Purpose Symptoms and medication use in patients with Parkinson’s disease (PD) affect the quality of life of patients and caregivers, yet prior research seldom focused on their experiences with medications. This study explored comprehensive living and medication experience from patients with PD and their caregivers. Methods Patients diagnosed with PD for ≥2 years, with or without their caregivers, were recruited from an outpatient clinic in Taiwan. Semi-structured in-depth interviews were conducted based on the Common Sense Model. A qualitative content analysis was used to identify salient themes from verbatim transcripts. Results In total, 15 patients and eight caregivers were interviewed. Five themes were derived: (1) symptoms and help-seeking behaviours before a diagnosis, (2) emotional impacts and life adaptations after a PD diagnosis, (3) life affected by medications, (4) experiences of caregivers in taking care of PD patients, and (5) communication between doctors and patients. Conclusions Patients frequently adjusted their daily schedules to live with PD and the medication side effects. Caregivers struggle to overcome caring burdens and to stay positive to support patients. More attention on providing medication information, mental support, and communication between stakeholders is needed to improve the quality of life of patients and caregivers.
Background The obesity paradox, which suggests that high body weight is positively associated with survival in some diseases, has not been proven in patients with hip fracture. In this study, meta-analysis of previous studies on the impacts of body weight on postoperative mortality following hip fracture surgery in older adults was conducted. Methods PubMed, Embase, and Cochrane library were searched for studies investigating the correlation between mortality after hip fracture surgery and body weight. The search main items included: (“Body mass index” OR “BMI” or “body weight”) and (“hip fracture” or “hip fractures”). Studies contained data on short-term (≤ 30-day) and long-term (≥ 1 year) mortality after hip fracture and its association with distinct body weight or BMI groups were reported as full-text articles were included in this meta-analysis. Results Eleven separate studies were included. The definitions of underweight and obesity differed among the included studies, but the majority of the enrolled studies used the average body weight definition of a BMI of 18.5 to 24.9 kg/m ² ; underweight referred to a BMI of < 18.5 kg/m ² ; and obesity pertained to a BMI of > 30 kg/m ² . Based on the generalized definitions of body-weight groups from the enrolled studies, the group with obesity had lower long-term (odds ratio [OR]: 0.63, 95% CI: 0.50–0.79, P < 0.00001) and short-term (OR: 0.63, 95% CI: 0.58–0.68, P ≤ 0.00001) mortality rates after hip fracture surgery when compared with patients with average-weight group. However, compared with the average-weight group, the underweight group had higher long-term (OR: 1.51, 95% CI: 1.15-1.98, P =0.003) and short-term (OR: 1.49, 95% CI: 1.29-1.72, P <0.00001) mortality rates after hip fracture surgery. Conclusions Current evidence demonstrates an inverse relation of body weight with long-term and short-term mortality after hip fracture surgery in older adults.
Background All types of movements involve the role of articular cartilage and bones. The presence of cartilage enables bones to move over one another smoothly. However, repetitive microtrauma and ischemia as well as genetic effects can cause an osteochondral lesion. Numerous treatment methods such as microfracture surgergy, autograft, and allograft, have been used, however, it possesses treatment challenges including prolonged recovery time after surgery and poses a financial burden on patients. Nowadays, various tissue engineering approaches have been developed to repair bone and osteochondral defects using biomaterial implants to induce the regeneration of stem cells. Methods In this study, a collagen (Col)/γ-polyglutamate acid (PGA)/hydroxyapatite (HA) composite scaffold was fabricated using a 3D printing technique. A Col/γ-PGA/HA 2D membrane was also fabricated for comparison. The scaffolds (four layers) were designed with the size of 8 mm in diameter and 1.2 mm in thickness. The first layer was HA/γ-PGA and the second to fourth layers were Col/γ-PGA. In addition, a 2D membrane was constructed from hydroxyapatite/γ-PGA and collagen/γ-PGA with a ratio of 1:3. The biocompatibility property and degradation activity were investigated for both scaffold and membrane samples. Rat bone marrow mesenchymal stem cells ( r BMSCs) and human adipose-derived stem cells ( h ADSCs) were cultured on the samples and were tested in-vitro to evaluate cell attachment, proliferation, and differentiation. In-vivo experiments were performed in the rat and nude mice models. Results In-vitro and in-vivo results show that the developed scaffold is of well biodegradation and biocompatible properties, and the Col-HA scaffold enhances the mechanical properties for osteochondrogenesis in both in-vitro and animal trials. Conclusions The composite would be a great biomaterial application for bone and osteochondral regeneration.
