The groups had similar preintervention OSATS scores. The F and FC groups demonstrated significant improvement in OSATS score after intervention, group C was not significantly different: F median of 11.25-19.75 points (P = 0.002); FC median of 11.75-21 points (P = 0.002); C median of 13-14 points (P = 0.2266). Between the groups FC and F both had significant performance improvement compared with C (P < 0.001 and P = 0.001 respectively). The FC group had a significantly higher rating of their enjoyment of the task on the postintervention survey compared with both the C and F groups with a median rating of 10 compared with 8 and 8 (P = 0.0052 and P = 0.0126, respectively). CONCLUSIONS: The combination of feedback and compliments was associated with improvement in performance on suturing and knot-tying similar to the feedback-only group. The FC group rated a higher level of enjoyment of the activity compared to feedback or compliments alone.

Mapping Teacher Informal Advice Networks as a Tool for District Administrators: A Case Study.

With few resources and little time for professional development, science education leaders need ways to efficiently disseminate effective pedagogical practices, improve instruction, and support science teachers (Shaked and Schecter, 2016). Efficient leader strategies are especially important as teachers and districts face reforms to existing standards. One potential avenue for dissemination is leveraging the informal social networks of teachers. Therefore, it is necessary to map and interpret informal teacher networks. We describe a case study involving a partnership of university researchers and a district science curriculum specialist who collected survey data to map district teacher informal advice-seeking networks. We also describe the kinds of network analysis information that science education leaders can use to make strategic decisions about the costs and benefits of efforts directed at all teachers (e.g. workshops, annual professional development time) and those directed at highly connected teachers who can become or already are informal leaders in their communities.

Host specificity shapes fish viromes across lakes on an isolated remote island.

Fish viromes often provide insights into the origin and evolution of viruses affecting tetrapods, including those associated with imporant human diseases. However, despite fish being the most diverse vertebrate group, their viruses are still understudied. We investigated the viromes of fish on Chatham Island (Rekohu), a geographically isolated island housing 9% of New Zealand's threatened endemic fish species. Using metatranscriptomics, we analyzed samples from seven host species across 16 waterbodies. We identified 19 fish viruses, including 16 potentially novel species, expanding families such as the Coronaviridae, Hantaviridae, Poxviridae, and the recently proposed Tosoviridae. Surprisingly, virome composition was not influenced by the ecological factors measured and smelt (Retropinna retropinna) viromes were consistent across lakes despite differences in host life history, seawater influence, and community richness. Overall, fish viromes across Rekohu were highly diverse and revealed a long history of co-divergence between host and virus despite their unique and geographically isolated ecosystem.

Decline Is Not Inevitable: Changes in Science Identity during the Progression through a U.S. Middle School among Boys and Girls.

In the United States, science capital is important for navigating many aspects of life. Yet during middle school, science interest declines more for girls than boys. It is unclear, however, whether science identity also declines during the middle school years and if there are differences by gender. The authors advance prior research by modeling changes in science identity and associations with changes in identity-relevant characteristics using growth curve analyses on four waves of data from 760 middle school youth. For girls and boys, science identity changes over time; about 40 percent of the variance is within-person change, with the remainder explained by aggregate between-person differences. The associations of all identity-relevant characteristics with science identity are not significantly different for girls and boys, yet declines in average values of identity-relevant characteristics are larger for girls than boys.

The Impact of Climate Change on Asthma and Allergic-Immunologic Disease.

PURPOSE OF REVIEW: This review discusses climate change-related impacts on asthma and allergic-immunologic disease, relevant US public health efforts, and healthcare professional resources. RECENT FINDINGS: Climate change can impact people with asthma and allergic-immunologic disease through various pathways, including increased exposure to asthma triggers (e.g., aeroallergens, ground-level ozone). Climate change-related disasters (e.g., wildfires, floods) disrupting healthcare access can complicate management of any allergic-immunologic disease. Climate change disproportionately affects some communities, which can exacerbate disparities in climate-sensitive diseases like asthma. Public health efforts include implementing a national strategic framework to help communities track, prevent, and respond to climate change-related health threats. Healthcare professionals can use resources or tools to help patients with asthma and allergic-immunologic disease prevent climate change-related health impacts. Climate change can affect people with asthma and allergic-immunologic disease and exacerbate health disparities. Resources and tools are available to help prevent climate change-related health impacts at the community and individual level.

Equitable access to speech practice for rural Australian children using the SayBananas! mobile game.

PURPOSE: To evaluate the effect, usage, and user-experience for SayBananas!, a Mario-style mobile game providing Australian children access to high-dose individualised speech therapy practice. METHOD: Participants were 45 rural Australian children with speech sound disorders (SSD; 4;4-10;5 years) with internet access. This mixed-methods study involved: (a) recruitment, (b) eligibility screening, (c) questionnaire, (d) online pre-assessment, (e) SayBananas! intervention using motor learning principles (4 weeks, 10-15 target words), and (f) online post-assessment and interview. Usage and performance were automatically monitored. RESULT: Most participants were highly engaged with SayBananas! completing a median of 44.71 trials/session (∼45% of the 100 trial/session target, range 7-194). After intervention, participants made significant gains on treated words and on formal assessment of percentage of consonants, vowels, and phonemes correct. There was no reliable change for parent-rated intelligibility or children's feelings about talking. The number of practice sessions was significantly correlated with percent change on treated words. On average, children rated the app as "happy/good/fun" providing detailed drawings of playing SayBananas!. Families provided high ratings of engagement, functionality, aesthetics, and quality. CONCLUSION: SayBananas! is a viable and engaging solution for rural Australian children with SSD to gain access to equitable, cost-effective speech practice. The amount of app use was associated with amount of speech production improvement over a 4-week period.

Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice.

The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, associated with two low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioenergetic impairment in the hippocampus, characterized by a decrease in both O2 consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by the two-hit protocol, here verified through the absence of a decrease in O2 consumption after uncoupled protein-1 inhibition and an increase in the reserve respiratory capacity. Impaired mitochondrial function was also observed in the liver of HFD+STZ juvenile mice, but not in their heart. These results indicate that exposure to HFD+STZ early in life has a detrimental impact on the bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment.

Induction of pyroptotic cell death as a potential tool for cancer treatment.

Cancer is a complex pathological disease and the existing strategies for introducing chemotherapeutic agents have restricted potential due to a lack of cancer cell targeting specificity, cytotoxicity, bioavailability, and induction of multi-drug resistance. As a prospective strategy in tackling cancer, regulating the inflammatory pyroptosis cell death pathway has been shown to successfully inhibit the proliferation and metastasis of various cancer cell types. Activation of inflammasomes such as the NLRP3 results in pyroptosis through cleavage of gasdermins, which forms pores in the cell membranes, inducing membrane breakage, cell rupture, and death. Furthermore, pyroptotic cells release pro-inflammatory cytokines such as IL-1ß and IL-18 along with various DAMPs that prime an auxiliary anti-tumor immune response. Thus, regulation of pyroptosis in cancer cells is a way to enhance their immunogenicity. However, immune escape involving myeloid-derived suppressor cells has limited the efficacy of most pyroptosis-based immunotherapy strategies. In this review, we comprehensively summarize the cellular and molecular mechanisms involved in the inflammasome-mediated pyroptosis pathways in cancer cells, exploring how it could modulate the tumor microenvironment and be beneficial in anti-cancer treatments. We discuss various existing therapeutic strategies against cancer, including immunotherapy, oncolytic virus therapy, and nanoparticle-based therapies that could be guided to trigger and regulate pyroptosis cell death in cancer cells, and reduce tumor growth and spread. These pyroptosis-based cancer therapies may open up fresh avenues for targeted cancer therapy approaches in the future and their translation into the clinic.

Inflammasome-Mediated Cytokines: A Key Connection between Obesity-Associated NASH and Liver Cancer Progression.

Liver cancer is one of the most lethal malignancies and is commonly diagnosed as hepatocellular carcinoma (HCC), a tumor type that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. HCC initiation and progression are deeply linked with changes in the hepatic microenvironment, with cytokines playing key roles. The understanding of the pathogenic pathways that connect these disorders to liver cancer remains poor. However, the inflammasome-mediated cytokines associated with both diseases are central actors in liver cancer progression. The release of the pro-inflammatory cytokines IL-1ß and IL-18 during inflammasome activation leads to several detrimental effects on the liver microenvironment. Considering the critical crosstalk between obesity, NASH, and HCC, this review will present the connections of IL-1ß and IL-18 from obesity-associated NASH with HCC and will discuss approaches to using these cytokines as therapeutic targets against HCC.

Development of New Natural Lipid-Based Nanoparticles Loaded with Aluminum-Phthalocyanine for Photodynamic Therapy against Melanoma.

Photodynamic therapy (PDT) mediated by photosensitizers loaded in nanostructures as solid lipid nanoparticles has been pinpointed as an effective and safe treatment against different skin cancers. Amazon butters have an interesting lipid composition when it comes to forming solid lipid nanoparticles (SLN). In the present report, a new third-generation photosensitizing system consisting of aluminum-phthalocyanine associated with Amazon butter-based solid lipid nanoparticles (SLN-AlPc) is described. The SLN was developed using murumuru butter, and a monodisperse population of nanodroplets with a hydrodynamic diameter of approximately 40 nm was obtained. The study of the permeation of these AlPc did not permeate the analyzed skin, but when incorporated into the system, SLN-AlPc allowed permeation of almost 100% with 8 h of contact. It must be emphasized that SLN-AlPc was efficient for carrying aluminum-phthalocyanine photosensitizers and exhibited no toxicity in the dark. Photoactivated SLN-AlPc exhibited a 50% cytotoxicity concentration (IC50) of 19.62 nM when applied to B16-F10 monolayers, and the type of death caused by the treatment was apoptosis. The exposed phospholipid phosphatidylserine was identified, and the treatment triggered a high expression of Caspase 3. A stable Amazon butter-based SLN-AlPc formulation was developed, which exhibits strong in vitro photodynamic activity on melanoma cells.

Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases.

Adipose tissues are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. Although white adipose tissue and brown adipose tissue are currently considered key endocrine organs, they differ functionally and morphologically. The existence of the beige or brite adipocytes, cells displaying intermediary characteristics between white and brown adipocytes, illustrates the plastic nature of the adipose tissue. These cells are generated through white adipose tissue browning, a process associated with augmented non-shivering thermogenesis and metabolic capacity. This process involves the upregulation of the uncoupling protein 1, a molecule that uncouples the respiratory chain from Adenosine triphosphate synthesis, producing heat. ß-3 adrenergic receptor system is one important mediator of white adipose tissue browning, during cold exposure. Surprisingly, hyperthermia may also induce beige activation and white adipose tissue beiging. Physical exercising copes with increased levels of specific molecules, including Beta-Aminoisobutyric acid, irisin, and Fibroblast growth factor 21 (FGF21), which induce adipose tissue browning. FGF21 is a stress-responsive hormone that interacts with beta-klotho. The central roles played by hormones in the browning process highlight the relevance of the individual lifestyle, including circadian rhythm and diet. Circadian rhythm involves the sleep-wake cycle and is regulated by melatonin, a hormone associated with UCP1 level upregulation. In contrast to the pro-inflammatory and adipose tissue disrupting effects of the western diet, specific food items, including capsaicin and n-3 polyunsaturated fatty acids, and dietary interventions such as calorie restriction and intermittent fasting, favor white adipose tissue browning and metabolic efficiency. The intestinal microbiome has also been pictured as a key factor in regulating white tissue browning, as it modulates bile acid levels, important molecules for the thermogenic program activation. During embryogenesis, in which adipose tissue formation is affected by Bone morphogenetic proteins that regulate gene expression, the stimuli herein discussed influence an orchestra of gene expression regulators, including a plethora of transcription factors, and chromatin remodeling enzymes, and non-coding RNAs. Considering the detrimental effects of adipose tissue browning and the disparities between adipose tissue characteristics in mice and humans, further efforts will benefit a better understanding of adipose tissue plasticity biology and its applicability to managing the overwhelming burden of several chronic diseases.

Obesity and adipose tissue impact on T-cell response and cancer immune checkpoint blockade therapy.

Many different types of cancer are now well known to have increased occurrence or severity in individuals with obesity. The influence of obesity on cancer and the immune cells in the tumor microenvironment has been thought to be a pleiotropic effect. As key endocrine and immune organs, the highly plastic adipose tissues play crucial roles in obesity pathophysiology, as they show alterations according to environmental cues. Adipose tissues of lean subjects present mostly anti-inflammatory cells that are crucial in tissue remodeling, favoring uncoupling protein 1 expression and non-shivering thermogenesis. Oppositely, obese adipose tissues display massive proinflammatory immune cell infiltration, dying adipocytes, and enhanced crown-like structure formation. In this review, we discuss how obesity can lead to derangements and dysfunctions in antitumor CD8+ T lymphocytes dysfunction. Moreover, we explain how obesity can affect the efficiency of cancer immunotherapy, depicting the mechanisms involved in this process. Cancer immunotherapy management includes monoclonal antibodies targeting the immune checkpoint blockade. Exhausted CD8+ T lymphocytes show elevated programmed cell death-1 (PD-1) expression and highly glycolytic tumors tend to show a good response to anti-PD-1/PD-L1 immunotherapy. Although obesity is a risk factor for the development of several neoplasms and is linked with increased tumor growth and aggressiveness, obesity is also related to improved response to cancer immunotherapy, a phenomenon called the obesity paradox. However, patients affected by obesity present higher incidences of adverse events related to this therapy. These limitations highlight the necessity of a deeper investigation of factors that influence the obesity paradox to improve the application of these therapies.

A literature review: Entrustable professional activities, an assessment tool for postgraduate dental training?

Assessing when dental trainees are ready to independently undertake clinical procedures at specialist level is critical for dental postgraduate programmes to determine when a trainee is 'work ready', in addition to ensuring patient safety. Entrustable professional activities (EPA) are a novel method of competency-based assessment. An EPA is a unit of professional practice or critical clinical activity identified within dental training programmes, which should be assessed during training, to establish if trainees are ready for independent practice, with a progressive decrease in supervision, based on supervisors' entrustment decisions. This article describes EPAs, entrustment decisions, including entrustment supervision scales and the process recommended to develop EPAs within dental curricula. EPAs have not been formally introduced for assessment within dental education programmes in the United Kingdom, but recent developments have been described in undergraduate dental education globally. Clinical significance: Competency-based assessments need to be continually developed to adapt to rapidly changing population health care and dental needs, to determine when dental trainees are ready for independent clinical practice. Early development of entrustable professional activities for assessment in undergraduate dental programmes has been well received by both trainees and supervisors. Further investigation is required to consider formal development of EPAs within postgraduate dental programmes.

Examining the Relationship Between Mild Traumatic Brain Injuries and Development of Mental Illness Disorders in a Mid-Term Follow-up Period.

OBJECTIVE: The sequalae of mild concussions continue to emerge with increased awareness in sports-related injuries. This study aimed to quantify the number of patients who are affected by a mental illness within 3 yrs of a concussion and identify whether demographic differences exist that may influence a mental illness diagnosis. DESIGN: Using a nationwide database, data were queried for a diagnosis of concussion, capturing patients aged 18-45 yrs with no previous mental illness, and then identified if these patients were diagnosed with a mental illness within 3 yrs of their concussion. The mental illnesses specifically chosen for this study included depression, anxiety, panic disorder, posttraumatic stress disorder, bipolar, and schizophrenia. RESULTS: Within 3 yrs after a concussion, 48% of patients were later diagnosed with a mental illness. All of the mental illnesses this study chose to evaluate were present in a higher proportion of patients after a concussion than the general population. CONCLUSIONS: The mechanism between concussions and mental illness remains unclear. A large proportion of patients who experience a concussion are later diagnosed with a mental illness within 3 yrs. Patients with a history of a previous concussion may benefit from screening for the development of a mental illness.

The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy.

