Pathology Deficits Research Articles

Trichostatin A ameliorates Alzheimer\u2019s disease-related pathology and cognitive deficits by increasing albumin expression and A\u03b2 clearance in APP/PS1 mice

BackgroundAlzheimer’s disease (AD) is an intractable neurodegenerative disorder in the elderly population, currently lacking a cure. Trichostatin A (TSA), a histone deacetylase inhibitor, showed some neuroprotective roles, but its pathology-improvement effects in AD are still uncertain, and the underlying mechanisms remain to be elucidated. The present study aims to examine the anti-AD effects of TSA, particularly investigating its underlying cellular and molecular mechanisms.MethodsNovel object recognition and Morris water maze tests were used to evaluate the memory-ameliorating effects of TSA in APP/PS1 transgenic mice. Immunofluorescence, Western blotting, Simoa assay, and transmission electron microscopy were utilized to examine the pathology-improvement effects of TSA. Microglial activity was assessed by Western blotting and transwell migration assay. Protein-protein interactions were analyzed by co-immunoprecipitation and LC-MS/MS.ResultsTSA treatment not only reduced amyloid β (Aβ) plaques and soluble Aβ oligomers in the brain, but also effectively improved learning and memory behaviors of APP/PS1 mice. In vitro study suggested that the improvement of Aβ pathology by TSA was attributed to the enhancement of Aβ clearance, mainly by the phagocytosis of microglia, and the endocytosis and transport of microvascular endothelial cells. Notably, a meaningful discovery in the study was that TSA dramatically upregulated the expression level of albumin in cell culture, by which TSA inhibited Aβ aggregation and promoted the phagocytosis of Aβ oligomers.ConclusionsThese findings provide a new insight into the pathogenesis of AD and suggest TSA as a novel promising candidate for the AD treatment.

Bone marrow-derived NCS-01 cells for ischemic stroke.

Stroke stands as one of the most common causes of death among adults worldwide. Currently, tissue plasminogen activator serves as the only approved drug by the Food and Drug Administration for the treatment of acute ischemic stroke. Stem cell therapy serves as a viable treatment option and has been deemed as a safe and effective treatment for stroke patients. Adult human bone marrow-derived NCS-01 cells serve as a potential treatment for stroke given their ability to reduce stroke-induced pathological deficits by increasing cell viability and mitochondrial activity. Recently, we demonstrated the use of adult bone marrow-derived NCS-01 cells both on both in vitro and in vivo models. Using NCS-01 cells in rat stroke models subjected to middle cerebral artery occlusion, an effective dosage of 7.5 × 106 cells/ml, administered through the intracarotid artery within 3 days poststroke, was shown to display significant improvements in motor and neurological behaviors, reductions in infarct area, and peri-infarct cell loss. NCS-01 cells, in comparison with other lines of stem cells (Li cells), are shown to produce greater therapeutic effects, most likely due to the observed filopodia formation that allows the stem cells to extend and target the ischemic cells. Given these findings, NCS-01 stem cells serve as a potential treatment for stroke through the demonstration of profound efficacy and further research that favors their filopodia-mediated mechanism of action.

Pitch and Duration Mismatch Negativity are Associated With Distinct Auditory Cortex and Inferior Frontal Cortex Volumes in the First-Episode Schizophrenia Spectrum.

BackgroundPitch and duration mismatch negativity (pMMN/dMMN) are related to left Heschl’s gyrus gray matter volumes in first-episode schizophrenia (FESz). Previous methods were unable to delineate functional subregions within and outside Heschl’s gyrus. The Human Connectome Project multimodal parcellation (HCP-MMP) atlas overcomes this limitation by parcellating these functional subregions. Further, MMN has generators in inferior frontal cortex, and therefore, may be associated with inferior frontal cortex pathology. With the novel use of the HCP-MMP to precisely parcellate auditory and inferior frontal cortex, we investigated relationships between gray matter and pMMN and dMMN in FESz. MethodspMMN and dMMN were measured at Fz from 27 FESz and 27 matched healthy controls. T1-weighted MRI scans were acquired. The HCP-MMP atlas was applied to individuals, and gray matter volumes were calculated for bilateral auditory and inferior frontal cortex parcels and correlated with MMN. FDR correction was used for multiple comparisons. ResultsIn FESz only, pMMN was negatively correlated with left medial belt in auditory cortex and area 47L in inferior frontal cortex. Duration MMN negatively correlated with the following auditory parcels: left medial belt, lateral belt, parabelt, TA2, and right A5. Further, dMMN was associated with left area 47L, right area 44, and right area 47L in inferior frontal cortex. ConclusionsThe novel approach revealed overlapping and distinct gray matter associations for pMMN and dMMN in auditory and inferior frontal cortex in FESz. Thus, pMMN and dMMN may serve as biomarkers of underlying pathological deficits in both similar and slightly different cortical areas.

