Medicine, Dentistry & Health Sciences Collected Works - Research Publications
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MUC13 overexpression in renal cell carcinoma plays a central role in tumor progression and drug resistance
Metastatic renal cell carcinoma is a largely incurable disease, and existing treatments targeting angiogenesis and tyrosine kinase receptors are only partially effective. Here we reveal that MUC13, a cell surface mucin glycoprotein, is aberrantly expressed by most renal cell carcinomas, with increasing expression positively correlating with tumor grade. Importantly, we demonstrated that high MUC13 expression was a statistically significant independent predictor of poor survival in two independent cohorts, particularly in stage 1 cancers. In cultured renal cell carcinoma cells MUC13 promoted proliferation and induced the cell cycle regulator, cyclin D1, and inhibited apoptosis by inducing the anti-apoptotic proteins, BCL-xL and survivin. Silencing of MUC13 expression inhibited migration and invasion, and sensitized renal cancer cells to killing by the multi-kinase inhibitors used clinically, sorafenib and sunitinib, and reversed acquired resistance to these drugs. Furthermore, we demonstrated that MUC13 promotion of renal cancer cell growth and survival is mediated by activation of nuclear factor κB, a transcription factor known to regulate the expression of genes that play key roles in the development and progression of cancer. These results show that MUC13 has potential as a prognostic marker for aggressive early stage renal cell cancer and is a plausible target to sensitize these tumors to therapy.
Bone turnover markers and bone mineral density in healthy mother-daughter pairs from South India
Bone turnover markers (BTMs) provide important insights into the dynamics of bone remodelling and are subjected to preanalytical and ethnic variations in addition to influence of genetic and environmental factors. AIM/OBJECTIVES: To derive ethnicity specific reference range for BTMs and to study their correlation with Bone Mineral Density (BMD) in a cohort of healthy postmenopausal women and their premenopausal daughters and to look at the impact of maternal bone mineral status on daughters bone health. MATERIAL AND METHODS: This community based cross sectional study included 300 subjects (150 mother-daughter pairs). Demographic details were collected. Fasting blood and a second void morning urine samples were obtained for measurement of BTMs (sCTX, sPTNP1, sOC and urine DPD respectively) and bone mineral parameters. BMD was measured by DXA scan. RESULTS: Osteoporosis was seen in 44·7% of the postmenopausal women. Ethnicity specific reference ranges of BTMs were derived for the study population. Significant inverse correlation was found between all BTMs (except urine DPD) and BMD(P < 0·05). Daughters of mothers with osteoporosis at spine and femoral neck had lower BMD, compared to daughters of mothers without osteoporosis(P = 0·03 & 0·05). CONCLUSION: Apart from deriving the ethnicity specific reference range for BTMs and finding a significant inverse correlation between BTM and BMD, this study found significantly lower BMD in daughters of mothers with osteoporosis at spine and femoral neck implicating the probable interplay of genetic, epigenetic and similar environmental factors.
Tropical Drosophila pandora carry Wolbachia infections causing cytoplasmic incompatibility or male killing
Wolbachia infections have been described in several Drosophila species, but relatively few have been assessed for phenotypic effects. Cytoplasmic incompatibility (CI) is the most common phenotypic effect that has been detected, while some infections cause male killing or feminization, and many Wolbachia infections have few host effects. Here, we describe two new infections in a recently described species, Drosophila pandora, one of which causes near-complete CI and near-perfect maternal transmission (the "CI" strain). The other infection is a male killer (the "MK" strain), which we confirm by observing reinitiation of male production following tetracycline treatment. No incompatibility was detected in crosses between CI strain males and MK strain females, and rare MK males do not cause CI. Molecular analyses indicate that the CI and MK infections are distantly related and the CI infection is closely related to the wRi infection of Drosophila simulans. Two population surveys indicate that all individuals are infected with Wolbachia, but the MK infection is uncommon. Given patterns of incompatibility among the strains, the infection dynamics is expected to be governed by the relative fitness of the females, suggesting that the CI infection should have a higher fitness. This was evidenced by changes in infection frequencies and sex ratios in population cages initiated at different starting frequencies of the infections.
'That red flag on your file': misinterpreting physical symptoms as mental illness.
AIMS AND OBJECTIVES: To ascertain the views and experiences of mental health consumers regarding the availability and quality of care and treatment received for their physical health needs. BACKGROUND: People diagnosed with mental illness have higher occurrence of physical health problems. Responsive health care services are crucial for prevention and management of physical health problems, and for reducing disparities in health between people diagnosed with mental illness and those who are not. There is limited research giving voice to consumer perspectives on their experiences with health care providers. DESIGN: Exploratory qualitative. METHODS: Focus group interviews with mental health consumers accessed via a consumer network group in a region of Australia (n = 31). All interview audio recordings were transcribed professionally. Interviews were thematically analysed. RESULTS: The main themes were: symptomising; failure to act and alertness to prejudice. The first two themes were consumer perceptions of the actions and behaviours of health professionals, and the third describes consumer responses to these behaviours and actions. Consumers described increased risks of illness and death because of undiagnosed physical illness despite their physical health advice-seeking as the reason for the health consultation. CONCLUSION: Health care providers' non-recognition of physical health problems presents a clear example of a significant and potentially life threatening health inequity. The service provider responses described by participants suggest that mental health consumers' physical health needs may not be taken seriously. RELEVANCE TO CLINICAL PRACTICE: Clinicians need to take seriously the physical health needs and concerns of people with mental illness. Nurses can play a crucial role in the prevention of diagnostic overshadowing as part of a broader direction of balancing biomedical perspectives with other approaches to health care.
Participative mental health consumer research for improving physical health care: An integrative review.
People with mental illness have a significantly lower life expectancy and higher rates of chronic physical illnesses than the general population. Health care system reform to improve access and quality is greatly needed to address this inequity. The inclusion of consumers of mental health services as co-investigators in research is likely to enhance service reform. In light of this, the current paper reviews mental health consumer focussed research conducted to date, addressing the neglect of physical health in mental health care and initiatives with the aim of improving physical health care. The international literature on physical healthcare in the context of mental health services was searched for articles, including mental health consumers in research roles, via Medline, CINAHL and Google Scholar, in October 2015. Four studies where mental health consumers participated as researchers were identified. Three studies involved qualitative research on barriers and facilitators to physical health care access, and a fourth study on developing technologies for more effective communication between GPs and patients. This review found that participatory mental health consumer research in physical health care reform has only become visible in the academic literature in 2015. Heightened consideration of mental health consumer participation in research is required by health care providers and researchers. Mental health nurses can provide leadership in increasing mental health consumer research on integrated care directed towards reducing the health gap between people with and without mental illness.
