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Primary lateral sclerosis (PLS) is an adult-onset upper motor neuron disease manifesting in progressive spasticity and gradually resulting in considerably motor disability. In the absence of early disease-specific diagnostic indicators, the majority of patients with PLS face a circuitous diagnostic journey. Until the recent publication of consensus diagnostic criteria, 4-year symptom duration was required to establish the diagnosis. The new diagnostic criteria introduced the category of 'probable PLS' for patients with a symptom duration of 2-4 years. "Evolving diagnostic criteria in primary lateral sclerosis: The clinical and radiological basis of "probable PLS" [1]. This dataset provides radiological metrics in a cohort of 'probable PLS' patients, 'definite PLS' patients and age-matched healthy controls. Region-of-interest radiological data include diffusivity metrics in the corticospinal tracts and corpus callosum as well as mean cortical thickness values in the pre- and para-central gyri in each hemisphere. Our data indicate considerable grey matter and relatively limited white matter involvement in 'probable PLS' which supports the rationale for this diagnostic category as a clinically useful entity. The introduction of this diagnostic category will likely facilitate the timely recruitment of PLS patients into research studies and pharmacological trials before widespread neurodegenerative change ensues., Competing Interests: None., (© 2020 The Author(s). Published by Elsevier Inc.)

Background: N-acetylaspartate (NAA) is synthesized only by neurons and is involved in neuronal metabolism and axonal myelination. NAA is the strongest signal on brain magnetic resonance spectroscopy, and its concentration have been associated with cognitive dysfunction in neurodegenerative diseases, obesity, and type 2 diabetes (T2D). Materials and Methods: We explored the impact of obesity and T2D on circulating NAA as well as the impact of bariatric surgery and antidiabetic treatments. We developed an LC-MS method for the accurate measurements of fasting plasma NAA levels in 505 subjects (156 subjects with normal glucose tolerance, 24 subjects with impaired glucose tolerance, and 325 patients with T2D) to examine the associations of NAA with obesity and dysglycemia. To validate cross-sectional findings, plasma NAA was measured 6 months after Roux-en-Y Gastric Bypass (RYGB) in 55 morbidly obese subjects, and after 1 year of antidiabetic treatment (with dapagliflozin, exenatide, or dapagliflozin plus exenatide) in 192 T2D patients. Results: In the whole population, NAA was associated with age ( r = 0.31, p <0.0001) and BMI ( r = -0.20, p <0.0001). Independently of age and BMI, NAA was reciprocally related to HbA1c and fasting plasma glucose (partial r = -0.13, both p = 0.01). Surgically-induced weight loss raised NAA (by 18 nmol/L on average, p <0.02). Glucose lowering treatment increased NAA in proportion to the drop in HbA1c ( r = 0.31, p <0.0001) regardless of the agent used. Conclusions: Circulating NAA concentrations are modulated by age, obesity, and glycemic control. Whether they may mark for the corresponding metabolic effects on brain function remains to be established by joint measurements of spectroscopic signal and cognitive function., (Copyright © 2020 Daniele, Campi, Saba, Codini, Ciccarone, Giusti, Del Prato, Esterline and Ferrannini.)

Unlabelled: Next-generation sequencing projects have underappreciated information management tasks requiring detailed attention to specimen curation, nucleic acid sample preparation and sequence production methods required for downstream data processing, comparison, interpretation, sharing and reuse. The few existing metadata management tools for genome-based studies provide weak curatorial frameworks for experimentalists to store and manage idiosyncratic, project-specific information, typically offering no automation supporting unified naming and numbering conventions for sequencing production environments that routinely deal with hundreds, if not thousands of samples at a time. Moreover, existing tools are not readily interfaced with bioinformatics executables, (e.g., BLAST, Bowtie2, custom pipelines). Our application, the Omics Metadata Management Software (OMMS), answers both needs, empowering experimentalists to generate intuitive, consistent metadata, and perform analyses and information management tasks via an intuitive web-based interface. Several use cases with short-read sequence datasets are provided to validate installation and integrated function, and suggest possible methodological road maps for prospective users. Provided examples highlight possible OMMS workflows for metadata curation, multistep analyses, and results management and downloading. The OMMS can be implemented as a stand alone-package for individual laboratories, or can be configured for webbased deployment supporting geographically-dispersed projects. The OMMS was developed using an open-source software base, is flexible, extensible and easily installed and executed. The OMMS can be obtained at http://omms.sandia.gov., Availability: The OMMS can be obtained at http://omms.sandia.gov.

