New insights into the therapeutic approaches for the treatment of tauopathies

Tauopathies are a group of neurological disorders,including Alzheimer’s disease and frontotemporal dementia,which involve progressive neurodegeneration,cognitive deficits,and aberrant tau protein accumulation.The development of tauopathies cannot currently be stopped or slowed down by treatment measures.Given the significant contribution of tau burden in primary tauopathies and the strong association between pathogenic tau accumulation and cognitive deficits,there has been a lot of interest in creating therapies that can alleviate tau pathology and render neuroprotective effects.Recently,small molecules,immunotherapies,and gene therapy have been used to reduce the pathological tau burden and prevent neurodegeneration in animal models of tauopathies.However,the major pitfall of the current therapeutic approach is the difficulty of drugs and gene-targeting modalities to cross the blood-brain barrier and their unintended side effects.In this review,the current therapeutic strategies used for tauopathies including the use of oligonucleotide-based gene therapy approaches that have shown a promising result for the treatment of tauopathies and Alzheimer’s disease in preclinical animal models,have been discussed.

Biological,pathological,and multifaceted therapeutic functions of exosomes to target cancer

Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological conditions.Also,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source.Moreover,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological actions.There are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor cells.Once the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological response.Even though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy.So,overcoming the pitfalls would give a desired quantity of exosomes with high purity.

Item-Level Analysis of the Revised Occupational Therapy Fieldwork Performance Evaluation Applied in Practice

Competency-based assessments for healthcare professionals are critical for safe and effective client outcomes. Rehabilitation clinical skill competency assessments must be validated and revised to produce safe and skilled practitioners. The revised American Occupational Therapy Association (AOTA) Fieldwork Performance Evaluation (FWPE) instrument measures occupational therapy student performance to determine readiness for practice. The assessment includes thirty-seven competencies that address both profession specific clinical skills and general professional behavior skills. The objective of this study was to use Rasch methods to explore the use of the revised FWPE in actual fieldwork practice and to determine the instrument’s psychometric properties when separating the item components into two distinct subdomains: General Health Professions Competences and Occupational Therapy-Specific Competencies. Internal construct validity and test reliability were analyzed using data from 149 occupational therapy students after completing their initial Level II A fieldwork clinical internship. This study examined the item difficulty hierarchy, item fit, person-fit to model, person separation index, person separation reliability coefficient, strata, ceiling and floor effect, and unidimensionality of the FWPE instrument as a whole and as two separate domains. With the exception of not meeting the criteria for unidimensionality, the full FWPE instrument and the Occupational Therapy-Specific Competencies subdomain showed acceptable item-level psychometrics for reliability and precision. While the General Health Professions Competencies subdomain showed good item-level psychometrics, it was below the criterion for reliability and only separated the sample into two strata. Results support the validity, reliability, and clinical use of the revised FWPE full instrument and the Occupational Therapy-Specific Competencies subdomain to measure entry-level clinical skill competencies in practice.

The Impact of Hearing Loss on Health: Interprofessional Guidance for Health and Primary Care Providers (PCPs)

In the United States, approximately one in eight (13 percent, or 30 million)individuals aged 12 years or older has bilateral hearing loss. Whenunaddressed and untreated, hearing loss is associated with and contributesto other significant health issues;specifically, social isolation, depression,stress, and anxiety, incidental falls, dementia and impaired cognition, andreduced quality of life. This is a public health concern. Health and primarycare providers are in a unique position to have a positive impact by probingthe hearing of the patients they see, providing information, and makingappropriate referrals to reduce deleterious effects when this impairmentoccurs.Abbreviations: Hertz (Hz);High frequency hearing loss (HFHL);Personallistening devices (PLDs);Sensorineural hearing loss (SNHL)Format: Small group discussion, classroom and clinical practicum settings.Target audience: The student and practicing health professions (e.g.occupational and physical therapy, psychologists, physician assistants,nursing, and medical) involved and the relevant point in their training andpractice.

Development, and validation of non-speech dichotic listening test

Background:Classic dichotic listening tests using speech stimuli result in right ear advantage,due to the dominant crossed pathway for speech and language.It is presumed that similar crossed dominance could exist for non-speech stimuli too.Hence,this is an attempt to develop and validate the dichotic nonspeech test using environmental stimuli and explore the effect of focused attention on this test.Materials and method:Three lists of dichotic stimuli were created using these sounds with fifteen tokens in each list.Four professionals and non-professionals validated these materials.Normative estimation was obtained by administering the newly developed test on 70 adults and 70 children using a free-recall and forced-recall condition.Result:The results showed a significant difference between the left ear and right scores where the left ear score was better than the right,depicting left ear advantage(LEA)for free recall condition in both groups.In the forced recall condition,LEA was not seen;rather the mean score was significantly higher in the attended ear,irrespective of the stimuli presented to the right or left ear.The test-retest reliability in free recall was good in both the ears and moderate for forced right ear conditions.Conclusion:The novel test consistently showed LEA with good reliability and can be used to assess the hemispheric asymmetry in normal subjects and also in test batteries for the clinical population.

Change in Functional Status from Preoperative to One Year Postoperative in Patients Who Have Undergone Elective Open-Heart Surgery: A Repeated-Measures Study

Purpose: Although patient-related factors affect surgical outcomes, preoperative functional status is not measured by any cardiac risk score. Functional status can, however, be objectively measured using validated outcome tools such as the Late-Life Function and Disability Instrument (LLFDI). The purpose of this study was to determine 1) if there was a change over time in functional status, as measured by the LLFDI, in patients who underwent elective cardiac surgery, and if so, 2) what specific aspect(s) of functional status changed. Methods: A prospective longitudinal study of one year was conducted on elective cardiac surgery patients (n = 43) using the self-reported LLFDI, which measures Disability Frequency (frequency of participation in social tasks), Disability Limitation (ability to participate in social tasks) and Function Total (ease in performing routine activities). Higher scores indicate increased function and decreased disability. LLFDI scores were compared at three times (preoperative, six-week and one-year postoperative) using repeated measures ANOVA. Post hoc pairwise comparison was conducted for specific interactions. Results: Both Function Total and Disability Frequency significantly changed over time (p = 0.047 and p = 0.013, respectively). Specifically, patients’ function level was significantly higher one-year postoperative compared to preoperative (M difference = +3.48, SE = 1.48, p = 0.026). Likewise, Disability Frequency scores were significantly higher (i.e. more active) at one-year postoperative versus preoperative (M difference= +5.98, SE = 2.19, p = 0.033). Disability Limitation scores were not significantly different between any time points (p > 0.05). Conclusion: By one-year postoperative, patients demonstrated increased ease in their routine physical activities and were more participatory in social life tasks. Individuals who underwent elective cardiac surgery took more than six weeks to detect notable improvement in functional status, which was expected with a sternotomy approach. This study provides support for the use of the LLFDI as an effective tool to capture functional status in the cardiac population. These findings may assist cardiac patients in recovery timeline expectations.

Recent advances on the role of long non-coding RNAs in Alzheimer’s disease

Dementia is a progressive cognitive impairment that affects the activities of daily living.Alzheimer’s disease (AD) is the most common form of the dementia worldwide accounting for 60-80%of all dementia cases.With an estimated cost exceeding$290 billion in the USA,understanding and development of future therapeutic strategies is vital.In this perspective,we will be examining the current thinking of AD research and therapeutic strategies,while proposing a possible new direction for diagnosis,understanding,and treatment targets.

Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis

Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs(DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis(RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase(JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type Ⅰcytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb's mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaL s(ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.

Hypertension and Heart Failure as Predictors of Mortality in an Adult Congenital Heart Defect Population

Early intervention to prevent premature mortality is vital for adults with congenital heart defects(CHD).Anatomic complexity and comorbid conditions are thought to contribute to CHD mortality.Since hypertension(HTN)and heart failure(HF)are the comorbid conditions among the most prevalent causes of death in the United States,and commonly accompany CHD,it is crucial to evaluate whether they are reliable predictors of mortality for adults with CHD(ACHD)independent of anatomic CHD complexity.A retrospective cross-sectional analysis of ACHD,aged 18–64,with concomitant HTN and/or HF and at least one health care encounter during 2008–2010 were assessed.Of 5,397 ACHD patients(18.3%HTN without HF,4.4%HF without HTN,8.3%with both),3.0%died(n=163)during the study period.Overall,the sample was 45.1%white,61.4%female,and 29.0%had a complex CHD.Among those who died,23.3%had HTN without HF,17.2%had HF without HTN,and 42.3%had both.Crude analyses revealed that older age,male gender,black race,and having public health insurance were associated with increased mortality during the three-year study period compared to ACHD patients who were younger,female gender,white race,and covered by private health insurance.ACHD patients diagnosed with non-complex CHD lesions(i.e.,shunts,valves,or shunts+valves)were at greater risk of dying compared to those with severe complex CHDs.When CHD type was assessed separately,those with valve lesions were more likely to die compared to those with complex CHD lesions.After adjustment for age,gender,race,insurance and CHD complexity,ACHD patients with HF,with or without HTN,were equally likely to die during the study period.However,ACHD patients with HF,without or without HTN,who had valve defects were more likely to die during the three-year study period compared to patients with complex CHDs.

Predictors of Retention and Passing the National Council Licensure Examination for Registered Nurses

Using Seidman’s retention formula as a theoretical foundation, this study investigated historical data from a Bachelor of Science (BSN) nursing program to determine whether the admission variables of the preprogram grade point averages (GPA), American College Testing (ACT) scores, anatomy and physiology course grades, and/or the Health Education System Inc. (HESI) Exit Exam scores could predict completing the nursing program, as well as passing the NCLEX-RN. A significant relationship (p < 0.01) was identified between the preprogram GPA, ACT scores, anatomy grades, and the HESI Exit Exam scores with the completion of the BSN program and passing the NCLEX-RN.

Benefits of laptop computer ergonomics education to graduate students

Laptop computers are used more often than desktop computers, especially among graduate students. Many common laptop habits can have severe physiological effects on the user ranging from eye strain, poor posture, upper extremity pain, and overuse injuries. Thus, it is important to educate students on the best ergonomic position to use laptops. This study investigates the efficacy of a laptop ergonomic education session and its effects on graduate students’ knowledge and behaviors regarding proper laptop use. A convenience sample of control and experimental groups was used and consisted of 83 occupational therapy (OT), 63 physical therapy (PT), and 26 nurse anesthesia (NA) graduate students. The sample size was 172, with 94 graduate students in the control group and 78 graduate students in the experimental. All study participants completed an initial ergonomics questionnaire. The experimental group was given an ergonomics education session following the questionnaire. Approximately 4 weeks after both groups completed the initial questionnaire;a follow up questionnaire was administered. Results showed that subjects demonstrated a statistically significant improvement in ergonomics knowledge after they completed the ergonomic educational session. Some participants reported making adaptations to laptop positioning and equipment use following the educational session. Thus, participating in ergonomic education can positively influence awareness of body mechanics relative to laptop workstation design.

Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments. AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD. METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD)(14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice. CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients.

Causal relationship between hypoalbuminemia and acute kidney injury

Our meta-analysis published in 2010 provided evidence that low levels of serum albumin(hypoalbuminemia) are a significant independent predictor of acute kidney injury(AKI) and death following AKI.Since then,a large volume of additional data from observational clinical studies has been published further evaluating the relationship between serum albumin and AKI occurrence.This is an updated review of the literature to re-evaluate the hypothesis that hypoalbuminemia is independently associated with increased AKI risk.Eligible studies published from September 2009 to December 2016 were sought in PubM ed(MEDLINE) and forty-three were retained,the great majority being retrospective observational cohort studies.These included a total of about 68000 subjects across a diverse range of settings,predominantly cardiac surgery and acute coronary interventions,infectious diseases,transplant surgery,and cancer.Appraisal of this latest data set served to conclusively corroborate and confirm our earlier hypothesis that lower serum albumin is an independent predictor both of AKI and death after AKI,across a range of clinical scenarios.The body of evidence indicates that hypoalbuminemia may causally contribute to development of AKI.Furthermore,administration of human albumin solution has the potential to prevent AKI;a randomized,controlled study provides evidence that correcting hypoalbuminemia may be renal-protective.Therefore,measurement of serum albumin to diagnose hypoalbuminemia may help identify high-risk patients who may benefit from treatment with exogenous human albumin.Multi-center,prospective,randomized,interventional studies are warranted,along with basic research to define the mechanisms through which albumin affords nephroprotection.

