Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 92
1.
Ann Hepatol ; 29(2): 101280, 2024.
Article En | MEDLINE | ID: mdl-38219950

INTRODUCTION AND OBJECTIVES: Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications of a lower ALT cut-off (>30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care. MATERIALS AND METHODS: All patients entering the iLFT diagnostic pathway had liver aetiological screening investigations if ALT >30 U/L. In those with MASLD the proportions with and without advanced fibrosis at different ALT thresholds: 31-41 U/L, 42-54 U/L and ≥55 U/L were compared. RESULTS: 16,373 patients underwent iLFT between March 2016 to April 2022. 762 (5 %) patients had MASLD with abnormal fibrosis scores, while 908 (6 %) had MASLD with normal fibrosis scores. 428 (56 %) patients were assessed in liver clinics, where 169 (39 %) had evidence of fibrosis. Of these, 22 (13 %) had ALT 31-41 U/L, 31 (18 %) had ALT 42-54 U/L and 116 (69 %) had ALT ≥55 U/L. 145 (86 %) patients had advanced fibrosis or cirrhosis, where 20 (14 %) had ALT 31-41 U/L, 28 (19 %) had ALT 42-54 U/L and 97 (67 %) had ALT ≥55 U/L. CONCLUSIONS: 33 % of MASLD patients with advanced fibrosis or cirrhosis had ALT 31-54 U/L, who would have been missed using the conventional ALT range. This suggests that lowering the ALT cut-off improves diagnosis of MASLD with advanced fibrosis in primary care.


Fatty Liver , Metabolic Diseases , Humans , Liver Cirrhosis/diagnosis , Alanine Transaminase
2.
Proc Natl Acad Sci U S A ; 120(50): e2221510120, 2023 Dec 12.
Article En | MEDLINE | ID: mdl-38064507

Effort-based decisions, in which people weigh potential future rewards against effort costs required to achieve those rewards involve both cognitive and physical effort, though the mechanistic relationship between them is not yet understood. Here, we use an individual differences approach to isolate and measure the computational processes underlying effort-based decisions and test the association between cognitive and physical domains. Patch foraging is an ecologically valid reward rate maximization problem with well-developed theoretical tools. We developed the Effort Foraging Task, which embedded cognitive or physical effort into patch foraging, to quantify the cost of both cognitive and physical effort indirectly, by their effects on foraging choices. Participants chose between harvesting a depleting patch, or traveling to a new patch that was costly in time and effort. Participants' exit thresholds (reflecting the reward they expected to receive by harvesting when they chose to travel to a new patch) were sensitive to cognitive and physical effort demands, allowing us to quantify the perceived effort cost in monetary terms. The indirect sequential choice style revealed effort-seeking behavior in a minority of participants (preferring high over low effort) that has apparently been missed by many previous approaches. Individual differences in cognitive and physical effort costs were positively correlated, suggesting that these are perceived and processed in common. We used canonical correlation analysis to probe the relationship of task measures to self-reported affect and motivation, and found correlations of cognitive effort with anxiety, cognitive function, behavioral activation, and self-efficacy, but no similar correlations with physical effort.


Decision Making , Physical Exertion , Humans , Decision Making/physiology , Physical Exertion/physiology , Individuality , Cognition/physiology , Reward , Motivation
3.
Open Forum Infect Dis ; 10(3): ofad144, 2023 Mar.
Article En | MEDLINE | ID: mdl-36998628

Persons with obesity (PwO) represent approximately 50% of acute bacterial skin and skin structure infections (ABSSSIs) in the United States (US). There are currently insufficient data in PwO for drugs used for ABSSSIs. We conducted a scoping review of randomized controlled trials (RCTs) published between 2000 and 2022 to describe how frequently body size measures were reported. Weight and/or body mass index (BMI) were recorded in approximately 50% of the 69 RCTs. The average weights or BMIs were lower than US averages for most RCTs reporting data. None evaluated the impact of body size on outcomes in the original publication. Only 30% of newly approved drugs mention PwO representation in the prescribing information. More representative recruitment of PwO into RCTs is needed to help clinicians evaluate efficacy in these patients. We suggest that the Food and Drug Administration require companies to submit plans to ensure adequate PwO inclusion and that authors of RCTs report subgroup results based on body size.