Potential Nutraceutical Properties of Leaves from Several Commonly Cultivated Plants.

Chronic dietary ingestion of suitable phytochemicals may assist with limiting or negating neurodegenerative decline. Current therapeutics used to treat Alzheimer disease elicit broad adverse drug reactions, and alternative sources of cholinesterase inhibitors (ChEIs) are required. Herein, we screened methanolic extracts from seven commonly cultivated plants for their nutraceutical potential; ability to inhibit acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE), and provision of antioxidant activity through their 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging capabilities. Potential neurotoxicity of plant extracts was examined via application to SHSY-5Y neuroblastoma cells and quantitation of cell viability. Methanolic extracts of Citrus limon (Lemon), Bombax ceiba (Red silk-cotton), Lawsonia inermis (Henna), Eucalyptus globulus (Eucalyptus), Ocimum basilicum (Basil), Citrus reticulata (Mandarin orange), and Mentha spicata (Spearmint) all displayed concentration-dependent inhibition of AChE and BuChE. The majority of extracts inhibited AChE and BuChE to near equipotency, with Henna and Eucalyptus extracts the two most potent ChEIs. All plant extracts were able to scavenge free radicals in a concentration-dependent manner, with Eucalyptus the most potent antioxidant. Toxicity of plant extracts to neuronal cells was concentration dependent, with Eucalyptus also the most toxic extract. Fractionation of plant extracts and analysis by mass spectrometry identified a number of plant polyphenols that might have contributed to the cholinesterase inhibition: 3-caffeoylquinic acid, methyl 4-caffeoylquinate, kaempferol-acetyl-glycoside, quercetin 3-rutinoside, quercetin-acetyl-glycoside, kaempferol 3-O-glucoside, and quercetin 3-O-glucoside. In silico molecular modeling of these polyphenols demonstrated their improved AChE and BuChE binding affinities compared to the current FDA-approved dual ChEI, galantamine. Collectively, all the plant extracts contained nutraceutical agents as antioxidants and ChEIs and, therefore, their chronic consumption may prove beneficial to combat the pathological deficits that accrue in Alzheimer disease.

Next-Generation RNA-Sequencing of Serum Small Extracellular Vesicles Discovers Potential Diagnostic Biomarkers for Dementia With Lewy Bodies

ObjectiveThere is an urgent clinical need for identifying blood-based diagnostic biomarkers for Dementia with Lewy Bodies (DLB). Transcriptomic studies have reported unique RNA changes in postmortem DLB brains. Small extracellular vesicles (SEV) that transport RNA between brain and peripheral circulation enable identifying molecular changes in living human brain. Hence, we aimed to identify differentially expressed RNA in serum SEVs from people with DLB. MethodsWe investigated serum SEV total RNA profiles in people with DLB (n = 10) and age and gender matched comparisons (n = 10) using next-generation RNA-sequencing. SEVs were separated by ultracentrifugation with density gradient and were characterized by nanoparticle analysis and western blotting. We verified the differential expression levels of identified differentially expressed genes (DEG) using high-throughput qPCR. Functional implications of identified DEG were evaluated using Ingenuity pathway analyses. ResultsWe identified 846 nominally significant DEG including 30 miRNAs in DLB serum SEVs. We identified significant downregulation of proinflammatory genes, IL1B, CXCL8, and IKBKB. Previously reported postmortem DLB brain DEGs were significantly enriched (χ2=4.99; df=1; p = 0.03) among the identified DEGs, and the differential expression of 40 postmortem DLB brain DEGs could be detected in serum SEVs of people living with DLB. Functional pathway and network analyses highlighted the importance of immunosenescence, ubiquitin proteasome system (UPS) dysfunction, DNA repair, and RNA post-transcriptional modification deficits in DLB pathology. ConclusionIdentified DEGs, especially reduced expression levels of inflammation, and UPS-associated RNA, may aid diagnosing DLB, and their biomarker potential warrants further investigation in larger clinical cohorts. Our findings corroborate the absence of chronic neuroinflammation in DLB.

Calpastatin Overexpression Protects against Excitotoxic Hippocampal Injury and Traumatic Spinal Cord Injury.

Small molecule inhibitors of calcium-dependent proteases, calpains (CAPNs), protect against neurodegeneration induced by a variety of insults including excitotoxicity and spinal cord injury (SCI). Many of these compounds, however, also inhibit other proteases, which has made it difficult to evaluate the contribution of calpains to neurodegeneration. Calpastatin is a highly specific endogenous inhibitor of classical calpains, including CAPN1 and CAPN2. In the present study, we utilized transgenic mice that overexpress human calpastatin under the prion promoter (PrP-hCAST) to evaluate the hypothesis that calpastatin overexpression protects against excitotoxic hippocampal injury and contusive SCI. The PrP-hCAST organotypic hippocampal slice cultures showed reduced neuronal death and reduced calpain-dependent proteolysis (α-spectrin breakdown production, 145 kDa) at 24 h after N-methyl-D-aspartate (NMDA) injury compared with the wild-type (WT) cultures (n = 5, p < 0.05). The PrP-hCAST mice (n = 13) displayed a significant improvement in locomotor function at one and three weeks after contusive SCI compared with the WT controls (n = 9, p < 0.05). Histological assessment of lesion volume and tissue sparing, performed on the same animals used for behavioral analysis, revealed that calpastatin overexpression resulted in a 30% decrease in lesion volume (p < 0.05) and significant increases in tissue sparing, white matter sparing, and gray matter sparing at four weeks post-injury compared with WT animals. Calpastatin overexpression reduced α-spectrin breakdown by 51% at 24 h post-injury, compared with WT controls (p < 0.05, n = 3/group). These results provide support for the hypothesis that sustained calpain-dependent proteolysis contributes to pathological deficits after excitotoxic injury and traumatic SCI.

Intracerebral transplantation of HLA-homozygous human iPSC-derived neural precursors ameliorates the behavioural and pathological deficits in a rodent model of ischaemic stroke.

ObjectivesHuman‐induced pluripotent stem cells (hiPSCs) are a promising cell source for treating ischaemic stroke. Although autologous hiPSCs provide the advantage of avoiding immune rejection, their practical limitations, such as substantial amount of time and costs to generate individual iPSC lines, have hampered their widespread application in clinical settings. In this study, we investigated the therapeutic potential of neural precursor cells derived from human HLA‐homozygous induced pluripotent stem cells (hiPSC‐NPCs) following intracerebral transplantation into a rodent model of middle cerebral artery occlusion (MCAo).Materials and MethodsWe differentiated a GMP‐grade HLA‐homozygous hiPSC line (CMC‐hiPSC‐004) into neural precursor cells for transplantation into rats at the subacute stage of ischaemic stroke (ie at 7 days after the induction of MCAo). To investigate functional recovery, the transplanted animals were subjected to five behavioural tests, namely the rotarod, stepping, mNSS, staircase and apomorphine‐induced rotation tests, for up to 12 weeks, followed by histological analyses.ResultsWe observed that the hiPSC‐NPC transplantation produced significant behavioural improvements. At 12 weeks post‐transplantation, a high proportion of transplanted cells survived and had differentiated into MAP2+ mature neurons, GABAergic neurons and DARPP32+ medium spiny neurons. The transplanted cells formed neuronal connections with striatal neurons in the host brain. In addition, hiPSC‐NPC transplantation gave rise to enhanced endogenous repair processes, including decreases of post‐stroke neuroinflammation and glial scar formation and an increase of proliferating endogenous neural stem cells in the subventricular zone as well as the perilesional capillary networks.ConclusionsThese results strongly suggest that HLA‐homozygous hiPSC‐NPCs may be useful for treating ischaemic stroke patients.

