Sub-Grouping Healthy Subjects’ Sensitivity to Pain and Its Relationship to Personality Traits: Results of a Cluster Analysis

Objective: Individual differences in the sensitivity to pain and the factors that may contribute to these differences are well studied. Nevertheless, there is no single test that can reliably classify subjects as being sensitive or insensitive to pain. Methods: In the present study, hierarchical clustering and K-means cluster analysis was used to identify subgroups among 191 healthy subjects (105 females, 86 males) according to their sensitivity to pain. Group determination was based on the subjects’ response to experimental noxious stimuli of heat (pain intensity), cold (cold pain threshold, tolerance, and intensity), and conditioned pain modulation (CPM, tested by co-administering repeated short painful heat stimuli and a conditioning tonic cold pain stimulation). In addition, in order to determine if the subjects in these subgroups differed on personality traits scores on Cloninger’s Tridimensional Personality Questionnaire (TPQ, outcome measure) for the three dimensions of personality: Novelty Seeking (NS);Harm Avoidance (HA);and Reward Dependence (RD) were calculated. Results: Based on pain scores, subjects were grouped as low pain (57%) with a low level of sensitivity in pain parameters, or high pain (43%) cluster members. The high pain had significant higher scores of HA (p = 0.05) and RD (p = 0.05) than the low pain group. Conclusions: This method of sub-grouping may be useful for identifying the mechanisms underlying individual variability in the sensitivity to pain and may point to groups at risk for experiencing high levels of clinical pain.

Nutrition and physical activity in NAFLD:An overview of the epidemiological evidence

Nonalcoholic fatty liver disease(NAFLD)has been recognized as a major health burden.The high prevalence of NAFLD is probably due to the contemporary epidemics of obesity,unhealthy dietary pattern,and sedentary lifestyle.The efficacy and safety profile of pharmacotherapy in the treatment of NAFLD remains uncertain and obesity is strongly associated with hepatic steatosis;therefore,the first line of treatment is lifestyle modification.The usual management of NAFLD includes gradual weight reduction and increased physical activity(PA)leading to an improvement in serum liver enzymes,reduced hepatic fatty infiltration,and,in some cases,a reduced degree of hepatic inflammation and fibrosis.Nutrition has been demonstrated to be associated with NAFLD and Non-alcoholic steatohepatitis(NASH)in both animals and humans,and thus serves as a major route of prevention and treatment.However,most human studies are observational and retrospective,allowing limited inference about causal associations.Large prospective studies and clinical trials are now needed to establish a causal relationship.Based on available data,patients should optimally achieve a 5%-10%weight reduction.Setting realistic goals is essential for long-term successful lifestyle modification and more effort must be devoted to informing NAFLD patients of the health benefits of even a modest weight reduction.Furthermore,all NAFLD patients,whether obese or of normal weight,should be informed that a healthy diet has benefits beyond weight reduction.They should be advised to reduce saturated/trans fat and increase polyunsaturated fat,with special emphasize on omega-3 fatty acids.They should reduce added sugar to its minimum,try to avoid soft drinks containing sugar,including fruit juices that contain a lot of fructose,and increase their fiber intake.For the heavy meat eaters,especially those of red and processed meats,less meat and increased fish intake should be recommended.Minimizing fast food intake will also help maintain a healthy diet.PA should be integrated into behavioral therapy in NAFLD,as even small gains in PA and fitness may have significant health benefits.Potentially therapeutic dietary supplements are vitamin E and vitamin D,but both warrant further research.Unbalanced nutrition is not only strongly associated with NAFLD,but is also a risk factor that a large portion of the population is exposed to.Therefore,it is important to identify dietary patterns that will serve as modifiable risk factors for the prevention of NAFLD and its complications.

Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification

AIM:To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease(NAFLD).METHODS:Cross-sectional study of subjects from the general population,a subgroup from the First Israeli National Health Survey,without excessive alcohol consumption or viral hepatitis.All subjects underwent anthropometric measurements and fasting blood tests.Evaluation of liver fat was performed using four noninvasive methods:the SteatoTest;the fatty liver index(FLI);regular abdominal ultrasound(AUS);and the hepatorenal ultrasound index(HRI).Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods:the HRI,the ratio between the median brightness level of the liver and right kidney cortex;and the SteatoTest,a biochemical surrogate marker of liver steatosis.The FLI is calculated by an algorithm based on triglycerides,body mass index,γ-glutamyl-transpeptidase and waist circumference,that has been validated only vs AUS.FLI < 30 rules out and FLI ≥ 60 rules in fatty liver.RESULTS:Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests.The prevalence rate of NAFLD was 31.1% according to AUS.The FLI was very strongly correlated with SteatoTest(r = 0.91,P < 0.001) and to a lesser but significant degree with HRI(r = 0.55,P < 0.001).HRI and SteatoTest were significantly correlated(r = 0.52,P < 0.001).The κ between diagnosis of fatty liver by SteatoTest(≥ S2) and by FLI(≥ 60) was 0.74,which represented good agreement.The sensitivity of FLI vs SteatoTest was 85.5%,specificity 92.6%,positive predictive value(PPV) 74.7%,and negative predictive value(NPV) 96.1%.Most subjects(84.2%) with FLI < 60 had S0 and none had S3-S4.The κ between diagnosis of fatty liver by HRI(≥ 1.5) and by FLI(≥ 60) was 0.43,which represented only moderate agreement.The sensitivity of FLI vs HRI was 56.3%,specificity 86.5%,PPV 57.0%,and NPV 86.1%.The diagnostic accuracy of FLI for steatosis > 5%,as predicted by SteatoTest,yielded an area under the receiver operating characteristic curve(AUROC) of 0.97(95% CI:0.95-0.98).The diagnostic accuracy of FLI for steatosis> 5%,as predicted by HRI,yielded an AUROC of 0.82(95% CI:0.77-0.87).The κ between diagnosis of fatty liver by AUS and by FLI(≥ 60) was 0.48 for the entire sample.However,after exclusion of all subjects with an intermediate FLI score of 30-60,the κ between diagnosis of fatty liver by AUS and by FLI either ≥ 60 or < 30 was 0.65,representing good agreement.Excluding all the subjects with an intermediate FLI score,the sensitivity of FLI was 80.3% and the specificity 87.3%.Only 8.5% of those with FLI < 30 had fatty liver on AUS,but 27.8% of those with FLI ≥ 60 had normal liver on AUS.CONCLUSION:FLI has striking agreement with SteatoTest and moderate agreements with AUS or HRI.However,if intermediate values are excluded FLI has high diagnostic value vs AUS.

A new category of “future planning” in the activity card sort: Continuity versus novelty in old age

The Activity Card Sort (ACS) is a widely used measure for assessing participation in instrumental, leisure, and social-cultural activities. The ACS addresses previous and current activities but not future activity plans. The purpose of the study was to extend the ACS to include future planning. Previous research indicates that participation in activities and future planning is positively related to life satisfaction, and increased well-being and that these positive effects were most pronounced for adults 60 years and older. The current study participants were 60 Israeli adults aged 55 - 74 years. The research finds future planning to be widespread, common and significant among older adults. Moreover, it was found that older people planned to continue previous activities more that they planned new activities for the future, indicating more continuity than innovation among the participants in this study. Participants with higher current or past activity levels planed a greater number of future activities. Construct validity using known group method showed the extended ACS to have discriminant validity with respect to age (younger participants were more active) and gender (highly physical activities were favored by men). MANOVA repeated measures and Pearson correlations demonstrated moderate-high test-retest reliability for the extended ACS.