Background Human traits, diseases susceptibility, and clinical outcomes vary hugely among individuals. Despite a fundamental understanding of genetic (or environmental) contributions, the detailed mechanisms of how genetic variation impacts molecular or cellular behaviours of a gene, and subsequently leads to such variability remain poorly understood. Methods Here, in addition to phenome-wide correlations, we leveraged multiomics to exploit mechanistic links, from genetic polymorphism to protein structural or functional changes and a cross-omics perturbation landscape of a germline variant. Results We identified a missense cis -acting expression quantitative trait locus in CLEC18A (rs75776403) in which the altered residue (T 151 →M 151 ) disrupts the lipid-binding ability of the protein domain. The altered allele carriage led to a metabolic and proliferative shift, as well as immune deactivation, therefore determines human anthropometrics (body height), kidney, and hematological traits. Conclusions Collectively, we uncovered genetic pleiotropy in human complex traits and diseases via CLEC18A rs75776403-regulated pathways.
Activated carbon (AC) with low-cost, high surface area and pore volume properties is common active material of commercial supercapacitor (SC). Producing AC using cigarette filters (CF) cannot only reduce serious CF pollution but also decrease ingredient costs. Also, activating agents have been reported to play important roles on energy storage ability of home-made AC. In this work, it is the first time to use CF to synthesize AC with ZnCl2, KOH and H3PO4 as activating agents. The CF-derived AC activated by KOH (CAC-KOH) shows abundant functional groups, larger surface area, well-constructed pore structure and suitable defect-to-graphene intensity. The CAC-KOH electrode achieves the largest specific capacitance (Csp) of 106.5 F/g at 0.5 A/g, while the CF-derived AC electrodes fabricated using ZnCl2 and H3PO4 show smaller Csp values of 4.2 and 9.4 F/g, respectively. The symmetric SC assembled using CAC-KOH electrodes presents a maximum energy density of 5.15 Wh/kg at 325 W/kg and a Csp retention of 73 % after 11,000 charge/discharge cycles. Synthesizing AC with polluted CF successfully opens new blueprints for using wastes to produce efficient active material. It is expected to further enhance energy storage ability of wastes-derived AC by refining the activation process in near future.
This study evaluated the feasibility of applying the wavelet transform (WT) combined with a phase-lead compensator (PLC) to our previously developed two-dimensional respiratory motion compensation system (RMCS). This system automatically and instantaneously adjusts PLC parameters according to different respiration signals to reduce influences of the system delay time, improving the compensation effect of the RMCS during respiratory motion compensation. This study performed respiratory movement compensation experiments with a two-dimensional respiratory motion simulation system (RMSS) and the RMCS. Human respiratory signals were captured using our previously developed ultrasound image tracking algorithm (UITA). In this study, a displacement compensation RMCS algorithm based on the combination of WT and PLC was developed by LabVIEW, which allows an automatic adjustment of the PLC parameters according to various respiratory waveforms, achieving a better compensation effect. The experiment results indicated that the compensation rate (CR) of right-left and superior-inferior directions had both improved 67.96–88.05% and 70.38–91.43%, respectively. In this study, the proposed method combined with WT and PLC applied in respiratory movement compensation experiments; the UITA was used for tracking diaphragm motion which substitutes for tumor motion. This noninvasive monitoring method also helps reduce side effects after treatment. The experimental results indicated that the effect of using the WT combined with the PLC to compensate for various respiratory signals was improved over our previously developed compensation algorithm.
Low treatment persistence and adherence in patients with dementia results in a rapid loss of disease control. This pilot study evaluated the impact of pharmacist‐provided caregiver counselling on treatment persistence, adherence, quality of life (QoL) in patients with dementia, as well as caregiver's knowledge of dementia, and caregiver burden. This prospective, randomized controlled study was performed at a hospital‐based pharmacist‐managed clinic from December 2017 to December 2019. Patients with mild‐to‐moderate Alzheimer's disease (AD), initiating cholinesterase inhibitors within 3 months, and coming with their caregivers were included and randomized 1:1 to intervention or control group. The intervention group received pharmacist counselling and education sheets about AD, whereas the control group only received standard of care. Patients' treatment persistence and adherence were assessed at months 3, 6, 9, and 12; QoL, and caregiver burden were assessed at baseline and month 12. Caregiver's knowledge of dementia was assessed at baseline and 2 weeks after counselling in the intervention group. Nonparametric statistics and generalized estimating equation models were used for statistical analysis. A total of 40 patients and 40 caregivers were included, with 20 pairs for each group. One‐year medication persistence (16/20 vs. 16/20) and adherence rates (87%–99%) were high in both groups without significant differences. Dementia knowledge scores improved significantly after counselling in the intervention group (77.5 vs. 95.8, p < 0.01). Although the change of caregiver burden was non‐significant between groups, the score decreased in the intervention group (−0.89; p = 0.78) but increased in the control group (+6.01; p = 0.07). In this pilot study, pharmacist's counselling for patients with dementia and their caregivers is feasible and can enhance caregiver knowledge of dementia. Further study with larger scale is needed to confirm the impact on these outcomes. Dementia knowledge scores improved significantly after counselling in the intervention group (77.5 vs. 95.8, p < 0.01). Although the change of caregiver burden was non‐significant between groups, the score decreased in the intervention group (−0.89; p = 0.78) but increased in the control group (+6.01; p = 0.07).
Cisplatin is a prevalent chemotherapeutic agent used for non-small cell lung cancer (NSCLC) that is difficult to treat by targeted therapy, but the emergence of resistance severely limits its efficacy. Thus, an effective strategy to combat cisplatin resistance is required. This study demonstrated that, at clinically achievable concentrations, the combination of selenium yeast (Se-Y) and fish oil (FO) could synergistically induce the apoptosis of cancer stem cell (CSC)-like A549 NSCLC sphere cells, accompanied by a reversal of their resistance to cisplatin. Compared to parental A549 cells, sphere cells have higher cisplatin resistance and possess elevated CSC markers (CD133 and ABCG2), epithelial–mesenchymal transition markers (anexelekto (AXL), vimentin, and N-cadherin), and cytoprotective endoplasmic reticulum (ER) stress marker (glucose-regulated protein 78) and increased oncogenic drivers, such as yes-associated protein, transcriptional coactivator with PDZ-binding motif, β-catenin, and cyclooxygenase-2. In contrast, the proapoptotic ER stress marker CCAAT/enhancer-binding protein homologous protein and AMP-activated protein kinase (AMPK) activity were reduced in sphere cells. The Se-Y and FO combination synergistically counteracted the above molecular features of A549 sphere cells and diminished their elevated CSC-like side population. AMPK inhibition by compound C restored the side population proportion diminished by this nutrient combination. The results suggest that the Se-Y and FO combination can potentially improve the outcome of cisplatin-treated NSCLC with phenotypes such as A549 cells.
Past historical events and experimental research have shown that complying with orders from an authority has a strong impact on harming/destructive behavior, but no one has ever looked into the potential intervention and its neural underpinning to reveal the toll of coercion. We used a paradigm of virtual obedience to authority, in which an experimenter ordered a volunteer to press a handheld button to initiate actions that carried different consequences, including harming or helping others. In this study, we scanned the brain with functional neuroimaging and applied transcranial direct current stimulation (tDCS) to modulate the activation of the right temporoparietal junction (rTPJ) in healthy volunteers in a single‐blinded, sham‐controlled, crossover trial with anodal, cathodal, and sham stimulation. We observed that cathodal stimulation, compared to anodal and sham stimulation, significantly reduced reaction times (RTs) to initiating harming actions. The effect of tDCS on the rTPJ, orbitofrontal cortex, and anterior cingulate cortex had opposite directions depending on coercive harming or helping actions. Cathodal tDCS‐induced changes in the strength of the functional connectivity between the rTPJ and amygdala predicted the effect of cathodal tDCS on harming RTs. The findings provide evidence supporting the rTPJ having a role in coercion‐induced changes in the sense of agency. Neuromodulation with tDCS might help in unveiling the power of authority and assisting in the emergence of prosocial behavior, thus shedding light on coping strategies against coercion beyond merely examining its effects. Cathodal stimulation, compared to anodal and sham stimulation, significantly reduced reaction times to initiating harming actions and the strength of functional connectivity between the rTPJ and amygdala. Our findings provide the first evidence supporting that the rTPJ has a role in the coercion‐induced change in the sense of agency. Neuromodulation with tDCS might help in unveiling the power of authority and assist in the emergence of prosocial behavior, thus, shedding light on coping strategies against coercion beyond merely examining its effects.