A tailored Cln3Q352X mouse model for testing therapeutic interventions in CLN3 Batten disease

CLN3 Batten disease (CLN3 disease) is a pediatric lysosomal storage disorder that presents with progressive blindness, motor and cognitive decline, seizures, and premature death. CLN3 disease results from mutations in CLN3 with the most prevalent mutation, a 966 bp deletion spanning exons 7–8, affecting ~ 75% of patients. Mouse models with complete Cln3 deletion or Cln3Δex7/8 mutation have been invaluable for learning about both the basic biology of CLN3 and the underlying pathological changes associated with CLN3 disease. These models, however, vary in their disease presentation and are limited in their utility for studying the role of nonsense mediated decay, and as a consequence, in testing nonsense suppression therapies and read-through compounds. In order to develop a model containing a disease-causing nonsense point mutation, here we describe a first-of-its-kind Cln3Q352X mouse model containing a c.1054C > T (p.Gln352Ter) point mutation. Similar to previously characterized Cln3 mutant mouse lines, this novel model shows pathological deficits throughout the CNS including accumulation of lysosomal storage material and glial activation, and has limited perturbation in behavioral measures. Thus, at the molecular and cellular level, this mouse line provides a valuable tool for testing nonsense suppression therapies or read through compounds in CLN3 disease in the future.

Neurometabolic Correlates of Reactive and Proactive Motor Inhibition in Young and Older Adults: Evidence from Multiple Regional 1H-MR Spectroscopy.

Suboptimal inhibitory control is a major factor contributing to motor/cognitive deficits in older age and pathology. Here, we provide novel insights into the neurochemical biomarkers of inhibitory control in healthy young and older adults and highlight putative neurometabolic correlates of deficient inhibitory functions in normal aging. Age-related alterations in levels of glutamate–glutamine complex (Glx), N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mIns) were assessed in the right inferior frontal gyrus (RIFG), pre-supplementary motor area (preSMA), bilateral sensorimotor cortex (SM1), bilateral striatum (STR), and occipital cortex (OCC) with proton magnetic resonance spectroscopy (1H-MRS). Data were collected from 30 young (age range 18–34 years) and 29 older (age range 60–74 years) adults. Associations between age-related changes in the levels of these metabolites and performance measures or reactive/proactive inhibition were examined for each age group. Glx levels in the right striatum and preSMA were associated with more efficient proactive inhibition in young adults but were not predictive for reactive inhibition performance. Higher NAA/mIns ratios in the preSMA and RIFG and lower mIns levels in the OCC were associated with better deployment of proactive and reactive inhibition in older adults. Overall, these findings suggest that altered regional concentrations of NAA and mIns constitute potential biomarkers of suboptimal inhibitory control in aging.

Please stop helping me!: Well-intentioned “dark” actors present others as less socially desirable to audiences

Machiavellianism, narcissism, psychopathy, and sadism are dark-personality constructs that relate to propensities to harm others. Accounts of these propensities tend to highlight malevolence or pathological deficits, but innocent cognitive mechanisms may also be relevant. In that regard, we tested the novel idea that well-intentioned people higher in dark-personality constructs are prone to present others' identities in a less socially desirable way. Participants imagined various scenarios that entailed helping someone shape his/her public identity and then rated the extent they would cultivate socially (un)desirable characteristics in the target, how beneficial these characteristics would be to the target, and how much they attempted to help the target. Generally, Machiavellianism, psychopathy, and sadism predicted enhanced cultivation of socially undesirable characteristics in targets. These effects corresponded with rating socially undesirable characteristics as more beneficial and could not be attributed to trying to be unhelpful. Hence, what can appear as a propensity amongst dark actors to harm others' good character can arise during well-intentioned behavior to help others make a “good” impression.

Implantation of the clinical-grade human neural stem cell line, CTX0E03, rescues the behavioral and pathological deficits in the quinolinic acid-lesioned rodent model of Huntington's disease

Huntington's disease (HD) is a devastating, autosomal‐dominant neurodegenerative disease, for which there are currently no disease‐modifying therapies. Clinical trials to replace the damaged striatal medium spiny neurons (MSNs) have been attempted in the past two decades but have met with only limited success. In this study, we investigated whether a clonal, conditionally immortalized neural stem cell line (CTX0E03), which has already shown safety and signals of efficacy in chronic ischemic stroke patients, could rescue deficits seen in an animal model of HD. After CTX0E03 transplantation into the quinolinic acid‐lesioned rat model of HD, behavioral changes were measured using the rotarod, stepping, and staircase tests. In vivo differentiation and neuronal connections of the transplanted CTX0E03 cells were evaluated with immunohistochemical staining and retrograde tracing with Fluoro‐Gold. We found that transplantation of CTX0E03 gave rise to a significant behavioral improvement compared with the sham‐ or fibroblast‐transplanted group. Transplanted CTX0E03 formed MSNs (DARPP‐32) and GABAergic neurons (GABA, GAD65/67) with BDNF expression in the striatum, while cortically transplanted cells formed Tbr1‐positive neurons. Using a retrograde label, we also found stable engraftment and connection of the transplanted cells with host brain tissues. CTX0E03 transplantation also reduced glial scar formation and inflammation, as well as increasing endogenous neurogenesis and angiogenesis. Overall, our results demonstrate that CTX0E03, a clinical‐grade neural stem cell line, is effective for preclinical test in HD, and, therefore, will be useful for clinical development in the treatment of HD patients.

Neurophysiological substrates of configural face perception in schizotypy

Face perception is a highly developed function of the human visual system. Previous studies of event-related potentials (ERPs) have identified a face-selective ERP component (negative peak at about 170 ms after stimulus onset, N170) in healthy participants. In contrast, patients with schizophrenia exhibit reduced amplitude of the N170, which may represent a pathological deficit in the neurophysiology of face perception. Interestingly, healthy humans with schizophrenia-like experiences (schizotypy) also exhibit abnormal processing of face perception. Yet, it has remained unknown how schizotypy in healthy humans is associated with the neurophysiological substrates of face perception. Here, we recruited 35 healthy participants and assessed their schizotypy by the magical ideation rating scale. We used high-density electroencephalography to obtain ERPs elicited by a set of Mooney faces (face and non-face visual stimuli). We investigated median and mean reaction times and visual ERP components in response to the stimuli. We observed a significant difference in N170 amplitude between the two face-stimulus conditions and found that the measured schizotypy scores were significantly correlated with both reaction times and N170 amplitude in response to the face stimuli across all participants. Our results thus support the model of schizotypy as a manifestation of a continuum between healthy individuals and patients with schizophrenia, where the N170 impairment serves as a biomarker for the degree of pathology along this continuum.

Green Coconut Water Attenuates Oxidative Damage, Amyloid Pathology and Cognitive Deficits in a Mouse Model of Alzheimer's disease

Green Coconut Water Attenuates Oxidative Damage, Amyloid Pathology and Cognitive Deficits in a Mouse Model of Alzheimer's disease

Dendritic NMDA receptors in parvalbumin neurons enable strong and stable neuronal assemblies.

Parvalbumin-expressing (PV+) GABAergic interneurons mediate feedforward and feedback inhibition and have a key role in gamma oscillations and information processing. The importance of fast synaptic recruitment and action potential initiation and repolarization, and rapid synchronous GABA release by PV+ cells, is well established. In contrast, the functional significance of PV+ cell NMDA receptors (NMDARs), which generate relatively slow postsynaptic currents, is unclear. Underlining their potential importance, several studies implicate PV+ cell NMDAR disruption in impaired network function and circuit pathologies. Here, we show that dendritic NMDARs underlie supralinear integration of feedback excitation from local pyramidal neurons onto mouse CA1 PV+ cells. Furthermore, by incorporating NMDARs at feedback connections onto PV+ cells in spiking networks, we show that these receptors enable cooperative recruitment of PV+ interneurons, strengthening and stabilising principal cell assemblies. Failure of this phenomenon provides a parsimonious explanation for cognitive and sensory gating deficits in pathologies with impaired PV+ NMDAR signalling.

Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A2A receptor.

Accumulating data support the role of tau pathology in cognitive decline in ageing and Alzheimer's disease, but underlying mechanisms remain ill-defined. Interestingly, ageing and Alzheimer's disease have been associated with an abnormal upregulation of adenosine A2A receptor (A2AR), a fine tuner of synaptic plasticity. However, the link between A2AR signalling and tau pathology has remained largely unexplored. In the present study, we report for the first time a significant upregulation of A2AR in patients suffering from frontotemporal lobar degeneration with the MAPT P301L mutation. To model these alterations, we induced neuronal A2AR upregulation in a tauopathy mouse model (THY-Tau22) using a new conditional strain allowing forebrain overexpression of the receptor. We found that neuronal A2AR upregulation increases tau hyperphosphorylation, potentiating the onset of tau-induced memory deficits. This detrimental effect was linked to a singular microglial signature as revealed by RNA sequencing analysis. In particular, we found that A2AR overexpression in THY-Tau22 mice led to the hippocampal upregulation of C1q complement protein-also observed in patients with frontotemporal lobar degeneration-and correlated with the loss of glutamatergic synapses, likely underlying the observed memory deficits. These data reveal a key impact of overactive neuronal A2AR in the onset of synaptic loss in tauopathies, paving the way for new therapeutic approaches.

Review of Shoulder Range of Motion in the Throwing Athlete: Distinguishing Normal Adaptations from Pathologic Deficits.

Overhand (OH) throwers demonstrate a unique motion profile of the shoulder joint complex. This manuscript reviews normal adaptations in the OH thrower and contrast findings with pathologic motion deficits. Multiple adaptations in range of motion have been associated with increased risk for arm injury. The use of a more conservative cutoff value for glenohumeral internal rotation deficit and horizontal adduction in younger throwers may help reduce injury risk. Deficits in glenohumeral internal rotation, total range of motion, shoulder flexion, and external rotation insufficiency have all been proposed as means to identify OH throwers at risk for arm injury, but conflicting evidence exists. Understanding normal adaptation due to repetitive stress of throwing is essential to effective management of these athletes. Adaptive change in bone and soft tissues is normal and contributes to the unique motion profiles expected in throwers. The causative link between normal adaptation and shoulder and elbow injury remains uncertain.

Oxymatrine can attenuate pathological deficits of Alzheimer's disease mice through regulation of neuroinflammation

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive learning and cognitive damage. Several hypotheses such as amyloid cascade hypothesis, hyper-phosphorylated τ hypothesis, and energy metabolism hypothesis have been proposed to elucidate the disease. However, the exact mechanism of AD remains unclear and current therapeutic strategies are miserable. Cumulative evidence showed that neuroinflammation plays a significant role in the pathogenesis of the AD. Oxymatrine (OMT), a plant-derived bioactive compound, has anti-viral, anti-fibrosis, and anti-tumor effects through the involvement of several immune-related signaling pathways. Whether OMT can attenuate the pathology of AD is largely unknown. In this manuscript, we found that treatment of OMT can significantly improve cognitive and learning abilities of AD mice during various behavioral test. Treatment of OMT can significantly reduce the densities of Aβ plaques and astrocyte clusters in the neocortex and hippocampus of AD mice. Furthermore, treatment of OMT significantly reduced the concentration of pro-inflammatory cytokines including IL-6, IL-1β, TNF-α and IL-17A in AD mice. Taken together, our data indicate that OMT may serve as a potential drug for AD.

Abstract # 3105 Inflammation Decreases Emotion Recognition – Evidence from the Vaccination Model of Inflammation

The ability to interpret someone’s mental state such as their emotions and intentions (denoted Theory of Mind, ToM), is key to human social interaction. This ability is impaired in several psychopathologies including major depression, and inflammation has been proposed as a candidate mechanism of such impairments. Experimental studies using LPS injection support a role of inflammation, but LPS-induced symptoms of sickness could themselves cause the observed reductions in ToM behaviors. Here we experimentally replicated these effects using a manipulation that minimized these potentially confounding side-effects. Forty healthy male participants (mean age = 25, SD= 5) completed the Reading the Mind in the Eyes Test (a measure of ToM) in this double-blind placebo-controlled within-subjects crossover triaI. Inflammation was induced using Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur) and saline-injection was used as a control. IL-6 was used as a marker of inflammation. Vaccination increased IL-6 levels (+419%, p .001), without inducing fever or sickness symptoms (e.g., nausea), or mood changes (all p > .10). The results showed that typhoid vaccination significantly reduced ToM performance compared to placebo (M = 71%, SD = 13%’ placebo M = 65%, SD = 13%; p .05). The present findings provide further support for the idea that emotion recognition is impaired during immune activation. Inflammation may in part drive social-cognitive deficits in pathologies that exhibit enhanced inflammation, such as major depression.

Limited developmental neurotoxicity from neonatal inhalation exposure to diesel exhaust particles in C57BL/6 mice

BackgroundRecent epidemiological studies indicate early-life exposure to pollution particulate is associated with adverse neurodevelopmental outcomes. The need is arising to evaluate the risks conferred by individual components and sources of air pollution to provide a framework for the regulation of the most relevant components for public health protection. Previous studies in rodent models have shown diesel particulate matter has neurotoxic potential and could be a health concern for neurodevelopment. The present study shows an evaluation of pathological and protracted behavioral alterations following neonatal exposure to aerosolized diesel exhaust particles (NIST SRM 1650b). The particular behavioral focus was on temporal control learning, a broad and fundamental cognitive domain in which reward delivery is contingent on a fixed interval schedule. For this purpose, C57BL/6 J mice were exposed to aerosolized NIST SRM 1650b, a well-characterized diesel particulate material, from postnatal days 4–7 and 10–13, for four hours per day. Pathological features, including glial fibrillary-acidic protein, myelin basic protein expression in the corpus callosum, and ventriculomegaly, as well as learning alterations were measured to determine the extent to which NIST SRM 1650b would induce developmental neurotoxicity.ResultsTwenty-four hours following exposure significant increases in glial-fibrillary acidic protein (GFAP) in the corpus callosum and cortex of exposed male mice were present. Additionally, the body weights of juvenile and early adult diesel particle exposed males were lower than controls, although the difference was not statistically significant. No treatment-related differences in males or females on overall locomotor activity or temporal learning during adulthood were observed in response to diesel particulate exposure.ConclusionWhile some sex and regional-specific pathological alterations in GFAP immunoreactivity suggestive of an inflammatory reaction to SRM 1650b were observed, the lack of protracted behavioral and pathological deficits suggests further clarity is needed on the developmental effects of diesel emissions prior to enacting regulatory guidelines.

Direct effect of short wave diathermy therapy and exercise with quadriceps bench against knee osteoarthritis patients with functional capabilities

Osteoarthritis (OA) is a disorder of joint cartilage characterized by changes in the clinical, histological and radiological. OA knee associated with various pathological deficits such as pain, decreased range of motion of the knee joint and the quadriceps muscle nirguna atrophy. This study was observational analytic and design research using cross-sectional design. Subjects in this study were 30 patients with osteoarthritis of the knee in outpatient IRM Hospital Dr. Soetomo aged 40-70 years were taken with consecutive sampling technique the period from March to April 2015, an assessment of functional ability before and after treatment using a scale jette. The data in normal distribution and statistical test was then performed using paired t-test. Jette scale mean pre- and post-treatment with Short Wave Diathermy (SWD) modalities and exercises with Quadriceps Bench (QB) in patients with knee osteoartriitis show was different, with a value of less significance (p <0.05). This can occured because, blood flow in the tissues increase, throw away the metabolite residual, and decrease muscle spasms, so the pain is reduced and the functional ability of the knee increases.