4.
Xenobiotica ; 52(8): 916-927, 2022 Aug.
Article En | MEDLINE | ID: mdl-36282181

Aggregates of the protein α-synuclein are associated with pathophysiology of Parkinson's disease and are present in Lewy Bodies found in the brains of Parkinson's patients. We previously demonstrated that bifunctional compounds composed of caffeine linked via a six carbon chain to either 1-aminoindan (C8-6-I) or nicotine (C8-6-N) bind α-synuclein and protect yeast cells from α-synuclein mediated toxicity.A critical step in development of positron emission tomography (PET) probes for neurodegenerative diseases is evaluation of their metabolic stability. We determined that C8-6-I, and C8-6-N both undergo phase 1 P450 metabolism in mouse, rat, and human liver microsomes. We utilised this metabolic information to guide the design of fluorinated analogues for use as PET probes and determined that the fluorine in 19F-C8-6-I and 19F-C8-6-N is stable to P450 enzymes.We have developed and validated an analytical HPLC-UV method following FDA and EMA guidelines to measure in vitro phase 1 kinetics of these compounds and determine their Vmax, KM and CLint,u in mouse liver microsomes. We found that C8-6-I and 19F-C8-6-I have a two- to fourfold lower CLint,u than C8-6-N, and 19F-C8-6-N. Our approach shows a simple, specific, and effective system to design and develop compounds as PET probes.


Parkinson Disease , alpha-Synuclein , Animals , Humans , Mice , Rats , alpha-Synuclein/chemistry , alpha-Synuclein/metabolism , Chromatography, High Pressure Liquid , Kinetics , Lewy Bodies/metabolism , Parkinson Disease/metabolism
5.
Urban Rail Transit ; 8(2): 99-120, 2022.
Article En | MEDLINE | ID: mdl-35582430

During COVID-19, certain means were proposed to improve crowd management in the Birmingham New Street railway station. To validate the current system of crowd management in the station, this paper examines the rail passenger flow in the concourse of the Birmingham New Street railway station and the passenger interactions and queueing phenomena associated with it, mainly at the ticket machines, offices and gates, prior to and during the implementation of COVID-19 measures. The passenger behaviour in the concourse of the station was simulated using the SIMUL8 event-based simulation modelling package. Three different scenarios were modelled to analyse the changes and impacts from pre-COVID-19 and within the COVID-19 context. The results revealed that passenger behaviour in railway stations is changing due to COVID-19. Specifically, passengers are more likely to buy tickets using their smartphones or online prior to or whilst entering the station so that they can go through the station concourse with minimal queuing times and avoid contact with a facility of common use at the station, whereas those without tickets are more likely to be in a queue to buy their tickets in the station. For pre-COVID, the results showed that even with a reduced number of ticket machines, overcrowding inside the station was unlikely to occur, as 80% of all passengers in the simulation completed service within a 15-minute time frame. However, during implementation of COVID-19 measures, as the number of passengers using the station dropped significantly and more passengers bought their tickets using their smartphones and/or online, queueing times were also shorter, and thus passengers spent less time in the system. The simulation results were in accordance with the expected practice; hence the effectiveness of the simulation model was verified. Overall, as a result of this study, the following suggestions to improve crowd management in a railway passenger station concourse are proposed: encourage passengers to purchase tickets on their smartphones, remove ticket gates and replace them with sensors, and provide a one-way passenger flow system in the main concourse of the station.

