The emerging role of exercise as a cancer treatment

Over the past few decades,exercise oncology has emerged as an important subfield within exercise science.Over that time,substantial progress has been made in understanding the role of exercise in people newly diagnosed with cancer,actively being treated for cancer,and recovering after cancer treatments.

Exploring impacts of COVID-19 on spatial and temporal patterns of visitors to Canadian Rocky Mountain National Parks from social media big data

COVID-19 posed challenges for global tourism management.Changes in visitor temporal and spatial patterns and their associated determinants pre-and peri-pandemic in Canadian Rocky Mountain National Parks are analyzed.Data was collected through social media programming and analyzed using spatiotemporal analysis and a geographically weighted regression(GWR)model.Results highlight that COVID-19 significantly changed park visitation patterns.Visitors tended to explore more remote areas peri-pandemic.The GWR model also indicated distance to nearby trails was a significant influence on visitor density.Our results indicate that the pandemic influenced tourism temporal and spatial imbalance.This research presents a novel approach using combined social media big data which can be extended to the field of tourism management,and has important implications to manage visitor patterns and to allocate resources efficiently to satisfy multiple objectives of park management.

Challenges and pitfalls of youth-onset type 2 diabetes

The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications.Indeed,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell function.Therefore,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in mid-life.Due to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment options.In this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

Expect the unexpected:Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism

Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium homeostasis.Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia.Brown tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical practice.The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass.Furthermore,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion.The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and PTH.Although when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic tumors.Treatment of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical intervention.However,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.

How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Sex Determination in Homo sapiens as a Multi-Step Process: Potential for Development of Variants and Sex Differences in Disease Risk

Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pregnancy, and menopause to ensure species survival. It will also discuss how variants in sex determination could contribute to sex differences in disease risk and how epigenetic modifications could play a role in such risk. .

Key challenges of post-liver transplant weight management

Liver transplantation serves as a life-saving intervention for patients with endstage liver disease,yet long-term survival remains a challenge.Post-liver transplant obesity seems to have a significant contribution to this challenge and it emerges as a significant risk factor for graft steatosis,metabolic syndrome and denovo malignancy development.This review synthesizes current literature on prevalence,risk factors and management strategies for post-liver transplant obesity,emphasizing its impact on graft and patient survival.Literature review consultation was conducted in Medline/PubMed,SciELO and EMBASE,with the combination of the following keywords:Weight management,liver transplantation,immunosuppressive therapy,lifestyle interventions,bariatric surgery.Immunosuppressive therapy has a significant influence on long-term survival of liver transplant patients,yet it seems to have lesser effect on post-transplant obesity development than previously thought.However,it significantly contributes to the development of other components of metabolic syndrome.Key predisposing factors for post-transplant obesity development encompass elevated recipient and donor body mass index,a history of alcoholic liver disease,hepatocellular carcinoma,male gender,the absence of cellular rejection and the marital status of the recipient.Tailored immunosuppressive regimens,pharmacotherapy,lifestyle interventions and bariatric surgery represent key components in mitigating post-transplant obesity and improving long-term survival and quality of life in this group of patients.Timely identification and intervention thus hold paramount importance.Further research is warranted to refine optimal management strategies and enhance outcomes in this patient population.

Unlocking a novel determinant of athletic performance:The role of the gut microbiota,short-chain fatty acids,and“biotics”in exercise

The gut microbiota refers to the collection of trillions of intestinal microorganisms that modulate central aspects of health and disease through influential effects on host physiology.Recently,a connection has been made between the gut microbiota and exercise.Initial investigations demonstrated the beneficial effects of exercise on the gut microbiota,with cross-sectional studies revealing positive correlations between exerciseassociated states,and healthy gut microbiota and exercise interventions showed post-intervention increases in the abundance of beneficial bacterial taxa.More recent investigations have focused on exploring the reverse relationship:the influence of the gut microbiota on exercise performance.Murine investigations have revealed that certain bacterial taxa may enhance endurance exercise performance by augmenting various aspects of lactate metabolism.Further,short-chain fatty acids—which modulate metabolism at various organ sites,including within skeletal muscle—have been shown to enhance endurance exercise capacity in mice.This review highlights what is currently known about the connection between the gut microbiota and exercise,with a particular focus on the ergogenic potential of the gut microbiota and how it may be leveraged to enhance endurance exercise performance.

Impacts of COVID-19 on tourism and management response from Banff National Park,Canada

The COVID-19 pandemic posed challenges to the tourism sector globally.We investigated changes in visitor demographics,satisfaction level,and its determinants pre-and peri-COVID-19.Data were collected using questionnaire surveys in 2019 and 2021 within Banff National Park(BNP).The data analyses were based on a sample size of 1183 respondents by conducting factor analysis,correlation analysis and stepwise regression analysis.Results highlight that there were fewer international visitors and more local and domestic visitors during the pandemic.Park attributes were evaluated at a higher satisfaction level peri-COVID-19.The quality of the Park facilities and services were the most important satisfaction determinants pre-and peri-COVID-19,and all the Park COVID-19 measures and actions received positive experience from visitors.This research fills this knowledge gap by developing a better understanding in the change of visitor demographics and satisfaction level in BNP under the context of the pandemic.It also provides implication for both scholars and practitioners to understand the impacts of the pandemic on Park visitation.The study can provide insights for utilizing the pandemic as a transformative strength and for mitigating its negative impact on tourism industry.

Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma:A systematic review and meta-analysis

BACKGROUND Hepatocellular carcinoma(HCC)is among the commonest malignancies associated with significant cancer-related death.The identification of chemopreventive agents following HCC treatments with the potential to lower the risk of HCC adverse course is intriguing.Metformin,a first-line agent used in the treatment of type 2 diabetes mellitus(T2DM),has been associated with inhibition of HCC growth.AIM To determine whether metformin can prevent adverse events(i.e.,death,tumor progression,and recurrence)after any HCC treatment in T2DM patients.METHODS A systematic review of the published literature was undertaken focused on the role of metformin on outcomes in patients with T2DM and HCC receiving any tumor therapy.A search of the PubMed and Cochrane Central Register of Controlled Trials Databases was conducted.RESULTS A total of 13 studies(n=14886 patients)were included in this review.With regard to the risk of death,a decreased risk was reported in cases receiving metformin,although this decrease was not statistically significant[odds ratio(OR)=0.89,P=0.42].When only patients treated with curative strategies were considered,a more marked correlation between metformin and favorable cases was reported(OR=0.70,P=0.068).When analyzing palliative treatment,there was no statistical significance in terms of the correlation between metformin and favorable cases(OR=0.74,P=0.66).As for the risks of progressive disease and recurrence,no obvious correlation between metformin use and reduced risk was reported.When sub-analyses were performed for patients from different regions,the results for patients from Eastern countries showed a tendency for decreased risk of death in T2DM cases receiving metformin(OR=0.69,P=0.17),but the same was not seen in patients from Western countries(OR=1.19,P=0.31).CONCLUSION Metformin failed to show a marked impact in preventing adverse effects after HCC treatment.A trend was reported in T2DM cases receiving curative therapies in relation to the risk of death,especially in patients from Eastern regions.Great heterogeneity was reported among the different studies.Further large studies are required to definitively clarify the real impact of metformin as a chemopreventive agent for HCC.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

The Paris 2024 Olympic and Paralympic Games

The first modern Olympic Games took place in Athens in 1896.While in those early days of the Olympics only amateur and gentleman athletes were allowed to participate,today Olympic athletes are highly trained professionals often dedicating decades of preparation for the chance to compete in the Olympic Games.In sharp contrast to these highly trained athletes,the world’s population becomes less physically active on average,resulting in an obesity epidemic with associated metabolic syndrome and increased mortality through non-communicable diseases(e.g.,Collins et al.^(1)).

Primary hyperparathyroidism-induced acute pancreatitis in pregnancy:A systematic review with a diagnostic-treatment algorithm