Obesity is nowadays considered a pandemic which prevalence's has been steadily increasingly in western countries. It is a dynamic, complex, and multifactorial disease which propitiates the development of several metabolic and cardiovascular diseases, as well as cancer. Excessive adipose tissue has been causally related to cancer progression and is a preventable risk factor for overall and cancer-specific survival, associated with poor prognosis in cancer patients. The onset of obesity features a state of chronic low-grade inflammation and secretion of a diversity of adipocyte-derived molecules (adipokines, cytokines, hormones), responsible for altering the metabolic, inflammatory, and immune landscape. The crosstalk between adipocytes and tumor cells fuels the tumor microenvironment with pro-inflammatory factors, promoting tissue injury, mutagenesis, invasion, and metastasis. Although classically established as a risk factor for cancer and treatment toxicity, recent evidence suggests mild obesity is related to better outcomes, with obese cancer patients showing better responses to treatment when compared to lean cancer patients. This phenomenon is termed obesity paradox and has been reported in different types and stages of cancer. The mechanisms underlying this paradoxical relationship between obesity and cancer are still not fully described but point to systemic alterations in metabolic fitness and modulation of the tumor microenvironment by obesity-associated molecules. Obesity impacts the response to cancer treatments, such as chemotherapy and immunotherapy, and has been reported as having a positive association with immune checkpoint therapy. In this review, we discuss obesity's association to inflammation and cancer, also highlighting potential physiological and biological mechanisms underlying this association, hoping to clarify the existence and impact of obesity paradox in cancer development and treatment.

Cost-effectiveness of specialist eating disorders services for children and adolescents with anorexia nervosa: a national surveillance study.

BACKGROUND: Evidence suggests specialist eating disorders services for children and adolescents with anorexia nervosa have the potential to improve outcomes and reduce costs through reduced hospital admissions. This study aimed to evaluate the cost-effectiveness of assessment and diagnosis in community-based specialist child and adolescent mental health services (CAMHS) compared to generic CAMHS for children and adolescents with anorexia nervosa. METHOD: Observational, surveillance study of children and adolescents aged 8 to 17, in contact with community-based CAMHS in the UK or Republic of Ireland for a first episode of anorexia nervosa. Data were reported by clinicians at baseline, 6 and 12-months follow-up. Outcomes included the Children's Global Assessment Scale (CGAS) and percentage of median expected body mass for age and sex (%mBMI). Service use data included paediatric and psychiatric inpatient admissions, outpatient and day-patient attendances. A joint distribution of incremental mean costs and effects for each group was generated using bootstrapping to explore the probability that each service is the optimal choice, subject to a range of values a decision-maker might be willing to pay for outcome improvements. Uncertainty was explored using cost-effectiveness acceptability curves. RESULTS: Two hundred ninety-eight children and adolescents met inclusion criteria. At 12-month follow-up, there were no significant differences in total costs or outcomes between specialist eating disorders services and generic CAMHS. However, adjustment for pre-specified baseline covariates resulted in observed differences favouring specialist services, due to significantly poorer clinical status of the specialist group at baseline. Cost-effectiveness analysis using CGAS suggests that the probability of assessment in a specialist service being cost-effective compared to generic CAMHS ranges from 90 to 50%, dependent on willingness to pay for improvements in outcome. CONCLUSIONS: Assessment in a specialist eating disorders service for children and adolescents with anorexia nervosa may have a higher probability of being cost-effective than assessment in generic CAMHS. TRIAL REGISTRATION: ISRCTN12676087 . Date of registration 07/01/2014.

Specialist eating disorders services may improve outcomes and reduce hospitalisations for children and adolescents with anorexia nervosa. Reductions in hospitalisation could save money for the NHS and are better for young people because hospitalisation disrupts their home life, social life and education. This study evaluated outcomes and costs of specialist eating disorders services compared to general child and adolescent mental health services (CAMHS) for children and adolescents with anorexia nervosa.Children and adolescents were identified by contacting child and adolescent psychiatrists in the UK and Ireland and asking them to report any new cases of anorexia nervosa. These psychiatrists identified 298 young people aged 8 to 17 with an anorexia nervosa diagnosis for the first time. The psychiatrists provided information on the health services these young people used and how they were doing when they were first diagnosed and 6 months and 1 year later.Children and adolescents in specialist services were more severely ill than those in CAMHS when they were first diagnosed. Despite this, care for the young people in specialist services cost about the same as for those diagnosed in CAMHS, and their outcomes after 1 year were similar. This work showed that specialist services may be better value for money than CAMHS.