We investigated the antimicrobial properties of the cationic polymer polyallylamine (PA) when covalently bonded to glass. The objective was to obtain a robust attachment, yet still allow extension of the polymer chain into solution to enable interaction with the bacteria. The PA film displayed strong antimicrobial activity against Staphylococcus epidermidis , Staphylococcus aureus , and Pseudomonas aeruginosa , which includes both Gram-positive and Gram-negative bacteria. Glass surfaces were prepared by a straightforward two-step procedure of first functionalizing with epoxide groups using 3-glycidoxypropyltrimethoxy silane (GOPTS) and then exposing to PA so that the PA could bind via reaction of a fraction of its amine groups. The surfaces were characterized using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy to verify the presence of the polymer on the surface, zeta potential measurements to estimate the surface charge of the films, and atomic force microscopy to determine the extension of the polymer chains into solution. Antimicrobial properties of these coatings were evaluated by spraying aqueous suspensions of bacteria on the functionalized glass slides, incubating them under agar, and counting the number of surviving cell colonies.

Aims: Patients receiving long-term anticoagulant treatment with dabigatran may need to undergo a percutaneous coronary intervention (PCI). We studied markers of coagulation activation during elective PCI in patients using dabigatran in order to investigate whether coagulation activation upon balloon inflation and stenting is suppressed by dabigatran without additional heparin treatment., Methods and Results: This phase IIa, exploratory, multicentre, randomised, open-label study included 50 stable patients having an elective PCI. Patients on standard dual antiplatelet therapy (DAPT) were randomised (2:2:1) to either pre-procedural dabigatran 110 mg BID (n=19) or 150 mg BID (n=21), as compared to standard intraprocedural unfractionated heparin (UFH) (n=10). Following PCI, a significant increase in the levels of prothrombin fragment 1+2 (F1+2) in the combined dabigatran group was observed compared to the level just before the start of PCI (159.1 [1.4] pmol/l; geometric mean [gSD]). Levels at 0.5, 1.0, 1.5 and 2 hrs after the start of PCI ranged from 193.5 (1.4) to 270.6 pmol/l (1.7); (p-value for paired analysis=0.015, 0.022, 0.2342, 0.0379, respectively). Also, thrombin-antithrombin (TAT) complexes were increased significantly in the combined dabigatran group compared to pre-PCI levels (4.2 [2.2] ug/l). Levels ranged from 5.2 (2.5) to 8.5 (2.3) (p=0.0497, 0.0343, 0.005 and 0.1628, respectively). In contrast, in the control group of patients treated with UFH, no increase was observed in F1+2 and TAT complexes during PCI. Five out of 40 (12.5%) patients required bail-out anticoagulation in the dabigatran group, of whom four experienced a procedural myocardial infarction (MI), versus one out of 10 in the UFH group, who had a stent thrombosis without MI prior to the study-PCI. One minor access-site bleeding occurred in the dabigatran group., Conclusions: Dabigatran treatment (110 mg or 150 mg BID) may not provide sufficient anticoagulation during PCI. EudraCT. No: 2007-007536-25.

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.

The purpose of this study was to compare emotional and biological responses of men and women who are spousal caregivers of patients with Alzheimer's disease (AD). Quality-of-life measurements, bioinstrumentation data, and immunophenotype assessments were obtained from female and male spousal caregivers of patients with AD. Spousal caregivers (women, n = 45 with average age 69.7; men, n = 16 with average age 71.4 years) completed questionnaires that assessed psychosocial variables. Blood was drawn and lymphocyte subsets (including natural killer [NK] cell number) were determined using flow cytometry. The degree of relaxation was determined measuring muscle tension (EMG) in the frontalis and trapezius muscles, skin conductance, skin temperature, and heart rate. Male spousal caregivers, as compared to female spousal caregivers, had significantly lower levels of stress, depression, caregiver burden (subjective), anxiety, anger-hostility, and somatic symptoms and higher levels of mental health, sense of coherence, NK cell number, and social and physical functioning. There were no statistically significant differences between the 2 groups in social support, coping resources, or T, T suppressor, or activated T cells. Women had more T helper cells and fewer NK cells than men. Men had fewer manifestations of a physiological stress response, as indicated by bioinstrumentation parameters. Unique sex-specific issues need to be considered when strategies are implemented to assist the increasing number of caregivers as our society ages.

A dental patient with post-traumatic stress disorder (PTSD) may present with greater dental and behavioral challenges than most dental patients. The background review of PTSD's initiating factors, diagnostic criteria, and medical management should help practitioners better understand and manage these challenges. Many of the challenges the clinician may encounter and managing recommendations are described. A case report of a PTSD patient complaining of constant bilateral tooth pain of the maxillary and mandibular bicuspids and molars is presented. Recommended techniques for identifying the tooth pain source and contributing factors are provided. The primary contributing factor for the patient's tooth pain was determined to be his severe tooth clenching activity. A maxillary acrylic appliance provided some pain reduction and a subsequent mandibular soft occlusal appliance worn opposing the maxillary appliance provided additional relief.

In this study the authors explored the relationship between five-factor model (FFM: Big Five) personality traits (J. M. Digman, 1990; R. R. McCrae & O. P. John, 1992; J. S. Wiggins & P. D. Trappnell, 1997) and universal-diverse orientation (UDO; M. L. Miville et al., 1999) in counselor trainees. FFM traits were measured using the NEO-Personality Inventory-Revised (P. T. Costa & R. R. McCrae, 1992). Statistically significant relationships were found between UDO and one of the Big Five personality traits (Openness to Experience) in counselor trainees. Further regression analysis suggested a relationship between UDO and a particular facet of Openness to Experience, Openness to Aesthetics. This finding suggests that counselor trainees who are open to the creative expressions of others may be comfortable working with a wide variety of clients. These results suggest that counselor training that encourages experiences of aesthetic diversity in addition to an exploration of values may promote trainees' ability to work with diverse clients.

A comparative analysis of the larval and presumptive juvenile neuromuscular systems among actinotroch larvae was performed using confocal laser microscopy with probes for F-actin and serotonin. Currently, there are two main categories of larval nervous systems based on the origin of the nerve fibers that innervate the larval tentacles. Characteristics of the serotonergic cells of the larval apical ganglion and juvenile nervous system have remained relatively conserved, but the structure of the secondary (hood) sense organ and the juvenile tentacles has diversified among species. Differences in larval musculature are mainly associated with differences in hood morphology. The presumptive, juvenile neuromuscular system is either integrated or separated from that of the larva based on the origin of the juvenile tentacles. Among species, the juvenile tentacles are made by remodeling the larval tentacles, developed from a basal tentacular thickening, or developed as a completely separate set in the larva. Differentiation of the neuromuscular structures of the juvenile tentacles is more diverse than their outward morphological characteristics would suggest. Importance of these larval characters is discussed in terms of current problems that exist within phoronid systematics. Evolutionary implications of these morphological characters are discussed among the phoronids, brachiopods, and related bilaterians. Overall, the integration or separation of larval and juvenile neuromuscular characters may yield insights into the evolution of lophotrochozoan body plans.

Amathia vidovici (Vesiculariidae) has a lecithotrophic coronate larva. The apical disc of A. vidovici larvae is more complex than that of other vesiculariids and includes a new cell type, which may be glial-like in function. A massive nerve nodule consists only of neural processes; as no ganglia or other evidence of interneurons were found, sensory cells apparently innervate their effectors directly. Putative synaptic junctions within the nerve nodule indicate that both receptor and effector cells send processes to this neuropile. Some 44 intercoronal cells of three types, two of which are new, are interspersed among the approximately 40 coronal cells. Juxtapapillary bodies, a unique sensory complex previously known only from Bowerbankia gracilis larvae, also occur in A. vidovici. A large refractile body, which is of uncertain function and is positioned near the center of the larva, is described for the first time. A comparison of vesiculariid larvae that have been studied at the ultrastructural level reveals that larvae of Amathia vidovici and Bowerbankia gracilis are more similar to each other than either is to B. imbricata. Differences between the two Bowerbankia species, however, may reflect relative detail of their study and differences in interpretation rather than intergenic plasticity. Nevertheless. a distinctive suite of larval characteristics are shared by other members of the family Vesiculariidae, justifying a specific name-vesiculariform-for their larvae. A number of the defining characteristics of vesiculariform larvae also appear in the carnosan superfamily Victorelloidae. This finding is consistent with arguments based on adult characteristics that the Victorelloidea are ancestral to the Vesicularioidea. If this geneology is correct, one can predict that those vesiculariform traits which originated in the victorellids are plesiomorphic not only to the Family Vesiculariidae but to all sister taxa placed in the Vesicularioidea. © 1993 Wiley-Liss, Inc., (Copyright © 1993 Wiley-Liss, Inc.)

Bracken Cave, a large natural cavern located 25 miles northeast of San Antonio, Texas, serves as nursery roost for millions of Mexican free-tailed bats (Tadarida brasiliensis). Ten days after spending several hours in the cave in early May 1979, three graduate students presented with signs and symptoms compatible with acute pulmonary histoplasmosis. A study was initiated to determine the presence and location of Histoplasma capsulatum in the cave and its inhabitants. The fungus was cultured directly from guano at five of nine sites sampled. Sentinel mice left for several hours at one of three positive sites developed histoplasmosis within 30 days after exposure. Autopsy was done on a total of 28 bats and their lungs, liver and spleen were cultured for viable H. capsulatum. In addition, sera from 58 bats were tested for antibodies to H. capsulatum, using a double diffusion test employing commercial reagents. All bat cultures and sera were negative. We conclude that the students were infected by massive exposure to viable H. capsulatum in aerosols created by disturbing guano deposits near the mouth of the cave. Tadarida brasiliensis contributes to a suitable environment for fungal proliferation, but does not appear to play an active role in the maintenance or dissemination of the fungus in Bracken Cave.

The larva of the ascophoran cheilstome Watersipora arcuata is described on the basis of serial 1-μ sections, light microscopy of whole mounts, and scanning electron microscopy. Using lightly osmicated specimens, it was possible to map almost every cell on the larval surface. Limited observations on hatching and larval behavior are provided in conjunction with the anatomical description. Tissues of the larva are partitioned between those that function exclusively during the larval period and are degraded at metamorphosis as transitory tissues and those that will have postmetamorphic fates in formation of the ancestrula. Significantly, W. arcuata has two possible anlagen for the ancestrular polypide, the infracoronal cells in the oral hemisphere and the epidermal blastemal cells in the aboral hemisphere, rather than only one or the other of these as reported in other species. Also detailed are the supracoronal flange and groove, which are unique to this genus and are involved in the transmission of mycoplasma-like organisms between successive generations of adults; two pairs of complex pigment cup ocelli; multiple intercoronal cells that are presumed to have varied sensory and mechanical functions; and the sensory, adhesive, and locomotory components of the pyriform organ. The larval anatomy of W. arcuata is compared with that of the larvae of the ctenostomes Alcyonidium gelatinosum (coronate), Bowerbankia imbricata (coronate), B. gracilis (coronate), and Flustrellidra hispida (shelled lecithotrophic) and of the cheilostomes Bugula neritina (coronate), Electra pilosa (cyphonautes), and Membranipora membranacea (cyphonautes). This study is the first detailed analysis of the larval structure of any ascophoran bryozoan and provides a necessary platform for subsequent analyses of embryology and metamorphosis., (Copyright © 1989 Wiley-Liss, Inc.)

Leydig cells prepared routinely (glutaraldehyde--osmium) for ultrastructural studies are generally found to be lacking in subcellular detail as a result of poor membrane preservation and a dense cytoplasmic matrix. A method modified after that of Karnovsky (1971), utilizing a ferrocyanide--osmium mixture for post-treating glutaraldehyde fixed tissued, was found to yield routinely excellent preservation of Leydig cells. The primary advantages of this method were the enhancement of contrast within the Leydig cell and greatly improved membrane preservation. In addition, the smooth endoplasmic reticulum always appeared as an extensive network of interconnected tubules of uniform diameter; mitochondria, lysosomes, peroxisomes, multivesicular bodies, and Golgi were especially prominent. Glycogen and microfilaments, not readily seen in routine preparations, were found to be abundant in these cells. New observations on the numbers and distributions of subcellular organelles are described and are discussed in relation to their possible role in the steroidogenic process. In view of the greatly improved tissue preservation observed in this study, it is suggested that this treatment be used routinely for preservation of rat Leydig cells.

Pachytene chromosomes of mice heterozygous for known translocations are clearly depicted by configurations of the synaptonemal complexes in spread (whole mount) preparations. In one autosomal and two X-autosome translocations analyzed, breakpoints are identifiable; localization by measurement agrees with mitotic data and shows the translocations to be reciprocal. Synapsis with the Y is inhibited in one translocation in which the breakpoint is the pairing region of the X.

The coronate larva of the ascophoran bryozoan Watersipora arcuata has a ring of 32 large, multiciliated coronal cells that are used for swimming. Fourteen pairs of small cells are intercalated between the lateral margins of adjacent coronal cells. These intercoronal cells are arranged in a precise pattern and are polymorphic: seven pairs have multiple cilia and seven pairs are mono- or oligociliated. Three pairs of multiciliated intercoronal cells have their cilia arranged as a whorl that is recessed in a pocket formed between the adjacent coronal cells, and they are thought to be photoreceptors that sense general light intensity. Two other pairs of multiciliated cells with cohesive tufts of cilia may be chemo- or mechanoreceptors. Roles of the other intercoronal cells in this species are not evident, but it is proposed that the majority, if not all, of them are sensory. The close proximity of all the intercoronal cells to the equatorial nerve ring is compatible with this interpretation. Analyses of the literature on cleavage patterns, pigment cup ocelli, and flagellar tufts that serve as balancers in coronate larvae lead us to propose that (1) an intercoronal cell is the sensory element of most, if not all, pigment cup ocelli of bryozoan larvae; and (2) intercoronal cells are not modified coronal cells but probably are specialized supra- and/or infracoronal ones that have migrated to an intercoronal position., (Copyright © 1989 Wiley-Liss, Inc.)

Embryos of the marine cheilo-ctenostome bryozoan Bugula neritina undergo a marked increase in volume (about 500-fold) during embryogenesis while being retained in a brood chamber. Previous morphological studies indicate that shortly after transfer of the zygote to the brood chamber, the epithelium of the maternally-derived portion of the brood chamber, the ooecial vesicle, differentiates in regions adjacent to the embryonary space from a squamous to a columnar form suggesting that the parent is involved as a source of extraembryonic nutrients required for the extensive growth of the embryo. Results of the present ultrastructural study indicate that hypertrophy of the epithelial cells occurs only in that region of the ooecial vesicle which opposes the embryo, that differentiation (and subsequent regression) of the lining are predictable events correlated with the onset (and termination) of embryonic growth, and that hypertrophied cells are well equipped for the synthesis and transport of macromolecular materials across the vesicle wall to the developing embryo. Further, that portion of the embryo's ectoderm (the presumptive metasomal sac) in contact with this hypertrophied epithelium is morphologically specialized for the uptake of nutrients. Finally, shortly before release of the larva, this intimate association of the metasomal sac tissue and the hypertrophied ooecial vesicle lining epithelium is terminated by invagination of the sac and atrophy of the lining., (Copyright © 1975 Wiley-Liss, Inc.)

The structure, attachment and subsequent metamorphosis of larvae of the marine bryozoan Bugula neritina were studied by light and electron microscopy. Two points of larval anatomy are of special significance to proper interpretation of the metamorphosis: 1 Two cytologically similar blastemal tissues, each laden with free ribosomes, occur as parts of the apical organ complex. The upper blastema directly contacts the larval surface, forming the non-ciliated rows of the apical organ. The lower blastema is internal and is oral to and contiguous with the upper blastema. 2 The epidermal tissues of the larva are joined in the following sequence, beginning at the aboral pole: a. apical organ complex; b. apical-connecting cell; c. infolded pallial sinus epithelium; d. vesicular-connecting cell; e. aboral vesicular epithelium; f. corona; g. oral vesicular epithelium; and i., j., and k. internal sac neck, wall and roof regions. The initial stages of metamorphosis involve a complex sequence of morphogenetic movements, including: 1 eversion of the internal sac, permanently attaching the larva to the substrate; 2 inrolling of the aboral vesicular epithelium, corona, oral vesicular and ciliated epithelia, and neck region of the internal sac into the larval interior; concomitantly the pallial sinus epithelium evaginates; 3 loss of connection between the invaginated tissues and the surface; 4 fusion of the pallial sinus epithelium with the wall region of the internal sac, maintaining the integrity of the body surface; 5 retraction of the apical organ complex and invagination of the pallial sinus epithelium with the simultaneous elevation of the internal sac wall region to the aboral pole. At the conclusion of these events the preancestrular surface is covered by the wall and roof regions of the internal sac. Cells of the wall region form the epidermis of the body wall except for the attachment disc and secrete a cuticular exoskeleton that is secondarily calcified; the attachment disc is formed by the roof region of the internal sac. Internally, the ectodermal upper blastema differentiates into the lophophore and digestive tract of the ancestrular polypide, while the lower blastema forms the lining of the lophophoral coelom and the splanchnic (but not the somatic) lining of the visceral coelom. The visceral somatic peritoneum is formed from cells that may originate from the mesodermally derived pigmented cells of the larva to which they are similar in pigmentation and cytology. Such a composite derivation of a coelomic lining has not been described previously., (Copyright © 1971 Wiley-Liss, Inc.)