Nonprogressive cerebellar disorder with mental retardation and autosomal recessive inheritance in hutterites

We report a nonprogressive neurological disorder in at least 11 Hutterites with healthy but consanguineous parents. In several of the affected, hypotonia was noted at birth. Retarded motor and mental development became apparent during the first year of life. The age of unsupported walking varied from 5–21 years. Consistent signs were unsteady, broadly based gait and stance, exaggerated deep tendon reflexes mainly in the lower limbs, and mild to moderate mental retardation. Variable signs were extensor plantar reflexes (9/11), short stature (–2SD in 8/11), strabismus (7/11), small muscle mass (6/11), mild intention tremor (3/11), cataracts (1/11), and epilepsy (1/11). CAT scans in two affected sisters showed slight enlargement of the fourth ventricle in one and hypoplasia of the cerebellum in both. The disorder is probably the same as that described earlier under the heading, dysequilibrium syndrome.     

Creativity and borderline personality disorder: evidence from a voxel-based morphometry study

Introduction: Throughout the history, various examples of eminent creative people suffering from mental disorders along with some empirical research reports strengthened the idea of a potential link between creativity and psychopathology.

Methods: This study investigated different facets of psychometrically determined creativity in 20 females diagnosed with borderline personality disorder (BPD) relative to 19 healthy female controls. In addition, group differences in grey matter (GM) were examined.

Results: Behavioural findings revealed no significant differences between the BPD group and healthy controls with respect to verbal and figural-graphic creative task performance and creativity-related personality characteristics. Whole-brain voxel-based morphometry analyses revealed a distinct pattern of GM reductions in the BPD group (relative to controls) in a network of brain regions closely associated with various cognitive and emotional functions (including the bilateral orbital inferior frontal gyri and the left superior temporal gyrus), partly overlapping with creativity-related brain regions. Correlation analyses moreover revealed that in the BPD group GM reductions in the orbital parts of the inferior and middle frontal gyri were associated with lower levels of creativity.

Conclusions: This study provides no indications in favour of the putative link between creativity and psychopathology, as sometimes reported in the literature.     

Analysis of inflammatory markers and metals in nasal lavage fluid of welders

ABSTRACT

Welding fumes may produce adverse health effects in the respiratory tract. To assess the relationship between exposure to welding fumes and inflammation in the upper airways, 190 male welders were examined from the WELDOX study (median age 40 yr, 54.7% smokers, and 32.9% atopics). Inhalable welding fumes were collected in the breathing zone of welders during a single shift. Chromium (Cr), nickel (Ni), manganese (Mn), and iron (Fe) were measured in the welding-fume samples and in postshift nasal lavage fluid (NALF). In addition, the numbers of particles and inflammatory biomarkers, including total and differential cell counts, interleukin (IL)-8, leukotriene (LT) B₄, 8-isoprostane (8-iso-PGF_2α), tissue inhibitor of metalloproteinase-1 (TIMP-1), and immunoreactive matrix metalloproteinase (MMP)-9, were determined. Metal concentrations in NALF correlated with airborne concentrations. No significant association was found between airborne metal concentrations and biomarkers of inflammation in NALF, whereas increasing metal concentrations in NALF resulted in increased concentrations of total protein, IL-8, MMP-9, and TIMP-1. LTB₄ and 8-iso PGF_2α were elevated at higher concentrations of Cr or Ni in NALF. The same was true for Fe, although the effects were less pronounced and of borderline significance. In conclusion, our results showed a significant association between the concentrations of metals and soluble inflammatory markers in the NALF of welders. The noninvasive collection of NALF is applicable in field studies, where it may serve as a suitable matrix to simultaneously assess biomarkers of exposure and effect in the upper respiratory tract in workers who are occupationally exposed to airborne hazardous substances.     

Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: A nested case‐control study in nonsmoking postmenopausal women from the EPIC cohort

Acrylamide, classified in 1994 by IARC as “probably carcinogenic to humans,” was discovered in 2002 in some heat‐treated, carbohydrate‐rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case‐control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non‐smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type‐I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HR_HbAA;Q5vsQ1: 0.84, 95%CI: 0.49–1.48; HR_HbGA;Q5vsQ1: 0.94, 95%CI: 0.54–1.63) or type‐I EC risk. Additionally, none of the subgroups investigated (BMI < 25 vs. ≥25 kg m^?2, alcohol drinkers vs. never drinkers, oral contraceptive users vs. non‐users) demonstrated effect measure modification. Hemoglobin adducts of acrylamide or glycidamide were not associated with EC or type‐I EC risk in 768 nonsmoking postmenopausal women from the EPIC cohort.     

Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen

Human cancer vaccines are often prepared with altered "analog" or "heteroclitic" antigens that have been optimized for HLA class I binding, resulting in enhanced immunogenicity. Here, we take advantage of CpG oligodeoxynucleotides as powerful vaccine adjuvants and demonstrate the induction of high T cell frequencies in melanoma patients, despite the use of natural (unmodified) tumor antigenic peptide. Compared with vaccination with analog peptide, natural peptide induced T cell frequencies that were approximately twofold lower. However, T cells showed superior tumor reactivity because of (i) increased functional avidity for natural antigen and (ii) enhancement of T cell activation and effector function. Thus, novel vaccine formulations comprising potent immune stimulators may allow to circumvent the need for modified antigens and can induce highly functional T cells with precise antigen specificity.     

Does continuity of care with a family physician reduce hospitalizations among older adults?

OBJECTIVE: To examine the relation between continuity of primary care and hospitalizations. METHODS: Survey data from a representative sample of older adults aged 67 or over living in the province of Manitoba (n = 1863) were linked to administrative data, which provide complete records of physician visits and hospitalizations. A visit-based measure of continuity of care was derived using a majority-of-care definition, whereby individuals who made 75% of all their visits to family physicians (FPs) to the same FP were classified as having high continuity of care, and those with less than 75% of their visits to the same FP as having low continuity of care. Whether individuals were hospitalized (for either ambulatory care-sensitive conditions or all conditions) was also determined from administrative records. RESULTS: High continuity of care was associated with reduced odds of ambulatory care-sensitive hospitalizations (adjusted odds ratio = 0.67, confidence interval 0.51-0.90) controlling for demographic and self-reported, health-related measures. It was not related to hospitalizations for all conditions, however. CONCLUSIONS: The study highlights the importance of continuity of primary care in reducing potentially avoidable hospitalizations.