Understanding Protective Factors for Men at Risk of Suicide Using the CHIME Framework: The Primacy of Relational Connectedness

Suicide is a global problem, ranking among the leading causes of death in many countries across the world. Most people who die by suicide are “under the radar”, having never seen a mental health professional or been diagnosed with a mental illness. This article describes the protective factors for men experiencing suicidal thoughts, plans, and/or attempts who are “under the radar”. Using in-depth qualitative interviews, we aimed to understand stakeholder perspectives on the protective factors that influence men’s wellbeing. The pervasiveness of relational connectedness in men’s narratives was identified as a central protective factor. Other key protective factors included meaningful activity, empowerment, and hope. These results have the potential to facilitate the development of focused community initiatives. More generally, the current research offers an example of a qualitative inquiry into men’s wellbeing that focuses on strengths and positive factors in their lives and may provide a guide for future community-based suicide prevention research

Structure Determination Feasibility of Three-Dimensional Electron Diffraction in Case of Limited Data

During the last two decades, three-dimensional electron diffraction (3D ED) has undergone a renaissance, starting with the introduction of precession (Precession Electron Diffraction Tomography, PEDT) that led to variations on the idea of collecting as much of the diffraction space as possible in order to solve crystal structures from sub-micron sized crystals. The most popular of these acquisition methods is based on the continuous tilting/rotation of the crystal (so-called Microcrystal Electron Diffraction, MicroED) akin to the oscillating crystal method in X-ray crystallography, which was enabled by the increase of sensitivity and acquisition speed in electron detectors. While 3D ED data is more complex than the equivalent X-ray data due to the higher proportion of dynamical scattering, the same basic principles of what is required in terms of data quality and quantity in order to solve a crystal structure apply; high completeness, high data resolution and good signal-to-noise statistics on measured reflection intensities. However, it may not always be possible to collect data in these optimum conditions, the most common limitations being the tilt range of the goniometer stage, often due to a small pole piece gap or the use of a non-tomography holder, or the position of the sample on the TEM grid, which may be too close to a grid bar and then the specimen of interest becomes occluded during tilting. Other factors that can limit the quality of the acquired data include the limited dynamic range of the detector, which can result on truncated intensities, or the sensitivity of the crystal to the electron beam, whereby the crystallinity of the particle is changing under the illumination of the beam. This limits the quality and quantity of the measured intensities and makes structure analysis of such data challenging. Under these circumstances, traditional approaches may fail to elucidate crystal structures, and global optimization methods may be used here as an alternative powerful tool. In this context, this work presents a systematic study on the application of a global optimization method to crystal structure determination from 3D ED data. The results are compared with known structure models and crystal phases obtained from traditional ab initio structure solution methods demonstrating how this strategy can be reliably applied to the analysis of partially complete 3D ED data

Reliable Characterization of Organic & Pharmaceutical Compounds with High Resolution Monochromated EEL Spectroscopy

Organic and biological compounds (especially those related to the pharmaceutical industry) have always been of great interest for researchers due to their importance for the development of new drugs to diagnose, cure, treat or prevent disease. As many new API (active pharmaceutical ingredients) and their polymorphs are in nanocrystalline or in amorphous form blended with amorphous polymeric matrix (known as amorphous solid dispersion-ASD), their structural identification and characterization at nm scale with conventional X-Ray/Raman/IR techniques becomes difficult. During any API synthesis/production or in the formulated drug product, impurities must be identified and characterized. Electron energy loss spectroscopy (EELS) at high energy resolution by transmission electron microscope (TEM) is expected to be a promising technique to screen and identify the different (organic) compounds used in a typical pharmaceutical or biological system and to detect any impurities present, if any, during the synthesis or formulation process. In this work, we propose the use of monochromated TEM-EELS, to analyze selected peptides and organic compounds and their polymorphs. In order to validate EELS for fingerprinting (in low loss/optical region) and by further correlation with advanced DFT, simulations were utilized

Novel characterization techniques for cultural heritage using a TEM orientation imaging in combination with 3D precession diffraction tomography: a case study of green and white ancient Roman glass tesserae

We present new transmission electron microscopy (TEM) based electron diffraction characterization techniques (orientation imaging combined with 3D precession electron diffraction tomography-ADT) applied on cultural heritage materials. We have determined precisely unit cell parameters, crystal symmetry, atomic structure, and orientation/phase mapping of various pigment/opacifier crystallites at nm scale which are present in green and white Roman glass tesserae. Such TEM techniques can be an alternative to Synchrotron based techniques, and allow to distinguish accurately at nm scale between different crystal structures even in cases of same/very close chemical composition, where is also possible to visualize between different crystal orientations and amorphous/crystalline phases. This study additionally demonstrates that although opacifiers in green and white tesserae are found to have average Pb2Sb2O7 cubic and CaSb2O6 trigonal structures, their pyrochlore related framework can host many other elements like Cu, Ca, Fe through ionic exchanges at high firing temperatures which in turn may also contribute to the tesserae colour appearance

Visualization of acetylcholine distribution in central nervous system tissue sections by tandem imaging mass spectrometry

Metabolite distribution imaging via imaging mass spectrometry (IMS) is an increasingly utilized tool in the field of neurochemistry. As most previous IMS studies analyzed the relative abundances of larger metabolite species, it is important to expand its application to smaller molecules, such as neurotransmitters. This study aimed to develop an IMS application to visualize neurotransmitter distribution in central nervous system tissue sections. Here, we raise two technical problems that must be resolved to achieve neurotransmitter imaging: (1) the lower concentrations of bioactive molecules, compared with those of membrane lipids, require higher sensitivity and/or signal-to-noise (S/N) ratios in signal detection, and (2) the molecular turnover of the neurotransmitters is rapid; thus, tissue preparation procedures should be performed carefully to minimize postmortem changes. We first evaluated intrinsic sensitivity and matrix interference using Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometry (MS) to detect six neurotransmitters and chose acetylcholine (ACh) as a model for study. Next, we examined both single MS imaging and MS/MS imaging for ACh and found that via an ion transition from m/z 146 to m/z 87 in MS/MS imaging, ACh could be visualized with a high S/N ratio. Furthermore, we found that in situ freezing method of brain samples improved IMS data quality in terms of the number of effective pixels and the image contrast (i.e., the sensitivity and dynamic range). Therefore, by addressing the aforementioned problems, we demonstrated the tissue distribution of ACh, the most suitable molecular specimen for positive ion detection by IMS, to reveal its localization in central nervous system tissues

The effect of different skin-ankle brace application pressures on quiet single-limb balance and electromyographic activation onset of lower limb muscles

<p>Abstract</p> <p>Background</p> <p>Several studies have been carried out in order to investigate the effect of ankle bracing on ankle joint function and performance. However, no study so far has examined the role of skin-brace interface pressure in neuromuscular control. The aim of this study was to investigate the effect of different skin-ankle brace interface pressures on quiet single limb balance and the electromyographic (EMG) activation sequence of four lower limb muscles.</p> <p>Methods</p> <p>Thirty three male physical education students who volunteered to take part in the study were measured under three ankle brace conditions: i) without brace, ii) with brace and 30 kPa application pressure and iii) with brace and 60 kPa application pressure. Single limb balance (anteroposterior and mediolateral parameter) was assessed on the dominant lower limb, with open and closed eyes, on a force platform, simultaneously with the EMG recording of four lower lower limb muscles' (gastrocnemius, peroneus longus, rectus femoris and biceps femoris) activation onset.</p> <p>Results</p> <p>The results showed that overall balance (total stability parameter) was not significantly affected in any of the three ankle brace conditions. However, the anteroposterior centre of pressure excursion and centre of pressure excursion velocity were significantly increased with the application of ankle brace, both with 30 and 60 kPa application pressures. Furthermore, it was found that single limb balance was significantly worse with closed eyes compared to open eyes. EMG measurements showed that the sequence of lower limb activation onset was not affected in any of the three ankle brace application conditions. The results of this study showed that the application of an ankle brace with two different skin-brace interface pressures had no effect on overall single limb balance and the sequence of lower limb muscle activation.</p> <p>Conclusion</p> <p>These findings suggest that peripheral joint receptors are either not adequately stimulated by the brace application and therefore are not able to alter the balance control strategy of the CNS, or that they play a less important role in the control of single limb balance. Further research is needed in this area with more dynamic and functional measurements, before the safe use of ankle bracing can be widely recommended.</p

Musculotopic organization of the motor neurons supplying the mouse hindlimb muscles: a quantitative study using Fluoro-Gold retrograde tracing

We have mapped the motor neurons (MNs) supplying the major hindlimb muscles of transgenic (C57/BL6J-ChAT-EGFP) and wild-type (C57/BL6J) mice. The fluorescent retrograde tracer Fluoro-Gold was injected into 19 hindlimb muscles. Consecutive transverse spinal cord sections were harvested, the MNs counted, and the MN columns reconstructed in 3D. Three longitudinal MN columns were identified. The dorsolateral column extends from L4 to L6 and consists of MNs innervating the crural muscles and the foot. The ventrolateral column extends from L1 to L6 and accommodates MNs supplying the iliopsoas, gluteal, and quadriceps femoris muscles. The middle part of the ventral horn hosts the central MN column, which extends between L2–L6 and consists of MNs for the thigh adductor, hamstring, and quadratus femoris muscles. Within these longitudinal columns, the arrangement of the different MN groups reflects their somatotopic organization. MNs innervating muscles developing from the dorsal (e.g., quadriceps) and ventral muscle mass (e.g., hamstring) are situated in the lateral and medial part of the ventral gray, respectively.MN pools belonging to proximal muscles (e.g., quadratus femoris and iliopsoas) are situatedventral to those supplying more distal ones (e.g., plantar muscles). Finally, MNs innervatingflexors (e.g., posterior crural muscles) are more medial than those belonging to extensors ofthe same joint (e.g., anterior crural muscles). These data extend and modify the MN maps in the recently published atlas of the mouse spinal cord and may help when assessing neuronal loss associated with MN diseases

Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3–5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans