Multimodal comparison of plasma proteins associated with blood-brain barrier impairment in Alzheimer’s disease

Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.

Incidence of Gonorrhea and Chlamydia in Urban Settings: The Case for Neighborhood Level Analysis in Boston

The sexually transmitted infections (STIs) gonorrhea and chlamydia are known to disproportionately affect impoverished communities and communities of color, especially in urban areas. Moreover, socioeconomic and demographic factors such as poverty and race/ethnicity may contribute to a difference in treatment setting choice as well as a delay in care seeking. In an urban metropolitan area such as Boston, the overall gonorrhea and chlamydia rates are higher than national rates, and such differences are even more marked in certain neighborhoods with greater proportions of individuals who are impoverished, young, and of color. Using a retrospective analysis of city wide data, we highlight the effects of socioeconomic and demographic variables on urban STI prevalence. High poverty rates, race/ethnicity and younger adult populations are linked to disproportionately high STI rates. Interestingly, STI rates do not appear to be influenced by the universal health care coverage offered to the whole Massachusetts’ resident populations. We examine the effects of these variables in Boston neighborhoods in conjunction to STI rates and hypothesize that the observed rates are underestimates of the true prevalence of infection. Future studies will investigate how these same socioeconomic and demographic factors influence which treatment settings are chosen and subsequently lead to a delay in treatment.

Osteoarticular manifestations of human brucellosis:A review

Brucellosis is a common global zoonotic disease, which is responsible for a range of clinical manifestations. Fever, sweating and musculoskeletal pains are observed in most patients. The most frequent complication of brucellosis is osteoarticular involvement, with 10% to 85% of patients affected. The sacroiliac(up to 80%) and spinal joints(up to 54%) are the most common affected sites.Spondylitis and spondylodiscitis are the most frequent complications of brucellar spinal involvement. Peripheral arthritis, osteomyelitis, discitis, bursitis and tenosynovitis are other osteoarticular manifestations, but with a lower prevalence. Spinal brucellosis has two forms: focal and diffuse. Epidural abscess is a rare complication of spinal brucellosis but can lead to permanent neurological deficits or even death if not treated promptly. Spondylodiscitis is the most severe form of osteoarticular involvement by brucellosis, and can have single-or multifocal involvement. Early and appropriate diagnosis and treatment of the disease is important in order to have a successful management of the patients with osteoarticular brucellosis. Brucellosis should be considered as a differential diagnosis for sciatic and back pain, especially in endemic regions. Patients with septic arthritis living in endemic areas also need to be evaluated in terms of brucellosis. Physical examination, laboratory tests and imaging techniques are needed to diagnose the disease. Radiography, computed tomography, magnetic resonance imaging(MRI) and bone scintigraphy are imaging techniques for the diagnosis of osteoarticular brucellosis. MRI is helpful to differentiate between pyogenic spondylitis and brucellar spondylitis. Drug medications(antibiotics)and surgery are the only two options for the treatment and cure of osteoarticular brucellosis.

Evaluation of the azoospermic male

When presented with an azoospermic patient, a thorough history and careful, considered physical examination often leads to a definite or presumptive diagnosis. An algorithmic, logical thought process is important to have in mind when embarking on the evaluation. Adjunctive laboratory tests, such as hormonal assays or genetic studies, are often complementary and/or additive and allow a very precise determination to be made as to the etiologies, either genetic or acquired. It is only with this information that a therapeutic plan can be made for the patient. As will be discussed, a targeted approach to testing is far more satisfying and cost-effective than a blind, shotgun approach.

Vitamin D for the prevention and treatment of pancreatic cancer

Pancreatic cancer is ranked fi fth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery. Moreover, pancreatic cancer doesn't respond well to traditional chemotherapy and radiotherapy, leaving little effective treatment for advanced pancreatic cancer cases. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the biologically active form of vitamin D3, was originally identifi ed during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body. Abundant evidence has shown that 1α,25(OH)2D3 has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells in vivo and in vitro, including breast, prostate, and colon. Similarly, the antitumor growth effect of 1α,25(OH)2D3 on pancreatic cells has been demonstrated. The clinical use of 1α,25(OH)2D3 is impeded by the lethal side effects of hypercalcemia and hypercalciuria. Therefore, 1α,25(OH)2D3 analogs, which are either equipotent or more potent than 1α,25(OH)2D3 in inhibiting tumor cell growth but with fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers. Recently, a pre-clinical study demonstrated that a less calcemic analog of 1α,25(OH)2D3, 19-nor-1α,25(OH)2D2 (Paricalcitol), is effective in inhibiting tumor growth in vitro and in vivo , via upregulation of p21 and p27 tumor suppressor genes. Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway.1α,25(OH)2D3 and its analogs are potentially attractive novel therapies for pancreatic cancer.

Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer

AIMTo review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer (CRC)]. METHODSWe performed a literature search using the National Library of Medicine through PubMed from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms (colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words (surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined non-advanced adenomas as 1-2 adenomas each 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC. RESULTSOur search strategy identified 592 candidate articles of which 8 met inclusion criteria and were relevant for assessment of histology (low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma. CONCLUSIONData on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification.

Current trends in the development and application of molecular technologies for cancer epigenetics

Current progress in epigenetic research supports the view that diet and dietary components are important in cancer etiology by enhancing or inhibiting carcinogenesis.Since diet and dietary factors may significantly contribute to the causation and progression of many cancers,it is important to find the molecular mechanisms of action of such dietary factors for cancer prevention and treatment.Recently,the role of epigenetic mechanisms in the cancer development and progression has attracted more attention as additional evidence along with traditional DNA sequence based mechanisms such as mutations and structural re-arrangements.Such an increasing interest in cancer epigenetics has also accelerated the development and application of molecular assays and tools for DNA methylation detection and histone modification enrichment analysis.In this paper,key assays and methods for epigenetic research are reviewed and discussed in terms of their utility and usability.In addition,more advanced methods for genome-wide analysis are introduced as part of upcoming research trends and directions.

Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation

Recognition and management of gastrointestinal and hepatic complications of hematopoietic stem cell transplantation has gained increasing importance as indications and techniques of transplantation have expanded in the last few years.The transplant recipient is at risk for several complications including conditioning chemotherapy related toxicities,infections,bleeding,sinusoidal obstruction syndrome,acute and chronic graftversus-host disease(GVHD) as well as other long-term problems.The severity and the incidence of many complications have improved in the past several years as the intensity of conditioning regimens has diminished and better supportive care and GVHD prevention strategies have been implemented.Transplant clinicians,however,continue to be challenged with problems arising from human leukocyte antigen-mismatched and unrelated donor transplants,expanding transplant indications and age-limit.This review describes the most commonly seen transplant related complications,focusing on their pathogenesis,differential diagnosis and management.

The use of hydrogel-delivered extracellular vesicles in recovery of motor function in stroke:a testable experimental hypothesis for clinical translation including behavioral and neuroimaging assessment approaches

Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNS)repair.It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes,making development of CNS therapeutics challenging.Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society,it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels.Extracellular vesicles(EVs),also known as exosomes,when derived from mesenchymal stem cells,are one of the most promising approaches that have been attempted thus far,as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation.At the same time,advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur,as well as the release of biomolecules facilitating or inducing the reparative processes.This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels.The rationale behind this hypothesis is presented,analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain.This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur.Finally,the importance of including nonhuman primate models in the clinical translation pipeline,as well as the added benefit of multi-modal neuroimaging analysis to establish non-invasive,in vivo,quantifiable imagingbased biomarkers for CNS repair are discussed,aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Impaired swallowing mechanics of post radiation therapy head and neck cancer patients: A retrospective videofluoroscopic study