Drug resistance in Mycobacterium tuberculosis (MTB) has long been a serious health issue worldwide. Most drug-resistant MTB isolates were identified due to treatment failure or in clinical examinations 3~6 months postinfection. In this study, we propose a whole-genome sequencing (WGS) pipeline via the Nanopore MinION platform to facilitate the efficacy of phenotypic identification of clinical isolates. We used the Nanopore MinION platform to perform WGS of clinical MTB isolates, including susceptible (n = 30) and rifampin- (RIF) or rifabutin (RFB)-resistant isolates (n = 20) according to results of a susceptibility test. Nonsynonymous variants within the rpoB gene associated with RIF resistance were identified using the WGS analytical pipeline. In total, 131 variants within the rpoB gene in RIF-resistant isolates were identified. The presence of the emergent Asp531Gly or His445Gln was first identified to be associated with the rifampin and rifabutin resistance signatures of clinical isolates. The results of the minimum inhibitory concentration (MIC) test further indicated that the Ser450Leu or the mutant within the rifampin resistance-determining region (RRDR)-associated rifabutin-resistant signature was diminished in the presence of novel mutants, including Phe669Val, Leu206Ile, or Met148Leu, identified in this study. IMPORTANCE Current approaches to diagnose drug-resistant MTB are time-consuming, consequently leading to inefficient intervention or further disease transmission. In this study, we curated lists of coding variants associated with differential rifampin and rifabutin resistant signatures using a single molecule real-time (SMRT) sequencing platform with a shorter hands-on time. Accordingly, the emerging WGS pipeline constitutes a potential platform for efficacious and accurate diagnosis of drug-resistant MTB isolates.
Context: Avermectin pesticides are widely used in agriculture, and are thought to have low toxicity in humans. However, information on their toxicity after accidental or deliberate ingestion is limited. Objective: The aim of this study was to evaluate the clinical manifestations of avermectin pesticide ingestion and identify factors associated with severe outcomes (death, intubation, or sustained hypotension requiring inotrope therapy). Materials and methods: This multicenter retrospective study included patients who visited the emergency departments of six teaching hospitals due to acute avermectin pesticide ingestion between January 2012 and May 2020. Patients who reported ingestion of any other pesticides, drugs, or substances were excluded. Results: In total, 64 patients (median age, 72 years) were included: 60 had ingested emamectin pesticides, and 4 had ingested abamectin. Almost all (98%) were cases of self-harm. The most common presentation was drowsiness (47%), with a median Glasgow Coma Scale (GCS) score of 14, followed by shortness of breath (SOB)/dyspnea (33%) and nausea/vomiting (22%). Concurrent methanol exposure (via the solvent) was confirmed or suspected in five patients. Seventeen patients (27%) were intubated. Three patients who developed respiratory failure were not intubated because of a "do-not-resuscitate" (DNR) order. Four patients developed sustained hypotension requiring inotrope therapy. Fifty patients (78%) were admitted, of whom 27 (42%) required intensive care unit (ICU) admission. Four patients died, three of whom had a DNR order. Based on our definition, 20 patients (31%) had severe outcomes. A multivariate logistic regression model showed that a GCS score < 13 (OR 68.1, 95% CI 3.8-999) and the presence of SOB/dyspnea (OR 50.2, 95% CI 3.0-849.9) were associated with severe outcomes. Conclusions: Most patients who intentionally ingested avermectin pesticides required inpatient treatment. Forty-two percent needed ICU care and 31% had severe outcomes. A GCS score < 13 and SOB/dyspnea were independently associated with severe outcomes.
