Phylogenetic position of Sphincterodiplostomum Dubois, 1936 (Digenea: Diplostomoidea) with description of a second species from Pantanal, Brazil.

Sphincterodiplostomum is a monotypic genus of diplostomid digeneans that parasitize fish-eating birds in the neotropics. The type species Sphincterodiplostomum musculosum has a unique, dorsal, tubular invagination in the opisthosoma with a muscular sphincter. Whereas larvae of S. musculosum are relatively commonly reported in Neotropical fish helminth surveys, adult specimens from birds are rarely collected. Prior to our study, no DNA sequence data for S. musculosum were available. Our molecular and morphological study of mature and immature adult Sphincterodiplostomum specimens from three species of birds and one species of crocodilian revealed the presence of at least two species of Sphincterodiplostomum in the neotropics. We provide the first molecular phylogeny of the Diplostomoidea that includes Sphincterodiplostomum. In addition, this is the first record of S. musculosum from caimans, along with the first record of fully mature adult S. musculosum from green kingfisher Chloroceryle americana. The new species of Sphincterodiplostomum (Sphincterodiplostomum joaopinhoi n. sp.) can be morphologically distinguished from S. musculosum based on the anterior extent of vitelline follicles, narrower prosoma, substantially smaller holdfast organ and structure of tegumental spines. Our data revealed 0.7% interspecific divergence in 28S and 10.6-11.7% divergence in cox1 sequences between the two Sphincterodiplostomum species.

Can the use of an inclinometer improve the positioning of the acetabular component in total hip arthroplasty?

Aims: Accurate placement of the acetabular component is essential in total hip arthroplasty (THA). The purpose of this study was to determine if the ability to achieve inclination of the acetabular component within the 'safe-zone' of 30° to 50° could be improved with the use of an inclinometer. Patients and Methods: We reviewed 167 primary THAs performed by a single surgeon over a period of 14 months. Procedures were performed at two institutions: an inpatient hospital, where an inclinometer was used (inclinometer group); and an ambulatory centre, where an inclinometer was not used as it could not be adequately sterilized (control group). We excluded 47 patients with a body mass index (BMI) of > 40 kg/m2, age of > 68 years, or a surgical indication other than osteoarthritis whose treatment could not be undertaken in the ambulatory centre. There were thus 120 patients in the study, 68 in the inclinometer group and 52 in the control group. The inclination angles of the acetabular component were measured from de-identified plain radiographs by two blinded investigators who were not involved in the surgery. The effect of the use of the inclinometer on the inclination angle was determined using multivariate regression analysis. Results: The mean inclination angle for the THAs in the inclinometer group was 42.9° (95% confidence interval (CI) 41.7° to 44.0°; range 29.0° to 63.8°) and 46.5° (95% CI 45.2° to 47.7°; range 32.8° to 63.2°) in the control group (p < 0.001). Regression analysis identified a 9.1% difference in inclination due to the use of an inclinometer (p < 0.001), and THAs performed without the inclinometer were three times more likely to result in inclination angles of > 50° (odds ratio (OR) 2.8, p = 0.036). The correlation coefficient for the interobserver reliability of the measurement of the two investigators was 0.95 (95% CI 0.93 to 0.97). Conclusion: The use of a simple inclinometer resulted in a significant reduction in the number of outliers compared with a freehand technique. Cite this article: Bone Joint J 2018;100-B:862-6.

First Record of Leucocytozoon (Haemosporida: Leucocytozoidae) in Amazonia: Evidence for Rarity in Neotropical Lowlands or Lack of Sampling for This Parasite Genus?

Birds harbor an astonishing diversity of haemosporidian parasites belonging to the genera Haemoproteus, Leucocytozoon, and Plasmodium. Currently there are more than 250 morphologically described avian haemosporidian species and 2,828 unique lineages found in virtually all avian clades and zoogeographic regions, except for Antarctica. Our report is based on PCR and microscopic screening of 1,302 individual avian samples from Brazil to detect the underrepresented genus Leucocytozoon. This survey primarily focuses on passerine birds collected from Amazonia, the Atlantic Rain Forest, and Pantanal. We also summarize studies conducted in Brazil that report haemosporidian prevalence using both microscopy and molecular tools and present for the first time a record of Leucocytozoon infecting an avian host population in Amazonia. Based on our findings, we suggest that high average temperatures may be constraining both the distribution and diversity of Leucocytozoon in lowland tropical South America.

Repeated exposure to systemic inflammation and risk of new depressive symptoms among older adults.

Evidence on systemic inflammation as a risk factor for future depression is inconsistent, possibly due to a lack of regard for persistency of exposure. We examined whether being inflamed on multiple occasions increases risk of new depressive symptoms using prospective data from a population-based sample of adults aged 50 years or older (the English Longitudinal Study of Ageing). Participants with less than four of eight depressive symptoms in 2004/05 and 2008/09 based on the Eight-item Centre for Epidemiologic Studies Depression scale were analysed. The number of occasions with C-reactive protein ⩾3 mg l-1 over the same initial assessments (1 vs 0 occasion, and 2 vs 0 occasions) was examined in relation to change in depressive symptoms between 2008/09 and 2012/13 and odds of developing depressive symptomology (having more than or equal to four of eight symptoms) in 2012/13. In multivariable-adjusted regression models (n=2068), participants who were inflamed on 1 vs 0 occasion showed no increase in depressive symptoms nor raised odds of developing depressive symptomology; those inflamed on 2 vs 0 occasions showed a 0.10 (95% confidence intervals (CIs)=-0.07, 0.28) symptom increase and 1.60 (95% CI=1.00, 2.55) times higher odds. In further analyses, 2 vs 0 occasions of inflammation were associated with increased odds of developing depressive symptoms among women (odds ratio (OR)=2.75, 95% CI=1.53, 4.95), but not among men (OR=0.70, 95% CI=0.29, 1.68); P-for-sex interaction=0.035. In this cohort study of older adults, repeated but not transient exposure to systemic inflammation was associated with increased risk of future depressive symptoms among women; this subgroup finding requires confirmation of validity.

Healthy obesity and risk of accelerated functional decline and disability.

BACKGROUND/OBJECTIVES: Some obese adults have a normal metabolic profile and are considered 'healthy', but whether they experience faster ageing than healthy normal-weight adults is unknown. We compared decline in physical function, worsening of bodily pain and likelihood of future mobility limitation and disability between these groups. SUBJECTS/METHODS: This was a population-based observational study using repeated measures over 2 decades (Whitehall II cohort data). Normal-weight (body mass index (BMI) 18.5-24.9 kg m-2), overweight (25.0-29.9 kg m-2) and obese (⩾30.0 kg m-2) adults were considered metabolically healthy if they had 0 or 1 of 5 risk factors (hypertension, low high-density lipoprotein cholesterol, high triacylglycerol, high blood glucose and insulin resistance) in 1991/1994. Decline in physical function and worsening of bodily pain based on change in Short Form Health Survey items using eight repeated measures over 18.8 years (1991/1994-2012/2013) were compared between metabolic-BMI groups using linear mixed models. Odds of mobility limitation based on objective walking speed (slowest tertile) and of disability based on limitations in ⩾1 of 6 basic activities of daily living, each using three repeated measures over 8.3 years (2002/2004-2012/2013), were compared using logistic mixed models. RESULTS: In multivariable-adjusted mixed models on up to 6635 adults (initial mean age 50 years; 70% male), healthy normal-weight adults experienced a decline in physical function of -3.68 (95% CI=-4.19, -3.16) score units per decade; healthy obese adults showed an additional -3.48 (-4.88, -2.08) units decline. Healthy normal-weight adults experienced a -0.49 (-1.11, 0.12) score unit worsening of bodily pain per decade; healthy obese adults had an additional -2.23 (-3.78, -0.69) units worsening. Healthy obesity versus healthy normal-weight conferred 3.39 (2.29, 5.02) times higher odds of mobility limitation and 3.75 (1.94, 7.24) times higher odds of disability. CONCLUSIONS: Our results suggest that obesity, even if metabolically healthy, accelerates age-related declines in functional ability and poses a threat to independence in older age.

Guillain Barré Syndrome is induced in Non-Obese Diabetic (NOD) mice following Campylobacter jejuni infection and is exacerbated by antibiotics.

Campylobacter jejuni is a leading cause of bacterial gastroenteritis linked to several serious autoimmune sequelae such as the peripheral neuropathies Guillain Barré syndrome (GBS) and Miller Fisher syndrome (MFS). We hypothesized that GBS and MFS can result in NOD wild type (WT) mice or their congenic interleukin (IL)-10 or B7-2 knockouts secondary to C. jejuni infection. Mice were gavaged orally with C. jejuni strains HB93-13 and 260.94 from patients with GBS or CF93-6 from a patient with MFS and assessed for clinical neurological signs and phenotypes, anti-ganglioside antibodies, and cellular infiltrates and lesions in gut and peripheral nerve tissues. Significant increases in autoantibodies against single gangliosides (GM1, GQ1b, GD1a) occurred in infected NOD mice of all genotypes, although the isotypes varied (NOD WT had IgG1, IgG3; NOD B7-2-/- had IgG3; NOD IL-10-/- had IgG1, IgG3, IgG2a). Infected NOD WT and NOD IL-10-/- mice also produced anti-ganglioside antibodies of the IgG1 isotype directed against a mixture of GM1/GQ1b gangliosides. Phenotypic tests showed significant differences between treatment groups of all mouse genotypes. Peripheral nerve lesions with macrophage infiltrates were significantly increased in infected mice of NOD WT and IL-10-/- genotypes compared to sham-inoculated controls, while lesions with T cell infiltrates were significantly increased in infected mice of the NOD B7-2-/- genotype compared to sham-inoculated controls. In both infected and sham inoculated NOD IL-10-/- mice, antibiotic treatment exacerbated neurological signs, lesions and the amount and number of different isotypes of antiganglioside autoantibodies produced. Thus, inducible mouse models of post-C. jejuni GBS are feasible and can be characterized based on evaluation of three factors-onset of GBS clinical signs/phenotypes, anti-ganglioside autoantibodies and nerve lesions. Based on these factors we characterized 1) NOD B-7-/- mice as an acute inflammatory demyelinating polyneuropathy (AIDP)-like model, 2) NOD IL-10-/- mice as an acute motor axonal neuropathy (AMAN)-like model best employed over a limited time frame, and 3) NOD WT mice as an AMAN model with mild clinical signs and lesions. Taken together these data demonstrate that C. jejuni strain genotype, host genotype and antibiotic treatment affect GBS disease outcomes in mice and that many disease phenotypes are possible.

Dynapenic obesity and the risk of incident Type 2 diabetes: the English Longitudinal Study of Ageing.

AIM: Obesity is a well-established risk factor for developing Type 2 diabetes. Evidence suggests that sarcopenia, the age-related decline in muscle mass and strength, may exacerbate diabetes risk in obese individuals. The aim of this study was to determine the combined effect of obesity and low muscle strength, dynapenia, on the risk of incident Type 2 diabetes in older adults. METHODS: Participants were 5953 (1670 obese) men and women from the English Longitudinal Study of Ageing without known Type 2 diabetes at baseline and for whom handgrip strength, biochemical and other clinical data were collected. A diagnosis of Type 2 diabetes was recorded from self-reported physician diagnosis over 6 years. RESULTS: For each unit increase in grip strength, there was a reduction in diabetes risk (age-, sex- and BMI adjusted HR; 0.98; 95% CI 0.96-0.99). The risk of Type 2 diabetes was elevated in all obese participants, but was greatest in those with low handgrip strength (HR = 4.93, 95% CI 2.85, 8.53) compared with non-obese individuals with high handgrip strength. Eleven per cent of the sample met the threshold for weakness (handgrip strength: men < 26 kg; women < 16 kg) that was associated with elevated Type 2 diabetes risk in obese (HR = 3.57, 95% CI 2.04, 6.24) but not in non-obese (HR = 0.86, 95% CI, 0.44, 1.68) compared with normal/non-obese participants. CONCLUSION: Dynapenic obesity, determined by high BMI and low handgrip strength, is associated with increased risk of incident Type 2 diabetes in older people.

Healthy obesity as an intermediate state of risk: a critical review.

INTRODUCTION: Obesity is a top public health priority but interventions to reverse the condition have had limited success. About one-in-three obese adults are free of metabolic risk factor clustering and are considered 'healthy', and much attention has focused on the implications of this state for obesity management. Areas covered: We searched for individual studies, systematic reviews, and meta-analyses which examined correlates and outcomes of metabolically healthy obesity. We discuss the key roles of fat distribution and physical activity in determining healthy vs. unhealthy obesity and report a greatly increased risk of incident type 2 diabetes associated with healthy obesity vs. healthy normal weight, among other outcomes. We argue that despite inconsistencies in the definition, patterns across studies clearly show that healthy obesity is a state of intermediate disease risk. Expert commentary: Given the current state of population-level evidence, we conclude that obesity and metabolic dysfunction are inseparable and that healthy obesity is best viewed only as a state of relative health but not of absolute health. We recommend that weight loss through energy restriction be a stand-alone target in addition to increased physical activity for minimising risk of future disease.

Metabolically healthy obesity and risk of incident type 2 diabetes: a meta-analysis of prospective cohort studies.

The risk of type 2 diabetes among obese adults who are metabolically healthy has not been established. We systematically searched Medline (1946-August 2013) and Embase (1947-August 2013) for prospective studies of type 2 diabetes incidence (defined by blood glucose levels or self-report) among metabolically healthy obese adults (defined by body mass index [BMI] and normal cardiometabolic clustering, insulin profile or risk score) aged ≥18 years at baseline. We supplemented the analysis with an original effect estimate from the English Longitudinal Study of Ageing (ELSA), with metabolically healthy obesity defined as BMI ≥ 30 kg m(-2) and <2 of hypertension, impaired glycaemic control, systemic inflammation, adverse high-density lipoprotein cholesterol and adverse triglycerides. Estimates from seven published studies and ELSA were pooled using random effects meta-analyses (1,770 healthy obese participants; 98 type 2 diabetes cases). The pooled adjusted relative risk (RR) for incident type 2 diabetes was 4.03 (95% confidence interval = 2.66-6.09) in healthy obese adults and 8.93 (6.86-11.62) in unhealthy obese compared with healthy normal-weight adults. Although there was between-study heterogeneity in the size of effects (I(2) = 49.8%; P = 0.03), RR for healthy obesity exceeded one in every study, indicating a consistently increased risk across study populations. Metabolically healthy obese adults show a substantially increased risk of developing type 2 diabetes compared with metabolically healthy normal-weight adults. Prospective evidence does not indicate that healthy obesity is a harmless condition.

Physician-patient interactions and outcomes in systemic lupus erythematosus (SLE): a conceptual model.

OBJECTIVE: The objective was to develop a conceptual model illustrating the relationships between the physician-patient relationship and patient outcomes, including health status and regimen satisfaction, in systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional survey of a geographically diverse sample of adults with SLE in the United States. Patients completed a Web-based survey that focused on physician interactions, clinical management, and patient outcomes, including patient perception of treatment regimen and health status. All survey variables related to physician interactions and patient perceptions of their health and satisfaction were evaluated for incorporation into a patient-centered model using cluster analysis. Structural equation modeling (SEM) was conducted to assess the inter-relationships observed among the variables to inform the development of a conceptual model of SLE patient-centered care. RESULTS: A total of 302 SLE patients completed the survey. The majority of patients were female (94.3%) with a mean age of 46 years. The cluster analysis resulted in six main factors: 1) physician interactions, 2) current health and hope, 3) satisfaction with treatment, 4) bedside manner, 5) discussion of lupus impacts during physician visits, and 6) steroid treatment. The significant relationships among the factors showed that positive physician interactions, such as including the patient in treatment decisions, were associated with higher satisfaction with treatment regimen and patients feeling that SLE was well controlled, a more favorable perception of current health, and being more hopeful about future health. Among the components of physician interactions, setting goals with patients is particularly important, as this was significantly associated with the patient being more hopeful about future health. Being steroid free was significantly related to higher treatment satisfaction. CONCLUSION: The study findings informed a conceptual model of SLE patient-centered care that may be used to create more targeted education programs in the management of SLE, with the goal to improve patient outcomes.

Outcome of infection of C57BL/6 IL-10(-/-) mice with Campylobacter jejuni strains is correlated with genome content of open reading frames up- and down-regulated in vivo.

