Objective methods of monitoring usage of orthotic devices for the extremities: a systematic review

Orthoses are commonly prescribed to relieve symptoms for musculoskeletal and neurological conditions; however, patients stop wearing orthoses as recommended for many reasons. When considering the effectiveness of orthoses, there needs to be an objective way to monitor whether participants wear the orthosis as instructed, because if this is not followed, the orthoses will not work as intended. This review aimed to identify, summarise, and compare objective methods used to measure compliance with orthoses applied to the extremities. Databases (Scopus, Web of Science, Embase, CINAHL, and MEDLINE) were searched for eligible studies. Twenty-three studies were accepted in the final review, including five studies that employed upper limb orthoses, two that employed hip orthoses, and fifteen that employed lower limb orthoses. To measure compliance objectively, studies utilised temperature sensors, pressure sensors, accelerometers, a step counter, or a combination of sensors. All sensor types have their own advantages and disadvantages and should be chosen based on study-specific parameters. Sensor-derived monitoring provides quantitative, objective data that are beneficial in both clinical and research settings. The ideal solution to monitoring compliance would consist of both objective and user-reported aspects that, in combination, would provide an all-encompassing picture of the orthotic treatment prescribed

Optimization of process variables for phyllanthin extraction from Phyllanthus amarus leaves by supercritical fluid using a Box-Behnken experimental design followed by HPLC identification

The response surface methodology using the Box-Behnken design was established to describe supercritical carbon dioxide assisted extraction of phyllanthin from Phyllanthus amarus Schum and Thonn leaves prior to HPLC analysis. The effects of extraction pressure, temperature, modifier concentration and extraction time on the yield of phyllanthin were investigated. By solving the regression equation, the optimum conditions were as follows: extraction pressure 23.2 MPa, temperature 40 °C, methanol as modifier at a concentration 10 % and time 90 min. Under these conditions, the phyllanthin yield was 12.83 ± 0.28 mg g-1, which was in good agreement with the predicted values. Modifier concentration and extraction time showed a significant effect on the phyllanthin yield

Therapy of pancreatic cancer via an EphA2 receptor-targeted delivery of gemcitabine.

First line treatment for pancreatic cancer consists of surgical resection, if possible, and a subsequent course of chemotherapy using the nucleoside analogue gemcitabine. In some patients, an active transport mechanism allows gemcitabine to enter efficiently into the tumor cells, resulting in a significant clinical benefit. However, in most patients, low expression of gemcitabine transporters limits the efficacy of the drug to marginal levels, and patients need frequent administration of the drug at high doses, significantly increasing systemic drug toxicity. In this article we focus on a novel targeted delivery approach for gemcitabine consisting of conjugating the drug with an EphA2 targeting agent. We show that the EphA2 receptor is highly expressed in pancreatic cancers, and accordingly, the drug-conjugate is more effective than gemcitabine alone in targeting pancreatic tumors. Our preliminary observations suggest that this approach may provide a general benefit to pancreatic cancer patients and offers a comprehensive strategy for enhancing delivery of diverse therapeutic agents to a wide range of cancers overexpressing EphA2, thereby potentially reducing toxicity while enhancing therapeutic efficacy

Utišani gga-miR-142-3p u pilećem embriju: ekspresija profila XPO1.