Gene expression profiling of reproductive meristem types in early rice inflorescences by laser microdissection
In rice, inflorescence architecture is established at early stages of reproductive development and contributes directly to grain yield potential. After induction of flowering, the complexity of branching, and therefore the number of seeds on the panicle, is determined by the activity of different meristem types and the timing of transitions between them. Although some of the genes involved in these transitions have been identified, an understanding of the network of transcriptional regulators controlling this process is lacking. To address this we used a precise laser microdissection and RNA-sequencing approach in Oryza sativa ssp. japonica cv. Nipponbare to produce quantitative data that describe the landscape of gene expression in four different meristem types: the rachis meristem, the primary branch meristem, the elongating primary branch meristem (including axillary meristems), and the spikelet meristem. A switch in expression profile between apical and axillary meristem types followed by more gradual changes during transitions in axillary meristem identity was observed, and several genes potentially involved in branching were identified. This resource will be vital for a mechanistic understanding of the link between inflorescence development and grain yield.
A randomised controlled trial comparing meat-based with human cadaveric models for teaching ultrasound-guided regional anaesthesia
The aim of this prospective, blinded, randomised controlled study was to compare novices' acquisition of the technical skills of ultrasound-guided regional anaesthesia using either a meat phantom model or fresh-frozen human cadavers. The primary outcome was the time taken to successfully perform an ultrasound-guided sciatic nerve block on a cadaver; secondary outcomes were the cumulative score of errors, and best image quality of the sciatic nerve achieved. After training, the median (IQR [range]) time taken to perform the block was 311(164-390 [68-600]) s in the meat model trained group and 210 (174-354 [85-600]) s in the fresh-frozen cadaver trained group (p = 0.24). Participants made a median (IQR [range]) of 18 (14-33 [8-55]) and 15 (12-22 [8-44]) errors in the two groups respectively (p = 0.39). The image quality score was also not different, with a median (IQR [range]) of 62.5 (59.4-65.6 [25.0-100.0])% vs 62.5 (62.5-75.0 [25.0-87.5])% respectively (p = 0.58). The training and deliberate feedback improved all participants' block performance, the median (IQR [range]) times being 310 (206-532 [110-600]) s before and 240 (174-354 [85-600]) s after training (p = 0.02). We conclude that novices taught ultrasound scanning and needle guidance skills using an inexpensive and easily constructed meat model perform similarly to those trained on a cadaveric model.
Lysine acetylation of the Mycobacterium tuberculosis HU protein modulates its DNA binding and genome organization
Nucleoid-associated protein HU, a conserved protein across eubacteria is necessary for maintaining the nucleoid organization and global regulation of gene expression. Mycobacterium tuberculosis HU (MtHU) is distinct from the other orthologues having 114 amino acid long carboxyl terminal extensions with a high degree of sequence similarity to eukaryotic histones. In this study, we demonstrate that the DNA binding property of MtHU is regulated by posttranslational modifications akin to eukaryotic histones. MtHU purified from M. tuberculosis cells is found to be acetylated on multiple lysine residues unlike the E. coli expressed recombinant protein. Using coimmunoprecipitation assay, we identified Eis as one of the acetyl transferases that interacts with MtHU and modifies it. Although Eis is known to acetylate aminoglycosides, the kinetics of acetylation showed that its protein acetylation activity on MtHU is robust. In vitro Eis modified MtHU at various lysine residues, primarily those located at the carboxyl terminal domain. Acetylation of MtHU caused reduced DNA interaction and alteration in DNA compaction ability of the NAP. Over-expression of the Eis leads to hyperacetylation of HU and decompaction of genome. These results provide first insights into the modulation of the nucleoid structure by lysine acetylation in bacteria.
Wide allelic heterogeneity with predominance of large IDS gene complex rearrangements in a sample of Mexican patients with Hunter syndrome
Hunter syndrome or mucopolysaccharidosis type II (MPSII) is caused by pathogenic variants in the IDS gene. This is the first study that examines the mutational spectrum in 25 unrelated Mexican MPSII families. The responsible genotype was identified in 96% of the families (24/25) with 10 novel pathogenic variants: c.133G>C, c.1003C>T, c.1025A>C, c.463_464delinsCCGTATAGCTGG, c.754_767del, c.1132_1133del, c.1463del, c.508-1G>C, c.1006+1G>T and c.(-217_103del). Extensive IDS gene deletions were identified in four patients; using DNA microarray analysis two patients showed the loss of the entire AFF2 gene, and epilepsy developed in only one of them. Wide allelic heterogeneity was noted, with large gene alterations (e.g. IDS/IDSP1 gene inversions, partial to extensive IDS deletions, and one chimeric IDS-IDSP1 allele) that occurred at higher frequencies than previously reported (36% vs 18.9-29%). The frequency of carrier mothers (80%) is consistent with previous descriptions (>70%). Carrier assignment allowed molecular prenatal diagnoses. Notably, somatic and germline mosaicism was identified in one family, and two patients presented thrombocytopenic purpura and pancytopenia after idursulfase enzyme replacement treatment. Our findings suggest a wide allelic heterogeneity in Mexican MPSII patients; DNA microarray analysis contributes to further delineation of the resulting phenotype for IDS and neighboring loci deletions.