The development of sialolithiasis is commonly related to local factors, such as the retrograde migration of foods, bacteria, or foreign bodies from the oral cavity. The association of sialolithiasis and saliva stasis resulting from decreased spontaneous secretion remains largely unexplored. The current study investigated the potential role of impaired spontaneous secretion in association with the formation of submandibular gland calculi. A retrospective cohort study. Between September 2016 and December 2017, 11 patients with unilateral submandibular gland sialolithiasis confirmed with sialendoscopy were assigned to the experimental group. Another 35 patients clinically diagnosed with parotid obstructive sialadenitis were assigned as the control group. The slope changes of the isotope count curve of the unaffected submandibular gland in the experimental group and the bilateral submandibular glands in the control group were calculated and compared to estimate the spontaneous secretion differences. The degree of spontaneous secretion was defined as the slope changes in the steady ascending stage of the scintigraphic exam. The slope decline (degree of spontaneous secretion) on the unaffected side in patients with single‐gland submandibular obstructive sialadenitis was significantly lower than that in the control individuals (p = .002). In contrast, the between‐group comparison in the unaffected parotid glands revealed no difference in the slope decline. The spontaneous secretion of the submandibular gland in patients with submandibular sialolithiasis was decreased compared to that in patients without submandibular sialolithiasis. This phenomenon might be associated with the development of sialolithiasis. 3.
Purpose: With increase of population aging, the prevalence of atherosclerotic cardiovascular disease (ASCVD) and elevated serum thyroid stimulating hormone (TSH) in elderly is increasing. High TSH level was reported to be associated with ASCVD and CVD mortality; however, few are studied in Chinese population, especially in the elderly. This study aimed to investigate the prevalence of elevated serum TSH and ASCVD in an elderly population of Chinese community and to explore the association between high serum TSH and ASCVD or CVD mortality. Patients and methods: We conducted a study involving 3814 adults who were at least 60 years of age. Questionnaires, physical examinations, and laboratory blood samples were collected in 2014, and a 78-months follow-up for cardiovascular and all-cause mortality was performed till December of 2020. Logistics regression was used to analyze the association between TSH and ASCVD. We used Cox models to assess the hazard ratios (HRs) for all-cause and CVD mortality across changes in serum TSH. Results: In this study, the prevalence of the elevated serum TSH was 19.8%, and significantly higher in women than in men (24.5% vs 13.9%, p < 0.001). The prevalence of ASCVD was 21.7%. In logistics regression models, elevated TSH was associated with ASCVD after adjusting for the risk factors of ASCVD in people over the age of 70 years (adjusted OR 1.054, P = 0.014). After a follow-up of 6.5 years, total 441 (11.6%) all-cause death and 174 (4.6%) death of CVD were observed. In Cox regression model, no significant correlation was found between TSH and all-cause mortality or CVD mortality in the elderly population. Conclusion: In the elderly population, there is high prevalence of elevated serum TSH and ASCVD. Elevated TSH seemed to be not associated with risk of all-cause or CVD mortality.
Nickel and cobalt layered double hydroxide (NiCo-LDH) has large specific surface area and interlayer spacing, multiple redox states and high ion-exchange capability, but poor electrical conductivity, severe agglomerations and structural defect restrict energy storage ability of NiCo-LDH as active materiel of battery supercapacitor hybrids (BSH). In this study, it is the first time to design sulfur-doped NiCo-LDH and polypyrrole nanotubes composites (NiCo-LDH-S/PNTs) from zeolitic imidazolate framework-67 (ZIF-67) as the efficient active material of BSH using electrospinning and hydrothermal processes. Effects of sulfur doping amounts are investigated. The one-dimensional hollow polypyrrole decorated with NiCo-LDH-S sheets with high aspect ratio provides straight charge-transfer routes and abundant contacts with electrolyte. The highest specific capacitance (CF) of 1936.3 F/g (specific capacity of 322.8 mAh/g) is achieved for the NiCo-LDH-S/PNTs with sulfur doping amount of 7% at 10 mV/s. The BSH comprising graphene LDH negative electrode and NiCo-LDH-S/PNTs positive electrode shows the maximum energy density of 16.28 Wh/kg at 650 W/kg. The CF retention of 74% and Coulombic efficiency of 90% are also achieved after 8000 charge/discharge cycles.
