Tag: nevin manimala

Gait Posture. 2021 Oct 11;91:79-85. doi: 10.1016/j.gaitpost.2021.10.010. Online ahead of print.

ABSTRACT

BACKGROUND: Walking adaptability is an obvious manifestation of Parkinson’s disease (PD). Augmented reality technologies such as interactive walkways may improve walking adaptability in patients with Parkinson’s Disease (PWP).

RESEARCH QUESTION: How effective is C-Mill gait adaptability training in the early and middle stages of PD for improving walking adaptability in motor subtypes of the disease?

METHODS: Fifty-two patients with early- or middle-stage PD were divided into two groups according to motor subtype (postural instability/gait disorder [PIGD] and non-PIGD) and received 7 days of training (0.5 h every day, 2 h after medication) on an augmented reality treadmill with built-in visual targets and obstacles. Functional assessments were performed before and after intervention, including posture control and walking, C-gait assessment, and participant experience. The Parkinson Disease Quality of Life questionnaire was administered at 3-month follow-up.

RESULTS: Both the PIGD (n = 29) and non-PIGD (n = 23) groups showed improved tandem walking, obstacle avoidance, and overall score in C-gait assessment and Timed Up and Go test after C-Mill training. However, there were no differences between the two groups. The PIGD group showed improvement in visually guided stepping and Speed adaptations, whereas the non-PIGD group did not improve. The non-PIGD group reported they could complete the training with less exertion after the intervention and at the 3-month follow-up, these patients reported improvement in quality of life.

SIGNIFICANCE: C-Mill gait adaptation training in the early and middle stages of PD improves walking adaptability in both motor subtypes. Cue strategies are the probable mechanism and may decrease fall risk after training. There was no difference between the groups in the improvements of perceived exertion and quality of life at follow-up. Although PIGD patients showed statistic improvements in visually guided stepping compared with non-PIGD patients, but the difference was not likely to be clinically meaningful. Specific effects of C-mill training for different types of PD were not observed in our study.

PMID:34656008 | DOI:10.1016/j.gaitpost.2021.10.010

Clin Nutr. 2021 Oct 1;40(11):5482-5485. doi: 10.1016/j.clnu.2021.09.040. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Immune modulating nutrition (IMN) has been shown to reduce postoperative infectious complications and length of stay in patients with gastrointestinal cancer. Two studies of IMN in patients undergoing surgery for head and neck cancer also suggested that this treatment might improve long-term survival and progression-free survival. In the present study, we analysed follow-up data from our previous randomised controlled trial of IMN, in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer, in order to evaluate the long-term impact on survival of postoperative IMN versus an isocaloric, isonitrogenous control feed.

METHODS: This study included patients undergoing surgery for cancers of the pancreas, oesophagus and stomach, who had been randomised in a double-blind manner to receive postoperative jejunostomy feeding with IMN (Stresson, Nutricia Ltd.) or an isonitrogenous, isocaloric feed (Nutrison High Protein, Nutricia) for 10-15 days. The primary outcome was long-term overall survival.

RESULTS: There was complete follow-up for all 108 patients, with 54 patients randomised to each group. There were no statistically significant differences between groups by demographics [(age, p = 0.63), sex (p = 0.49) or site of cancer (p = 0.25)]. 30-day mortality was 11.1% in both groups. Mortality in the intervention group was 13%, 31.5%, 70.4%, 85.2%, 88.9%, and 96.3% at 90 days, and 1, 5, 10, 15 and 20 years respectively. Corresponding mortality in the control group was 14.8%, 35.2%, 68.6%, 79.6%, 85.2% and 98.1% (p > 0.05 for all comparisons).

CONCLUSION: Early postoperative feeding with arginine-enriched IMN had no impact on long-term survival in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer.

PMID:34656029 | DOI:10.1016/j.clnu.2021.09.040

Neurobiol Aging. 2021 Sep 17;109:64-77. doi: 10.1016/j.neurobiolaging.2021.09.013. Online ahead of print.

ABSTRACT

In Alzheimer disease, Tau pathology is thought to propagate from cell to cell throughout interconnected brain areas. However, the forms of Tau released into the brain interstitial fluid (ISF) in vivo during the development of Tauopathy and their pathological relevance remain unclear. Combining in vivo microdialysis and biochemical analysis, we find that in Tau transgenic mice, human Tau (hTau) present in brain ISF is truncated and comprises at least 10 distinct fragments spanning the entire Tau protein. The fragmentation pattern is similar across different Tau transgenic models, pathological stages and brain areas. ISF hTau concentration decreases during Tauopathy progression, while its phosphorylation increases. ISF from mice with established Tauopathy induces Tau aggregation in HEK293-Tau biosensor cells. Notably, immunodepletion of ISF phosphorylated Tau, but not Tau fragments, significantly reduces its ability to seed Tau aggregation and only a fraction of Tau, separated by ultracentrifugation, is seeding-competent. These results indicate that ISF seeding competence is driven by a small subset of Tau, which potentially contribute to the propagation of Tau pathology.

PMID:34655982 | DOI:10.1016/j.neurobiolaging.2021.09.013

J Infect Public Health. 2021 Oct 7;14(11):1701-1707. doi: 10.1016/j.jiph.2021.10.002. Online ahead of print.

ABSTRACT

BACKGROUND: Dengue fever is one of the major viral diseases worldwide transmitted by mosquitoes. Depending on the severity of disease it can range from mild fever to severe fatal cases. Rapid decline of platelet levels is one of indicators of clinical worsening. The role of viral factors in dengue pathogenesis and correlation with clinical and laboratory parameters remain unclear.

METHODS: Between September 2017 to December 2018, 102 dengue confirmed paediatric cases were analysed for various viral and host parameters. Based on symptoms, they were classified into dengue without warning signs (DOS), dengue with warning signs (DWS) and severe dengue (SD) as per 2009 WHO classification. Quantitative analysis of NS1, IgM and IgG in were done by ELISA. IgM/IgG ratio revealed primary or secondary dengue infection. Serotyping of virus in serum was done by nested multiplex RT-PCR. Viral load (VL) was determined by quantitative real time polymerase chain reaction. Association between VL and NS1 in patient sera with clinical and laboratory parameters was statistically analysed.

RESULTS: It was found that disease severity (as per 2009 WHO classification) significantly associated with secondary dengue infection. DENV3 was found to be the only serotype detected. The present study reports neither NS1 nor VL significantly associated with disease severity or type of infection (primary or secondary). However, VL positively correlated with haematocrit (p < 0.05). Viral load above 10⁶ copies/mL was found in 61% of patients. Further, high viral load (>10⁶ copies/mL) negatively correlated with platelet levels (p < 0.05).

CONCLUSION: Thus, viral load could be an important predictive parameter in dengue related severe symptoms like thrombocytopenia and elevated hematocrit when it goes above a certain threshold (>10⁶ copies/ mL).

PMID:34655984 | DOI:10.1016/j.jiph.2021.10.002

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Oct 9;267(Pt 2):120471. doi: 10.1016/j.saa.2021.120471. Online ahead of print.

ABSTRACT

The decarboxylation of Δ9-tetrahydrocannabinolic acid (THCA) plays pivotal role in the potency of medical cannabis and its extracts. Our present work aims to draw attention to mid-infrared (MIR) spectroscopy to in-situ monitor and decipher the THCA decarboxylation reaction in the solid state. The initial TG/DTG curves of THCA, for a first time, outlined the solid-solid decarboxylation dynamics, defined the endpoint of the process and the temperature of the maximal conversion rate, which aided in the design of the further IR experiment. Temperature controlled IR spectroscopy experiments were performed on both THCA standard and cannabis flower by providing detailed band assignment and conducting spectra-structure correlations, based on the concept of functional groups vibrations. Moreover, a multivariate statistical analysis was employed to address the spectral regions of utmost importance for the THCA → THC interconversion process. The principal component analysis model was reduced to two PCs, where PC1 explained 94.76% and 98.21% of the total spectral variations in the THCA standard and in the plant sample, respectively. The PC1 plot score of the THCA standard, as a function of the temperature, neatly complemented to the TG/DTG curves and enabled determination of rate constants for the decarboxylation reaction undertaken on several selected temperatures. The predictive capability of MIR was further demonstrated with PLS (R2X = 0.99, R2Y = 0.994 and Q2 = 0.992) using thermally treated flower samples that covered broad range of THCA/THC content. Consequently, a progress in elucidation of kinetic models of THCA decarboxylation in terms of fitting the experimental data for both, solid state standard substance and a plant flower, was achieved. The results open the horizon to promote an appropriate process analytical technology (PAT) in the outgrowing medical cannabis industry.