BACKGROUND Primary hyperparathyroidism(PHPT)-induced acute pancreatitis(AP)during pregnancy has rarely been described.Due to this rarity,there are no diagnostic or treatment algorithms for pregnant patients.AIM To determine appropriate diagnostic methods,therapeutic options,and factors related to maternal and fetal outcomes for PHPT-induced AP in pregnancy.METHODS A literature search of articles in English,Japanese,German,Spanish,and Italian was performed using PubMed(1946-2023),PubMed Central(1900-2023),and Google Scholar.The Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA)protocol was followed.The search terms included“pancreatite acuta,”“iperparatiroidismo primario,”“gravidanza,”“travaglio,”“puerperio,”“postpartum,”“akute pankreatitis,”“primärer hyperparathyreoidismus,”“Schwangerschaft,”“Wehen,”“Wochenbett,”“pancreatitis aguda,”“hiperparatiroidismo primario,”“embarazo,”“parto,”“puerperio,”“posparto,”“acute pancreatitis,”“primary hyperparathyroidism,”“pregnancy,”“labor,”“puerperium,”and“postpartum.”Additional studies were identified by reviewing the reference lists of retrieved studies.Demographic,imaging,surgical,obstetric,and outcome data were obtained.RESULTS Fifty-four cases were collected from the 51 studies.The median maternal age was 29 years.PHPT-induced AP starts at the 20th gestational week;higher gestational weeks were seen in mothers who died(mean gestational week 28).Median values of amylase(1399,Q1-Q3=519-2072),lipase(2072,Q1-Q3=893-2804),serum calcium(3.5,Q1-Q3=3.1-3.9),and parathormone(PTH)(384,Q1-Q3=123-910)were reported.In 46 cases,adenoma was the cause of PHPT,followed by 2 cases of carcinoma and 1 case of hyperplasia.In the remaining 5 cases,the diagnosis was not reported.Neck ultrasound was positive in 34 cases,whereas sestamibi was performed in 3 cases,and neck computed tomography or magnetic resonance imaging was performed in 9 cases(the enlarged parathyroid gland was not localized in 3 cases).Surgery was the preferred treatment during pregnancy in 33 cases(median week of gestation 25,Q1-Q3=20-30)and postpartum in 12 cases.The timing was not reported in the remaining 9 cases,or surgery was not performed.AP was managed surgically in 11 cases and conservatively in 43(79.6%)cases.Maternal and fetal mortality was 9.3%(5 cases).Surgery was more common in deceased mothers(60.0%vs 16.3%;P=0.052),and PTH values tended to be higher in this group(910 pg/mL vs 302 pg/mL;P=0.059).Maternal mortality was higher with higher serum lipase levels and earlier delivery week.Higher calcium(4.1 mmol/L vs 3.3 mmol/L;P=0.009)and PTH(1914 pg/mL vs 302 pg/mL;P=0.003)values increased fetal/child mortality,as well as abortions(40.0%vs 0.0%;P=0.007)and complex deliveries(60.0%vs 8.2%;P=0.01).CONCLUSION If serum calcium is not tested during admission,definitive diagnosis of PHPT-induced AP in pregnancy is delayed,while early diagnosis and immediate intervention lead to excellent maternal and fetal outcomes.

Associations between health-related fitness and patient-reported symptoms in newly diagnosed breast cancer patients

Background:Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and survival.Preventing and managing breast cancer-related symptoms soon after diagnosis is essential.The purpose of this study was to investigate the associations between health-related fitness(HRF)and patient-reported symptoms in newly diagnosed breast cancer patients.Methods:This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of diagnosis.HRF measures included peak cardiopulmonary fitness(peak volume of oxygen consumption(VO_(2peak))),maximal muscular strength and endurance,flexibility,and body composition.Symptom measures included depression,sleep quality,and fatigue.Adjusted multivariable logistic regression was performed for analyses.Results:Of 1458 participants,51.5%reported poor sleep quality,26.5%reported significant fatigue,and 10.4%reported moderate depression.In multivariable-adjusted models,lower relative VO_(2peak)was independently associated with a greater likelihood of all symptom measures,including moderate depression(p<0.001),poor sleep quality(p=0.009),significant fatigue(p=0.008),any symptom(p<0.001),and multiple symptoms(p<0.001).VO_(2peak)demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest quartile.The strength of the threshold associations varied by the symptom measure with odds ratios ranging from-1.5 for poor sleep quality to-3.0 for moderate depression and multiple symptoms.Moreover,lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner(p=0.001),and higher body weight was independently associated with poor sleep quality in an inverted U pattern(p=0.021).Conclusion:Relative VO_(2peak)appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diagnosed breast cancer patients.Other HRF parameters may also be important for specific symptoms.Exercise interventions targeting different HRF components may help newly diagnosed breast cancer patients manage specific symptoms and improve outcomes.

Commentary on"Speed and surface steepness affect internal tibial loading during running"

It is a pleasure to write a commentary on the work of Dr.Hannah Rice and colleagues,l who have advanced our understanding of how the mechanical loading environment of the tibia changes as a function of running grade and speed.It is important that we understand how the tibia is loaded during conditions that an individual is likely to encounter when running as it is these internal loads which we believe are responsible for the development of bone-stress injuries.

Managing end-stage carcinoid heart disease:A case report and literature review

BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of life.Cardiovascular complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic disease.CASE SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases.During the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to follow-up.After 10 years,he presented to the emergency room with signs and symptoms of right-sided heart failure.Panneuroendocrine markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic metastases.Computed tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis.Furthermore,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart disease.The patient was not a candidate for valve replacement.He started octreotide acetate treatment,and the dose escalated to 80 mg IM monthly.Although biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart failure.Carcinoid heart disease and tumor burden are major prognostic factors of poor survival.Therefore,they must be actively sought by available biochemical markers and imaging techniques.Moreover,imaging techniques aiding tumor detection and staging,somatostatin receptor positron emission tomography/CT,and CT or magnetic resonance imaging,should be performed at the time of diagnosis and in 3-to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery.Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered,while any delay can worsen right-sided ventricular failure.

Towards precision 24-hour movement behavior recommendations—The next new paradigm?

1.Background The importance of physical activity(PA)for health is unequivocal.^(1)Accordingly,population-based recommendations for exercise,and more recently public health guidelines for PA,have been developed and released by authoritative groups for many decades.^(2)Such guidelines emerged with leadership from the exercise physiology discipline and were rooted in,and loyal to,the importance of moderate-to-vigorous intensity PA(MVPA)or exercise.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.

Are treatment options used for adult-onset type 2 diabetes mellitus(equally)available and effective for children and adolescents?

Youth-onset type 2 diabetes mellitus(T2DM),influenced by an increase in obesity,is a rising problem worldwide.Pathophysiological mechanisms of this early-onset T2DM include both peripheral and hepatic insulin resistance,along with increa-sed hepatic fasting glucose production accompanied by inadequate first and second-phase insulin secretion.Moreover,the incretin effect is reduced.The initial presentation of type 2 diabetes can be dramatic and symptoms may overlap with those of type 1 diabetes mellitus.Therefore,immediate therapy should address hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type,while further therapy adjustments are prone to patients’pheno-type.New agents with proven glycemic and beyond glycemia benefits,such as Glucagon-like polypeptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors,used in the adult population of T2DM patients,might become increasingly important in the treatment armamentarium.Moreover,metabolic surgery is an option for markedly obese(body mass index>35 kg/m^(2))children and adolescents suffering from T2DM who have uncontrolled glycemia and/or serious comorbidities when lifestyle and pharmacologic interventions fail.In this mini-review,we will discuss the potential of treatment options considering new data available from randomized control trials,including individuals with adult-onset type diabetes mellitus.

Symptom presentation and evolution in the first 48 hours after injury are associated with return to play after concussion in elite Rugby Union

Background:Return to play(RTP)in elite rugby is managed using a 6-stage graduated RTP protocol,which can result in clearance to play within 1 week of injury.We aimed to explore how symptom,cognitive,and balance presentation and evolution during concussion screens 2 h(head injury assessment(HIA2)and 48 h(HIA3)after injury were associated with time to RTP)to identify whether a more conservative graduated RTP may be appropriate.Methods:A retrospective cohort study was conducted in 380 concussed rugby players from elite men’s rugby over 3 consecutive seasons.Players were classified as shorter or longer returns,depending on whether RTP occurred within 7 days(allowing them to be considered to play the match 1 week after injury)or longer than 8 days,respectively.Symptom,cognitive,and balance performance during screens was assessed relative to baseline(normal or abnormal)and to the preceding screen(improving or worsening).Associations between sub-test abnormalities and RTP time were explored using odds ratios(OR,longer vs.shorter).Median day absence was compared between players with abnormal or worsening results and those whose results were normal or improving.Results:Abnormal symptom results during screens 2 h and 48 h after concussion were associated with longer return time(HIA2:OR=2.21,95%confidence interval(95%CI):1.39-3.50;HIA3:OR=3.30,95%CI:1.89-5.75).Worsening symptom number or severity from the time of injury to 2 h and 48 h post-injury was associated with longer return(HIA2:OR=2.49,95%CI:1.36-4.58;HIA3:OR=3.34,95%CI:1.10-10.15).Median days absence was greater in players with abnormal symptom results at both HIA2 and HIA3.Cognitive and balance performance were not associated with longer return and did not affect median days absence.Conclusion:Symptom presentation and evolution within 48 h of concussion were associated with longer RTP times.This may guide a more conservative approach to RTP,while still adhering to individualized concussion management principles.