The Use of the Anticoagulant Heparin and Corticosteroid Dexamethasone as Prominent Treatments for COVID-19.

COVID-19 is spreading worldwide at disturbing rates, overwhelming global healthcare. Mounting death cases due to disease complications highlight the necessity of describing efficient drug therapy strategies for severe patients. COVID-19 severity associates with hypercoagulation and exacerbated inflammation, both influenced by ACE2 downregulation and cytokine storm occurrence. In this review, we discuss the applicability of the anticoagulant heparin and the anti-inflammatory corticosteroid dexamethasone for managing severe COVID-19 patients. The upregulated inflammation and blood clotting may be mitigated by administrating heparin and its derivatives. Heparin enhances the anticoagulant property of anti-thrombin (AT) and may be useful in conjunction with fibrinolytic drugs for severe COVID-19 patients. Besides, heparin can also modulate immune responses, alleviating TNF-α-mediated inflammation, impairing IL-6 production and secretion, and binding to complement proteins and leukotriene B4 (LTB4). Moreover, heparin may present anti-SARS-CoV-2 potential once it can impact viral infectivity and alter SARS-CoV-2 Spike protein architecture. Another feasible approach is the administration of the glucocorticoid dexamethasone. Although glucocorticoid's administration for viral infection managing is controversial, there is increasing evidence demonstrating that dexamethasone treatment is capable of drastically diminishing the death rate of patients presenting with Acute Respiratory Distress Syndrome (ARDS) that required invasive mechanical ventilation. Importantly, dexamethasone may be detrimental by impairing viral clearance and inducing hyperglycemia and sodium retention, hence possibly being deleterious for diabetics and hypertensive patients, two major COVID-19 risk groups. Therefore, while heparin's multitarget capacity shows to be strongly beneficial for severe COVID-19 patients, dexamethasone should be carefully administered taking into consideration underlying medical conditions and COVID-19 disease severity. Therefore, we suggest that the multitarget impact of heparin as an anti-viral, antithrombotic and anti-inflammatory drug in the early stage of the COVID-19 could significantly reduce the need for dexamethasone treatment in the initial phase of this disease. If the standard treatment of heparins fails on protecting against severe illness, dexamethasone must be applied as a potent anti-inflammatory shutting-down the uncontrolled and exacerbated inflammation.

The Positive Impact of Resistance Training on Muscle Mass and Serum Leptin Levels in Patients 2-7 Years Post-Roux-en-Y Gastric Bypass: A Controlled Clinical Trial.

PURPOSE: Resistance training program (RTP) assist the maintenance of optimal body composition and inflammatory response modulation in individuals in late Roux-en-Y gastric bypass (RYGB). This study aimed to investigate the effect of RTP on body composition and serum inflammatory profile in individuals 2-7 years post-RYGB. METHODS: Volunteers were matched on body mass index (BMI), age, sex, and years after surgery, and they were allocated as control or RTP group. Body composition, visceral fat area (VFA), and inflammatory serum markers were measured at baseline and after 12 weeks of RTP. RESULTS: The sample baseline characteristics (n = 63; BMI = 29.7 ± 5.3 kg/m2) were similar between the groups. After intervention, the RTP group presented higher fat-free mass (Δ 1.17 ± 1.12 kg, p = 0.003) and skeletal muscle mass (Δ 0.77 ± 0.66 kg, p = 0.002) and decreased leptin levels (Δ -0.15 ± 0.60 pg/mL, p = 0.028). Ultrasensitive C-reactive protein (CRPus), interleukin-6, adiponectin, and monocyte chemotactic protein-1 showed no significant time-by-group interaction. After the categorization of RTP group individuals by VFA median values (129.8 cm2, IQR 90.9; 152.5), participants with VFA values above the median presented a significant decrease in CRPus (Δ -0.20 mg/L, IQR -7.59; -0.03, p = 0.022) when compared to the participants with VFA values below the median. CONCLUSION: The RTP improved individuals' body composition by a modest but significant enhancing muscle mass and decreasing serum leptin and CRPus levels, especially in individuals with VFA values above the median. RTPs assist in maintaining the adequate body composition as they contribute to a decrease in proinflammatory markers in long-term RYGB.