Objective:
Suicide prevention remains a challenge across communities in North America and abroad. We examine a suicide prevention effort that is widely used, termed gatekeeper training. There are 2 ...aims: review the state of the evidence on gatekeeper training for suicide prevention, and propose directions for further research.
Method:
Studies were identified by searching MEDLINE (PubMed) and PsycINFO from inception to the present for the key words suicide, suicide prevention, and gatekeeper. In addition, a manual scan of relevant articles' bibliographies was undertaken.
Results:
Gatekeeper training has been implemented and studied in many populations, including military personnel, public school staff, peer helpers, clinicians, and Aboriginal people. This type of training has been shown to positively affect the knowledge, skills, and attitudes of trainees regarding suicide prevention. Large-scale cohort studies in military personnel and physicians have reported promising results with a significant reduction in suicidal ideation, suicide attempts, and deaths by suicide.
Conclusions:
Gatekeeper training is successful at imparting knowledge, building skills, and molding the attitudes of trainees; however, more work needs to be done on longevity of these traits and referral patterns of gatekeepers. There is a need for randomized controlled trials. In addition, the unique effect of gatekeeper training on suicide rates needs to be fully elucidated.
To evaluate whether vitamin D is associated with multiple sclerosis (MS) status and disease severity in African Americans.
Serum 25-hydroxyvitamin D was compared in a cross-sectional sample of 339 ...African Americans with MS and 342 African American controls. Correlations between disease severity (Multiple Sclerosis Severity Score MSSS) and 25-hydroxyvitamin D levels were sought.
A total of 71% of controls and 77% of patients with MS were vitamin D deficient (<50 nmol/L; <20 ng/mL), and 93% of controls and 94% of patients with MS were vitamin D insufficient (<75 nmol/L; <30 ng/mL). Median unadjusted (29.7 vs 36.6 nmol/L, p = 0.0001) and deseasonalized (p = 0.0013) 25-hydroxyvitamin D levels were lower in the MS group. Multivariable analysis revealed that differences in latitude and ultraviolet index accounted for much of this association. The median (interquartile range) MSSS was 6.1 (4.8-8.1). There was no apparent association between the MSSS and vitamin D status. A greater proportion of European genetic ancestry, a measure of genetic admixture, was positively correlated with 25-hydroxyvitamin D (p = 0.007).
Levels of 25-hydroxyvitamin D were lower in African Americans with MS than controls, an observation primarily explained by differences in climate and geography. There was no apparent association between vitamin D status and disease severity. These results are consistent with observations in other populations that lower 25-hydroxyvitamin D is associated with having MS, but also highlight the importance of climate and ancestry in determining vitamin D status.
ABSTRACT
Introduction
Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerves from an autoimmune response against water channel ...aquaporin‐4 (AQP4). We report 2 patients with transient hyperCKemia associated with NMO suggesting possible skeletal muscle damage. Methods: Patient 1 was a 72‐year‐old man who presented with muscle soreness and elevated serum creatine kinase (CK) preceding an initial attack of NMO. Patient 2 was a 25‐year‐old woman with an established diagnosis of NMO who presented with diffuse myalgias, proximal upper extremity weakness, and hyperCKemia. Muscle biopsies were obtained for histopathologic evaluation, protein gel electrophoresis, immunofluorescence, and complement staining. Results: In both patients the muscle showed only mild variation in fiber diameter. There were no inflammatory changes or muscle fiber necrosis, though there was reduced AQP4 expression and deposition of activated complement. Conclusions: Complement‐mediated sarcolemmal injury may lead to hyperCKemia in NMO. Muscle Nerve 50: 859–862, 2014
To characterize nuclear and mitochondrial DNA (mtDNA) in spent culture media from normally developing blastocysts to determine whether it could be used for noninvasive genetic assessment.
Prospective ...embryo cohort study.
Academic center and private in vitro fertilization (IVF) clinic.
Seventy patients undergoing intracytoplasmic sperm injection (ICSI) and 227 blastocysts.
Culture media assessment, artificial blastocoele fluid collapse and DNA analysis using digital polymerase chain reaction (dPCR), long-range PCR, quantitative PCR (qPCR), and DNA fingerprinting.
Presence of nuclear and mtDNA in three different commercial culture media from Vitrolife and Irvine Scientific, spent embryo media assessment at the cleavage and blastocyst stages of development, and analysis of the internal media controls for each patient that had been exposed to identical conditions as embryo media but did not come into contact with embryos.
Higher levels of nuclear and mtDNA were observed in the culture media that had been exposed to embryos compared with the internal media controls. Nuclear DNA (∼4 copies) and mtDNA (∼600 copies) could be detected in spent media, and the levels increased at the blastocyst stage. No increase in DNA was detected after artificial blastocoele fluid collapse. Mixed sex chromosome DNA was detected. This originated from contamination in the culture media and from maternal (cumulus) cells. Due to the limited amount of template, the presence of embryonic nuclear DNA could not be confirmed by DNA fingerprinting analysis.
Currently DNA from culture media cannot be used for genetic assessment because embryo-associated structures release DNA into the culture medium and the DNA is of mixed origin.
Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised ...extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis.
We did this single-centre, 150-day, double-blind, randomised, placebo-controlled, crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients who fulfilled international panel criteria for diagnosis with disease duration of less than 15 years were eligible. Patients were randomly assigned (1:1) via block randomisation using a random number generator to receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for 60 days (group 2). The primary outcome was shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked potentials. We analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02040298.
Between Jan 1, 2014, and April 11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25). All patients completed the study. The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5–2·9; p=0·0048) when analysing the trial as a crossover. Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported.
To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage.
University of California, San Francisco and the Rachleff Family.
Mutations in mitochondrial DNA (mtDNA) are a common cause of genetic disease. Pathogenic mutations in mtDNA are detected in approximately 1 in 250 live births and at least 1 in 10,000 adults in the ...UK are affected by mtDNA disease. Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. Mitochondrial DNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach for the prevention of transmission of human mtDNA disease. Here we show that transfer of pronuclei between abnormally fertilized human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimizing the procedure we found the average level of carry-over after transfer of two pronuclei is less than 2.0%, with many of the embryos containing no detectable donor mtDNA. We believe that pronuclear transfer between zygotes, as well as the recently described metaphase II spindle transfer, has the potential to prevent the transmission of mtDNA disease in humans.
cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS ...tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT‐NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles—relating to classification categories, approaches to classification, nomenclature, and grading—that the group hopes will also inform the future classification of CNS neoplasms.
Abstract Nanoparticle tracking analysis (NTA) is commonly used to count and size nano-sized particles. A sample loading pump can be used to analyse a larger sample volume, but it is unclear whether ...accuracy is affected. Using a NanoSight NS300 with the manufacturer-supplied pump, we examined synthetic silica and latex microspheres, liposomes and placental extracellular vesicles at different flow speeds. Analysis at flow speeds of 20 or 50 significantly reduced the measured concentration and mean/modal size of particles, particularly for mono-dispersed samples. We identify sample flow speed as a crucial instrument setting which should be reported in all studies that use NTA.
Key points
Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes.
We ...demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight‐specific basis.
Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep.
Among all fetuses, blood O2 saturation and plasma glucose, insulin and insulin‐like growth factor‐1 were positively associated and norepinephrine was negatively associated with hindlimb weight.
These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion.
Reduced skeletal muscle mass in the fetus with intrauterine growth restriction (IUGR) persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake and protein accretion rates in skeletal muscle, late gestation control (CON) (n = 8) and IUGR (n = 13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate and fractional synthetic rate were lower in IUGR compared to CON (P < 0.05). Absolute hindlimb blood flow was reduced in IUGR (IUGR: 32.9 ± 5.6 ml min−1; CON: 60.9 ± 6.5 ml min−1; P < 0.005), although flow normalized to hindlimb weight was similar between groups. Hindlimb oxygen consumption rate was lower in IUGR (IUGR: 10.4 ± 1.4 μmol min−1 100 g−1; CON: 14.7 ± 1.3 μmol min−1 100 g−1; P < 0.05). Hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was lower in IUGR (IUGR: 1.3 ± 0.5 μmol min−1 100 g−1; CON: 2.9 ± 0.2 μmol min−1 100 g−1; P < 0.05). Blood O2 saturation (r2 = 0.80, P < 0.0001) and plasma glucose (r2 = 0.68, P < 0.0001), insulin (r2 = 0.40, P < 0.005) and insulin‐like growth factor (IGF)‐1 (r2 = 0.80, P < 0.0001) were positively associated and norepinephrine (r2 = 0.59, P < 0.0001) was negatively associated with hindlimb weight. Slower hindlimb linear growth and muscle protein synthesis rates match reduced hindlimb blood flow and oxygen consumption rates in the IUGR fetus. Metabolic adaptations to slow hindlimb growth are probably hormonally‐mediated by mechanisms that include increased fetal norepinephrine and reduced IGF‐1 and insulin.
Key points
Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes.
We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight‐specific basis.
Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep.
Among all fetuses, blood O2 saturation and plasma glucose, insulin and insulin‐like growth factor‐1 were positively associated and norepinephrine was negatively associated with hindlimb weight.
These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion.
The development of polyaniline (PANI)/biomaterial composites as humidity sensor materials represents an emerging area of advanced materials with promising applications. The increasing attention to ...biopolymer materials as desiccants for humidity sensor components can be explained by their sustainability and propensity to absorb water. This review represents a literature survey, covering the last decade, which is focused on the interrelationship between the core properties and moisture responsiveness of multicomponent polymer/biomaterial composites. This contribution provides an overview of humidity-sensing materials and the corresponding sensors that emphasize the resistive (impedance) type of PANI devices. The key physicochemical properties that affect moisture sensitivity include the following: swelling, water vapor adsorption capacity, porosity, electrical conductivity, and enthalpies of adsorption and vaporization. Some key features of humidity-sensing materials involve the response time, recovery time, and hysteresis error. This work presents a discussion on various types of humidity-responsive composite materials that contain PANI and biopolymers, such as cellulose, chitosan and structurally related systems, along with a brief overview of carbonaceous and ceramic materials. The effect of additive components, such as polyvinyl alcohol (PVA), for film fabrication and their adsorption properties are also discussed. The mechanisms of hydration and proton transfer, as well as the relationship with conductivity is discussed. The literature survey on hydration reveals that the textural properties (surface area and pore structure) of a material, along with the hydrophile-lipophile balance (HLB) play a crucial role. The role of HLB is important in PANI/biopolymer materials for understanding hydration phenomena and hydrophobic effects. Fundamental aspects of hydration studies that are relevant to humidity sensor materials are reviewed. The experimental design of humidity sensor materials is described, and their relevant physicochemical characterization methods are covered, along with some perspectives on future directions in research on PANI-based humidity sensors.
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