Differential expression of gga-miR-142-3p microRNA of haemopoeitic origin during immune organ development and functional stages in chicken embryos creates new opportunities for understanding its pivotal role during embryonic developmental stages. To decipher the role of gga-miR-142-3p in-ovo knockdown was carried out with LNA modified anti-miR-gga-miR-142-3p via intravenous route at developmental and functional stages of the immune organs and other organs. Bioinformatic analysis of the genes targeted by gga-miRNA-142-3p revealed that the predicted gene XPO1 conserved binding sites at 3’UTR. The target gene XPO1 was evaluated as the validated target of gga-miR-142-3p by employing qPCR SYBR green based technology, which was evidenced by its increased expression in the tissues of gga-miR-142-3p knockdown chicken embryos. Histopathological alterations in the immune organs and visceral organs indicated that the systemic knockdown of gga-miR-124-3p led to over expression of the XPO1 gene during the embryonic stages, and changed the environment of the immune organs related to structural integrity, immune response, signal transduction and migration of B and T cells during the embryonic developmental stage in the chicken embryos. The results clearly indicated that these changes could alter the postnatal development and functions of these immune organs, and may lead to development of immuno-compromised chickens.Različita ekspresija gga-miR-142-3p mikroRNA hemopoetskog podrijetla daje nove mogućnosti razumijevanja njezine ključne uloge u embrionalnom razvoju limfnih organa i funkcionalnih zbivanja u pilećem zametku. Za otkrivanje uloge gga-miR-142-3p in ovo provedeno je utišavanje zaključanom nukleinskom kiselinom što preko anti-miR-gga-miR-142-3p preinačuje razvojne i funkcionalne sposobnosti limfnih i drugih organa. Bioinformatička analiza ciljnih gena za gga-miRNA-142-3p otkriva da gen XPO1 ima konzervirana mjesta vezanja na 3’UTR. Gen XPO1 bio je potvrđen kao cilj za gga-miR-142-3p uporabom tehnologije temeljene na qPCR SYBR zelenilu, što je bilo dokazano njegovom povećanom ekspresijom u tkivima pilećih zametaka s utišanim gga-miR-142-3p. Patohistološke promjene u imunosnim i unutarnjim organima pokazuju da sustavno utišavanje gga-miR-124-3p vodi do prevelike ekspresije gena XPO1 tijekom embrionalnog razvoja. To mijenja zadaću imunosnih organa s obzirom na strukturni integritet, imunosni odgovor, prijenos poruka te migraciju B i T limfocita tijekom razvoja pilećih zametaka. Rezultati jasno naznačuju da te promjene mogu preinačiti postnatalni razvoj i funkcije imunosnih organa te mogu dovesti do razvoja imunološki oslabljenih pilića

Are There Sensitive Time Periods for Dementia Caregivers? The Occurrence of Behavioral and Psychological Symptoms in the Early Stages of Dementia

ABSTRACT Background: The behavioral and psychological symptoms associated with dementia (BPSD) can be burdensome to informal/family caregivers, negatively affecting mental health and expediting the institutionalization of patients. Because the dementia patient-caregiver relationship extends over long periods of time, it is useful to examine how BPSD impact caregiver depressive symptoms at varied stages of illness. The goal of this study was to assess the association of BPSD that occur during early stage dementia with subsequent caregiver depressive symptoms. Methods: Patients were followed from the early stages of dementia every six months for up to 12 years or until death (n = 160). Caregiver symptoms were assessed on average 4.5 years following patient's early dementia behaviors. A generalized estimating equation (GEE) extension of the logistic regression model was used to determine the association between informal caregiver depressive symptoms and BPSD symptoms that occurred at the earliest stages dementia, including those persistent during the first year of dementia diagnosis. Results: BPSD were common in early dementia. None of the individual symptoms observed during the first year of early stage dementia significantly impacted subsequent caregiver depressive symptoms. Only patient agitation/aggression was associated with subsequent caregiver depressive symptoms (OR = 1.76; 95% CI = 1.04-2.97) after controlling for concurrent BPSD, although not in fully adjusted models. Conclusions: Persistent agitation/aggression early in dementia diagnosis may be associated with subsequent depressive symptoms in caregivers. Future longitudinal analyses of the dementia caregiving relationship should continue to examine the negative impact of persistent agitation/aggression in the diagnosis of early stage dementia on caregivers

Regional Cerebral Blood Flow in Mood Disorders. II. Comparison of Major Depression and Alzheimer's Disease

We contrasted regional cerebral blood flow in matched groups of 30 patients with major depression,30 patients with Alzheimer's disease and 30 normal controls using the 133Xe inhalation technique. Whereas both the depressed and AIzheimer's disease groups had markedly reduced global cortical blood flow, the Scaled Subproflle Model,developed to identify abnormalities in regional networks, indicated that they had distinct topographic profiles. Previous findings of an abnormal regional network in major depression were unaltered by the inclusion of Alzheimer's disease patients in the analysis. Alzheimer's disease was associated with a distinct parietotemporal deficit and the degree of this abnormality strongly covaried with cognitive impairment. Alzheimer's disease patients also had abnormal manifestation of three other regional networks. We illustrate a method for distinguishing when a disease imposes a new pattern of interactions among brain regions and when a disease alters the expression of regional patterns characteristic of normal functioning

Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): evaluation using an endogenous HCC model

Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an important role in promoting HCC. A small molecule inhibitor of LSF, Factor Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in nude mice without harming normal cells. Here we evaluated the efficacy of FQI1 and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC was induced in a transgenic mouse with hepatocyte-specific overexpression of c-myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2 treatment after tumor development. LSF inhibitors markedly decreased tumor burden in Alb/c-myc mice with a corresponding decrease in proliferation and angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1. Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine significantly prevented FQI-induced mitotic arrest. A significant induction of apoptosis was also observed upon treatment with FQI. These effects of LSF inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be highly potent and effective therapeutics for HCC either alone or in combination with currently existing therapies.The present study was supported in part by grants from The James S. McDonnell Foundation, National Cancer Institute Grant R01 CA138540-01A1 (DS), National Institutes of Health Grant R01 CA134721 (PBF), the Samuel Waxman Cancer Research Foundation (SWCRF) (DS and PBF), National Institutes of Health Grants R01 GM078240 and P50 GM67041 (SES), the Johnson and Johnson Clinical Innovation Award (UH), and the Boston University Ignition Award (UH). JLSW was supported by Alnylam Pharmaceuticals, Inc. DS is the Harrison Endowed Scholar in Cancer Research and Blick scholar. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research. The authors acknowledge Dr. Lauren E. Brown (Dept. Chemistry, Boston University) for the synthesis of FQI1 and FQI2, and Lucy Flynn (Dept. Biology, Boston University) for initially identifying G2/M effects caused by FQI1. (James S. McDonnell Foundation; R01 CA138540-01A1 - National Cancer Institute; R01 CA134721 - National Institutes of Health; R01 GM078240 - National Institutes of Health; P50 GM67041 - National Institutes of Health; Samuel Waxman Cancer Research Foundation (SWCRF); Johnson and Johnson Clinical Innovation Award; Boston University Ignition Award; Alnylam Pharmaceuticals, Inc.)Published versio

Sertraline Treatment of Elderly Patients with Depression and Cognitive Impairment

Background There is little information on the efficacy and side effects of antidepressant treatment in elderly patients with combined depression and cognitive impairment without dementia (DEP-MCI), and it is unclear if cognitive performance improves with antidepressant response in these patients. Methods In 39 elderly DEP-MCI patients, changes in depression and cognitive impairment were evaluated with open sertraline treatment up to 200 mg/day for 12 weeks. Results Of the 26 completers, 17 were responders and nine were non-responders. Diagnostic subtype of depression was unrelated to response. ANCOVA on WAIS-R digit symbol percent change scores revealed a significant effect for responder status (F = 5.59, p < 0.03), and age (F = 0.24, p < 0.64) and education (F = 1.64, p < 0.22) were not significant covariates. From pre-trial to post-trial, responders improved in WAIS-R digit symbol percent change scores (Mean −10% SD 24) while non-responders declined (Mean 14% SD 18; t = 2.60, p < 0.02). Other neuropsychological measures were unrelated to response. Percent change in HRSD scores showed significant inverse correlations with percent change in several cognitive measures. Conclusions DEP-MCI patients showed moderate clinical response to sertraline treatment. When responders were compared to non-responders, cognitive improvement was limited to one measure of attention and executive function. Overall, there was little cognitive improvement with antidepressant treatment. The findings indirectly suggest that lack of improvement in cognition following treatment of depression in DEP-MCI patients may be associated with increased risk of meeting diagnostic criteria for dementia during follow-up