Meigs syndrome: a case report and literature review

No Abstrac

Advanced central nervous system imaging biomarkers in radiologically isolated syndrome: a mini review

Radiologically isolated syndrome is characterised by central nervous system white-matter hyperintensities highly suggestive of multiple sclerosis in individuals without a neurological history of clinical demyelinating episodes. It probably represents the pre-symptomatic phase of clinical multiple sclerosis but is poorly understood. This mini review summarises our current knowledge regarding advanced imaging techniques in radiologically isolated syndrome that provide insights into its pathobiology and prognosis. The imaging covered will include magnetic resonance imaging-derived markers of central nervous system volumetrics, connectivity, and the central vein sign, alongside optical coherence tomography-related metrics

Interplay of Mre11 Nuclease with Dna2 plus Sgs1 in Rad51-Dependent Recombinational Repair

The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a double-strand break, resulting in 5′ to 3′ exonuclease degradation creating a single-stranded 3′ overhang competent for strand invasion into the unbroken chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a nuclease, but it has 3′ to 5′, rather than 5′ to 3′ activity. Furthermore, mutations that inactivate only the nuclease activity of Mre11 but not its other repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests that another nuclease can catalyze 5′ to 3′ degradation. One candidate nuclease that has not been tested to date because it is encoded by an essential gene is the Dna2 helicase/nuclease. We recently reported the ability to suppress the lethality of a dna2Δ with a pif1Δ. The dna2Δ pif1Δ mutant is IR-resistant. We have determined that dna2Δ pif1Δ mre11-D56N and dna2Δ pif1Δ mre11-H125N strains are equally as sensitive to IR as mre11Δ strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out repair. The dna2Δ pif1Δ mre11-D56N triple mutant is complemented by plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase and functional nuclease, demonstrating that the nuclease of Dna2 compensates for the absence of Mre11 nuclease in IR repair, presumably in 5′ to 3′ degradation at DSB ends. We further show that sgs1Δ mre11-H125N, but not sgs1Δ, is very sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway

Are autistic traits measured equivalently in individuals with and without an Autism Spectrum Disorder?:An invariance analysis of the Autism Spectrum Quotient Short Form

It is common to administer measures of autistic traits to those without autism spectrum disorders (ASDs) with, for example, the aim of understanding autistic personality characteristics in non-autistic individuals. Little research has examined the extent to which measures of autistic traits actually measure the same traits in the same way across those with and without an ASD. We addressed this question using a multi-group confirmatory factor invariance analysis of the Autism Quotient Short Form (AQ-S: Hoekstra et al. in J Autism Dev Disord 41(5):589-596, 2011) across those with (n = 148) and without (n = 168) ASD. Metric variance (equality of factor loadings), but not scalar invariance (equality of thresholds), held suggesting that the AQ-S measures the same latent traits in both groups, but with a bias in the manner in which trait levels are estimated. We, therefore, argue that the AQ-S can be used to investigate possible causes and consequences of autistic traits in both groups separately, but caution is due when combining or comparing levels of autistic traits across the two group

Unilateral spontaneous rupture of a testicular implant thirteen years after bilateral insertion: a case report

<p>Abstract</p> <p>Introduction</p> <p>We describe a case of spontaneous, non traumatic rupture of a single artificial testis in a patient who had undergone bilateral, staged radical orchidectomy followed by prosthesis insertion. The consequences and radiological appearances of implant rupture are discussed. We believe it is the longest time interval recorded between prosthesis insertion and rupture.</p> <p>Case presentation</p> <p>A 50 year old Caucasian man presented to our outpatient department with an altered consistency in his right testicular prosthesis without any systemic symptoms or local inflammation. His left testicular prosthesis had retained its consistency since insertion.</p> <p>Conclusion</p> <p>The majority of cases reported to date have required exploration due to symptoms but we describe a case that was managed conservatively.</p

The common p.R114W <i>HNF4A </i>mutation causes a distinct clinical subtype of monogenic diabetes

HNF4A mutations cause increased birth weight, transient neonatal hypoglycaemia and maturity onset diabetes of the young (MODY). The most frequently reported HNF4A mutation is p.R114W (previously p.R127W) but functional studies have shown inconsistent results, there is lack of co-segregation in some pedigrees and an unexpectedly high frequency in public variant databases. We confirm that p.R114W is a pathogenic mutation with an odds ratio of 30.4 (95% CI: 9.79 - 125, P=2x10(-21)) for diabetes in our MODY cohort compared to controls. p.R114W heterozygotes do not have the increased birth weight of patients with other HNF4A mutations (3476g vs. 4147g, P=0.0004) and fewer patients responded to sulfonylurea treatment (48% vs. 73%, P=0.038). p.R114W has reduced penetrance; only 54% of heterozygotes developed diabetes by age 30 compared to 71% for other HNF4A mutations. We re-define p.R114W as a pathogenic mutation causing a distinct clinical subtype of HNF4A MODY with reduced penetrance, reduced sensitivity to sulfonylurea treatment and no effect on birth weight. This has implications for diabetes treatment, management of pregnancy and predictive testing of at-risk relatives. The increasing availability of large-scale sequence data is likely to reveal similar examples of rare, low-penetrance MODY mutations.</p

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Long-term safety of Mometasone Furoate administered via a dry powder inhaler in children: Results of an open-label study comparing Mometasone Furoate with Beclomethasone Dipropionate in children with persistent asthma

<p>Abstract</p> <p>Background</p> <p>To assess the long-term pediatric safety of 2 doses of mometasone furoate administered via a dry powder inhaler (MF-DPI) for mild-to-moderate persistent asthma and compare them with that of beclomethasone dipropionate administered via a metered dose inhaler (BDP-MDI) in the treatment of persistent asthma. Both MF-DPI doses tested are twice the approved pediatric dosage of 100 μg once-daily (QD) for children aged 4–11 years.</p> <p>Methods</p> <p>Children (N = 233) aged 4–11 years were randomized to 52 weeks of treatment with MF-DPI 200 μg QD AM, MF-DPI 100 μg twice daily (BID), or BDP-MDI 168 μg BID. Patients had used inhaled corticosteroids (ICSs) daily for ≥ 30 days before the screening visit and were on stable ICS doses for ≥ 2 weeks before screening. The primary safety variable was the incidence of adverse events. Secondary safety variables were laboratory tests (including cortisol concentrations), vital signs, and physical examination.</p> <p>Results</p> <p>The incidence of adverse events was similar in all 3 treatment groups. The most frequently reported adverse event was upper respiratory tract infection, reported by 47%–49% of the MF-DPI-treated patients and 51% of the BPD-treated patients. Most adverse events were considered unrelated to study drug. The most frequently reported related adverse events were headache (MF-DPI 200 μg QD AM, 8%; MF-DPI 100 μg BID, 4%; BDP-MDI 168 μg BID, 2%) and oral candidiasis (4% in each treatment group). No clinically relevant changes in laboratory values, including plasma cortisol, vital signs, or physical examinations were noted in any treatment group.</p> <p>Conclusion</p> <p>Both MF-DPI doses were well tolerated, with no unusual or unexpected adverse events or safety concerns, and had a similar adverse event profile to that of BDP-MDI 168 μg BID.</p

Cancer Incidence among Glyphosate-Exposed Pesticide Applicators in the Agricultural Health Study

Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate. We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide use and other factors was obtained from a self-administered questionnaire completed at time of enrollment (1993–1997). Among private and commercial applicators, 75.5% reported having ever used glyphosate, of which > 97% were men. In this analysis, glyphosate exposure was defined as a) ever personally mixed or applied products containing glyphosate; b) cumulative lifetime days of use, or “cumulative exposure days” (years of use × days/year); and c) intensity-weighted cumulative exposure days (years of use × days/year × estimated intensity level). Poisson regression was used to estimate exposure–response relations between glyphosate and incidence of all cancers combined and 12 relatively common cancer subtypes. Glyphosate exposure was not associated with cancer incidence overall or with most of the cancer subtypes we studied. There was a suggested association with multiple myeloma incidence that should be followed up as more cases occur in the AHS. Given the widespread use of glyphosate, future analyses of the AHS will allow further examination of long-term health effects, including less common cancers

Priming the Semantic Neighbourhood during the Attentional Blink

Background: When two targets are presented in close temporal proximity amongst a rapid serial visual stream of distractors, a period of disrupted attention and attenuated awareness lasting 200–500 ms follows identification of the first target (T1). This phenomenon is known as the ‘‘attentional blink’ ’ (AB) and is generally attributed to a failure to consolidate information in visual short-term memory due to depleted or disrupted attentional resources. Previous research has shown that items presented during the AB that fail to reach conscious awareness are still processed to relatively high levels, including the level of meaning. For example, missed word stimuli have been shown to prime later targets that are closely associated words. Although these findings have been interpreted as evidence for semantic processing during the AB, closely associated words (e.g., day-night) may also rely on specific, well-worn, lexical associative links which enhance attention to the relevant target. Methodology/Principal Findings: We used a measure of semantic distance to create prime-target pairs that are conceptually close, but have low word associations (e.g., wagon and van) and investigated priming from a distractor stimulus presented during the AB to a subsequent target (T2). The stimuli were words (concrete nouns) in Experiment 1 and the corresponding pictures of objects in Experiment 2. In both experiments, report of T2 was facilitated when this item was preceded by a semantically-related distractor