Human Campylobacter jejuni infection can result in an asymptomatic carrier state, watery or bloody diarrhea, bacteremia, meningitis, or autoimmune neurological sequelae. Infection outcomes of C57BL/6 IL-10(-/-) mice orally infected with twenty-two phylogenetically diverse C. jejuni strains were evaluated to correlate colonization and disease phenotypes with genetic composition of the strains. Variation between strains was observed in colonization, timing of development of clinical signs, and occurrence of enteric lesions. Five pathotypes of C. jejuni in C57BL/6 IL-10(-/-) mice were delineated: little or no colonization, colonization without disease, colonization with enteritis, colonization with hemorrhagic enteritis, and colonization with neurological signs with or without enteritis. Virulence gene content of ten sequenced strains was compared in silico; virulence gene content of twelve additional strains was compared using a C. jejuni pan-genome microarray. Neither total nor virulence gene content predicted pathotype; nor was pathotype correlated with multilocus sequence type. Each strain was unique with regard to absences of known virulence-related loci and/or possession of point mutations and indels, including phase variation, in virulence-related genes. An experiment in C. jejuni 11168-infected germ-free mice showed that expression levels of ninety open reading frames (ORFs) were significantly up- or down-regulated in the mouse cecum at least two-fold compared to in vitro growth. Genomic content of these ninety C. jejuni 11168 ORFs was significantly correlated with the capacity to colonize and cause enteritis in C57BL/6 IL-10(-/-) mice. Differences in gene expression levels and patterns are thus an important determinant of pathotype in C. jejuni strains in this mouse model.

Laboratory work and adverse pregnancy outcomes.

BACKGROUND: Laboratory workers are commonly exposed to chemical, biological and physical agents. They also may adopt poor postures for long periods and be engaged in moving and handling. These factors may increase the risk of adverse pregnancy outcome in female laboratory workers. AIMS: To assess whether laboratory work during pregnancy increases the risk of adverse pregnancy outcomes. METHODS: The 1990-2006 Finnish Medical Birth Registry was used to identify all singleton newborns of all Finnish laboratory workers (n = 5425) and those of teachers (n = 21,438) as the reference population. The main outcomes were sexual differentiation (female gender), low birth weight, high birth weight, preterm delivery, post-term delivery, small-for-gestational age (SGA), large-for-gestational age and perinatal death. The generalized estimating equation (GEE) analysis was used to estimate odds ratios (ORs) adjusted for maternal age, parity, marital status and maternal smoking during pregnancy. RESULTS: In the GEE analysis, the risk of low birth weight (adjusted OR: 1.27, 95% CI: 1.08-1.45) and SGA (adjusted OR: 1.27, 95% CI: 1.02-1.52) was higher in laboratory workers than in teachers. Correspondingly the prevalence of high birth weight (> or = 4000 g) was lower in newborns of laboratory workers (adjusted OR: 0.90, 95% CI: 0.83-0.98). The prevalence of post-term deliveries was close to being significantly higher among newborns of laboratory workers (adjusted OR: 1.16, 95% CI: 1.00-1.31). CONCLUSIONS: This large population-based study provides evidence that laboratory work may be associated with reduced foetal growth.

Environmental enrichment influences survival rate and enhances exploration and learning but produces variable responses to the radial maze in old rats.

Wistar rats at 7 (mature), 16 (aging), and 22 (old) months of age spent 70 days in normal laboratory (Social), impoverished (Isolated) or dynamic Enrichment cages. The Enriched cage emphasized spatial re-arrangements of significant items, and the learning of new routes. Subsequently, Enriched rats at all ages entered a novel environment and escaped from a bright light with significantly shorter latencies than rats from either of the other environments. Mature, aging and some of the old Enriched rats also significantly outperformed their Isolated and Social counterparts in the radial maze. However old Enriched and Isolated animals showed significant variability in relation to the measure of the proportion reaching criterion on this task, and a significantly lower proportion than of old Social rats reached criterion. Enriched rats had a significantly higher survival rate than Social and Isolated animals. These findings are discussed in terms of learning efficiency and behaviors that conserve energy and thereby enhance survival.

Genetic background of IL-10(-/-) mice alters host-pathogen interactions with Campylobacter jejuni and influences disease phenotype.

We hypothesized that particular genetic backgrounds enhance rates of colonization, increase severity of enteritis, and allow for extraintestinal spread when inbred IL-10(-/-) mice are infected with pathogenic C. jejuni. Campylobacter jejuni stably colonized C57BL/6 and NOD mice, while congenic strains lacking IL-10 developed typhlocolitis following colonization that mimicked human campylobacteriosis. However, IL-10 deficiency alone was not necessary for the presence of C. jejuni in extraintestinal sites. C3H/HeJ tlr4(-/-) mice that specifically express the Cdcs1 allele showed colonization and limited extraintestinal spread without enteritis implicating this interval in the clinical presentation of C. jejuni infection. Furthermore, when the IL-10 gene is inactivated as in C3Bir tlr4(-/-) IL-10(-/-) mice, enteritis and intensive extraintestinal spread were observed, suggesting that clinical presentations of C. jejuni infection are controlled by a complex interplay of factors. These data demonstrate that lack of IL-10 had a greater effect on C. jejuni induced colitis than other immune elements such as TLR4 (C3H/HeJ, C3Bir IL-10(-/-)), MHC H-2g7, diabetogenic genes, and CTLA-4 (NOD) and that host genetic background is in part responsible for disease phenotype. C3Bir IL-10(-/-) mice where Cdcs1 impairs gut barrier function provide a new murine model of C. jejuni and can serve as surrogates for immunocompromised patients with extraintestinal spread.

Development of a fibre optic goniometer system to measure lumbar and hip movement to detect activities and their lumbar postures.

If sitting postures influence the risk of developing low back pain then it is important that quantification of sedentary work activities and simultaneous measurement of lumbar postural characteristics takes place. The objective of this study was to develop a system for identifying activities and their associated lumbar postures using fibre optic goniometers (FOGs). Five student subjects wore two FOGs attached to the lumbar spine and hip for 8 min while being recorded using a video camera when sitting, standing and walking. Observer Software was used to code the video recording, enabling the sagittal movement characteristics of each FOG to be described for individual activities. Results indicated that each activity produced unique data, and could be independently identified from their motion profiles by three raters (k = 1). The data will be used to develop algorithms to automate the process of activity detection. This system has the potential to measure behaviour in non-clinical settings.

C57BL/6 and congenic interleukin-10-deficient mice can serve as models of Campylobacter jejuni colonization and enteritis.

Campylobacter jejuni is a globally distributed cause of human food-borne enteritis and has been linked to chronic joint and neurological diseases. We hypothesized that C. jejuni 11168 colonizes the gastrointestinal tract of both C57BL/6 mice and congenic C57BL/6 interleukin-10-deficient (IL-10(-/-)) mice and that C57BL/6 IL-10(-/-) mice experience C. jejuni 11168-mediated clinical signs and pathology. Individually housed mice were challenged orally with C. jejuni 11168, and the course of infection was monitored by clinical examination, bacterial culture, C. jejuni-specific PCR, gross pathology, histopathology, immunohistochemistry, and anti-C. jejuni-specific serology. Ceca of C. jejuni 11168-infected mice were colonized at high rates: ceca of 50/50 wild-type mice and 168/170 IL-10(-/-) mice were colonized. In a range from 2 to 35 days after infection with C. jejuni 11168, C57BL/6 IL-10(-/-) mice developed severe typhlocolitis best evaluated at the ileocecocolic junction. Rates of colonization and enteritis did not differ between male and female mice. A dose-response experiment showed that as little as 10(6) CFU produced significant disease and pathological lesions similar to responses seen in humans. Immunohistochemical staining demonstrated C. jejuni antigens within gastrointestinal tissues of infected mice. Significant anti-C. jejuni plasma immunoglobulin levels developed by day 28 after infection in both wild-type and IL-10-deficient animals; antibodies were predominantly T-helper-cell 1 (Th1)-associated subtypes. These results indicate that the colonization of the mouse gastrointestinal tract by C. jejuni 11168 is necessary but not sufficient for the development of enteritis and that C57BL/6 IL-10(-/-) mice can serve as models for the study of C. jejuni enteritis in humans.