青少年及儿童唐氏综合症患者的体质和体力活动(英文)

Children(5-12 years) and adolescents(13-19 years) with Down syndrome(DS) possess a set of health,anatomical,physiological, cognitive,and psycho-social attributes predisposing them to limitations on their physical fitness and physical activity(PA) capacities.The paucity of studies and their conflicting findings prevent a clear understanding and/or substantiation of these limitations.The purpose of this article was to review the measurement,determinants and promotion of physical fitness and PA for youth(i.e.,children and adolescents) with DS. The existing body of research indicates that youth with DS:1) have low cardiovascular and muscular fitness/exercise capacity;2) demonstrate a greater prevalence of overweight and obesity;3) a large proportion do not meet the recommended amount of daily aerobic activity;and 4) their PA likely declines through childhood and into adolescence.Future research should focus on:1) strength testing and training protocols;2) methodologies to determine PA levels;and 3) practical interventions to increase PA.

Caution needed when interpreting muscle activity patterns during extremely low pedaling cadence

Dear editor,We noticed recent research that has just been published in Journal of Sport and Health Science(JSHS),comparing the muscular activity patterns in 1-and 2-legged cycling by Park and Caldwell.1 The authors reported that changes in muscle activities with 1-legged pedaling are due to a variety of changes in mechanical aspects of the pedaling motion,including altered crank torque patterns within the crank cycle,decreased pelvis stability,and the need for increased knee and ankle stiffness during the upstroke.The experiment was welldesigned and the discussion was fascinating.However,the testing protocol does not support the significance of the project,as stated in the first sentence of the abstract,“One-legged pedaling is of interest to elite cyclists and clinicians.”Their testing was conducted at 30 revolutions per min(rpm)and 30 watts(W),and both are too low for any kind of mechanical demand for cycling,either competitive sports or rehabilitation.The preferred cadences of experienced cyclists are approximately 85-95 rpm,whereas the most economic cadences are approximately 55-60 rpm.

Oxidative stress and female reproductive disorder: A review

Oxidative stress arises from an imbalance between the body’s pro-oxidants and antioxidants.Recently,oxidative stress has been proven a contributing factor to many female reproductive disorders including infertility,preeclampsia,endometriosis and polycystic ovarian syndrome.Herein,we review the mechanistic role of oxidative stress in inducing the most common female reproductive disorders.The current review has also highlighted the protective role of vitamin C,necessary for certain female reproductive hormone secretion by the antral follicle and corpus luteum and also essential for collagen production in ovarian tissue remodeling after ovulation,in alleviating oxidative stress and thus improving female reproductive outcomes.

Intrahepatic cholestasis of pregnancy is associated with increased risk of hepatobiliary disease and adverse fetal outcomes: A systematic review and meta-analysis

Background and aims:The aim of this study was to review the literature and perform a meta-analysis to clarify the association between intrahepatic cholestasis of pregnancy and risks of long-term maternal hepatobiliary disease as well as adverse fetal outcomes including preterm birth,meconium-stained amniotic fluid,and stillbirth.Methods:This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.A comprehensive literature search was performed using Cochrane,Embase,and PubMed databases to identify observational or cohort studies comparing pregnant women with intrahepatic cholestasis of pregnancy(ICP)to pregnant women without ICP.Data from the included studies were analyzed using the Review Manager 5.4.1 software.Results:The meta-analysis showed a significant association between ICP and the risk of hepatobiliary diseases(pooled risk ratio[RR]:2.81,95%confidence interval[CI]:2.66–2.97,p<0.00001),hepatitis C(HC):a significant association between ICP and risk of HC(pooled RR:4.02,95%CI:3.12–5.19,p<0.00001),meconium-stained amniotic fluid(MSAF):ICP was significantly associated with an increased risk of MSAF(pooled RR:1.91,95%CI:1.65–2.21,p<0.00001),and preterm birth:the meta-analysis demonstrated a significant association between ICP and preterm birth(pooled RR:2.11,95%CI:2.01–2.21,p<0.00001).Conclusion:ICP demonstrated statistically significant associations with increased risks of hepatobiliary disease,HC,MSAF,and preterm birth.

Pilot study of atomoxetine in patients with Parkinson’s disease and dopa-unresponsive Freezing of Gait

Background:Freezing of gait(FoG)is a common and debilitating condition in Parkinson’s disease(PD)associated with executive dysfunction.A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency.This pilot study explores the effects of atomoxetine on gait in PD patients with dopaunresponsive FoG using a novel paradigm for objective gait assessment.Findings:Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study.Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning,while performing a dual task.Clinical,and subjective assessments of gait,quality of life,and safety were also administered.The primary outcome was a validated subjective assessment for FoG(FOG-Q).Atomoxetine was well tolerated,however,no significant change was observed in the primary outcome.The gait analysis protocol correlated well with clinical scales,but not with subjective assessments.DBS patients were more likely to increase gait velocity(p=0.033),and improved in other clinical assessments.Conclusions:Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population,and may be superior correlates of FoG severity than subjective measures.These findings can inform future trials in this population.

Electromyographic and Mechanomyographic Responses During Isokinetic Leg Extensions in Children Versus Adolescents

Purpose The purpose of this study was to examine peak torque(PT),mean power(MP),electromyographic(EMG)amplitude,mechanomyographic(MMG)amplitude,and neuromuscular efficiency from EMG and MMG amplitude(NME_(EMG)and NME_(MMG),respectively)across the velocity spectrum in children versus adolescents.Methods Seventeen children(n=8 males,n=9 females)and 22 adolescents(n=11 males,n=11 females)participated.Participants completed maximal concentric isokinetic leg extensions at 60,120,180,240 and 300°/s.PT,MP,EMG amplitude,and MMG amplitude were quantified during all muscle actions.NME_(EMG)and NME_(MMG)were quantified by expressing PT relative to EMG and MMG amplitude,respectively,for each muscle action.Results PT,MP,NME_(EMG),and NME_(MMG)were greater for the adolescents than the children collapsed across sex and veloc-ity(P≤0.021).There were no significant differences for EMG amplitude(P≥0.051),while MMG amplitude increased significantly from 60 to 240°/s(P<0.001)then decreased significantly from 240 to 300°/s(P<0.001)for all groups.Conclusion Overall,regardless of velocity,the expression of PT relative to EMG and MMG amplitude(NME_(EMG)and NME_(MMG),respectively),in conjunction with measurements of torque and power production,may provide practitioners a unique method of examining growth and development-related augmentations in neuromuscular function during dynamic movements.

Effectiveness of craniosacral therapy,Bowen therapy,static touch and standard exercise program on sleep quality in fibromyalgia syndrome:A randomized controlled trial

Background:Sleep disturbance is commonly seen in fibromyalgia syndrome (FMS);however,high quality studies involving manual therapies that target FMS-linked poor sleep quality are lacking for the Indian population.Objective:Craniosacral therapy (CST),Bowen therapy and exercises have been found to influence the autonomic nervous system,which plays a crucial role in sleep physiology.Given the paucity of evidence concerning these effects in individuals with FMS,our study tests the effectiveness of CST,Bowen therapy and a standard exercise program against static touch (the manual placebo group) on sleep quality in FMS.Design,setting,participants and intervention:A placebo-controlled randomized trial was conducted on132 FMS participants with poor sleep at a hospital in Bangalore.The participants were randomly allocated to one of the four study groups,including CST,Bowen therapy,standard exercise program,and a manual placebo control group that received static touch.CST,Bowen therapy and static touch treatments were administered in once-weekly 45-minute sessions for 12 weeks;the standard exercise group received weekly supervised exercises for 6 weeks with home exercises until 12 weeks.After 12 weeks,all study participants performed the standard exercises at home for another 12 weeks.Main outcome measures:Sleep quality,pressure pain threshold (PPT),quality of life and fibromyalgia impact,physical function,fatigue,pain catastrophizing,kinesiophobia,and positive–negative affect were recorded at baseline,and at weeks 12 and 24 of the intervention.Results:At the end of 12 weeks,the sleep quality improved significantly in the CST group (P=0.037) and Bowen therapy group (P=0.023),and the PPT improved significantly in the Bowen therapy group(P=0.002) and the standard exercise group (P<0.001),compared to the static touch group.These improvements were maintained at 24 weeks.No between-group differences were observed for other secondary outcomes.Conclusion:CST and Bowen therapy improved sleep quality,and Bowen therapy and standard exercises improved pain threshold in the short term.These improvements were retained within the groups in the long term by adding exercises.CST and Bowen therapy are treatment options to improve sleep and reduce pain in FMS.