Sarcoidosis of the hypothalamus and pituitary stalk

We report a rare case of sarcoidosis of the hypothalamic and suprasellar region, with clinical course and the magnetic resonance imaging follow-up

A Compromise between Neutrino Masses and Collider Signatures in the Type-II Seesaw Model

A natural extension of the standard $SU(2)_{\rm L} \times U(1)_{\rm Y}$ gauge model to accommodate massive neutrinos is to introduce one Higgs triplet and three right-handed Majorana neutrinos, leading to a $6\times 6$ neutrino mass matrix which contains three $3\times 3$ sub-matrices $M_{\rm L}$, $M_{\rm D}$ and $M_{\rm R}$. We show that three light Majorana neutrinos (i.e., the mass eigenstates of $\nu_e$, $\nu_\mu$ and $\nu_\tau$) are exactly massless in this model, if and only if $M_{\rm L} = M_{\rm D} M_{\rm R}^{-1} M_{\rm D}^T$ exactly holds. This no-go theorem implies that small but non-vanishing neutrino masses may result from a significant but incomplete cancellation between $M_{\rm L}$ and $M_{\rm D} M_{\rm R}^{-1} M_{\rm D}^T$ terms in the Type-II seesaw formula, provided three right-handed Majorana neutrinos are of ${\cal O}(1)$ TeV and experimentally detectable at the LHC. We propose three simple Type-II seesaw scenarios with the $A_4 \times U(1)_{\rm X}$ flavor symmetry to interpret the observed neutrino mass spectrum and neutrino mixing pattern. Such a TeV-scale neutrino model can be tested in two complementary ways: (1) searching for possible collider signatures of lepton number violation induced by the right-handed Majorana neutrinos and doubly-charged Higgs particles; and (2) searching for possible consequences of unitarity violation of the $3\times 3$ neutrino mixing matrix in the future long-baseline neutrino oscillation experiments.Comment: RevTeX 19 pages, no figure

An epidemiologic study of early biologic effects of benzene in Chinese workers.

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans

Anisotropic Radial Layout for Visualizing Centrality and Structure in Graphs

This paper presents a novel method for layout of undirected graphs, where nodes (vertices) are constrained to lie on a set of nested, simple, closed curves. Such a layout is useful to simultaneously display the structural centrality and vertex distance information for graphs in many domains, including social networks. Closed curves are a more general constraint than the previously proposed circles, and afford our method more flexibility to preserve vertex relationships compared to existing radial layout methods. The proposed approach modifies the multidimensional scaling (MDS) stress to include the estimation of a vertex depth or centrality field as well as a term that penalizes discord between structural centrality of vertices and their alignment with this carefully estimated field. We also propose a visualization strategy for the proposed layout and demonstrate its effectiveness using three social network datasets.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

Altered stress hormone response following acute exercise during prostate cancer treatment

Exercise training reduces the side effects of cancer treatments; however, the stress hormone response to acute exercise during prostate cancer (PCa) treatment is unclear. The study purpose was to examine the effects of acute exercise on circulating cortisol, epinephrine (Epi), and norepinephrine (NE) concentrations during PCa treatment with and without androgen deprivation therapy (ADT). Men with PCa (n = 11), with PCa on ADT (n = 11), and with non-cancer controls (n = 8) had blood samples for stress hormones collected before and immediately (0 hour), 2 hours, and 24 hours after 45 minutes of intermittent cycling at 60% of peak wattage. NE increased by 385% (P < .001) at 0 hour and remained elevated at 2 hours (P < .05) with no group differences. Overall, cortisol significantly increased at 0 hour (36%, P < .012) and then significantly decreased below baseline at 2 hours (-24%, P < .001) before returning to resting levels at 24 hours. Cortisol levels during ADT were 32% lower than PCa (P = .006) with no differences vs controls. Epi increased immediately after exercise more in controls (817%, P < .001) than with ADT (700%) and PCa (333%) patients, and both cancer groups' absolute levels were attenuated relative to controls (ADT: -54%, PCa: -52%, P = .004). Compared with age-matched controls, PCa and ADT patients exhibited similar stress hormone responses with acute exercise for NE and cortisol but an attenuated EPI response that suggests altered adrenal function. Future studies should examine the physical stress of multiple exercise bouts to verify these findings and to explore the functional hormonal effects, such as immune and metabolic responses, during cancer treatment

Association between the mood stabilizing treatment of bipolar disorder and risk of suicide attempts: A self-controlled case series study

Bipolar disorder (BPD) is associated with high rates of suicide attempts but the anti-suicidal effect of mood stabilizing agents remains unclear. This study aimed to examine the association between mood stabilizing agents (lithium, valproate, lamotrigine, carbamazepine or antipsychotics) and risk of suicide attempts in patients with BPD using self-controlled case series study design. Among 14,087 patients with BPD who received mood stabilizing agents from 2001 to 2020 in Hong Kong, 1316 patients had at least one suicide attempts during the observation period. An increased risk of suicide attempts was observed 14 days before treatment initiation compared to non-exposed period. Following treatment initiation, an increased risk with smaller magnitude was found with the use of mood stabilizing agents. A lower risk was observed with lithium and antiepileptics while the risk remained attenuated with decreasing magnitude with antipsychotics. During 30-day post-treatment period, the risk was elevated. Therefore, this study suggests that use of mood stabilizing agents is not causally associated with an increased risk of suicide attempts. Indeed, there are potential protective effects of lithium and antiepileptics against suicide attempts. Assiduous monitoring of symptoms relapse and warning signs of suicide should be part of the management plan and discussed between clinicians, caregivers and patients

Toxicity of Three Insecticides to Lysiphlebus fabarum, a Parasitoid of the Black Bean Aphid, Aphis fabae

The toxicity of three insecticides to Lysiphlebus fabarum (Marshall) (Hymenoptera: Braconidae: Aphidiinae), a parasitoid of Aphis fabae Scopoli (Hemiptera: Aphididae), was investigated using IOBC/wprs protocols. Abamectin 1.8 EC, imidacloprid 350 SC, and pymetrozine 25 WP were tested under laboratory conditions at recommended field rates. Immature stages of the parasitoid were exposed to materials by briefly dipping mummified aphids into insecticide solutions/suspensions or water (controls). Abamectin, imidacloprid, and pymetrozine caused 44.8, 58.5, and 14.5% mortality of mummies, respectively. Insecticides were also applied to broad bean foliage until run-off using a hand sprayer and the contact toxicity of residues was investigated after 1, 5, 16 and 30 day periods of outdoor weathering by caging adult wasps on treated plants for 24 h. One day-old residues of abamectin, imidacloprid, and pymetrozine produced 52.5, 90.0 and 57.0% mortality, respectively, and 5 day-old residues produced 28.1, 77.0 and 18.6% mortality. Sixteen day-old residues produced 8.8, 22.4 and 13.6% mortality, whereas 30 day-old residues produced 0.0, 3.2 and 1.1% mortality, respectively. On the basis of these results, abamectin and pymetrozine were classified as short-lived compounds (Class A) and imidacloprid as a slightly persistent compound (Class B)

Rationale, design and methods of the Study of Work and Pain (SWAP): a cluster randomised controlled trial testing the addition of a vocational advice service to best current primary care for patients with musculoskeletal pain (ISRCTN 52269669)

Background Musculoskeletal pain is a major contributor to short and long term work absence. Patients seek care from their general practitioner (GP) and yet GPs often feel ill-equipped to deal with work issues. Providing a vocational case management service in primary care, to support patients with musculoskeletal problems to remain at or return to work, is one potential solution but requires robust evaluation to test clinical and cost-effectiveness. Methods/Design This protocol describes a cluster randomised controlled trial, with linked qualitative interviews, to investigate the effect of introducing a vocational advice service into general practice, to provide a structured approach to managing work related issues in primary care patients with musculoskeletal pain who are absent from work or struggling to remain in work. General practices (n = 6) will be randomised to offer best current care or best current care plus a vocational advice service. Adults of working age who are absent from or struggling to remain in work due to a musculoskeletal pain problem will be invited to participate and 330 participants will be recruited. Data collection will be through patient completed questionnaires at baseline, 4 and 12 months. The primary outcome is self-reported work absence at 4 months. Incremental cost-utility analysis will be undertaken to calculate the cost per additional QALY gained and incremental net benefits. A linked interview study will explore the experiences of the vocational advice service from the perspectives of GPs, nurse practitioners (NPs), patients and vocational advisors. Discussion This paper presents the rationale, design, and methods of the Study of Work And Pain (SWAP) trial. The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for musculoskeletal pain patients with work-related issues. Trial registration Current Controlled Trials ISRCTN52269669

Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps

Peer reviewedPublisher PD

Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP)

BACKGROUND: Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. The intravenous (IV) N-acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively unchanged. This involves 3 different infusion regimens (dose and time) lasting over 20 hours. The same weight-related dose of NAC is used irrespective of paracetamol dose. Complications include frequent nausea and vomiting, anaphylactoid reactions and dosing errors. We designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard NAC and a modified, shorter, regimen. METHODS/DESIGN: We designed a double-blind trial using a 2 × 2 factorial design involving four parallel groups. Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was stratified on: paracetamol dose, perceived risk factors, and time to presentation. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions and end of treatment liver function documented. Where clinically necessary further doses of NAC were administered as per standard UK protocols at the end of the first antidote course. DISCUSSION: This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first attempt to formally examine new methods of administering IV NAC in paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new NAC regimen. In addition as anaphylactoid response appears related to plasma concentrations of both NAC and paracetamol anaphylactoid reactions should be less likely. This study is not powered to assess the relative efficacy of the two NAC regimens, however it will give useful information to power future studies. As the first formal randomised clinical trial in this patient group in over 30 years this study will also provide information to support further studies in patients in paracetamol overdose, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk. TRIAL REGISTRATION: EudraCT number 2009-017800-10, ClinicalTrials.gov IdentifierNCT0105027