AIM: To determine swallowing outcomes and hyolaryngeal mechanics associated with post radiation therapy head and neck cancer(rt HNC) patients using videofluoroscopic swallow studies. METHODS: In this retrospective cohort study, video-fluoroscopic images of rt HNC patients(n = 21) were compared with age and gender matched controls(n = 21). Penetration-aspiration of the bolus and bolus residue were measured as swallowing outcome variables. Timing and displacement measurements of the anterior and posterior muscular slings elevating the hyolaryngeal complex were acquired. Coordinate data of anatomical landmarks mapping the action of the anterior muscles(suprahyoid muscles) and posterior muscles(long pharyngeal muscles) were used to calculate the distance measurements, and slice numbers were used to calculate time intervals. Canonical variate analysis with post-hoc discriminant function analysis was performed on coordinate data to determine multivariate mechanics of swallowing associated with treatment. Pharyngeal constriction ratio(PCR) was also measured to determine if weak pharyngeal constriction is associated with post radiation therapy.RESULTS: The rt HNC group was characterized by poor swallowing outcomes compared to the control group in regards to: Penetration-aspiration scale(P < 0.0001), normalized residue ratio scale(NRRS) for the valleculae(P = 0.002) and NRRS for the piriform sinuses(P = 0.003). Timing and distance measurements of the anterior muscular sling were not significantly different in the two groups, whereas for the PMS time of displacement was abbreviated(P = 0.002) and distance of excursion was reduced(P = 0.02) in the rt HNC group. A canonical variate analysis shows a significant reduction in pharyngeal mechanics in the rt HNC group(P < 0.0001). The PCR was significantly higher in the test group than the control group(P = 0.0001) indicating reduced efficiency in pharyngeal clearance. CONCLUSION: Using videofluoroscopy, this study shows rt HNC patients have worse swallowing outcomes associated with reduced hyolaryngeal mechanics and pharyngeal constriction compared with controls.

The physiological and pharmacological basis for the ergogenic effects of androgens in elite sports

Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do not have good experimental evidence to support the presumption that androgen administration improves physical function or athletic performance. Androgens do not increase specific force or whole body endurance measures. The anabolic effects of testosterone on the skeletal muscle are mediated through androgen receptor signaling. Testosterone promotes myogenic differentiation of multipotent mesenchymal stem cells and inhibits their differentiation into the adipogenic lineage. Testosterone binding to androgen receptor induces a conformational change in androgen receptor protein, causing it to associate with beta-catenin and TCF-4 and activate downstream Wnt target genes thus promoting myogenic differentiation. The adverse effects of androgens among athletes and recreational bodybuilders are under reported and include acne, deleterious changes in the cardiovascular risk factors, including a marked decrease in plasma high-density lipoproteins （HDL） cholesterol level, suppression of spermatogenesis resulting in infertility, increase in liver enzymes, hepatic neoplasms, mood and behavioral disturbances, and long term suppression of the endogenous hypothalamic-pituitary-gonadal axis. Androgens are often used in combination with other drugs which may have serious adverse events of their own. In spite of effective methods for detecting androgen doping, the policies for screening of athletes are highly variable in different countries and organizations and even existing policies are not uniformly enforced.

Adverse effects of androgen deprivation therapy in men with prostate cancer： a focus on metabolic and cardiovascular complications

Prostate cancer （PCa） is the most common malignancy in men. Prostate being an androgen responsive tissue, androgen deprivation therapy （ADT） is used in the management of locally advanced （improves survival） and metastatic （improves pain and quality of life） PCa. Over the past two decades, the use of ADT has significantly increased as it is also being used in patients with localized disease and those experiencing biochemical recurrences, though without any evidence of survival advantage. Hypogonadism resulting from ADT is associated with decreased muscle mass and strength, increased fat mass, sexual dysfunction, vasomotor symptoms, decreased quality of life, anemia and bone loss. Insulin resistance, diabetes and cardiovascular disease have recently been added to the list of these complications. As the majority of men with PCa die of conditions other than their primary malignancy, recognition and management of these adverse effects is paramount. Here we review data evaluating metabolic and cardiovascular complications of ADT.

Role of apolipoproteins,ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins

In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.