6.
J Am Med Dir Assoc ; 23(5): 707-714, 2022 05.
Article En | MEDLINE | ID: mdl-35183490

OBJECTIVE: This study aimed to determine the comparative effectiveness of interventions in treatment of sarcopenia. The primary outcome was the measure of treatment effect on muscle mass, and secondary outcomes were the treatment effect on muscle strength and physical performance. DESIGN: Systematic review and network meta-analysis (NMA). SETTING AND PARTICIPANTS: Participants with sarcopenia receiving interventions targeting sarcopenia in any setting. METHODS: Data sources: Relevant RCTs were identified by a systematic search of several electronic databases, including CINAHL, Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) from January 1995 to July 2019. Duplicate title and abstract and full-text screening, data extraction, and risk of bias assessment were performed. DATA EXTRACTION: All RCTs examining sarcopenia interventions [mixed exercise (combined aerobic and resistance exercise), aerobic exercise, resistance exercise, balance exercise, physical activity and protein or nutrition supplementation, acupuncture, whole-body vibration, protein supplement or interventions to increase protein intake, any nutritional intervention other than protein, and pharmacotherapy] were included. Comparators were standard care, placebo, or another intervention. DATA SYNTHESIS: We performed Bayesian NMA; continuous outcome data were pooled using the standardized mean difference effect size. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome. RESULTS: A total of 59 RCTs were included after screening of 4315 citations and 313 full-text articles. Network meta-analysis of muscle mass outcome (including 46 RCTs, 3649 participants, 11 interventions) suggested that mixed exercise were the most effective intervention (SUCRA = 93.94%) to increase muscle mass. Physical activity and protein or nutrition supplementation, and aerobic exercise were the most effective interventions to improve muscle strength and physical performance, respectively. Overall, mixed exercise is the most effective intervention in increasing muscle mass and was one of the 3 most effective interventions in increasing muscle strength and physical performance. CONCLUSIONS AND IMPLICATIONS: Mixed exercise and physical activity with nutritional supplementation are the most effective sarcopenia interventions. Most of the included studies have a high risk of bias. More robust RCTs are needed to increase the confidence of our NMA results and the quality of evidence.


Sarcopenia , Bayes Theorem , Humans , Muscle Strength/physiology , Network Meta-Analysis , Randomized Controlled Trials as Topic , Sarcopenia/therapy
7.
Transl Neurodegener ; 11(1): 9, 2022 02 10.
Article En | MEDLINE | ID: mdl-35139916

BACKGROUND: Accumulating α-synuclein (α-syn) aggregates in neurons and glial cells are the staples of many synucleinopathy disorders, such as Parkinson's disease (PD). Since brain adenosine becomes greatly elevated in ageing brains and chronic adenosine A1 receptor (A1R) stimulation leads to neurodegeneration, we determined whether adenosine or A1R receptor ligands mimic the action of known compounds that promote α-syn aggregation (e.g., the amphetamine analogue 2-aminoindan) or inhibit α-syn aggregation (e.g., Rasagiline metabolite 1-aminoindan). In the present study, we determined whether adenosine, A1R receptor agonist N6-Cyclopentyladenosine (CPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) could directly interact with α-syn to modulate α-syn aggregation and neurodegeneration of dopaminergic neurons in the substantia nigra (SN). METHODS: Nanopore analysis and molecular docking were used to test the binding properties of CPA and DPCPX with α-syn in vitro. Sprague-Dawley rats were administered with 7-day intraperitoneal injections of the A1R ligands and 1- and 2-aminoindan, and levels of α-syn aggregation and neurodegeneration were examined in the SN pars compacta and hippocampal regions using confocal imaging and Western blotting. RESULTS: Using nanopore analysis, we showed that the A1R agonists (CPA and adenosine) interacted with the N-terminus of α-syn, similar to 2-aminoindan, which is expected to promote a "knot" conformation and α-syn misfolding. In contrast, the A1R antagonist DPCPX interacted with the N- and C-termini of α-syn, similar to 1-aminoindan, which is expected to promote a "loop" conformation that prevents α-syn misfolding. Molecular docking studies revealed that adenosine, CPA and 2-aminoindan interacted with the hydrophobic core of α-syn N-terminus, whereas DPCPX and 1-aminoindan showed direct binding to the N- and C-terminal hydrophobic pockets. Confocal imaging and Western blot analyses revealed that chronic treatments with CPA alone or in combination with 2-aminoindan increased α-syn expression/aggregation and neurodegeneration in both SN pars compacta and hippocampus. In contrast, DPCPX and 1-aminoindan attenuated the CPA-induced α-syn expression/aggregation and neurodegeneration in SN and hippocampus. CONCLUSIONS: The results indicate that A1R agonists and drugs promoting a "knot" conformation of α-syn can cause α-synucleinopathy and increase neuronal degeneration, whereas A1R antagonists and drugs promoting a "loop" conformation of α-syn can be harnessed for possible neuroprotective therapies to decrease α-synucleinopathy in PD.


Parkinson Disease , Synucleinopathies , Animals , Dopaminergic Neurons/metabolism , Ligands , Molecular Docking Simulation , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Adenosine A1/metabolism , alpha-Synuclein/metabolism
8.
Int Urol Nephrol ; 54(9): 2239-2245, 2022 Sep.
Article En | MEDLINE | ID: mdl-35084650

PURPOSE: This study tested the hypothesis that progression of chronic kidney disease (CKD) is less aggressive in patients whose primary cause of CKD was nephrectomy, compared with non-surgical causes. METHODS: A sample of 5983 patients from five specialist nephrology practices was ascertained from the Queensland CKD Registry. Rates of kidney failure/death were compared on primary aetiology of CKD using multivariable Cox proportional hazards models. CKD progression was compared using multivariable linear and logistic regression analyses. RESULTS: Of 235 patients with an acquired single kidney as their primary cause of CKD, 24 (10%) and 38 (17%) developed kidney failure or died at median [IQR] follow-up times of 12.9 [2.5-31.0] and 33.6 [18.0-57.9] months after recruitment. Among patients with an eGFR < 45 mL/min per 1.73m2 at recruitment, patients with diabetic nephropathy and PCKD had the highest rates (per 1000 person-years) of kidney failure (107.8, 95% CI 71.0-163.8; 75.5, 95% CI 65.6-87.1); whereas, patients with glomerulonephritis and an acquired single kidney had lower rates (52.9, 95% CI 38.8-72.1; 34.6, 95% CI 20.5-58.4, respectively). Among patients with an eGFR ≥ 45 mL/min per 1.73m2, those with diabetic nephropathy had the highest rates of kidney failure (16.6, 95% CI 92.5-117.3); whereas, those with glomerulonephritis, PCKD and acquired single kidney had a lower risk (11.3, 95% CI 7.1-17.9; 11.7, 95% CI 3.8-36.2; 10.7, 95% CI 4.0-28.4, respectively). CONCLUSION: Patients who developed CKD after nephrectomy had similar rates of adverse events to most other causes of CKD, except for diabetic nephropathy which was consistently associated with worse outcomes. While CKD after nephrectomy is not the most aggressive cause of kidney disease, it is by no means benign, and is associated with a tangible risk of kidney failure and death, which is comparable to other major causes of CKD.


Diabetic Nephropathies , Glomerulonephritis , Renal Insufficiency, Chronic , Solitary Kidney , Diabetic Nephropathies/complications , Disease Progression , Glomerular Filtration Rate , Glomerulonephritis/complications , Humans , Nephrectomy/adverse effects , Proportional Hazards Models , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Solitary Kidney/complications
9.
PLoS One ; 16(9): e0256939, 2021.
Article En | MEDLINE | ID: mdl-34478454

Social role disruption is a state involving upheaval of social identities, routines and responsibilities. Such disruption is presently occurring at a global scale due to the COVID-19 pandemic, which poses a threat not only to health and security but also to the social roles that underlie people's daily lives. Our collective response to combat the virus entails, for example, parents homeschooling children, friends socializing online, and employees working from home. While these collective efforts serve the greater good, people's social roles now lack continuity from what was authentic to the roles before the pandemic began. This, we argue, takes a psychological toll. Individuals feel inauthentic, or alienated and out-of-touch from their "true" selves, to the extent their social roles undergo change. As evidence, we report survey (Studies 1 & 4) and experimental (Studies 2 & 3) evidence that COVID-19-related role changes indeed increase inauthenticity. This effect occurs independent of (a) how positively/negatively people feel about COVID-19 (Study 2) and (b) how positively/negatively people feel about the role change itself (Studies 3 & 4). Moreover, we identify two moderators of this effect. First, this effect occurs when (and ostensibly because) the social roles undergoing change are central to an individual's sense of self (Study 2). Second, this effect depends on an individual's temporal perspective. People can safeguard their self-authenticity in the face of changing social roles if they stay focused on the here-and-now (the present and immediate future), rather than focusing on the past (pre-COVID-19) or future (post-COVID-19) (Studies 3 & 4). This advantage for present-focused coping is observed in both the U.S.A. (Study 3) and Hong Kong (Study 4). We suggest that the reason people feel more authentically themselves when they maintain a present focus is because doing so makes the discontinuity of their social roles less salient.