PMID:34655978 | DOI:10.1016/j.saa.2021.120471

Mult Scler Relat Disord. 2021 Oct 4;56:103311. doi: 10.1016/j.msard.2021.103311. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity is linked to increased risk of multiple sclerosis (MS) and worsening disease severity. Recent experimental and clinical data indicates that adipokines are involved in regulating immune response and serve as cross talk between immune and neural system. Dimethyl fumarate (DMF) is an oral MS medication with unknown mechanism of action. It upregulates the nuclear factor E2-related factor 2 (Nrf2) pathway, a pathway for adipocyte differentiation. To determine a possible relationship between treatment with dimethyl fumarate, serum adipokine profiles and treatment response in patients with MS, we conducted an observational cohort study and measured serum adipokine and Vitamin D levels before and after treatment with DMF and examined their association with treatment response.

METHODS: We identified patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB) study who were treated with dimethyl fumarate and had available serum samples. Longitudinal pre-treatment and on-treatment samples were available in 23 patients. Cross-sectional on-treatment samples were available in 91 patients, who were classified into DMF responders and non-responders based on radiologic and clinical relapse activity or disability progression. We measured serum leptin, adiponectin, resistin, ghrelin, fatty acid binding protein-4 (FABP-4) and-5 (FABP-5), vitamins D2 and D3. Statistical analysis was performed with paired t-tests, Wilcoxon signed-rank and Mann-Whitney U tests.

RESULTS: After treatment with DMF, serum adiponectin levels significantly increased, whereas FABP-4 levels significantly decreased compared to baseline levels, without a statistically significant change in the patients’ BMI. Ghrelin levels were insignificantly lower post-treatment. FABP-4 levels were significantly higher in DMF responders compared to non-responders. This effect was sex-specific, with higher FABP4 levels associated with treatment response in males, but not females.

CONCLUSION: DMF treatment is associated with significant changes in serum adipokine levels, primarily adiponectin and FABP-4. Sex may affect the association between FABP-4 and treatment response.

PMID:34655958 | DOI:10.1016/j.msard.2021.103311

Drug Alcohol Depend. 2021 Sep 28;229(Pt B):109111. doi: 10.1016/j.drugalcdep.2021.109111. Online ahead of print.

ABSTRACT

BACKGROUND: An efficacious pharmacotherapy for cannabis use disorder (CUD) has yet to be established. This study preliminarily evaluated the safety and efficacy of varenicline for CUD in a proof-of-concept clinical trial.

METHODS: Participants in this 6-week randomized, placebo-controlled pilot trial received either varenicline (n = 35) or placebo (n = 37), added to a brief motivational enhancement therapy intervention. Outcomes included cannabis withdrawal, cannabis abstinence, urine cannabinoid levels, percent cannabis use days, and cannabis sessions per day.

RESULTS: Both treatment groups noted significant decreases in self-reported cannabis withdrawal, percentage of days used, and use sessions per day during treatment compared to baseline. While this pilot trial was not powered to detect statistically significant between-group differences, participants randomized to varenicline evidenced numerically greater rates of self-reported abstinence at the final study visit [Week 6 intent-to-treat (ITT): Varenicline: 17.1% vs. Placebo: 5.4%; RR = 3.2 (95% CI: 0.7,14.7)]. End-of-treatment urine creatinine corrected cannabinoid levels were numerically lower in the varenicline group and higher in the placebo group compared to baseline [Change from baseline: Varenicline -1.7 ng/mg (95% CI: -4.1,0.8) vs. Placebo: 1.9 ng/mg (95% CI: -0.4,4.3); Δ = 3.5 (95% CI: 0.1,6.9)]. Adverse events related to study treatment did not reveal new safety signals.

CONCLUSIONS: Findings support the feasibility of conducting clinical trials of varenicline as a candidate pharmacotherapy for CUD, and indicate that a full-scale efficacy trial, powered based on effect sizes and variability yielded in this study, is warranted.

PMID:34655945 | DOI:10.1016/j.drugalcdep.2021.109111

Appl Radiat Isot. 2021 Oct 12;178:109982. doi: 10.1016/j.apradiso.2021.109982. Online ahead of print.

ABSTRACT

The aim of this study was to develop local diagnostic reference levels (LDRL) during Transarterial chemoembolization (TACE). This cross-sectional study reports radiation dose indicators of 108 patients in a Mexican hospital, obtained over a period of 35 months. Kerma-area product (P_KA), air-kerma at the reference point (K_{a, r}), and descriptive statistical analysis were examined according to sociodemographic characteristics of the sample patients. The LDRL obtained were then compared to a similar international framework. The present study contributes to the establishment of a TACE LDRL and identifies significant correlations among radiology factors and dosimetric quantities obtained.

PMID:34655924 | DOI:10.1016/j.apradiso.2021.109982

J Mech Behav Biomed Mater. 2021 Sep 30;125:104866. doi: 10.1016/j.jmbbm.2021.104866. Online ahead of print.

ABSTRACT

Accurate biomechanical properties of the human cranial dura mater are paramount for computational head models, artificial graft developments and biomechanical basic research. Yet, it is unclear whether areas of the dura containing meningeal vessels biomechanically differ from avascular areas. Here, 244 dura mater samples with or without vessels from 32 cadavers were tested in a quasi-static uniaxial tensile testing setup. The thicknesses of the meningeal and periosteal dura in vascular and avascular areas were histologically investigated in 36 samples using van Gieson staining. The elastic modulus of 112 MPa from dura samples containing vessels running transversely was significantly lower than samples with vessels running longitudinally (151 MPa; p < 0.001). The ultimate tensile strength of dura samples with transversely running vessels (11.1 MPa) was significantly lower in comparison to both avascular samples (14.9 MPa; p < 0.001) and samples with a longitudinally running vessel (15.0 MPa; p < 0.001). The maximum force of dura samples with longitudinally running vessels was 37 N (p < 0.001), this was significantly higher compared to the other groups which were 23 N (p < 0.001). The meningeal and periosteal dura layer thicknesses were not statistically different in avascular areas (p > 0.222). However, around the vessels, the meningeal dura layer was significantly thicker compared to the periosteal layer (p ≤ 0.019). The sum of the meningeal and periosteal layers was similar between vascular and avascular areas (p ≥ 0.071). Vascular areas of the human cranial dura mater withstand the same forces as avascular areas when being stretched. When stretched along the vessel, the dura-vessel composite can withstand even higher tensile forces compared to avascular areas. Vascular areas of the cranial dura mater seem to be similar when compared to avascular areas making their separate simulation in computational models non-essential.

PMID:34655943 | DOI:10.1016/j.jmbbm.2021.104866

Neuroimage Clin. 2021 Oct 12;32:102850. doi: 10.1016/j.nicl.2021.102850. Online ahead of print.

ABSTRACT

Progressive supranuclear palsy is a neurodegenerative disorder characterized primarily by tau inclusions and neurodegeneration in the midbrain, basal ganglia, thalamus, premotor and frontal cortex. Neurodegenerative change in progressive supranuclear palsy has been assessed using MRI. Degeneration of white matter tracts is evident with diffusion tensor imaging and PET methods have been used to assess brain metabolism or presence of tau protein deposits. Patients with progressive supranuclear palsy present with a variety of clinical syndromes; however early onset of gait impairments and postural instability are common features. In this study we assessed the relationship between multimodal imaging biomarkers (i.e., MRI atrophy, white matter tracts degeneration, flortaucipir-PET uptake) and laboratory-based measures of gait and balance abnormalities in a cohort of nineteen patients with progressive supranuclear palsy, using univariate and multivariate statistical analyses. The PSP rating scale and its gait midline sub-score were strongly correlated to gait abnormalities but not to postural imbalance. Principal component analysis on gait variables identified velocity, stride length, gait stability ratio, length of gait phases and dynamic stability as the main contributors to the first component, which was associated with diffusion tensor imaging measures in the posterior thalamic radiation, external capsule, superior cerebellar peduncle, superior fronto-occipital fasciculus, body and splenium of the corpus callosum and sagittal stratum, with MRI volumes in frontal and precentral regions and with flortaucipir-PET uptake in the precentral gyrus. The main contributor to the second principal component was cadence, which was higher in patients presenting more abnormalities on mean diffusivity: this unexpected finding might be related to compensatory gait strategies adopted in progressive supranuclear palsy. Postural imbalance was the main contributor to the third principal component, which was related to flortaucipir-PET uptake in the left paracentral lobule and supplementary motor area and white matter disruption in the superior cerebellar peduncle, putamen, pontine crossing tract and corticospinal tract. A partial least square model identified flortaucipir-PET uptake in midbrain, basal ganglia and thalamus as the main correlate of speed and dynamic component of gait in progressive supranuclear palsy. Although causality cannot be established in this analysis, our study sheds light on neurodegeneration of brain regions and white matter tracts that underlies gait and balance impairment in progressive supranuclear palsy.

PMID:34655905 | DOI:10.1016/j.nicl.2021.102850