The Effectiveness of a Multimedia Messaging Service Reminder System in the Management of Knee Osteoarthritis: A Pilot Study

Background: Patient compliance to home exercise programs is significantly linked to improved treatment outcomes. Finding ways of encouraging patient conformity to these programs is imperative. For patients with osteoarthritis (OA) of the knee, a condition that causes pain, disability and lessens the quality of life, exercise is essential for effective control of the condition. Aim: to investigate the effectiveness of multimedia messaging services (MMS) in improving patient adherence and functional outcome to home based exercise programs for patients suffering from knee OA. Methods: Fourteen patients diagnosed with knee OA and were referred to an exercise group therapy (for a total of six sessions) participated in this pilot study. The patients were randomly assigned to either the research or control group. The research group received MMS messages additional to the exercise sessions (video of exercises up to 10 seconds in length) to their mobile phone. Outcome measurement included the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire, combined Focus On Therapeutic Outcomes (FOTO) questionnaire, Visual Analog Scale for Pain (VAS), Fear-Avoidance Beliefs Questionnaire (FABQ) and a general questionnaire. Results: The research group had baseline scores representing slightly higher disability, pain and fear avoidance than the control group as observed by the lower FOTO score and the higher FABQ, VAS and WOMAC scores. Analyzing the difference between initial and final scores revealed that the research group had a slightly higher perceived functional improvement. Conclusions: This study addressed the feasibility of short video messaging via mobile phones in increasing compliance to home exercise programs prescribed to patients suffering from knee OA. This pilot study provides an indication for the potential of success and a larger sample study should be conducted.

Polymeric nanocarriers for nose-to-brain drug delivery in neurodegenerative diseases and neurodevelopmental disorders

Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.

Cardiovascular morbidity and mortality as a confounder of prognosis in thyroid cancer

Thyroid cancer(TC)constitutes more than 95%of all endocrine tumors.Differentiated thyroid carcinoma(DTC),which includes the papillary and follicular types,constitutes about 90%of all TCs and 2.1%of all cancers.The incidence of DTC has increased significantly worldwide,with papillary cancer leading this trend and being the most prevalent.Whereas the prognosis of patients with DTC is generally favorable,with the overall 5-year survival rate reaching up to 95%,long-term follow-up also discloses increased propensity for cardiovascular and cerebrovascular risk factors,morbidity,and mortality.Cardiovascular events are linked to TC particularly in subjects aged 45 years or more.The present review and analysis seek to highlight the significance of cardiovascular disease in the overall prognosis among TC survivors and explore potential mechanisms which might link treatment choices in DTC to cardiovascular risk and disease outcome.

Significant exercise limitations after recovery from MIS-C related myocarditis

Background Myocarditis is one of the presentations of multisystemic infammatory syndrome in children(MIS-C)following coronavirus disease 2019(COVID-19).Although the reported short-term prognosis is good,data regarding medium-term functional capacity and limitations are scarce.This study aimed to evaluate exercise capacity as well as possible cardiac and respiratory limitations in children recovered from MIS-C related myocarditis.Methods Fourteen patients who recovered from MIS-C related myocarditis underwent spirometry and cardiopulmonary exercise testing(CPET),and their results were compared with an age-,sex-,weight-and activity level-matched healthy control group(n=14).Results All participants completed the CPET with peak oxygen uptake(peak.V O2),and the results were within the normal range(MIS-C 89.3%±8.9%and Control 87.9%±13.7%predicted.V O2).Five post-MIS-C patients(35%)had exerciserelated cardio-respiratory abnormalities,including oxygen desaturation and oxygen-pulse fattening,compared to none in the control group.The MIS-C group also had lower peak exercise saturation(95.6±3.5 vs.97.6±1.1)and lower breathing reserve(17.4%±7.5%vs.27.4%±14.0%of MVV).Conclusions Patients who recovered from MIS-C related myocarditis may present exercise limitations.Functional assessment(e.g.,CPET)should be included in routine examinations before allowing a return to physical activity in post-MIS-C myocarditis.Larger,longer term studies assessing functional capacity and focusing on physiological mechanisms are needed.