COVID-19/epidemiology , COVID-19/psychology , Pandemics , SARS-CoV-2/isolation & purification , Adaptation, Psychological , Adolescent , Adult , COVID-19/virology , Child , Emotions , Female , Hong Kong , Humans , Male , Personality/physiology , SARS-CoV-2/pathogenicity , Surveys and Questionnaires , Young Adult
10.
Xenobiotica ; 51(8): 885-900, 2021 Aug.
Article En | MEDLINE | ID: mdl-34187286

A challenge in the development of novel 18F-labelled positron emission tomography (PET) imaging probes is identification of metabolically stable sites to incorporate the 18F radioisotope. Metabolic loss of 18F from PET probes in vivo can lead to misleading biodistribution data as displaced 18F can accumulate in various tissues.In this study we report on in vitro hepatic microsomal metabolism of novel caffeine containing bifunctional compounds (C8-6-I, C8-6-N, C8-6-C8) that can prevent in vitro aggregation of α-synuclein, which is associated with the pathophysiology of Parkinson's disease. The metabolic profile obtained guided us to synthesize stable isotope 19F-labelled analogues in which the fluorine was introduced at the metabolically stable N7 of the caffeine moiety.An in vitro hepatic microsomal metabolism study of the 19F-labelled analogues resulted in similar metabolites to the unlabelled compounds and demonstrated that the fluorine was metabolically stable, suggesting that these analogues are appropriate PET imaging probes. This straightforward in vitro strategy is valuable for avoiding costly stability failures when designing radiolabelled compounds for PET imaging.


Fluorine Radioisotopes , alpha-Synuclein , Positron-Emission Tomography , Tissue Distribution
11.
J Hypertens ; 39(3): 428-436, 2021 03 01.
Article En | MEDLINE | ID: mdl-33031179

INTRODUCTION: Accurate comparisons of carotid--femoral pulse wave velocity (cfPWV) within and across studies require standardized procedures. Guidelines suggest reporting the average of at least two cfPWV measurements; if the difference exceeds 0.5 m/s, a third measurement should be taken, and the median reported. Another method involves repeating measurements until two values are within 0.5 m/s. However, in many studies, duplicate measurements are averaged irrespective of the difference between readings. We evaluated the impact of these methods on the reported cfPWV value. METHODS: Measurements of cfPWV (SphygmoCor) from five studies included individuals spanning a wide age range, with or without comorbid conditions, and pregnant women. In participants with at least three high-quality measurements, differences between the median value (MED) and the average of the first two cfPWV measurements (AVG1) and the average of two cfPWV measurements within 0.5 m/s (AVG2) were evaluated using paired t-tests and Bland--Altman plots. RESULTS: Participants' mean age was 50 ±â€Š14 years and BMI was 28.0 ±â€Š5.5 kg/m2 (N = 306, 79% women). The overall mean difference was -0.10 m/s (95% CI 0.17 to -0.04) between MED and AVG1, and 0.11 m/s (95% CI 0.05--0.17) between MED and AVG2. The absolute difference exceeded 0.5 m/s in 34% (MED-AVG1) and 22% (MED-AVG2) of participants, and 1 m/s in 8% of participants (both MED-AVG1 and MED-AVG2). Scatter around the bias line increased with higher mean cfPWV values. CONCLUSION: Although the overall mean difference in cfPWV between protocols was not clinically relevant, large variation led to absolute differences exceeding 0.5 m/s in a large proportion of participants.


Vascular Stiffness , Adolescent , Carotid Arteries , Carotid-Femoral Pulse Wave Velocity , Female , Humans , Male , Manometry , Pregnancy , Pulse Wave Analysis
12.
Case Rep Orthop ; 2020: 8271471, 2020.
Article En | MEDLINE | ID: mdl-33014492

Lomentospora prolificans is an emerging pathogen that is difficult to treat due to its intrinsic resistance to currently available antifungal agents. Current evidence demonstrates synergy between Azoles and Terbinafine against L. prolificans infections, while adjunct use of antifungal agent-loaded bone cement has also shown favourable outcomes. We report a case of an immunosuppressed adult with rheumatoid arthritis who developed L. prolificans osteomyelitis in his right wrist following trauma and subsequent exposure to commercially available fertiliser. The infection was successfully eradicated via a combination of aggressive, staged surgical source control, antifungal therapy using voriconazole and Terbinafine, and insertion of voriconazole-loaded bone cement into the wrist and carpus. The utility of this approach supports the synergistic effects of voriconazole and Terbinafine and, more broadly, the clinical benefits of antifungal-loaded bone cement, as demonstrated in previous case reports and in vitro studies. As such, combination antifungal therapy and voriconazole-loaded bone cement should be considered the therapy of choice in cases of osteomyelitis where L. prolificans is proven to be the causative organism.

13.
J Cardiothorac Surg ; 15(1): 318, 2020 Oct 15.
Article En | MEDLINE | ID: mdl-33059696

BACKGROUND: The standard for clinical staging of lung cancer is the use of CT and PET scans, however, these may underestimate the burden of the disease. The use of serum tumor markers might aid in the detection of subclinical advanced disease. The aim of this study is to review the predictive value of tumor markers in patients with clinical stage I NSCLC. METHODS: A comprehensive search was performed using the Medline, EMBASE, Scopus data bases. Abstracts included based on the following inclusion criteria: 1) adult ≥18 years old, 2) clinical stage I NSCLC, 3) Tumor markers (CEA, SCC, CYFRA 21-1), 4) further imaging or procedure, 5) > 5 patients, 6) articles in English language. The primary outcome of interest was utility of tumour markers for predicting nodal involvement and oncologic outcomes in patients with clinical stage I NSCLC. Secondary outcomes included sub-type of lung cancer, procedure performed, and follow-up duration. RESULTS: Two hundred seventy articles were screened, 86 studies received full-text assessment for eligibility. Of those, 12 studies were included. Total of 4666 patients were involved. All studies had used CEA, while less than 50% used CYFRA 21-1 or SCC. The most common tumor sub-type was adenocarcinoma, and the most frequently performed procedure was lobectomy. Meta-analysis revealed that higher CEA level is associated with higher rates of lymph node involvement and higher mortality. CONCLUSION: There is significant correlation between the CEA level and both nodal involvement and survival. Higher serum CEA is associated with advanced stage, and poor prognosis. Measuring preoperative CEA in patient with early stage NSCLC might help to identify patients with more advanced disease which is not detected by CT scans, and potentially identify candidates for invasive mediastinal lymph node staging, helping to select the most effective therapy for patients with potentially subclinical nodal disease. Further prospective studies are needed to standardize the use of CEA as an adjunct for NSCLC staging.


Carcinoembryonic Antigen/blood , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/mortality , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung Neoplasms/blood , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Neoplasm Staging , Predictive Value of Tests , Survival Analysis
14.
PLoS One ; 15(3): e0230586, 2020.
Article En | MEDLINE | ID: mdl-32203543

Planar cell polarity (PCP) pathway is crucial for tissue morphogenesis. Mutations in PCP genes cause multi-organ anomalies including dysplastic kidneys. Defective PCP signaling was postulated to contribute to cystogenesis in polycystic kidney disease. This work was undertaken to elucidate the role of the key PCP gene, Vangl2, in embryonic and postnatal renal tubules and ascertain whether its loss contributes to cyst formation and defective tubular function in mature animals. We generated mice with ubiquitous and collecting duct-restricted excision of Vangl2. We analyzed renal tubules in mutant and control mice at embryonic day E17.5 and postnatal days P1, P7, P30, P90, 6- and 9-month old animals. The collecting duct functions were analyzed in young and adult mutant and control mice. Loss of Vangl2 leads to profound tubular dilatation and microcysts in embryonic kidneys. Mechanistically, these abnormalities are caused by defective convergent extension (larger tubular cross-sectional area) and apical constriction (cuboidal cell shape and a reduction of activated actomyosin at the luminal surface). However, the embryonic tubule defects were rapidly resolved by Vangl2-independent mechanisms after birth. Normal collecting duct architecture and functions were found in young and mature animals. During embryogenesis, Vangl2 controls tubular size via convergent extension and apical constriction. However, rapidly after birth, PCP-dependent control of tubular size is switched to a PCP-independent regulatory mechanism. We conclude that loss of the Vangl2 gene is dispensable for tubular elongation and maintenance postnatally. It does not lead to cyst formation and is unlikely to contribute to polycystic kidney disease.