Examining the N400m in affectively negative sentences: A magnetoencephalography study
Magnetoencephalography was used to examine the effect on the N400m of reading words that create emotional violations in sentences. The beginnings of the sentences were affectively negative and were completed with either a negative congruous, positive incongruous, or neutral incongruous adjective (e.g., "My mother was killed and I felt bad/great/normal"). The task conditions were also manipulated to favor semantic over affective processing. Compared to the sentences with the congruous negative adjectives, the results of sensor space analysis showed that there was an N400m effect with the sentences with the neutral but not positive adjectives, despite both types of sentences containing an emotional violation. Source localization results showed a similar pattern where the sentences with the incongruous positive versus congruous negative adjectives showed no significant N400m effect in the temporal and frontal areas examined, but the sentences with the incongruous neutral versus incongruous positive adjectives in the temporal areas did, particularly the left middle temporal gyrus. These results suggest that (a) the N400m effect was likely to be caused by the incongruous neutral adjectives being comparatively harder to integrate into a negative emotional context than the incongruous positive ones, (b) emotional context created by the negative sentence stems caused deeper semantic processing of the incongruous positive adjectives to be bypassed, and (c) negative affective context was generated from reading the sentences even in task conditions where it has not been generated with isolated words.
Embedding a physical health nurse consultant within mental health services: Consumers' perspectives.
The life expectancy of people living with mental illness is significantly shorter than that of the rest of the population. Despite the profound impact of physical health issues on both quality of life and life expectancy, the perspectives of mental health consumers have yet to be thoroughly explored. Furthermore, research has focused far more on describing barriers than on identifying solutions. This paper reports on findings from a qualitative exploratory research study, with the aim to examine the potential role of a specialist nurse with advanced physical health-care skills. Focus groups were conducted with 31 consumers. Data were analysed thematically. The concept of a role like this was supported; however, participants stressed: (i) the importance of integration between health professionals and various components of the health-care system; and (ii) the need for culture change for nurses to work from a less medically-dominated approach. Previous research literature suggests that a nursing position dedicated to physical health care and coordination might produce positive outcomes for mental health consumers. The findings from the current research project emphasize the need for consumers to be identified as key stakeholders in a solution-focused approach to improved physical health care for mental health consumers.
Evaluating a Muscle Ultrasound Education Program: Theoretical Knowledge, Hands-on Skills, Reliability, and Satisfaction of Critical Care Physiotherapists.
(Elsevier BV, 2021-09)
Objective: To evaluate learning results of critical care physiotherapists participating in a muscle ultrasound (MUS) educational program. Design: Cross-sectional study. Setting: A custom-made 20-hour MUS course was performed over a 2-week time period, including knobs familiarization, patient positioning, anatomic landmarks, image acquisition, and limb muscle measurements. Participants: Nineteen critical care physiotherapists with little to no prior experience in ultrasound (N=19). Interventions: Not applicable. Main Outcome Measures: Theoretical knowledge, hands-on skills acquisition, and satisfaction were assessed. Inter- and intrarater reliability on landmarks, thickness, and pennation angle of quadriceps between participants was evaluated using intraclass correlation coefficients (ICCs). Reliability among instructors measured prior to the course was also reported as a reference. Results: The percentage score (mean±SD) of knowledge questionnaires was 69±11 (pre-course), 89±10 (post-course), and 92±9 (hands-on skills). Course satisfaction scores ranged from 90%-100%. Pooled interrater reliability of participants (median ICC [interquartile range]) was good (0.70 [0.59-0.79]) for thickness, moderate (0.47 [0.46-0.92]) for landmarks, and absent (0.00 [0.00-0.05]) for pennation angle and the intrarater reliability was good (0.76 [0.51-0.91]) for thickness and weak (0.35 [0.29-0.52]) for pennation angle. Interrater ICC values for instructors were excellent (0.90) for thickness, good (0.67) for landmarks, and moderate (0.41) for pennation angle and intrarater ICC values were excellent (0.94) for thickness and good (0.75) for pennation angle. Conclusions: Although our sample was quite small and homogeneous, increased theoretical knowledge, high hands-on performance acquisition, and good satisfaction of physiotherapists were observed. Reliability was moderate to excellent for thickness and landmarks and absent to weak for pennation angle. Landmarking and pennation angle remain challenges for physiotherapist training in the application of MUS. Further studies are needed to identify variables that could modify reliability during MUS training.
A Rare Case of Extra-Gonadal Oestrogen-Secreting Choriocarcinoma in a Male.
(SMC Media, 2021)
This report describes a rare case of an extra-gonadal oestrogen-secreting tumour in a male patient. An otherwise healthy 60-year-old man presented to our hospital with a 3-month history of shortness of breath and weight loss. Blood panels and histology supported the diagnosis of an oestrogen-secreting choriocarcinoma. Unfortunately, the patient died soon after his diagnosis. The highlighting features of this case are: (1) the difficulty of confirming a diagnosis in a rapidly deteriorating patient; (2) the rarity of oestrogen-secreting extra-gonadal tumours in males; and (3) the aggressive rate of tumour progression seen on sequential imaging. LEARNING POINTS: Extra-gonadal oestrogen-secreting tumours in males are rare, but early empiric chemotherapy can be of benefit if this diagnosis is suspected.Tumour progression can be rapid, and so prompt referral to oncology services is critical for emergent management of the condition.Full endocrine blood panels including oestrogen, β human chorionic gonadotrophin and α fetoprotein are useful to help diagnose the condition.
Total Body Sodium Balance in Chronic Kidney Disease
(HINDAWI LTD, 2021-09-22)
Excess sodium intake is a leading but modifiable risk factor for mortality, with implications on hypertension, inflammation, cardiovascular disease, and chronic kidney disease (CKD). This review will focus mainly on the limitations of current measurement methods of sodium balance particularly in patients with CKD who have complex sodium physiology. The suboptimal accuracy of sodium intake and excretion measurement is seemingly more marked with the evolving understanding of tissue (skin and muscle) sodium. Tissue sodium represents an extrarenal influence on sodium homeostasis with demonstrated clinical associations of hypertension and inflammation. Measurement of tissue sodium has been largely unexplored in patients with CKD. Development and adoption of more comprehensive and dynamic assessment of body sodium balance is needed to better understand sodium physiology in the human body and explore therapeutic strategies to improve the clinical outcomes in the CKD population.
Activated osteoarthritis following immune checkpoint inhibitor treatment: an observational study
(BMJ PUBLISHING GROUP, 2021-09-01)
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but can result in toxicities, known as immune-related adverse events (irAEs), due to a hyperactivated immune system. ICI-related inflammatory arthritis has been described in literature, but herewith we introduce and characterize post-ICI-activated osteoarthritis (ICI-aOA). We conducted a multicenter, retrospective, observational study of patients with cancer treated with ICIs and diagnosed with ICI-aOA by a rheumatologist. ICI-aOA was defined by (1) an increase in non-inflammatory joint pain after ICI initiation, (2) in joints characteristically affected by osteoarthritis, and (3) lack of inflammation on exam. Cases were graded using the Common Terminology Criteria for Adverse Events (CTCAE) V.6.0 rubric for arthralgia. Response Evaluation Criteria in Solid Tumors V.1.1 (v.4.03) guidelines determined tumor response. Results were analyzed using χ2 tests of association and multivariate logistic regression. Thirty-six patients had ICI-aOA with a mean age at time of rheumatology presentation of 66 years (51-81 years). Most patients had metastatic melanoma (10/36, 28%) and had received a PD-1/PD-L1 inhibitor monotherapy (31/36, 86%) with 5/36 (14%) combination therapy. Large joint involvement (hip/knee) was noted in 53% (19/36), small joints of hand 25% (9/36), and spine 14% (5/36). Two-thirds (24/36) suffered multiple joint involvement. Three of 36 (8%) had CTCAE grade 3, 14 (39%) grade 2 and 19 (53%) grade 1 manifestations. Symptom onset ranged from 6 days to 33.8 months with a median of 5.2 months after ICI initiation; five patients suffered from ICI-aOA after ICI cessation (0.6, 3.5, 4.4, 7.3, and 15.4 months after ICI cessation). The most common form of therapy was intra-articular corticosteroid injections only (15/36, 42%) followed by non-steroidal anti-inflammatory drugs only (7/36, 20%). Twenty patients (56%) experienced other irAEs, with rheumatic and dermatological being the most common. All three patients with high-grade ICI-aOA also had another irAE diagnosis at some point after ICI initiation. ICI-aOA should be recognized as an adverse event of ICI immunotherapy. Early referral to a rheumatologist can facilitate the distinction between ICI induced inflammatory arthritis from post-ICI mechanical arthropathy, the latter of which can be managed with local therapy that will not compromise ICI efficacy.
Systematic Review and Meta-Analysis of Inflammatory Bowel Disease Adverse Events with Anti-Interleukin 17A Agents and Tumor Necrosis Factor Inhibitors in Rheumatic Disease and Skin Psoriasis
INTRODUCTION: The aim of this work is to perform a systematic review and meta-analysis of anti-tumor necrosis factor (anti-TNF) and anti-interleukin-17 (anti-IL-17) trials for spondyloarthritis, psoriatic arthritis, and psoriasis comparing rates of inflammatory bowel disease (IBD) events compared to placebo. METHODS: MEDLINE, EMBASE, and The Cochrane Library were searched for double-blind, randomized placebo-controlled anti-TNF and anti-IL-17 trials of included diseases. Inflammatory bowel disease events from the RCT period were pooled and meta-analyzed using statistical methods suitable for low-event-rate meta-analysis (Peto's, Mantel-Haenszel, hypergeometric-normal model, and Shuster-Guo-Skyler). When observed data were insufficient, we performed an exploratory sensitivity analysis to compare methods. RESULTS: We identified 9551 original papers, and included 96 publications: 65 anti-TNF and 31 anti-IL-17 trials, containing 21 new and 12 flare IBD events in 28,209 participants. New IBD on anti-IL-17 occurred 0.23/100 patient-years (PY) in psoriasis, 0.61/100 PY in PsA and 1.63/100 PY in spondyloarthritis, rates similar to observational cohorts, and less commonly on anti-TNF (0/100 PY, 0/100 PY, 0.32/100 PY, respectively). No evidence of difference between groups was found, with wide CI from many pooled counts of zero, especially in placebo arms. CONCLUSIONS: IBD events were rare, occurring at rates similar to biologic-naive groups. We could not find statistically significant differences in risk of new or recurrent IBD between treatment and control groups using selected meta-analytical methods for low event rate scenarios. Meta-analyses of this topic require more IBD events, ideally without pooling heterogeneous groups. Larger, thoroughly reported trials with systematic and detailed safety reporting are required to improve risk estimation and to make accurate inferences.
Immediate effect of the COVID-19 pandemic on patient health, health-care use, and behaviours: results from an international survey of people with rheumatic diseases
Background: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. Findings: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjögren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. Funding: American College of Rheumatology.
Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey
(BMJ PUBLISHING GROUP, 2021-09-01)
BACKGROUND: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine. METHODS: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination. RESULTS: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%. CONCLUSION: Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.
Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus
(BLACKWELL PUBLISHING, 2007-06-01)
Adenosine is well known to be released during cerebral metabolic stress and is believed to be neuroprotective. ATP release under similar circumstances has been much less studied. We have now used biosensors to measure and compare in real time the release of ATP and adenosine during in vitro ischaemia in hippocampal slices. ATP release only occurred following the anoxic depolarisation, whereas adenosine release was apparent almost immediately after the onset of ischaemia. ATP release required extracellular Ca2+. By contrast adenosine release was enhanced by removal of extracellular Ca2+, whilst TTX had no effect on either ATP release or adenosine release. Blockade of ionotropic glutamate receptors substantially enhanced ATP release, but had only a modest effect on adenosine release. Carbenoxolone, an inhibitor of gap junction hemichannels, also greatly enhanced ischaemic ATP release, but had little effect on adenosine release. The ecto-ATPase inhibitor ARL 67156, whilst modestly enhancing the ATP signal detected during ischaemia, had no effect on adenosine release. Adenosine release during ischaemia was reduced by pretreatment with homosysteine thiolactone suggesting an intracellular origin. Adenosine transport inhibitors did not inhibit adenosine release, but instead they caused a twofold increase of release. Our data suggest that ATP and adenosine release during ischaemia are for the most part independent processes with distinct underlying mechanisms. These two purines will consequently confer temporally distinct influences on neuronal and glial function in the ischaemic brain.
Design and methodology of SNAP-1: a Sprint National Anaesthesia Project to measure patient reported outcome after anaesthesia
(BIOMED CENTRAL LTD, 2015-01-01)
BACKGROUND: Patient satisfaction is an important metric of health-care quality. Accidental awareness under general anaesthesia (AAGA) is a serious complication of anaesthesia care which may go unrecognised in the immediate perioperative period but leads to long-term psychological harm for affected patients. The SNAP-1 study aimed to measure patient satisfaction with anaesthesia care and the incidence of AAGA, reported on direct questioning within 24 h of surgery, in a large multicentre cohort. A secondary aim of SNAP-1 was to test the effectiveness of a new network of Quality Audit and Research Coordinators in NHS anaesthetic departments, to achieve widespread study participation and high patient recruitment rates. This manuscript describes the study methodology. METHODS: SNAP-1 was a prospective observational cohort study. The study protocol was approved by the National Research Ethics Service. All UK NHS hospitals with anaesthetic departments were invited to participate. Adult patients undergoing any type of non-obstetric surgery were recruited in participating hospitals on 13th and 14th May 2014. Demographic data were collected by anaesthetists providing perioperative care. Patients were then approached within 24 h of surgery to complete two questionnaires-the Bauer patient satisfaction questionnaire (to measure patient reported outcome) and the modified Brice questionnaire (to detect possible accidental awareness). Completion of postoperative questionnaires was taken as evidence of implied consent. Results were recorded on a standard patient case report form, and local investigators entered anonymised data into an electronic database for later analysis by the core research team. RESULTS: Preliminary analyses indicate that over 15,000 patients were recruited across the UK, making SNAP-1 the largest NIHR portfolio-adopted study in anaesthesia to date. Both descriptive and analytic epidemiological analyses will be used to answer specific questions about the patient perception of anaesthesia care overall and in surgical sub-specialties and to determine the incidence of AAGA. CONCLUSIONS: The SNAP-1 study recruited a large number of UK hospitals and thousands of perioperative patients using newly established networks in the UK anaesthetic profession. The results will provide benchmarking information to aid interpretation of patient satisfaction data and also determine the incidence of AAGA reported on a single postoperative visit.
Safety and Feasibility of an Interdisciplinary Treatment Approach to Optimize Recovery From Critical Coronavirus Disease 2019.
(Ovid Technologies (Wolters Kluwer Health), 2021-08)
OBJECTIVES: Examine the safety and feasibility of a multimodal in-person or telehealth treatment program, administered in acute recovery phase for patients surviving critical coronavirus disease 2019. DESIGN: Pragmatic, pre-post, nonrandomized controlled trial with patients electing enrollment into one of the two recovery pathways. SETTING: ICU Recovery Clinic in an academic medical center. PATIENTS: Adult patients surviving acute respiratory failure due to critical coronavirus disease 2019. INTERVENTIONS: Patients participated in combined ICU Recovery clinic and 8 weeks of physical rehabilitation delivered: 1) in-person or 2) telehealth. Patients received medical care by an ICU Recovery Clinic interdisciplinary team and physical rehabilitation focused on aerobic, resistance, and respiratory muscle training. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients enrolled with mean age 57 ± 12, 62% were male, and the median Sequential Organ Failure Assessment score was 9.5. There were no differences between the two groups except patients in telehealth pathway (n = 10) lived further from clinic than face-to-face patients (162 ± 60 vs 31 ± 47 kilometers, t = 6.06, p < 0.001). Four safety events occurred: one minor adverse event in the telehealth group, two minor adverse events, and one major adverse event in the in-person group. Three patients did not complete the study (two in-person and one telehealth). Six-minute walk distance increased to 101 ± 91 meters from pre to post (n = 29, t = 6.93, p < 0.0001), which was similar between the two groups (110 vs 80 meters, t = 1.34, p = 0.19). Self-reported levels of anxiety, depression, and distress were high in both groups with similar self-report quality of life. CONCLUSIONS: A multimodal treatment program combining care from an interdisciplinary team in an ICU Recovery Clinic with physical rehabilitation is safe and feasible in patients surviving the ICU for coronavirus disease 2019 acute respiratory failure.
Examining the association of social risk with heart failure readmission in the Veterans Health Administration
BACKGROUND: Previous research has found that social risk factors are associated with an increased risk of 30-day readmission. We aimed to assess the association of 5 social risk factors (living alone, lack of social support, marginal housing, substance abuse, and low income) with 30-day Heart Failure (HF) hospital readmissions within the Veterans Health Affairs (VA) and the impact of their inclusion on hospital readmission model performance. METHODS: We performed a retrospective cohort study using chart review and VA and Centers for Medicare and Medicaid Services (CMS) administrative data from a random sample of 1,500 elderly (≥ 65 years) Veterans hospitalized for HF in 2012. Using logistic regression, we examined whether any of the social risk factors were associated with 30-day readmission after adjusting for age alone and clinical variables used by CMS in its 30-day risk stratified readmission model. The impact of these five social risk factors on readmission model performance was assessed by comparing c-statistics, likelihood ratio tests, and the Hosmer-Lemeshow goodness-of-fit statistic. RESULTS: The prevalence varied among the 5 risk factors; low income (47 % vs. 47 %), lives alone (18 % vs. 19 %), substance abuse (14 % vs. 16 %), lacks social support (2 % vs. <1 %), and marginal housing (< 1 % vs. 3 %) among readmitted and non-readmitted patients, respectively. Controlling for clinical factors contained in CMS readmission models, a lack of social support was found to be associated with an increased risk of 30-day readmission (OR 4.8, 95 %CI 1.35-17.88), while marginal housing was noted to decrease readmission risk (OR 0.21, 95 %CI 0.03-0.87). Living alone (OR: 0.9, 95 %CI 0.64-1.26), substance abuse (OR 0.91, 95 %CI 0.67-1.22), and having low income (OR 1.01, 95 %CI 0.77-1.31) had no association with HF readmissions. Adding the five social risk factors to a CMS-based model (age and comorbid conditions; c-statistic 0.62) did not improve model performance (c-statistic: 0.62). CONCLUSIONS: While a lack of social support was associated with 30-day readmission in the VA, its prevalence was low. Moreover, the inclusion of some social risk factors did not improve readmission model performance. In an integrated healthcare system like the VA, social risk factors may have a limited effect on 30-day readmission outcomes.
The effect of low-level red and near-infrared photobiomodulation on pain and function in tendinopathy: a systematic review and meta-analysis of randomized control trials
BACKGROUND: Tendinopathy is a common clinical condition that can significantly affect a person's physical function and quality of life. Despite exercise therapy being the mainstay of tendinopathy management, there are many potential adjunct therapies that remain under investigated, one of which is photobiomodulation (PBM). PBM uses varied wavelengths of light to create a biological effect. While PBM is used frequently in the management of tendinopathy, high quality evidence supporting its utility is lacking. METHODS: A systematic search of the Pubmed, CINAHL, SCOPUS, Cochrane Database, Web of Science and SPORTSDICUS databases was performed for eligible articles in August 2020. Randomized Control Trials that used red or near-infrared PBM to treat tendinopathy disorders that made comparisons with a sham or 'other' intervention were included. Pain and function data were extracted from the included studies. The data were synthesized using a random effects model. The meta-analysis was performed using the mean difference (MD) and standardized mean difference (SMD) statistics. RESULTS: A total of 17 trials were included (n = 835). When compared solely to other interventions PBM resulted in similar decreases in pain (MD -0.09; 95% CI - 0.79 to 0.61) and a smaller improvement in function (SMD -0.52; 95% CI - 0.81 to - 0.23). When PBM plus exercise was compared to sham treatment plus exercise, PBM demonstrated greater decreases in pain (MD 1.06; 95% CI 0.57 to 1.55) and improved function (MD 5.65; 95% CI 0.25 to 11.04). When PBM plus exercise was compared to other interventions plus exercise, no differences were noted in pain levels (MD 0.31; 95% CI - 0.07 to 0.70). Most studies were judged as low-risk of bias. The outcome measures were classified as very low to moderate evidence quality according to the Grading of Recommendation, Development and Evaluation tool. CONCLUSION: There is very-low-to-moderate quality evidence demonstrating that PBM has utility as a standalone and/or adjunctive therapy for tendinopathy disorders. TRIAL REGISTRATION: PROPERO registration number: CRD42020202508 .
Spoonful of honey or a gallon of vinegar? A conditional COVID-19 vaccination policy for front-line healthcare workers.
Seven COVID-19 vaccines are now being distributed and administered around the world (figure correct at the time of submission), with more on the horizon. It is widely accepted that healthcare workers should have high priority. However, questions have been raised about what we ought to do if members of priority groups refuse vaccination. Using the case of influenza vaccination as a comparison, we know that coercive approaches to vaccination uptake effectively increase vaccination rates among healthcare workers and reduce patient morbidity if properly implemented. Using the principle of least restrictive alternative, we have developed an intervention ladder for COVID-19 vaccination policies among healthcare workers. We argue that healthcare workers refusing vaccination without a medical reason should be temporarily redeployed and, if their refusal persists after the redeployment period, eventually suspended, in order to reduce the risk to their colleagues and patients. This 'conditional' policy is a compromise between entirely voluntary or entirely mandatory policies for healthcare workers, and is consistent with healthcare workers' established professional, legal and ethical obligations to their patients and to society at large.
Establishing a multidisciplinary initiative for interoperable electronic health record innovations at an academic medical center.
(Oxford University Press (OUP), 2021-07)
Objective: To establish an enterprise initiative for improving health and health care through interoperable electronic health record (EHR) innovations. Materials and Methods: We developed a unifying mission and vision, established multidisciplinary governance, and formulated a strategic plan. Key elements of our strategy include establishing a world-class team; creating shared infrastructure to support individual innovations; developing and implementing innovations with high anticipated impact and a clear path to adoption; incorporating best practices such as the use of Fast Healthcare Interoperability Resources (FHIR) and related interoperability standards; and maximizing synergies across research and operations and with partner organizations. Results: University of Utah Health launched the ReImagine EHR initiative in 2016. Supportive infrastructure developed by the initiative include various FHIR-related tooling and a systematic evaluation framework. More than 10 EHR-integrated digital innovations have been implemented to support preventive care, shared decision-making, chronic disease management, and acute clinical care. Initial evaluations of these innovations have demonstrated positive impact on user satisfaction, provider efficiency, and compliance with evidence-based guidelines. Return on investment has included improvements in care; over $35 million in external grant funding; commercial opportunities; and increased ability to adapt to a changing healthcare landscape. Discussion: Key lessons learned include the value of investing in digital innovation initiatives leveraging FHIR; the importance of supportive infrastructure for accelerating innovation; and the critical role of user-centered design, implementation science, and evaluation. Conclusion: EHR-integrated digital innovation initiatives can be key assets for enhancing the EHR user experience, improving patient care, and reducing provider burnout.
Characterization of a novel KCNQ1 mutation for type 1 long QT syndrome and assessment of the therapeutic potential of a novel IKs activator using patient-specific induced pluripotent stem cell-derived cardiomyocytes
(BIOMED CENTRAL LTD, 2015-03-19)
INTRODUCTION: Type 1 long QT syndrome (LQT1) is a common type of cardiac channelopathy associated with loss-of-function mutations of KCNQ1. Currently there is a lack of drugs that target the defected slowly activating delayed rectifier potassium channel (IKs). With LQT1 patient-specific human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs), we tested the effects of a selective IKs activator ML277 on reversing the disease phenotypes. METHODS: A LQT1 family with a novel heterozygous exon 7 deletion in the KCNQ1 gene was identified. Dermal fibroblasts from the proband and her healthy father were reprogrammed to hiPSCs and subsequently differentiated into hiPSC-CMs. RESULTS: Compared with the control, LQT1 patient hiPSC-CMs showed reduced levels of wild type KCNQ1 mRNA accompanied by multiple exon skipping mRNAs and a ~50% reduction of the full length Kv7.1 protein. Patient hiPSC-CMs showed reduced IKs current (tail current density at 30 mV: 0.33±0.02 vs. 0.92±0.21, P<0.05) and prolonged action potential duration (APD) (APD 50 and APD90: 603.9±39.2 vs. 319.3±13.8 ms, P<0.005; and 671.0±41.1 vs. 372.9±14.2 ms, P<0.005). ML277, a small molecule recently identified to selectively activate KV7.1, reversed the decreased IKs and partially restored APDs in patient hiPSC-CMs. CONCLUSIONS: From a LQT1 patient carrying a novel heterozygous exon7 deletion mutation of KCNQ1, we generated hiPSC-CMs that faithfully recapitulated the LQT1 phenotypes that are likely associated with haploinsufficiency and trafficking defect of KCNQ1/Kv7.1. The small molecule ML277 restored IKs function in hiPSC-CMs and could have therapeutic value for LQT1 patients.