Objectives To provide a concept of measuring pressure changes under constant fluid infusion for the diagnosis of sialolithiasis, termed the sialodynamic test, in a porcine head model. Methods Using a porcine head model, a constant infusion of water into the submandibular gland of the two groups over 30 s was performed and the outlet pressure was measured. Metal beads were inserted into the salivary duct for obstruction simulation after the normal submandibular gland sialodynamic measurements were completed. Statistical analyses were performed to evaluate the differences between the measured individuals and the experimental group ( n = 3). Results The results showed no significant difference between individuals in the control group, but intergroup variation was noted in the simulated sialolithiasis group. The volume-dependent linear increase in pressure was exacerbated in the simulated sialolithiasis group compared with the control. Conclusion This study indicated that evaluating the relationship between pressure and volume changes can help to determine whether stones are present in the submandibular gland. The sialodynamic test might serve as a potential diagnostic method for salivary diseases.
Background The effectiveness of transversus abdominis plane block (TAP) on pain management after laparoscopic colorectal surgery (CRS) remains unclear since the only relevant meta-analysis on this topic did not separate laparoscopic CRS from open CRS. The aim of the study was to compare the analgesic efficacy and safety of TAP with non-TAP in patients undergoing laparoscopic CRS. Methods Four databases were searched for randomized controlled trials (RCTs) on this topic using relevant keywords. Two authors independently completed evidence selection, data extraction, and critical appraisal. Available data were pooled in the random-effects model, and point estimates with 95% confidence interval (CI) were reported for postoperative pain at rest and on coughing, opioid consumption, length of hospital stay, and adverse events. Results A total of 14 RCTs (n = 1216) contributed to the present synthesis. Pooled result showed that patients in the TAP group had lower pain at rest than those in the non-TAP group at postoperative 2-hour (mean difference [MD] = -1.42; P < 0.05), 4-hour (MD = −0.97; P < 0.05), 12-hour (MD = −0.75; P < 0.05), and 24-hour (MD = −0.61; P < 0.05). Patients in the TAP group also had lower postoperative pain on coughing than those in the non-TAP group on the first day (MD = −1.02; P < 0.05). Moreover, TAP had lesser postoperative opioid consumption than non-TAP (standardized mean difference, −0.26; P < 0.05; I-square = 20%), and there were non-significant differences in hospital stay and adverse event between the two groups. Conclusion Intraoperative TAP is safe and feasible pain management for laparoscopic CRS, particularly it is recommended when patient-controlled analgesia is not delivered. Therefore, laparoscopic TAP block might be a favorable administered strategy.
Identification of specific leukemia subtype is one of the keys to successful risk-directed therapy in childhood acute lymphoblastic leukemia (ALL). Although RNA sequencing (RNA-seq) is the best approach to identify virtually all specific leukemia subtypes, the routine use of this method is too costly for patients in resource-limited countries. This study enrolled 295 patients with pediatric ALL from 2010 to 2020. Routine screening could identify major cytogenetic alterations in approximately 69% B-cell (B)-ALL cases by reverse transcription (RT)-PCR, DNA index, and multiplex ligation-dependent probe amplification (MLPA). STIL-TAL1 was present in 33% of T-cell (T)-ALL cases. The remaining samples were submitted for RNA-seq. Over 96% B-ALL cases and 74% T-ALL cases could be identified based on the current molecular classification using this sequential approach. Patients with Philadelphia chromosome-like (Ph-like) ALL constituted only 2.4% of the entire cohort, a rate even lower than those with ZNF384-rearranged (4.8%), DUX4-rearranged (6%), and Ph+ (4.4%) ALL. Patients with ETV6-RUNX1, high hyperdiploidy, PAX5 alteration, and DUX4 rearrangement had favorable prognosis, whereas those with hypodiploid and KMT2A and MEF2D rearrangement ALL had unfavorable outcomes. Using MLPA, DNA index, and RT-PCR in B-ALL and RT-PCR in T-ALL followed by RNA-seq, childhood ALL can be better classified to improve clinical assessments.
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