Cell Polarity/genetics , Kidney/embryology , Kidney/metabolism , Nerve Tissue Proteins/genetics , Adult , Animals , Gene Deletion , Humans , Kidney/cytology , Mice , Nerve Tissue Proteins/deficiency , Signal Transduction
15.
Obes Surg ; 30(3): 1061-1067, 2020 Mar.
Article En | MEDLINE | ID: mdl-31786719

INTRODUCTION: Recent research has demonstrated an association between obesity and migraine headaches. Furthermore, studies have demonstrated that migraine improvement can occur with significant weight loss. Given that bariatric surgery is the most effective intervention for obesity and obesity-related comorbidities, there is potential for bariatric surgery to improve migraine symptoms. The objective of this study was to conduct a systematic review and meta-analysis to determine the effect of bariatric surgery on migraine headaches. METHODS: A comprehensive literature search from database inception to December 2018 was conducted for studies examining the effect of bariatric surgery on migraines. Patients of all ages who had a history of migraines undergoing primary bariatric surgery were included. Primary outcomes included migraine frequency, severity, and disability. RESULTS: Four studies were included (n = 159). Frequency of migraines was markedly reduced after bariatric surgery, with fewer symptomatic days suffered by patients per month post-operatively (mean difference [MD] - 5.56 days, 95%CI 0.14 to 10.99, p = 0.04). The degree of migraine headache-related disability as measured by the Migraine Disability Assessment Scale (MIDAS) was also significantly lower following bariatric surgery (MD - 14.72, 95%CI 10.08 to 19.36, p < 0.001). The severity of migraine headache pain before and after surgery was reduced with borderline statistical significance (MD - 3.53, 95%CI - 0.12 to 7.17, p = 0.06). CONCLUSION: Migraine severity, frequency, and headache-related disability were improved 6 months after bariatric surgery. However, this systematic review was limited by a low number of studies and larger high-quality, randomized trials are needed to determine the effect of bariatric surgery on migraine headaches.


Bariatric Surgery , Migraine Disorders , Obesity, Morbid , Humans , Obesity , Obesity, Morbid/surgery , Weight Loss
16.
Polymers (Basel) ; 11(4)2019 Apr 09.
Article En | MEDLINE | ID: mdl-30970621

This review paper initially summarizes the latest developments in impact testing on polymer matrix composites collating the various analytical, numerical, and experimental studies performed since the year 2000. Subsequently, the scientific literature investigating nanofiller reinforced polymer composite matrices as well as self-healing polymer matrix composites by incorporating core-shell nanofibers is reviewed in-depth to provide a perspective on some novel advances in nanotechnology that have led to composite developments. Through this review, researchers can gain a representative idea of the state of the art in nanotechnology for polymer matrix composite engineering, providing a platform for further study of this increasingly industrially significant material, and to address the challenges in developing the next generation of advanced, high-performance materials.

17.
Hum Factors ; 60(7): 947-961, 2018 11.
Article En | MEDLINE | ID: mdl-29995441

OBJECTIVE: To investigate whether use of a movement intervention when undertaking prolonged standing affected discomfort and cognitive function. BACKGROUND: Alternate work positions to break up prolonged sitting for office workers are being trialed, such as standing. Prolonged standing has potential negative health implications, including low back and lower limb discomfort, and may influence cognitive function. Introducing movement during standing may provide a healthy and productive alternative work posture. METHOD: Twenty adult participants undertook a laboratory study of 2 hr of standing and standing with movement (using a footrest) while performing computer work. Changes in discomfort and cognitive function, with muscle fatigue, low back angle, pelvis movement, lower limb swelling, and mental state, were investigated. RESULTS: Discomfort increased significantly over time across all body regions. Ankle/foot differed between conditions (incident rate ratio [95% confidence interval]: 1.89 [1.10-3.23]), with higher discomfort during standing with movement. Creative problem-solving errors increased during standing with movement and decreased during standing (Time × Condition: ß = 0.64 [0.10-1.18]), with no other cognitive function measure differences. Mental state deteriorated over time for both conditions, greater during standing with movement (Time × Condition: ß = 2.44 [0.23-4.66]). No significant interaction effects were found for the other outcome variables. CONCLUSION: Standing with movement provided no advantage in discomfort or cognitive function. There were some negative effects for ankle/foot discomfort and creative problem solving. An alternate footrest design and protocol for use may yield more favorable results. APPLICATION: Based on the results from this study, footrest use to raise alternative foot for forced 5-min intervals would not be recommended to assist with managing discomfort while prolonged standing in workplaces.


