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We utilized a sample of 299 adult females aged between 19 and 86 years, carrying fragile X mental retardation ( FMR1) alleles with small CCG expansions ranging from 50 to 141 repeats to analyse the relationships between psychological symptoms as assessed by the Symptom Checklist-90-Revised ( SCL-90-R) and the size of the CGG repeat in the FMR1 gene. There were highly significant (negative) correlations between the size of the CGG repeat and a great majority of SCL-90-R subscale scores and all the global indices, suggesting that carriers of premutations in the mid-size CGG repeat range may be at greatest risk for the development of psychiatric disorder. [ABSTRACT FROM AUTHOR]

1. We apply a cost-benefit model to investigate whether bimodal turtles change their diving behaviour in response to changing energetic costs of aerial vs. aquatic respiration. This question is significant both in the context of the evolution of specialized respiratory structures in bimodal turtles, and the ecological role of respiratory partitioning. 2. Elseya albagula is a bimodally respiring turtle that can extract oxygen from water via specialized cloacal bursae and can vary its reliance on aquatic respiration. We examined the effect of water depth, velocity and temperature on the surfacing frequency of E. albagula through analysis of submergence durations (dive length). We applied a model of resource gain maximization to predict that as the cost of surfacing increases there will be longer dives made possible by the increased reliance on aquatic respiration. Diving behaviour of juvenile turtles was recorded in a large observation tank at varying water depths (50, 100 and 150 cm) and temperatures (20, 25 and 30 °C). Diving behaviour of adult turtles was also monitored in a flume at water velocities of 5, 15 and 30 cm s−1. 3. Dive length significantly increased with water depth, with dives at 150 cm twofold longer than dives at 50 cm. Dive length was also significantly influenced by temperature, with shorter dives at 30 °C than at 20 °C. In contrast, water velocity had no effect on dive length or on the proportion of a trial adult E. albagula spent using a velocity refuge. 4. Juvenile E. albagula possess the flexibility to adjust dive length in response to changes in water depth and temperature in a manner we would expect if energy use were being optimized. We advance the proposition that the driving force for the evolution of specialized aquatic gas exchange structures in E. albagula is the reduced cost of transport to and from the surface. [ABSTRACT FROM AUTHOR]

The article presents a case of a 21-year-old health professional with a one-year history of a gradual decrease in speech output and social withdrawal in Australia. The symptoms started after the birth of her son, which represented postnatal depression. It was found out that the patient has G389R Tau mutation with frontotemporal dementia (FTD) and Parkinsonism linked to chromosome 17. Her case is considered the youngest reported age of onset in FTD-17t.

Mohs micrographic surgery (MMS) is the gold standard for the excision of locally invasive cutaneous malignancies in human dermatological surgery. Using a unique horizontal sectioning technique, MMS enables 100% surgical margin assessment and provides the lowest recurrence rates for locally invasive tumours. The purposes of this preliminary study were to explore the feasibility of application of MMS in the veterinary setting and to establish practical advantages and limitations of its use in a pilot programme. It was hypothesized that MMS technique could provide 100% tumour margin assessment using frozen and/or formalin-fixed horizontal histopathologic sections. Tumour excision and colour-coded mapping were performed, and specimen tissue was fixed using either frozen sections or formalin-fixed sections. Horizontal sections were assessed for quality and presence and location of neoplastic cells based on the mapped orientation. The MMS technique was used in the excision of six squamous cell carcinomas and five mast cell tumours. In all cases, the MMS permitted 100% tumour margins examination. [ABSTRACT FROM AUTHOR]

ABSTRACT- A case of primary hepatocellular carcinoma is described in a patient with long-standing sarcoidosis of the liver associated with chronic active hepatitis, and the MZ alpha-1-antitrypsin phenotype. This association appears to be unique. The respective roles of alpha-1-antitrypsin deficiency, sarcoidosis and chronic active hepatitis in the development of hepatocellular carcinoma in this case are uncertain. [ABSTRACT FROM AUTHOR]

Study Objective: What is the association between anticholinergic burden and specific domains of cognitive function in older adults who are initially without major cognitive impairment?, Design: Post-hoc analysis of longitudinal observational data from the ASPirin in Reducing Events in the Elderly (ASPREE) study., Patients: 19,114 participants from Australia and the United States aged 70 years and older (65 years and older for US minorities) were recruited and followed for a median of 4.7 years. At enrollment, participants were free of known cardiovascular disease, major physical disability, or dementia., Measurements: Cognitive assessments administered at baseline and biennially at follow-up visits included the Modified Mini-Mental State examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall, Controlled Oral Word Association Test (COWAT), and Symbol Digit Modalities Test (SDMT). Anticholinergic burden was calculated at baseline using the Anticholinergic Cognitive Burden (ACB) scale and grouped as scores of 0 (no burden), 1-2 (low to moderate), or 3+ (high)., Main Results: Linear mixed effects models were used to assess the relationship between ACB score and cognition over time. After adjusting for sex, age, education, minority status, smoking status, hypertension, diabetes, depression, chronic kidney disease, country, and frailty, participants with a high ACB score had worse performance over time for 3MS (Adjusted [Adj] B=-0.092, P=0.034), HVLT-R delayed recall (Adj B=-0.104, P<0.001), COWAT (Adj B=-0.151, P<0.001), and SDMT (Adj B=-0.129, P=0.026), than participants with an ACB score of 0. A low to moderate ACB score was also associated with worse performance over time for HVLT-R delayed recall (Adj B=-0.037, P=0.007) and COWAT (Adj B=-0.065, P=0.003), compared to those with no ACB., Conclusions: Anticholinergic burden predicts worse cognitive function over time in initially dementia-free older adults, particularly for executive function (COWAT) and episodic memory (HVLT-R)., (© 2021 Pharmacotherapy Publications, Inc.)

Background Blood pressure variability (BPV) in midlife increases risk of late-life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow-up visits. Time-to-event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction P =0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19-2.39) but not women (HR, 1.01; 95% CI, 0.72-1.42). For cognitive decline, similar increased risks were observed for men and women (interaction P =0.15; men: HR, 1.36; 95% CI, 1.16-1.59; women: HR, 1.14; 95% CI, 0.98-1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583; isrctn.com. Identifier: ISRCTN83772183.

Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older individuals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by APOE genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrolment, participants had no history of diagnosed dementia, cardiovascular disease, physical disability or cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence for all-cause dementia and cognitive decline was calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non-APOE variants. During a median 4.5 years of follow-up, 324 participants developed dementia, 503 died. Cumulative incidence of dementia to age 85 years was 7.4% in all participants, 12.6% in APOE ε3/ε4 and 26.6% in ε4/ε4. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3-fold increased dementia risk and 1.4/1.8-fold cognitive decline risk, versus ε3/ε3 (p < 0.001 for both). High PRS tertile was associated with a 1.4-fold dementia risk versus low (CI 1.04-1.76, p = 0.02), but was not associated with cognitive decline (CI 0.96-1.22, p = 0.18). Incidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not., (© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Examining occupations other than those held when asthma symptoms first developed may not correctly identify occupations with higher risk of asthma onset., Methods: To determine the occupation held when individuals first developed asthma symptoms, we examined 2010 National Health Interview Survey data for working adults with current asthma., Results: Overall 37.1% of working adults with current asthma developed asthma while employed. Of these, the highest proportions of individuals identified office and administrative support (13.3%), sales and related (9.4%), and management (8.5%) as the occupation held when asthma first developed; 37.8% had a different current occupation than at asthma onset, and estimates of a change in occupation were highest for those who developed asthma while working in business and financial operations (49.3%), sales and related (48.6%), and healthcare support (43.8%) occupations., Conclusion: Future population-based studies should further examine associations between asthma and occupation held at time of asthma onset., (Copyright © 2013 Wiley Periodicals, Inc.)

We report a three-generation Caucasian family of Macedonian origin with dentatorubral-pallidoluysian atrophy (DRPLA), manifesting as very mild elderly onset, severe young adult onset, and severe childhood onset presentations in the three generations. The grandparental trinucleotide expansion size (52 repeats) is the smallest overtly pathogenic mutation yet reported. This 67-year-old man displayed only subtle neurological and cognitive deficits on formal examination and very slight signs on MRI. His son had developed a choreiform disorder at age 32 years, and by his 40s suffered severe dementia and motor decline. The grandson, the proband, presented as a teenager with progressive myoclonic epilepsy, dysarthria, ataxia, and cognitive decline, having manifesting learning difficulties from the age 5 years. Atrophin-1 expansion sizes of 52, 57, and 66 repeats were demonstrated in the three patients, respectively. Given an absence of any other indicative history in the family, we speculate that the mutation may have expanded from a 'high-end' normal allele to a pathogenic size at the grandfather's conception, or that one of his parents may have had a pathogenic mutation at the lowest end of the expanded range., (Copyright 2005 Wiley-Liss, Inc.)

Background: It is widely believed that development of hypersensitivity pneumonitis (HP) is forestalled in cigarette smokers. We encountered the largest outbreak of HP in metalworkers yet reported [Hodgson et al. (2001): Am J Ind Med 39:616-628] and subsequently did a chart review of the 61 patients seen in connection with the outbreak [Dangman et al. (2002a): Am J Resp Crit Care Med 165(8):A528; Dangman et al. (2002b): Am J Ind Med 42:150-162], developing a diagnostic index for this disease., Methods: A re-examination of data from the chart review was carried out to explore possible effects of cigarette smoking on the clinical tests used to diagnose HP [Hodgson et al. (2001): Am J Ind Med 39:616-628]., Results: Cigarette smokers with HP were less likely than non-smokers with HP to develop crackles in the lungs, elevated erythrocyte sedimentation rates (ESRs), and restrictive spirometry. Smoking habits had little effect on diffusion capacity and alveolar-arterial oxygen gradients in the patients with HP. Smokers were more likely to have abnormal gallium scans than non-smokers., Conclusions: It appears that cigarette smoking can affect the physical examination findings, spirometry, and ESR changes associated with HP, making these tests less sensitive and specific, and potentially obscuring the diagnosis. Such changes may contribute to the apparent "protective" effect of smoking on the development of HP.

Background: Since 1993, several outbreaks of hypersensitivity pneumonitis (HP) have been reported in metalworkers. We report the largest outbreak of HP in metalworkers yet known. It occurred in a Connecticut factory that produces precision parts for the aerospace industry. The workers typically presented with systemic and respiratory problems ("sick fatigue," myalgias, cough, dyspnea, wheezing, and chest tightness). They had variable findings on clinical tests, which complicated diagnosis. An HP diagnostic index was developed to help reduce the uncertainties in case identification., Methods: Data from 16 biopsy-confirmed cases and 14 non-HP patients were compared, and the HP diagnostic index was derived using variables that best discriminated between the two groups. The index is based on (a) work-related symptoms, (b) dry crackles on auscultation, (c) restrictive spirometry, (d) decreased diffusion capacity and/or increased A-a oxygen gradient, (e) elevated erythrocyte sedimentation rate, (f) abnormal radiographic images, and (g) abnormal gallium scans. We then applied the HP diagnostic index and, for comparison, the "Kenosha epidemiological case criteria" (developed during a recent HP outbreak in an automobile factory) to our data set., Results: The HP diagnostic index and the Kenosha criteria confirmed HP in overlapping sets of 36 and 34 patients, respectively, that were both in good agreement with the clinical diagnoses., Conclusions: The HP diagnostic index relies less heavily on symptoms, subjective evaluations, and invasive tests than the Kenosha criteria, but both identified similar subsets of the 61 patients as having HP. The HP diagnostic index could provide a useful tool in future HP outbreaks, which are increasingly being recognized in metalworking facilities., (Copyright 2002 Wiley-Liss, Inc.)

Background: An outbreak of lung disease among workers in a metal-working plant included 16 biopsy-confirmed cases of hypersensitivity pneumonitis and additional patients with asthma, bronchiolitis and emphysema, usual interstitial pneumonitis, and sarcoidosis. Study design Clinical examination of patients; cross-sectional questionnaire survey of the outbreak plant and two control plant areas, one with and one without MWF exposures, in a separate facility; industrial hygiene survey with laboratory characterization of microbial flora; and immunological investigation., Methods: Patients with suspected hypersensitivity pneumonitis underwent a clinical examination including detailed lung function, imaging, and tissue studies. A plant walk-through identified metal-working processes, microbial aerosols, and work practices. Microbial characteristics of the three microbial aerosol-producing processes were characterized. Antibodies to those agents were determined in patient sera. A questionnaire survey was conducted in the case plant and in two areas of a control plant, one with and one without metal-working fluids exposure., Results: Thirty-nine (79.6%) patients described symptoms consistent with work-related lung disease, eight received other diagnoses, and two did not complete their examinations. Sixteen patients had hypersensitivity pneumonitis confirmed on biopsy. Mean decrements in lung forced expiratory volume in 1 s and force vital capacity from before to after work were similar in the 16 biopsy-confirmed cases of hypersensitivity pneumonitis ( - 6.3%; - 7.2%) and the 19 symptomatic patients without biopsies ( - 11.2%, - 10.1%). Symptoms were more common in the case plant than in a non-MWF control plant area. Three sources of water-based aerosols were identified that grew similar microbial flora. Although machining increased airborne bacterial levels, the increase was not related to the concentration of viable bacteria in the sumps. Antibody testing did not identify a specific single organisms. Endotoxin levels were similar in case and MWF control plant., Conclusions: Lung disease in environments with water-based aerosols may be more common than usually recognized. Patients with HP often present with only subtle abnormalities and may be missed if multiple clinical abnormalities are required to document disease., (Copyright 2001 Wiley-Liss, Inc.)

We and colleagues have shown that the amyloid protein precursor of Alzheimer's disease (APP) is distributed along the surface of neurites of fixed but nonpermeabilized neurons in primary culture in a segmental pattern, which shows colocalization with some markers of adhesion patches. This is in contrast to the diffuse pattern of immunoreactivity seen after permeabilization. We have also recently demonstrated that the APP in these surface patches is likely to be integral to the membrane rather than secreted and re-adsorbed, based on alkali stripping experiments and on soluble APP adsorption experiments. Total cellular APP has previously been shown to have a short half-life of approximately 30-60 min. We confirm this in neurons in primary culture in pulse-chase experiments using short labelling times. Additionally, we provide evidence that a separate, stable pool of neuronal APP can be demonstrated in pulse-chase experiments using long labelling times. Experiments involving inhibition of protein synthesis suggest that this corresponds with the surface, segmental pool. Metabolic labelling followed by surface biotinylation and two-stage precipitation demonstrates that the surface APP is trans-membrane and full-length (not carboxyl-terminal truncated), and confirms that the surface APP belongs to the stable pool. This two-stage procedure is necessary as the surface APP appears to be present in low copy number, and is difficult to detect by direct labelling. This information is consistent with a role for APP in stable cell-matrix or cell-cell interactions.

A case of progressive necrotizing myelopathy occurring in the context of multiple myeloma is described, and the pathology illustrated. This association has not been previously reported.