Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards an integrated morphological and molecular WHO diagnosis of central nervous system tumors: a paradigm shift.

PURPOSE OF REVIEW It is now fully clear that information on the molecular underpinnings of tumors of the central nervous system (CNS) can be used for a more robust characterization of at least selected neoplasms. During a meeting organized in Haarlem, The Netherlands, in May 2014, about 30 neuropathologists discussed how exactly molecular information could be incorporated in the routine classification of CNS tumors. RECENT FINDINGS This meeting laid the groundwork for an update of the WHO CNS tumor classification that integrates histopathological and molecular findings. Furthermore, a layered diagnostic approach was proposed that not only allows for integration of relevant molecular information in the pathological diagnosis, but also retains the option for rendering a diagnosis based on histopathological analysis alone. An integrated morphological and molecular definition of CNS tumors brings new challenges as well. For example, criteria for grading within molecularly defined categories of diffuse gliomas will require modification, and some tests used in clinical practice for the detection of molecular features, may provide false positive or false negative results. SUMMARY The evolving paradigm shift represents a major leap forward in the diagnosis of CNS tumors that will contribute substantially to optimizing interobserver reproducibility and clinico-pathological predictions.
Integrin‐linked kinase regulates endothelial cell nitric oxide synthase expression in hepatic sinusoidal endothelial cells

Portal hypertension results from endothelial dysfunction after liver injury caused in part by abnormal production of endothelial cell derived nitric oxide synthase (eNOS). Here, we have postulated that endothelial mechanosensing pathways involving integrin‐linked kinase (ILK) may play a critical role in portal hypertension, eNOS expression and function. In this study, we investigated the role of ILK and the small GTP‐binding protein, Rho, in sinusoidal endothelial cell (SEC) eNOS regulation and function.
Input timing for spatial processing is precisely tuned via constant synaptic delays and myelination patterns in the auditory brainstem

Significance Neural computation depends on precisely timed synaptic inputs, but the way that the timing of inputs is tuned to match postsynaptic processing requirements is not well understood. Here, we studied the same brainstem sound localization pathway in two species with dissimilar temporal processing requirements. Two factors that limit precise timing are synaptic delay and axonal conduction time. In gerbils, which depend on precise timing for sound localization, synaptic delays in fast conducting axons are stable across activity level, and axon myelination is adapted to minimize conduction delays. In mice, which do not depend on precise timing, these specializations are absent. Our results suggest that both axonal and synaptic properties are optimized to the specific functional requirements of neural computation, advancing our understanding of the mechanisms that optimize neural circuits. Precise timing of synaptic inputs is a fundamental principle of neural circuit processing. The temporal precision of postsynaptic input integration is known to vary with the computational requirements of a circuit, yet how the timing of action potentials is tuned presynaptically to match these processing demands is not well understood. In particular, action potential timing is shaped by the axonal conduction velocity and the duration of synaptic transmission delays within a pathway. However, it is not known to what extent these factors are adapted to the functional constraints of the respective circuit. Here, we report the finding of activity-invariant synaptic transmission delays as a functional adaptation for input timing adjustment in a brainstem sound localization circuit. We compared axonal and synaptic properties of the same pathway between two species with dissimilar timing requirements (gerbil and mouse): In gerbils (like humans), neuronal processing of sound source location requires exceptionally high input precision in the range of microseconds, but not in mice. Activity-invariant synaptic transmission and conduction delays were present exclusively in fast conducting axons of gerbils that also exhibited unusual structural adaptations in axon myelination for increased conduction velocity. In contrast, synaptic transmission delays in mice varied depending on activity levels, and axonal myelination and conduction velocity exhibited no adaptations. Thus, the specializations in gerbils and their absence in mice suggest an optimization of axonal and synaptic properties to the specific demands of sound localization. These findings significantly advance our understanding of structural and functional adaptations for circuit processing.
Effects of chronic, post-injury Cyclosporin A administration on motor and sensorimotor function following severe, experimental traumatic brain injury.

PURPOSE Cyclosporin A (CsA) is widely used in clinical situations to attenuate graft rejection following organ and central nervous system transplantation. Previous studies demonstrated that CsA administration is neuroprotective in models of traumatic brain injury (TBI). However, no studies, to date, have evaluated the influence of post-injury CsA administration on behavioral recovery after TBI. METHODS Rats (n = 33) were anesthetized and subjected to severe, lateral fluid percussion brain injury. Fifteen minutes thereafter, animals were randomized to receive the first of 28 daily injections of either CsA (10 mg/kg, ip) or saline. Sham-operated animals (n = 14) were anesthetized and surgically prepared without injury and treated daily either with CsA or saline. Motor and sensorimotor functions were assessed at one day before and two days after injury, and weekly thereafter up to 4 wks post-injury. Cognition was assessed at 1 and 4 wks post-injury using a Morris Water Maze test. RESULTS Injured animals showed significant impairments in motor, sensorimotor and cognitive function over the 4-week post-injury period. Injured animals treated with CsA showed a significant improvement in motor function assessed using a composite neuroscore (at day 28) and in sensorimotor function assessed using a sticky paper test (at days 2, 14, and 28) (p < 0.05, when compared to vehicle treated, injured animals). No beneficial effects on cognitive function were observed following CSA administration. CONCLUSION These data suggest that daily post-injury treatment with CsA improves certain aspects of motor and sensorimotor function following experimental TBI.
Effects of Constraint-Induced Therapy Versus Bilateral Arm Training on Motor Performance, Daily Functions, and Quality of Life in Stroke Survivors

Background and Objective. This study investigated the relative effects of distributed constraint-induced therapy (CIT) and bilateral arm training (BAT) on motor performance, daily function, functional use of the affected arm, and quality of life in patients with hemiparetic stroke. Methods. A total of 60 patients were randomized to distributed CIT, BAT, or a control intervention of less specific but active therapy. Each group received intensive training for 2 hours/day, 5 days/week, for 3 weeks. Pretreatment and posttreatment measures included the Fugl—Meyer Assessment (FMA), Functional Independence Measure (FIM), Motor Activity Log (MAL), and Stroke Impact Scale (SIS). The proximal and distal scores of FMA were used to examine separate upper limb (UL) elements of movement. Results . The distributed CIT and BAT groups showed better performance in the overall and the distal part score of the FMA than the control group. The BAT group exhibited greater gains in the proximal part score of the FMA than the distributed CIT and control groups. Enhanced performance was found for the distributed CIT group in the MAL, the subtest of locomotion in the FIM, and certain domains of the SIS (eg, ADL/IADL). Conclusion. BAT may uniquely improve proximal UL motor impairment. In contrast, distributed CIT may produce greater functional gains for the affected UL in subjects with mild to moderate chronic hemiparesis.
High Plasma Insulin and Triglyceride Concentrations and Blood Pressure in Offspring of People with Impaired Glucose Tolerance

The plasma glucose and insulin response to an oral glucose challenge, fasting plasma lipid concentration, and blood pressure were compared in 13 offspring of parents previously diagnosed as having impaired glucose tolerance (IGT) and 13 offspring of parents previously shown to have normal glucose tolerance. The parents with IGT had higher plasma glucose, insulin and triglyceride concentration, and blood pressure than parents with normal glucose tolerance. The two groups of offspring were young and non‐obese, and similar in terms of age, gender distribution, and body mass index. However, the total integrated plasma insulin response during a 75 g oral glucose tolerance test was significantly higher (p<0.05, Student's t‐test) in offspring of parents with IGT (718±71 pmol I−1 h) than in the subjects whose parents had normal glucose tolerance (524±47 pmol I−1 h). In addition, serum triglyceride concentration was somewhat higher in offspring of parents with IGT (1.17±0.11 vs 0.92±0.08 mmol I−1, 0.10 > p > 0.05), as were both systolic (132±5 vs 118±3 mmHg, p<0.05) and diastolic (79±3 vs 70±2 mmHg, p<0.05) blood pressure. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that these changes have a genetic component.
Mycobacterium tuberculosis-Specific CD8+ T Cells Require Perforin to Kill Target Cells and Provide Protection In Vivo1

Optimal immunity to Mycobacterium tuberculosis (Mtb) infection requires CD8+ T cells, and several current Mtb vaccine candidates are being engineered to elicit enhanced CD8+ T cell responses. However, the function of these T cells and the mechanism by which they provide protection is still unknown. We have previously shown that CD8+ T cells specific for the mycobacterial Ags CFP10 and TB10.4 accumulate in the lungs of mice following Mtb infection and have cytolytic activity in vivo. In this study, we determine which cytolytic pathways are used by these CD8+ T cells during Mtb infection. We find that Mtb-specific CD8+ T cells lacking perforin have reduced cytolytic capacity in vivo. In the absence of perforin, the residual cytolytic activity is CD95 and TNFR dependent. This is particularly true in Mtb-infected lung tissue where disruption of both perforin and CD95 eliminates target cell lysis. Moreover, adoptive transfer of immune CD8+ T cells isolated from wild-type, but not perforin-deficient mice, protect recipient mice from Mtb infection. We conclude that CD8+ T cells elicited following Mtb infection use several cytolytic pathways in a hierarchical and compensatory manner dominated by perforin-mediated cytolysis. Finally, although several cytolytic pathways are available, adoptively transferred Mtb-specific CD8+ T cells require perforin-mediated cytolysis to protect animals from infection. These data show that CD8+ T cell-mediated protection during Mtb infection requires more than the secretion of IFN-γ and specifically defines the CD8+ cytolytic mechanisms utilized and required in vivo.
Preoperative Skin Preparation and Intraoperative Pelvic Irrigation: Impact on Post- Cesarean Endometritis and Wound Infection

Objective: To determine the impact of two skin preparation methods and two techniques of pelvic irrigation on the incidence of post-cesarean endometritis and wound infection in an indigent patient population. Methods: A randomized study was performed in 100 cesarean patients. Subjects were assigned to one of four groups, involving either standard skin preparation (povidone- iodine [7.5%] scrub followed by povidone-iodine [10%] solution) or special skin preparation (5-minute scrub with parachlorometaxylenol followed by povidone scrub and solution), and either normal saline or antibiotic (cefazolin sodium, 1 g in 500 mL normal saline) irrigation of the pelvis and subcutaneous tissue at uterine and fascial closure. Four groups of patients were formed: standard skin preparation plus normal saline irrigation, standard preparation plus antibiotic irrigation, special preparation plus normal saline irrigation, and special preparation plus antibiotic irrigation. Results: Endometritis occurred significantly more often in the combined groups that did not include antibiotic irrigation than in the combined groups involving antibiotic irrigation (P < .001). In contrast, comparison of skin preparation methods between povidone-iodine alone versus preparation including parachlorometaxylenol indicated no significant difference (P = .22). Conclusion: Skin preparation with an antibacterial scrub in addition to standard povidone-iodine scrub and solution does not appear to play as significant a role in the reduction of post-cesarean endometritis or wound infection as does intraoperative pelvic irrigation with antibiotic solution.
Myelomatosis: clinical and laboratory features in Nigerians.

BACKGROUND The objective was to investigate the factors influencing survival of Nigerians with Myelomatosis. MATERIALS AND METHODS The pre-therapy clinical and laboratory features of patients managed at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, between June 1986 and May 2001 were studied. Diagnosis was based on history of bone pain, marrow plasmacytosis, osteolytic bone lesions, serum biochemical profile, monoclonal (M) band, and/or Bence-Jones proteinuria. RESULTS Twenty-seven patients (22 males, 5 females) aged 15 to 81 (median, 60) years were managed within the study period. Of the 27, 5 (18.5%) were 40 years or younger while 14(51.8%) were 60 years or older. Multiple myeloma (MM) is the main sub-type seen (81.5%). Majority presented with bone pain, weakness, fatigue and inability to walk. Anaemia, high erythrocyte sedimentation rate and bone marrow plasmacytosis were the significant haematological findings. Serum protein electrophoresis showed M-band in 6 cases of MM, with 3 of them also having Bence-Jones proteinuria. Renal function impairment and hypercalcaemia occurred mainly in those with MM. Multiple osteolytic lesions and pathological fractures were recorded in 44% of those with MM and Solitary Myeloma of Bone. Twelve patients were already dead at the time of analysis, with renal failure being the cause in 8 and anaemia in the rest. The median survival was 1.2 months. CONCLUSIONS We could conclude that the presenting features of Nigerian patients with myelomatosis are not different from reports elsewhere, but high default rate and short survival are particularly noted.
Evidence for a visual subsector within the zona incerta

Here we examine the patterns of connections between the zona incerta (ZI) of the thalamus and the major visual centers of the rat brain, namely the retina, dorsal lateral geniculate nucleus (LGd), superficial layers of the superior colliculus (SCs), and occipital cortex (Oc1). Injections of the tracers biotinylated dextran or cholera toxin subunit b were made into each of these centers, as well as ZI itself, by using stereotaxic coordinates. Rat brains were then aldehyde-fixed and processed using standard methods. We show that the retina, LGd, SCs, and Oc1 all have connections with ZI; moreover, that each of these connections make a very distinct territory or subsector within the most lateral ZI regions. This subsector of connectivity with the visual centers does not respect the well-defined cytoarchitectonic sectors of ZI, being made up of small zones in the dorsal, ventral, and caudal sectors. Often, a distinctive “horse-shoe” pattern is evident, particularly after retinal and Oc1 injections. Tracer injections into topographically distinct regions of the LGd, SCs, or Oc1 results in no shift in the spatial location of labelling within ZI; after each injection, labelling is always seen within the lateral edge of the nucleus. Labelled terminals and cells are seen after LGd and SCs injections, while only labelled terminals are seen after retinal and Oc1 injections. Although the precise function of this novel visual subsector is not known, these early findings suggest that ZI may be in a position to integrate visual information together with the other somatosensory, motor, and visceral information that it receives.
Substance Use Disorders in Forensic Psychiatry

This is the first study that compared different types of offenders in forensic outpatient treatment (i.e., offenders of general violence [GV], intimate partner violence [IPV], sex crimes, and “other offenses” such as drug smuggling and property crimes) regarding the prevalence of substance use disorders at the time of the offense. In total, 35.8% of participants (n = 187) were diagnosed with any substance use disorder. Specifically, 61.5% of GV perpetrators, 30.9% of IPV perpetrators, 9.1% of sex offenders, and 26.7% of “other offenders” were diagnosed with substance abuse or dependence. More GV offenders and less sex offenders fulfilled diagnostic criteria for a substance use disorder. Furthermore, 29.9% of the offenders were intoxicated by substances at the moment they committed the offense (48.5% of GV perpetrators, 25.0% of IPV perpetrators, 17.4% of sex offenders, and 21.0% of other offenders). More GV perpetrators were intoxicated during the offense. As there is a clear association between substance abuse and criminal behavior, substance abuse in offenders should be assessed and, if present, be treated.
Implementing Sustainable Evidence-Based Interventions in the Community: A Fidelity-Focused Training Framework for the Savvy Caregiver Program

Evidence-based (EB) programs provide a tested means for addressing serious public health concerns. While establishing and maintaining fidelity to these programs is critical for high-quality outcomes, unfortunately, implementation reports rarely describe the strategies used to train and monitor fidelity in community-based implementations. Thus, an essential translational ingredient is a clearly articulated model for establishing a systemic, sustainable fidelity framework. This article provides a detailed description of the fidelity-focused framework developed for Michigan’s statewide implementation of the Savvy Caregiver Program. This framework, titled Creating Confident Caregivers® (CCC), instilled conceptual understanding of fidelity, practice adherence, and competence via ongoing progressive practitioner training, peer observation, participant evaluation, and experiential assessments. Practitioners maintained very high evaluations from participants, and a select cadre of practitioners achieved master trainer status to monitor regional fidelity. This framework promotes sustainable fidelity to EB interventions and provides a replicable platform for other community-based implementations.
Age-associated chromatin relaxation is enhanced in Huntington's disease mice

Expansion of polyglutamine stretch in the huntingtin (HTT) protein is a major cause of Huntington's disease (HD). The polyglutamine part in HTT interacts with various proteins implicated in epigenetic regulation of genes, suggesting that mutant HTT may disturb the integrity of the epigenetic system. Here, we used a PCRseq-based method to examine expression profile of 395 exonic segments from 260 “epi-driver” genes in splenic T lymphocytes from aged HD mice. We identified 67 exonic segments differentially expressed between young and aged HD mice, most of them upregulated in the aged. Polycomb-repressive complex (PRC)-regulated genes (PRGs) were markedly upregulated in aged HD mice, consistent with downregulation of PRC genes. Epi-driver gene categories of lysine-methylation, lysine-demethylation, arginine-methylation, and PRG showed differential age-associated changes between HD and control. Analyzing the pattern of change in epi-driver gene expressions hinted at an enhanced shift in HD chromatin to a more accessible state with age, which was experimentally demonstrated by DNase-I-hypersensitivity sequencing showing increased chromatin accessibility in HD cells compared to control. We suggest the global change can potentially relieve chromatin-induced repression of many genes, and the unintended expressions of some detrimental proteins could alter T cell function to a greater degree in aged HD mice.
Galanin Fragments and Analogues: Effects on Glucose‐Stimulated Insulin Secretion from Isolated Rat Islets

Galanin occurs in intrapancreatic nerves and inhibits insulin secretion both in vivo and in vitro. To investigate which part of the galanin molecule accounts for this inhibition, we studied the effect of porcine galanin, four galanin fragments and three galanin analogues with substitutions of the 2nd amino acid in galanin, on glucose-stimulated insulin secretion from isolated rat islets cultured overnight. The islets were incubated for 1 h at 8.3 mM glucose. Porcine galanin inhibited insulin secretion at dose levels from 10−8 M to 1(T6 M (p <0.001). Also, the galanin fragments GAL1–15 GAL2–29, and GAL. 29 significantly inhibited insulin secretion at and above concentrations of M (p <0.001), 10−8 M (p <0.001), and 10−7M (p <0.001), respectively. Galanin analogues where the 2nd N-terminal amino acid had been changed from tryptophan to tyrosine (GAL-TYR2) or isoleucine (GAL-ILE2) inhibited insulin secretion, as did porcine galanin,1–29 whereas after substitution with phenylalanine (GAL-PHE2) no effect was observed. Furthermore, the C-terminal fragment GAL10–29, did not influence insulin secretion. We conclude that the inhibitory action by galanin on glucose-stimulated insulin secretion from normal islets resides in the N-terminal part of the molecule. In contrast, the C-terminal part of galanin apparently does not influence insulin secretion.
Solides des rejets pluviaux urbains : caracterisation et traitabilite

Cette etude comporte deux objectifs principaux. Le premier est de donner des ordres de grandeur et des gammes de variation des parametres traduisant : (1) la taille, la masse volumique, la vitesse de chute des soudes transportes par temps de pluie a l'aval des reseaux d'assainissement; (2) la repartition, dans les rejets urbains de temps de pluie, entre pollution dissoute et pollution fixee sur ces solides, ainsi que la repartition de cette pollution entre classes de particules. Le deuxieme objectif est de fournir des eclairages pour des options ou des solutions techniques visant a fonder une politique de lutte contre la pollution des rejets urbains par temps de pluie. La premiere partie de ce memoire est consacree aux questions de methode (selection des parametres a mesurer, choix des sites de mesure, ajustement des procedures de prelevement et de mesure). Nous analysons ensuite, dans la deuxieme partie, les resultats obtenus au cours de neuf pluies, reparties sur quatre sites tres differents par leur situation geographique, par la nature du reseau et par la dimension du bassin versant. La derniere partie aborde les trois themes suivants : (1) flux polluants et volumes associes ; (2) identification des sources de cette pollution ; (3) dimensionnement et mode de gestion des capacites a mettre en place pour intercepter et traiter la pollution.