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Aims.After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population.Methods.Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year.Results.We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30–1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12–1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10–2.40).Conclusion.The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.

Incidents involving low levels of adhesion between the wheel and rail are a recurrent issue in the rail industry. The problem has been mitigated using friction modifiers and traction enhancers, but a significant number of incidents still occur throughout the year. This study looks at the environmental conditions that surround periods of low adhesion in order to provide an insight into why low adhesion events occur. Network Rail Autumn data, which provided details on the time and location of low adhesion incidents, were compared against weather data on a national and then local scale. Low adhesion incidents have often been attributed to contamination on the rails, such as organic leaf matter, but these incidents also occur when no contamination is visible. The time, date and location of incidents were linked to local weather data to establish any specific weather conditions that could lead to these events. The effects of precipitation, temperature and humidity on rails were analysed in order to further the understanding of low adhesion in the wheel–rail contact, which will lead to adopting better methods of mitigating this problem.

Our objective was to estimate the effectiveness of disease-modifying drugs (DMDs) in delaying multiple sclerosis (MS) disability progression in relapsing-onset (R-onset) definite MS patients under “real-world” conditions.

Introduction:Previous studies have shown that social determinants not directly involved in the disease process may be implicated in the timing of dementia diagnosis. This study explores the relationship between a patient’s living situation and the severity of dementia at diagnosis. Methods:Data were collected from the baseline interviews of 1,325 patients with cognitive decline enrolled in the Consortium for the Investigation of Vascular Impairment of Cognition study. Data collected included: age, sex, living situation and scores on the Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), the Functional Rating Scale (FRS), the Disability Assessment for Dementia (DAD) scale and the Cumulative Illness Rating Scale (CIRS). Living situation was grouped as: (1) lives alone, (2) lives with spouse, (3) lives with child, relative or other and (4) lives in a nursing home. A general linear model univariate analysis was used to compare patients by their respective living situations for differences in mean scores on each of the 4 measures of dementia severity. Results:Statistical analysis of both unadjusted data and data adjusted for age, sex and CIRS scores showed significant differences among the groups. Those who lived alone were diagnosed at an earlier stage (mean scores: MMSE 21.4, GDS 3.6, FRS 20.0, DAD 29.8) followed by those who lived with a spouse (mean scores: MMSE 20.5, GDS 3.7, FRS 20.4, DAD 28.0), those who lived with a child or other (mean scores: MMSE 19.3, GDS 3.9, FRS 22.5, DAD 24.9) and finally those who lived in a nursing home (mean scores: MMSE 15.2, GDS 4.8, FRS 27.5, DAD 16.9). Conclusion:Living situation is related to the severity of dementia at diagnosis. Primary care providers should have a low threshold for case-finding in older adults who live with family or friends.

We report an initial step toward the development of sulfonamide-based complements for extended peptide strands. A molecule containing one secondary sulfonamide unit and one valine residue linked by a turn-forming segment was found by IR and NMR to exhibit a doubly hydrogen-bonded folding pattern in chloroform.

We show that a tetrapeptide with a heterogeneous backbone, i.e., with two different classes of amino acid residues, adopts a hairpin conformation in which each type of residue plays a different structural role. The α-residues at the ends form hydrogen bonds characteristic of antiparallel β-sheet secondary structure, while the central di-β-peptide segment forms a reverse turn. The configuration of the turn residues is critical to sheet formation.

Background.The prairie dog has become the established animal gallstone model. This species has a unique propensity to form cholesterol gallstones in response to dietary manipulations. The development of a reliable gallbladder cell culture technique is critical for understanding pathogenic mechanisms of gallstone formation.

The performance of patients with progressive supranuclear palsy on visual search and scanning tasks was related to the pattern of ocular motor deficits observed in these patients during horizontal refixation. Comparisons were made to age-matched normals and patients with Parkinson disease or cerebellar damage. The poor performance of the progressive supranuclear palsy group on visual search and scanning could not be attributed to the restricted range of vertical gaze or the large number of hypometric saccades during horizontal reification. Instead, we believe that their impaired scanning resulted from the presence of square-wave jerks during attempted fixation.

1. The ability to move the forearm between remembered elbow joint angles immediately after rapid increases or decreases of the background gravitoinertial force (G) level was measured. The movements had been well-practiced in a normal 1G environment before the measurements in high-(1.8G) and low-force (0G) environments. The forearm and upper arm were always unsupported to maximize the influence of altered G-loading and to minimize extraneous cues about arm position. 2. Horizontal and vertical movement planes were studied to measure the effects of varying the G load in the movement plane within a given G background. Rapid and slow movements were studied to assess the role of proprioceptive feedback. 3. G level did not affect the amplitude of rapid movements, indicating that subjects were able to plan and to generate appropriate motor commands for the new G loading of the arm. The amplitude of slow movements was affected by G level, indicating that proprioceptive feedback is influenced by G level. 4. The effects of G level were similar for horizontal and vertical movements, indicating that proprioceptive information from supporting structures, such as the shoulder joint and muscles, had a role in allowing generation of the appropriate motor commands. 5. The incidence and size of dynamic overshoots were greater in 0G and for rapid movements. This G-related change in damping suggests a decrease in muscle spindle activity in 0G. A decrease in muscle spindle activity in 0G and an increase in 1.8G are consistent with the results of our prior studies on the tonic vibration reflex, locomotion, and perception of head movement trajectory in varying force backgrounds.

The cases constituting the basis of this report were studied at the U. S. Army Base Hospital, Camp Merritt, N. J., during the period from December, 1918, to March, 1919. As this institution evacuated the wounded to hospitals of the interior, the treatment given these patients during their brief stay was of a temporary nonsurgical nature. As a consequence, no therapeutic deductions were made from the treatment applied to this group of cases. The tables appended (Tables 1, 2 and 3) give a detailed analysis of the cases.The 415 instances occurred in 328 patients, 76 of whom had two or more lesions. Of these multiple injuries, which occur with much greater frequency in lesions of the upper extremities, the commonest combinations are analyzed in Table 2.These cases have been examined at this hospital, on an average of from three to five months after the original injury was sustained;

AbstractAimsAlthough immune-mediated inflammatory diseases (IMID) are associated with multiple mental health conditions, there is a paucity of literature assessing personality disorders (PDs) in these populations. We aimed to estimate and compare the incidence of any PD in IMID and matched cohorts over time, and identify sociodemographic characteristics associated with the incidence of PD.MethodsWe used population-based administrative data from Manitoba, Canada to identify persons with incident inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) using validated case definitions. Unaffected controls were matched 5:1 on sex, age and region of residence. PDs were identified using hospitalisation or physician claims. We used unadjusted and covariate-adjusted negative binomial regression to compare the incidence of PDs between the IMID and matched cohorts.ResultsWe identified 19 572 incident cases of IMID (IBD n= 6,119, MS n= 3,514, RA n= 10 206) and 97 727 matches overall. After covariate adjustment, the IMID cohort had an increased incidence of PDs (incidence rate ratio [IRR] 1.72; 95%CI: 1.47–2.01) as compared to the matched cohort, which remained consistent over time. The incidence of PDs was similarly elevated in IBD (IRR 2.19; 95%CI: 1.69–2.84), MS (IRR 1.79; 95%CI: 1.29–2.50) and RA (IRR 1.61; 95%CI: 1.29–1.99). Lower socioeconomic status and urban residence were associated with an increased incidence of PDs, whereas mid to older adulthood (age 45–64) was associated with overall decreased incidence. In a restricted sample with 5 years of data before and after IMID diagnosis, the incidence of PDs was also elevated before IMID diagnosis among all IMID groups relative to matched controls.ConclusionsIMID are associated with an increased incidence of PDs both before and after an IMID diagnosis. These results support the relevance of shared risk factors in the co-occurrence of PDs and IMID conditions.

During viremia, the HIV-specific memory response in lymph nodes is mediated by T-bethiB cells that inefficiently participate in affinity selection.

Background:Primary Progressive Aphasia (PPA) involves an isolated impairment of language function at disease onset. The cholinergic system is implicated in language and cholinergic deficits are seen in brains of individuals with PPA. One major source of cholinergic innervation is the nucleus basalis of Meynert (NBM) within which lies the nucleus subputaminalis (NSP). We quantified cholinergic neurons in the NBM and NSP of PPA and controls. Also explored was whether individuals with PPA who subsequently developed different clinical and neuropathological profiles, showed similar cholinergic deficits in the NSP. Methods:Cytoarchitecture of the basal forebrain was studied using Nissl staining in control (n=5) and PPA (n=5) brains. Choline acetyltransferase immunohistochemical staining labelled cholinergic neurons, quantified using Neurolucida software. Results:Compared to matched controls, PPA showed reduction of cholinergic neurons in the NBM, t(4) = 4.224, p = 0.013; Cohen’s d=1.89 and the NSP, t(4) = 4.013, p = 0.016; Cohen’s d= 1.79. The average percent of cholinergic neuronal loss was higher in the NSP (64.66%) compared to NBM (17.66%). Conclusions:Regardless of underlying pathology, all cases presenting with PPA showed marked loss of cholinergic neurons in the NSP providing further evidence for the importance of this nucleus in language function.