Tocotrienol is a cardioprotective agent against ageing-associated cardiovascular disease and its associated morbidities
Ageing is a nonmodifiable risk factor that is linked to increased likelihood of cardiovascular morbidities. Whilst many pharmacological interventions currently exist to treat many of these disorders such as statins for hypercholesterolemia or beta-blockers for hypertension, the elderly appear to present a greater likelihood of suffering non-related side effects such as increased risk of developing new onset type 2 diabetes (NODM). In some cases, lower efficacy in the elderly have also been reported. Alternative forms of treatment have been sought to address these issues, and there has been a growing interest in looking at herbal remedies or plant-based natural compounds. Oxidative stress and inflammation are implicated in the manifestation of ageing-related cardiovascular disease. Thus, it is natural that a compound that possesses both antioxidative and anti-inflammatory bioactivities would be considered. This review article examines the potential of tocotrienols, a class of Vitamin E compounds with proven superior antioxidative and anti-inflammatory activity compared to tocopherols (the other class of Vitamin E compounds), in ameliorating ageing-related cardiovascular diseases and its associated morbidities. In particular, the potential of tocotrienols in improving inflammaging, dyslipidemia and mitochondrial dysfunction in ageing-related cardiovascular diseases are discussed.
Identification of an I-Na-dependent and I-to-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient
(NATURE PUBLISHING GROUP, 2018-07-26)
Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS.
A Veterinary Vaccine for SARS-CoV-2: The First COVID-19 Vaccine for Animals
As coronaviruses have a wide range of host species, many animals harbor these pathogens, however only a handful of them become severely infected [...].
COVID-19 Vaccines in the Pipeline, Are Antibodies Adequate?
The COVID-19 pandemic caused by the novel coronavirus strain SARS-CoV-2 has already led to catastrophic consequences in global physical and psychological health, as well as economic recession [...].
Low Birthweight Is Associated with Higher Risk of High Blood Pressure in Chinese Girls: Results from a National Cross-Sectional Study in China
OBJECTIVE: To investigate the relationship between low birthweight (LBW) and blood pressure and to assess whether LBW leads to a higher risk of high blood pressure (HBP) by gender in Chinese students aged 6-18 years. Also, to investigate whether the association was affected by childhood obesity. METHODS: Data was obtained from a baseline dataset of a national school-based program. Anthropometric parameters, including height, weight, and blood pressure, were measured, while birthweight and other characteristics were obtained from questionnaires. Stratified chi-squared tests were used to compare the prevalence of HBP between LBW and normal birthweight (NBW) groups in each age and sex category. Multivariable logistic regressions were conducted to estimate the HBP risks in each birthweight group. RESULTS: Both systolic and diastolic blood pressure showed a U-shaped relationship with increased birthweight. Compared to NBW groups, LBW girls showed a higher HBP risk, with an odds ratio of 1.29 (95% confidence interval (CI): 1.02, 1.64, p = 0.033), regardless of their current body mass index status, while no significant association in boys was found. Conclusions: Low birthweight is associated with higher HBP risk in adolescent girls, regardless of their childhood BMI status.
Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis (vol 21, pg 1958, 2019)
(NATURE PUBLISHING GROUP, 2019-09-01)
In the original version of this Article, the affiliation details for Lei Zhang were given as Monash University. While working on the Article Dr. Zhang was also affiliated with the Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR China. This has now been corrected in both the PDF and HTML versions of the Article.
A prospective evaluation of health-related quality of life after skull base re-irradiation
PURPOSE: To report cancer control outcomes and health-related quality of life (HRQoL) outcomes after highly conformal skull-based re-irradiation (re-RT). METHODS: Patients planned for curative intent re-RT to a recurrent or new skull base tumor were enrolled. HRQoL were assessed using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) and the anterior skull base surgery quality of life (ASBQ) questionnaires. RESULTS: Thirty-nine patients were treated with stereotactic body RT or intensity modulated RT. Median follow-up was 14 months. Progression free survival was 71% at 1-year. There was mild clinically significant worsening of fatigue, lack of appetite and drowsiness (MDASI-BT), and physical function (ASBQ) at the end of RT, followed by recovery to baseline on subsequent follow-ups. Subjective emotions were clinically improved at 12 months, with patients reporting feeling less tense/nervous. CONCLUSION: Conformal skull base re-RT is associated with mild immediate deterioration in physical function followed by rapid and sustained recovery.
Surveillance imaging for patients with head and neck cancer treated with definitive radiotherapy: A partially observed Markov decision process model
BACKGROUND: A possible surveillance model for patients with head and neck cancer (HNC) who received definitive radiotherapy was created using a partially observed Markov decision process. The goal of this model is to guide surveillance imaging policies after definitive radiotherapy. METHODS: The partially observed Markov decision process model was formulated to determine the optimal times to scan patients. Transition probabilities were computed using a data set of 1508 patients with HNC who received definitive radiotherapy between the years 2000 and 2010. Kernel density estimation was used to smooth the sample distributions. The reward function was derived using cost estimates from the literature. Additional model parameters were estimated using either data from the literature or clinical expertise. RESULTS: When considering all forms of relapse, the model showed that the optimal time between scans was longer than the time intervals used in the institutional guidelines. The optimal policy dictates that there should be less time between surveillance scans immediately after treatment compared with years after treatment. Comparable results also held when only locoregional relapses were considered as relapse events in the model. Simulation results for the inclusive relapse cases showed that <15% of patients experienced a relapse over a simulated 36-month surveillance program. CONCLUSIONS: This model suggests that less frequent surveillance scan policies can maintain adequate information on relapse status for patients with HNC treated with radiotherapy. This model could potentially translate into a more cost-effective surveillance program for this group of patients.
