Bipolar Disorder

Bipolar disorder is a mental disorder that causes severe swings in mood, energy, activity, concentration, and activities of daily living. These mood swings range from extremely euphoric, irritable, or animated behavior (manic) to despondent, apathetic, or dejected periods (depressive). This phenomenon was why this disorder was known as manic-depressive or manic depression. The need to understand the multiple factors regarding the disease process of this disorder, and the importance of treatment is vital for the safety and health of people across the world inflicted by bipolar disorder. Education is the key to how this disorder affects the entire trajectory of the human experience

Cross-Sectional Nutrition Profile of Palliative Home Care Clients in Ontario and Performance of the interRAI Palliative Care Nutrition Clinical Assessment Protocol

Background: The nutrition profile of palliative home care clients is unknown. This study describes this group and their nutrition issues and evaluates the performance of the interRAI nutrition Clinical Assessment Protocol (CAP). Methods: This was a cross-sectional secondary analysis using Ontario interRAI Palliative Care (interRAI PC) Assessment data. The sample represents 74,963 unique Ontario home care clients assessed between 2011 and 2018. Frequencies and standardized differences (stdiffs) of nutrition characteristics were presented for cancer (n = 62,394) and noncancer (n = 12,569) diagnostic subgroups. Rates of triggering the nutrition CAP were presented by nutrition issue to evaluate its performance. Results: Of this sample, 16.7% were ≥85 years of age, 52.6% had a prognosis between 6 weeks and 6 months, and 41.4% required assistance with eating. The prevalence was higher among those with nervous/mental/behavioral disorders (72.6%) compared with those with cancer (37.6%; stdiff = 0.75). However, most nutrition issues experienced were similar (stdiff \u3c 0.20) across diagnostic groups. Of the entire sample, 21% triggered the nutrition CAP, indicating a need for further evaluation or intervention. Yet, 73.4% of those who experienced dry mouth, 71.8% of those who required assistance with eating, and 68.4% of those who received a nutrition consult within the last 3 days did not trigger the nutrition CAP. Conclusions: Nutrition issues are prevalent in palliative home care clients, regardless of diagnosis; yet the nutrition CAP identified a small fraction of this group. There is a need to focus research and care guidelines toward life-limiting illnesses beyond cancer and address nutrition-related issues in this population

Impact of Electronic Alerts for Acute Kidney Injury on patient outcomes:interrupted time-series analysis of population cohort data

Background: Automated acute kidney injury (AKI) electronic alerts (e-alerts) are rule-based warnings triggered by changes in creatinine, and are intended to facilitate earlier detection in AKI. We assessed the impact of the introduction in the Tayside region of Scotland in April 2015 of automated AKI e-alerts with an accompanying education programme.Methods: Interrupted time-series analysis using segmented regression was performed involving all adults with AKI aged ≥18 years who had a serum creatinine measured between 1st April 2013 and 31st March 2017. Analysis evaluated associations of AKI e-alert introduction on rate and severity (stage 2-3) of AKI as well as mortality and occupied hospital bed days per patient per month in the population with AKI.Results: There were 32,320 episodes of AKI during the observation period. Implementation of e-alerts had no effect on the rate of any AKI (incidence rate ratio [IRR] 0.996, 95% CI 0.991 to 1.001, p=0.086) or on the rate of severe AKI (IRR 0.995, 95% CI 0.990 to 1.000, p=0.061). Subgroup group analysis found no impact on the rate or severity of AKI in hospital or in the community. 30-day mortality following AKI did not improve (IRR 0.998, 95% CI 0.987 to 1.009, p=0.688). There was a slight reduction in occupied bed days (β-coefficient -0.059, 95% CI -0.094 to -0.025, p=0.002).Conclusions: Introduction of automated AKI e-alerts was not associated with a change in the rate, severity or mortality associated with AKI but there was a small reduction in occupied hospital bed days

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Light Chain Amyloidosis: Patient Experience Survey from the Amyloidosis Research Consortium

The Author(s) 2015. This article is published with open access at Springerlink.com Introduction: Information detailing the experience of patients with light chain (AL) amyloidosis is lacking. The primary aim of this study was to gather data on the patient experience to understand the challenges i

Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates

Protein homeostasis is critical for cellular survival and its dysregulation has been implicated in Alzheimer's disease (AD) and other neurodegenerative disorders. Despite the growing appreciation of the pathogenic mechanisms involved in familial forms of AD, much less is known about the sporadic cases. Aggregates found in both familial and sporadic AD often include proteins other than those typically associated with the disease. One such protein is a mutant form of ubiquitin, UBB+1, a frameshift product generated by molecular misreading of a wild-type ubiquitin gene. UBB+1 has been associated with multiple disorders. UBB+1 cannot function as a ubiquitin molecule, and it is itself a substrate for degradation by the ubiquitin/proteasome system (UPS). Accumulation of UBB+1 impairs the proteasome system and enhances toxic protein aggregation, ultimately resulting in cell death. Here, we describe a novel model system to investigate how UBB+1 impairs UPS function and whether it plays a causal role in protein aggregation. We expressed a protein analogous to UBB+1 in yeast (Ubext) and demonstrated that it caused UPS impairment. Blocking ubiquitination of Ubext or weakening its interactions with other ubiquitin-processing proteins reduced the UPS impairment. Expression of Ubext altered the conjugation of wild-type ubiquitin to a UPS substrate. The expression of Ubext markedly enhanced cellular susceptibility to toxic protein aggregates but, surprisingly, did not induce or alter nontoxic protein aggregates in yeast. Taken together, these results suggest that Ubext interacts with more than one protein to elicit impairment of the UPS and affect protein aggregate toxicity. Furthermore, we suggest a model whereby chronic UPS impairment could inflict deleterious consequences on proper protein aggregate sequestration

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention