Defining dormancy in mycobacterial disease.

Tuberculosis remains a threat to global health and recent attempts to shorten therapy have not succeeded mainly due to cases of clinical relapse. This has focussed attention on the importance of "dormancy" in tuberculosis. There are a number of different definitions of the term and a similar multiplicity of different in vitro and in vivo models. The danger with this is the implicit assumption of equivalence between the terms and models, which will make even more difficult to unravel this complex conundrum. In this review we summarise the main models and definitions and their impact on susceptibility of Mycobacterium tuberculosis. We also suggest a potential nomenclature for debate. Dormancy researchers agree that factors underpinning this phenomenon are complex and nuanced. If we are to make progress we must agree the terms to be used and be consistent in using them

Geometry of the Intervertebral Volume and Vertebral Endplates of the Human Spine

Replacement of a degenerated vertebral disc with an artificial intervertebral disc (AID) is currently possible, but poses problems, mainly in the force distribution through the vertebral column. Data on the intervertebral disc space geometry will provide a better fit of the prosthesis to the vertebrae, but current literature on vertebral disc geometry is very scarce or not suitable. In this study, existing CT-scans of 77 patients were analyzed to measure the intervertebral disc and vertebral endplate geometry of the lumbar spine. Ten adjacent points on both sides of the vertebrae (S1-superior to T12-inferior) and sagittal and transverse diameters were measured to describe the shape of the caudal and cranial vertebral planes of the vertebrae. It was found that the largest endplate depth is located in the middle or posterior regions of the vertebra, that there is a linear relationship between all inferior endplate depths and the endplate location (p < 0.0001) within the spinal column, and that the superior endplate depth increases with age by about 0.01 mm per year (p < 0.02). The wedge angle increases from T12-L1 to L5-S1. The results allow for improvement of the fit of intervertebral disc-prostheses to the vertebrae and optimized force transmission through the vertebral column

Dyspraxia and autistic traits in adults with and without autism spectrum conditions

BACKGROUND: Autism spectrum conditions (ASC) are frequently associated with motor coordination difficulties. However, no studies have explored the prevalence of dyspraxia in a large sample of individuals with and without ASC or associations between dyspraxia and autistic traits in these individuals. METHODS: Two thousand eight hundred seventy-one adults (with ASC) and 10,706 controls (without ASC) self-reported whether they have been diagnosed with dyspraxia. A subsample of participants then completed the Autism Spectrum Quotient (AQ; 1237 ASC and 6765 controls) and the Empathy Quotient (EQ; 1147 ASC and 6129 controls) online through the Autism Research Centre website. The prevalence of dyspraxia was compared between those with and without ASC. AQ and EQ scores were compared across the four groups: (1) adults with ASC with dyspraxia, (2) adults with ASC without dyspraxia, (3) controls with dyspraxia, and (4) controls without dyspraxia. RESULTS: Adults with ASC were significantly more likely to report a diagnosis of dyspraxia (6.9%) than those without ASC (0.8%). In the ASC group, those with co-morbid diagnosis of dyspraxia did not have significantly different AQ or EQ scores than those without co-morbid dyspraxia. However, in the control group (without ASC), those with dyspraxia had significantly higher AQ and lower EQ scores than those without dyspraxia. CONCLUSIONS: Dyspraxia is significantly more prevalent in adults with ASC compared to controls, confirming reports that motor coordination difficulties are significantly more common in this group. Interestingly, in the general population, dyspraxia was associated with significantly higher autistic traits and lower empathy. These results suggest that motor coordination skills are important for effective social skills and empathy

Antenatal risk factors for peanut allergy in children

<p>Abstract</p> <p>Background</p> <p>Prenatal factors may contribute to the development of peanut allergy. We evaluated the risk of childhood peanut allergy in association with pregnancy exposure to Rh immune globulin, folic acid and ingestion of peanut-containing foods.</p> <p>Methods</p> <p>We conducted a web-based case-control survey using the Anaphylaxis Canada Registry, a pre-existing database of persons with a history of anaphylaxis. A total of 1300 case children with reported peanut allergy were compared to 113 control children with shellfish allergy. All were evaluated for maternal exposure in pregnancy to Rh immune globulin and folic acid tablet supplements, as well as maternal avoidance of dietary peanut intake in pregnancy.</p> <p>Results</p> <p>Receipt of Rh immune globulin in pregnancy was not associated with a higher risk of peanut allergy (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.51 to 1.45), nor was initiation of folic acid tablet supplements before or after conception (OR 0.53, 95% CI 0.19 to 1.48). Complete avoidance of peanut-containing products in pregnancy was associated with a non-significantly lower risk of peanut allergy (OR 0.53, 95% CI 0.27 to 1.03).</p> <p>Conclusion</p> <p>The risk of childhood peanut allergy was not modified by the following common maternal exposures in pregnancy: Rh immune globulin, folic acid or peanut-containing foods.</p> <p>Clinical implications</p> <p>Rh immune globulin, folic acid supplement use and peanut avoidance in pregnancy have yet to be proven to modulate the risk of childhood anaphylaxis to peanuts.</p> <p>Capsule Summary</p> <p>Identification of prenatal factors that contribute to peanut allergy might allow for prevention of this life-threatening condition. This article explores the role of three such factors.</p

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

A pilot Internet "Value of Health" Panel: recruitment, participation and compliance

Objectives To pilot using a panel of members of the public to provide preference data via the Internet Methods A stratified random sample of members of the general public was recruited and familiarised with the standard gamble procedure using an Internet based tool. Health states were perdiodically presented in "sets" corresponding to different conditions, during the study. The following were described: Recruitment (proportion of people approached who were trained); Participation (a) the proportion of people trained who provided any preferences and (b) the proportion of panel members who contributed to each "set" of values; and Compliance (the proportion, per participant, of preference tasks which were completed). The influence of covariates on these outcomes was investigated using univariate and multivariate analyses. Results A panel of 112 people was recruited. 23% of those approached (n = 5,320) responded to the invitation, and 24% of respondents (n = 1,215) were willing to participate (net = 5.5%). However, eventual recruitment rates, following training, were low (2.1% of those approached). Recruitment from areas of high socioeconomic deprivation and among ethnic minority communities was low. Eighteen sets of health state descriptions were considered over 14 months. 74% of panel members carried out at least one valuation task. People from areas of higher socioeconomic deprivation and unmarried people were less likely to participate. An average of 41% of panel members expressed preferences on each set of descriptions. Compliance ranged from 3% to 100%. Conclusion It is feasible to establish a panel of members of the general public to express preferences on a wide range of health state descriptions using the Internet, although differential recruitment and attrition are important challenges. Particular attention to recruitment and retention in areas of high socioeconomic deprivation and among ethnic minority communities is necessary. Nevertheless, the panel approach to preference measurement using the Internet offers the potential to provide specific utility data in a responsive manner for use in economic evaluations and to address some of the outstanding methodological uncertainties in this field

Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study.

PURPOSE: Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION). The purpose of this study was to examine the prevalence of ODD in young patients with NA-AION. DESIGN: Retrospective, cross-sectional multicenter study. METHODS: All patients with NA-AION 50 years old or younger, seen in neuro-ophthalmology clinics of the international ODDS (Optic Disc Drusen Studies) Consortium between April 1, 2017, and March 31, 2019, were identified. Patients were included if ODD were diagnosed by any method, or if ODD were excluded by enhanced-depth imaging optical coherence tomography (EDI-OCT) using ODDS Consortium guidelines. NA-AION eyes with ODD were termed "ODD-AION"; those without were termed "NODD-AION". RESULTS: A total of 65 patients (127 eyes) with NA-AION were included (mean 41 years old). Of the 74 eyes with NA-AION, 51% had ODD-AION, whereas 43% of fellow eyes without NA-AION had ODD (P = .36). No significant differences were found between ODD-AION and NODD-AION eyes in terms of Snellen best-corrected VA or perimetric mean deviation. According to EDI-OCT results, 28% of eyes with NODD-AION had peripapillary hyperreflective ovoid mass-like structures (PHOMS); 7% had hyperreflective lines, whereas 54% with ODD-AION had PHOMS; and 66% had hyperreflective lines (P = .006 and P < .001, respectively). CONCLUSIONS: Most of these young NA-AION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NA-AION, at least in younger patients. This study suggests ODD-AION be recognized as a novel diagnosis

Immune Response and Mitochondrial Metabolism Are Commonly Deregulated in DMD and Aging Skeletal Muscle

Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors

The multiphase gas structure and kinematics in the circumnuclear region of NGC 5728

We report on our combined analysis of HST, VLT/MUSE, VLT/SINFONI, and ALMA observations of the local Seyfert 2 galaxy, NGC 5728 to investigate in detail the feeding and feedback of the active galactic nucleus (AGN). The data sets simultaneously probe the morphology, excitation, and kinematics of the stars, ionized gas, and molecular gas over a large range of spatial scales (10 pc to 10 kpc). NGC 5728 contains a large stellar bar that is driving gas along prominent dust lanes to the inner 1 kpc where the gas settles into a circumnuclear ring. The ring is strongly star forming and contains a substantial population of young stars as indicated by the lowered stellar velocity dispersion and gas excitation consistent with H II regions. We model the kinematics of the ring using the velocity field of the CO (2–1) emission and stars and find it is consistent with a rotating disc. The outer regions of the disc, where the dust lanes meet the ring, show signatures of inflow at a rate of 1 M⊙ yr−1. Inside the ring, we observe three molecular gas components corresponding to the circular rotation of the outer ring, a warped disc, and the nuclear stellar bar. The AGN is driving an ionized gas outflow that reaches a radius of 250 pc with a mass outflow rate of 0.08 M⊙ yr−1 consistent with its luminosity and scaling relations from previous studies. While we observe distinct holes in CO emission which could be signs of molecular gas removal, we find that largely the AGN is not disrupting the structure of the circumnuclear region

Mnesic imbalance: a cognitive theory about autism spectrum disorders

Autism is characterized by impairments in social interaction, communicative capacity and behavioral flexibility. Some cognitive theories can be useful for finding a relationship between these irregularities and the biological mechanisms that may give rise to this disorder. Among such theories are mentalizing deficit, weak central coherence and executive dysfunction, but none of them has been able to explain all three diagnostic symptoms of autism. These cognitive disorders may be related among themselves by faulty learning, since several research studies have shown that the brains of autistic individuals have abnormalities in the cerebellum, which plays a role in procedural learning. In keeping with this view, one may postulate the possibility that declarative memory replaces faulty procedural memory in some of its functions, which implies making conscious efforts in order to perform actions that are normally automatic. This may disturb cognitive development, resulting in autism symptoms. Furthermore, this mnesic imbalance is probably involved in all autism spectrum disorders. In the present work, this theory is expounded, including preliminary supporting evidence