Gender and tachycardia： independent modulation of platelet reactivity in patients with atrial fibrillation

Background Female patients with atrial fibrillation （AF） experience increased risk of thromboembolism compared to males, an observation that is reflected by its inclusion in the CHA2DS2VASc score. New onset AF （often associated with tachycardia） also confers upon patients increased thromboembolic risk. The mechanisms underlying this risk are uncertain, but new onset AF is associated with profound impairment of platelet nitric oxide （NO） signalling. Given that cardiovascular responses to catecholamines are gender-dependent, and that the presence of tachycardia in new onset AF may represent a response to catecholaminergic stimulation, we explored the potential impact of gender and tachycardia on platelet aggregation and NO signalling. Methods Interactions were sought in 87 AF patients between the extent of adenosine diphosphate （ADP）-induced platelet aggregation, the anti-aggregatory effects of the NO donor, sodium nitroprusside, gender, and admission heart rate. The potential impact of platelet expression of thioredoxin-interacting protein （Txnip） was also evaluated. Results Analysis ofcovariance confLrmed the presence of physiological antagonism between platelet ADP and NO responses [F （1, 74） = 12.212, P 〈 0.01 ], while female sex correlated with impaired NO responses independent of platelet aggregability [F （2, 74） = 8.313, P 〈 0.01]. Admission heart rate correlated directly with platelet aggregation （r = 0.235, P 〈 0.05）, and inversely with NO response （r = -0.331, P 〈 0.01）. Txnip expression varied neither with gender nor with heart rate. Conclusions These results indicate, that gender and heart rate are independent determinants of platelet fimction. Prospective studies of the putative benefit of reversal of tachycardia on restoration of normal platelet function are therefore a priority.

Evidence based review of negative pressure wound therapy

Vacuum-assisted closure, sometimes referred to as microdeformational wound therapy or most commonly negative pressure wound therapy(NPWT), has significantly improved wound care over the past two decades. NPWT is known to affect wound healing through four primary mechanisms(macrodeformation, microdeformation, fluid removal, and alteration of the wound environment) and various secondary mechanisms(including neurogenesis, angiogenesis, modulation of inflammation, and alterations in bioburden) which are described in this review. In addition, the technique has many established uses, for example in wound healing of diabetic and pressure ulcers, as well as burn and blast wounds. This therapy also has many uses whose efficacy has yet to be confirmed, for example the use in digestive surgery. Modifications of the traditional NPWT have also been established and are described in detail. This therapy has various considerations and contraindications which are summarized in this review. Finally, future perspectives, such as the optimal cycling of the treatment and the most appropriate interface material, are touched upon in the final segment. Overall, despite the fact that questions remain to be answered about NPWT, this technology is a major breakthrough in wound healing with significant potential use both in the hospital but also in the community.

Evaluation of atherosclerotic lesions in cholesterol-fed mice during treatment with paclitaxel in lipid nanoparticles： a magnetic resonance imaging study

Cholesterol-core nanoparticles （LDE） have been shown to be recognized by low-density lipoprotein receptors （LDLR） after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel （4 mg/kg） while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area （14%） and stenosis （22%） by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.

Neuritogenic function of microglia in maternal immune activation and autism spectrum disorders

Autism spectrum disorder and maternal immune activation: Environmental factors during pregnancy, such as infections, maternal stress or autoimmune disorders, are closely associated with the prevalence of neurodevelopmental disorders including autism spectrum disorder(ASD), bipolar disorder and schizophrenia.It has been shown that severe infections during pregnancy cause maternal immune activation(MIA) and significantly increase the risk of ASD in the offspring although the mechanisms are poorly understood.Many rodent MIA studies support this causal link by showing that offspring of dams administered with polyinosinic:polycytidylic acid(poly I:C), a viral mimetic Toll-like receptor 3 agonist, exhibit longlasting ASD-like behavioral abnormalities such as increased repetitive behavior, impaired social interaction and communication.Interestingly, MIA alters inflammatory cytokine expressions persisting through development and adulthood in the brain of the offspring, suggesting that chronic neuroimmune dysfunction plays a role in mediating the deleterious effects of MIA on neurodevelopment(Garay et al., 2013).

Phosphorylated low-density lipoprotein receptor-related protein 6 is prevalent in hippocampal progenitor cells and circuits of aged human hippocampus

Wnt signaling has been implicated in Alzheimer’s disease (AD) pathogenesis, but no studies have described Wnt signaling in aging brain. Phosphorylation of the Wnt coreceptor, low-density lipoprotein receptor-related protein 6 (Lrp6), is a sensitive indicator of Wnt ligand-receptor interaction and canonical Wnt signaling. We report that in aged human temporal lobe, the phospho-Lrp6 (pLrp6) epitope localizes to neurons in the entorhinal cortex (EC), the dentate gyrus (DG), and the hippocampal formation, especially in the CA3 field. Activated Lrp6 is detected in neuronal soma and in neuronal processes, particularly in the mossy fiber terminals in the stratum lucidum of CA3. These three regions and their connectivity represent the afferent arm of the major hippocampal circuit. In the DG, cells positive for pLrp6 include Type 1 and Type 2 hippocampal progenitor cells. Overall, these data indicate regional Wnt receptor activation in the human hippocampus that is most prominent in the cells comprising the afferent arm of the major hippocampal circuit that is associated with learning and memory functions. These findings are consistent with data from rodent studies which suggest an important role for Wnts in adult neurogenesis in the human DG. We speculate that Wnt signaling may be an activity-dependent trophic influence in the hippocampus.

Association of adverse effects with monoamine oxidase type B inhibitor and catechol-o-methyl transferase inhibitor combination therapy in Parkinson’s disease patients

Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy of a monoamine oxidase type B inhibitor (MAOBI) with levodopa or a catechol-O-methyl transferase inhibitor (COMTI) with levodopa provides benefits to PD patients. Direct comparison of efficacy and side effect profiles is complex. The aim of this study is to investigate the different AE profiles of MAOBI and COMTI combination therapies. Data used to analyze the AEs of different PD medications were retrieved from “The Boston University Medical Center’s Parkinson’s Disease and Movement Disorder Database”. Ten categories of AEs were compared between patients receiving MAOBI and COMTI combination treatment. In total, 87 subjects were included in the analysis. Out of ten AEs, the presence of dementia was signifi- cantly different between the MAOBI and COMTI groups with an OR of 6.9 (COMTI vs MAOBI, 95% CI 1.3 - 37.0). Motor fluctuations were also found to be differently distributed in the two medication groups with an OR of 3.1 (COMTI vs MAOBI, 95% CI 1.0 - 9.8). In this retrospective database analysis of patients treated with combination treatment for PD, combination therapy of a COMTI with levodopa was more likely to be associated with dementia and motor fluctuations than a MAOBI with levodopa.

Effects of Electrical Stimulation in People with Post-Concussion Syndromes: A Pilot Study

Post-concussion syndrome (PCS) is a complex disorder with various symptoms. There is limited evidence to support that any intervention enhances recovery after a concussion. This pilot study aimed to examine the efficacy of neck paraspinal muscles electrical stimulation (ES) in conjunction with physical therapy (PT) on reducing the severity of post concussive symptoms. Twenty-four individuals with PCS were randomly assigned to the ES group (PT + ES) or the control group (PT only). Both groups received the intervention twice a week for eight weeks. Clinical measures including the Concussion Signs/Symptoms Checklist, balance error scoring system, King-Devick test, ImPACT, and the Standardized Assessment of Concussion were used to evaluate the symptoms. We investigated the recovery rate by calculating slopes of changes over time for each participant. A changing slope was derived by linearly fitting the symptoms severity over time with the initial severity score as the intercept. Significant overall improvement was observed in both groups after the interventions. There was no significant difference seen in total symptom recovery rate between two groups (-1.49 ± 1.59 versus -1.2 ± 1.56, p = 0.32). The cognitive symptoms recovery rate of the ES group was faster than the control group (-0.5 ± 0.49 and -0.13 ± 0.46 respectively, p = 0.04). Physical therapy targeting the cervical region is beneficial for persons with PCS. Moreover, peripheral electrical stimulation on the paraspinal muscles surrounding the neck region could potentially advance the cognitive function recovery of persons with PCS.