Early Detection of Muscle Weakness and Functional Limitations in the Critically Ill: A Retrospective Evaluation of Bioimpedance Spectroscopy
BACKGROUND: The potential for bioimpedance spectroscopy (BIS) to identify muscle weakness and functional limitations in critical illness is unknown; this study aimed to determine association of BIS with strength/function and differences between 3 intensive care units (ICUs). METHODS: A retrospective post hoc analysis of BIS, strength, and functional data from adults who required ≥48 hours of mechanical ventilation was conducted. Measures of body composition included the proportion (%) of total body water (TBW), fat mass (FM), and fat-free mass (FFM). The Medical Research Council sum score (MRC-ss) and Physical Function in ICU Test-Scored (PFIT-s) were used for strength and functional assessments. Nonparametric cross-sectional analyses were done at enrollment (≤48 hours of admission: site-A, site-C) and awakening from sedation (site-A, site-B). Raw impedance variables including 50-kHz phase angle (PA) and impedance ratio (IR) were available from site-A and site-B. RESULTS: Participants were 135 adults (site-A n=59, site-B n=33, site-C n=44), with a median (interquartile range) age of 59 (50-69) years. At enrollment, TBW%, FM%, and FFM% were similar between site-A and site-C (P>.05); pooled data were not associated with MRC-ss at awakening or MRC-ss/PFIT-s at ICU discharge. At awakening, there was less TBW%, less FFM%, and greater FM% at site-B vs site-A (P≤.001) but no associations with MRC-ss/PFIT-s when using pooled data. Trends with pooled data of a lower PA and higher IR being associated with awakening MRC-ss were confirmed within site-B (PA ρ=0.70, P≤.001; IR ρ=-0.79, P≤.001). CONCLUSION: Site-by-site data suggest that raw impedance variables might be useful for screening weakness and poor function.
A linkage and exome study implicates rare variants of KANK4 and CAP2 in bipolar disorder in a multiplex family
OBJECTIVES: Bipolar disorder (BD) is a neuropsychiatric disorder with a complex pattern of inheritance. Although many genetic studies have been conducted on BD, its genetic correlates remain uncertain. This study was aimed at identifying the genetic underpinnings of the disorder in an Indian family, which has been under comprehensive clinical evaluation and follow-up for over 12 years. METHODS: We analysed a four-generation family with several of its members diagnosed for BD employing a combination of genetic linkage and exome analysis. RESULTS: We obtained suggestive LOD score for a chromosome 1 and a chromosome 6 marker (D1S410; LOD = 3.01, Ө = 0; and D6S289; LOD = 1.58, Ө = 0). Manual haplotyping of the regions encompassing these two markers helped delimit a critical genomic interval of 32.44 Mb (D1S2700-D1S435; chromosome 1p31.1-13.2) and another of 10.34 Mb (D6S470-D6S422; chromosome 6p22.3-22.2). We examined the exomic sequences corresponding to these two intervals and found rare variants, NM_181712.4: c.2461G>T (p.Asp821Tyr) in KANK4 at 1p31.1-13.2; and NM_006366:c.-93G>A, in the 5' UTR of CAP2 at 6p22.3-22.2. CONCLUSIONS: Our studysuggests involvement of KANK4 or CAP2 or both in BD in this family. Further analysis of these two genes in BD patients and functional evaluation of the allelic variants identified are suggested.
Disclosure of maternal HIV infection to children among Chinese women with HIV: The application of the Theory of Planned Behaviour and the role of various norms
Maternal HIV disclosure to children has numerous benefits for both mothers and children. However, the prevalence of maternal HIV disclosure to children remains low in many countries. The present study examined factors associated with intention to disclose maternal HIV status to children among Chinese HIV+ women who have not disclosed their HIV status to their child. Factors from the Theory of Planned Behavior and various norms (injunctive, descriptive and moral norm) were examined. Findings from 179 HIV+ women revealed that only 16.8% intended to disclose their HIV status to their child in the future. Adjusted for significant background variables, all factors from the TPB and various norms (i.e. attitude, injunctive norm, descriptive norm, moral norm, perceived behavioural control) were associated with intention to disclose HIV status (adjusted odds ratios ranged from 3.22, 15.85). Stepwise logistic regression showed that attitude (ORm = 6.96) and injunctive norm (ORm = 6.81) were associated with intention to disclose HIV status. Interventions to promote maternal HIV disclosure were warranted to promote attitude, perceived behavioural control, and various norms associated with HIV disclosure.
Application of nanomaterials in three-dimensional stem cell culture.
Petri dish cultured cells have for long provided scientists an aperture to understanding cell's behavior both in normal and disease states as well as in vitro and in vivo. But recent advances have brought to light how the architecture and composite nature of the immediate environment within which the cell is proliferated can profoundly influence its phenotypic features and functions, thus making obvious, limitations of the conventional two-dimensional cell culture despite it cost effectiveness. Fortunately, the transition to three-dimensional (3D) cell culture has occurred concurrently with expanded knowledge of nanoscience and materials, thereby lending significant impetus for innovative research. This review is focused on the application of nanoparticles in 3D stem cell breeding, recent trends and developments in medical sciences for improved drug delivery, and treatment approaches to some human diseases. We also reviewed prevailing challenges and concerns of nanotoxicity as it continues to impede and delay clinical applications as well the ongoing concerted and multidisciplinary efforts to overcome them.
'It is meant to be heart rather than head'; International perspectives of teaching from lived experience in mental health nursing programs.
Consumer participation is a clear expectation of contemporary mental health policy. Most activity has concentrated in direct service delivery, and academic roles for mental health consumers have been slow to establish. An international project was undertaken to implement and evaluate meaningful consumer involvement in mental health nursing education. A learning module was co-produced between 'Experts by Experience' (drawing on experience of mental distress and service use) and Mental Health Nurse Academics. This qualitative exploratory study aimed to capture how Experts by Experience perceive their contribution. Interviews were undertaken with Experts by Experience who delivered the learning module. Data were analysed thematically and subsequently interpreted with Critical Social Theory. Two main themes emerged from the findings: 'there wasn't a barrier' described how personal narratives enhanced relationships between Experts by Experience and students; and 'made the human being visible', described their experiences of allowing students to see the person behind a diagnosis. These findings suggest Experts by Experience teaching is valuable and potentially a tool in redressing stigma. Addressing poor public perceptions could attract higher numbers of quality practitioners to mental health and meet identified workforce shortages. The findings presented here strengthen the evidence base for Expert by Experience roles in mental health professional education. These findings can be considered in international curricula reviews and aid progress towards a more socio-political, humanistic focus in mental health nursing, congruent with rights-based reform agendas.