Biomechanical Phenomena/physiology , Ergonomics , Movement/physiology , Musculoskeletal Physiological Phenomena , Occupational Diseases/physiopathology , Standing Position , Adult , Female , Humans , Male , Muscle Fatigue/physiology , Young Adult
18.
Ergonomics ; 61(7): 877-890, 2018 Jul.
Article En | MEDLINE | ID: mdl-29388500

Due to concerns about excessive sedentary exposure for office workers, alternate work positions such as standing are being trialled. However, prolonged standing may have health and productivity impacts, which this study assessed. Twenty adult participants undertook two hours of laboratory-based standing computer work to investigate changes in discomfort and cognitive function, along with muscle fatigue, movement, lower limb swelling and mental state. Over time, discomfort increased in all body areas (total body IRR [95% confidence interval]: 1.47[1.36-1.59]). Sustained attention reaction time (ß = 18.25[8.00-28.51]) deteriorated, while creative problem solving improved (ß = 0.89[0.29-1.49]). There was no change in erector spinae, rectus femoris, biceps femoris or tibialis anterior muscle fatigue; low back angle changed towards less  lordosis, pelvis movement increased, lower limb swelling increased and mental state decreased. Body discomfort was positively correlated with mental state. The observed changes suggest replacing office work sitting with standing should be done with caution. Practitioner Summary: Standing is being used to replace sitting by office workers; however, there are health risks associated with prolonged standing. In a laboratory study involving 2 h prolonged standing discomfort increased (all body areas), reaction time and mental state deteriorated while creative problem-solving improved. Prolonged standing should be undertaken with caution.


Cognition/physiology , Cognitive Dysfunction/etiology , Musculoskeletal Diseases/etiology , Occupational Diseases/etiology , Posture/physiology , Adult , Attention , Cognitive Dysfunction/psychology , Computers , Ergonomics , Female , Humans , Male , Muscle Fatigue , Muscle, Skeletal , Musculoskeletal Diseases/psychology , Occupational Diseases/psychology , Reaction Time , Time Factors , Work/physiology , Work/psychology , Workplace/psychology
19.
RSC Adv ; 8(40): 22460-22468, 2018 Jun 19.
Article En | MEDLINE | ID: mdl-35539732

In the near future, the oil and gas industry is poised to become one of the greatest sources of revenue generation across the world. The adaptation of scalable manufacturing technology, commonly known as additive manufacturing (AM) in the oil and gas industry, offers huge potential to transfigure the way high quality 3D objects are designed, manufactured and distributed. The adoption of AM technologies in this sector also allows a high degree of freedom of design and could exponentially reduce the time taken for the product to reach the market. In this arena, AM can be a method of producing lower volume and highly efficient intricate products with various materials like polymers, metals, ceramics and their composites. Although AM has been around for several years, its adoption in this sector has been slow and limited. As it is in the initial stages, rigorous research needs to be done to standardize the materials and manufacturing process. In addition, there is a particular need to end the requirement of a finishing procedure. Continuous and significant growth has been seen since the beginning and the successful outcomes until now allow for optimism that AM has a significant role in the future of manufacturing. This review will mainly focus on ongoing efforts to bring widespread adoption of AM into highly regulated industry i.e. oil and gas, and will also identify future perspectives in this area.

20.
Appl Ergon ; 67: 218-224, 2018 Feb.
Article En | MEDLINE | ID: mdl-29122193

Prolonged standing is common in many occupations and has been associated with low back discomfort (LBD). No recent studies have investigated a footrest as an intervention to reduce LBD associated with prolonged standing. This study investigated the effect of a footrest on LBD and sought to determine if LBD changes were accompanied by changes in muscle fatigue and low back end-range posture and movement. Twenty participants stood for two 2-h trials, one with and one without a footrest. LBD, lumbar erector spinae electromyography, upper lumbar (UL) and lower lumbar (LL) angles were measured. A significant increase in LBD occurred in both conditions but the footrest did not significantly decrease LBD. The only significant finding between conditions was that UL lordosis became more similar to usual standing over time with footrest use. These findings suggest that footrest use may not reduce LBD development and that development of LBD with prolonged standing is unlikely to be due to muscle fatigue or end-range posture mechanisms.


Lordosis/prevention & control , Low Back Pain/prevention & control , Occupational Diseases/prevention & control , Orthotic Devices , Posture/physiology , Adult , Biomechanical Phenomena , Female , Humans , Lordosis/etiology , Lordosis/physiopathology , Low Back Pain/etiology , Low Back Pain/physiopathology , Lumbar Vertebrae/physiology , Male , Movement , Muscle Fatigue , Occupational Diseases/etiology , Occupational Diseases/physiopathology , Paraspinal Muscles/physiology , Range of Motion, Articular/physiology , Time Factors , Work/physiology
...