Early-stage volume losses in the corpus callosum and thalamus predict the progression of brain atrophy in patients with multiple sclerosis.

BACKGROUND: A method that can be used in the early stage of multiple sclerosis (MS) to predict the progression of brain volume loss (BVL) has not been fully established. METHODS: To develop a method of predicting progressive BVL in patients with MS (pwMS), eighty-two consecutive Japanese pwMS-with either relapsing-remitting MS (86%) or secondary progressive MS (14%)-and 41 healthy controls were included in this longitudinal retrospective analysis over an observational period of approximately 3.5 years. Using a hierarchical cluster analysis with multivariate imaging data obtained by FreeSurfer analysis, we classified the pwMS into clusters. RESULTS: At baseline and follow-up, pwMS were cross-sectionally classified into three major clusters (Clusters 1, 2, and 3) in ascending order by disability and BVL. Among the patients included in Cluster 1 at baseline, approximately one-third of patients (12/52) transitioned into Cluster 2 at follow-up. The volumes of the corpus callosum, the thalamus, and the whole brain excluding the ventricles were significantly decreased in the transition group compared with the nontransition group and were found to be the most important predictors of transition. CONCLUSION: Decreased volumes of the corpus callosum and thalamus in the relatively early stage of MS may predict the development of BVL.

Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer's Disease Proteinopathy: Possible Therapeutic Role of Curcumin.

For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and health. It has been noted that dietary curcumin is one of the regulators that may positively influence changes in the brain after ischemia. Curcumin is a natural polyphenolic compound with pleiotropic biological properties. The observed death of pyramidal neurons in the CA1 region of the hippocampus and its atrophy are considered to be typical changes for post-ischemic brain neurodegeneration and for Alzheimer's disease. Additionally, it has been shown that one of the potential mechanisms of severe neuronal death is the accumulation of neurotoxic amyloid and dysfunctional tau protein after cerebral ischemia. Post-ischemic studies of human and animal brains have shown the presence of amyloid plaques and neurofibrillary tangles. The significant therapeutic feature of curcumin is that it can affect the aging-related cellular proteins, i.e., amyloid and tau protein, preventing their aggregation and insolubility after ischemia. Curcumin also decreases the neurotoxicity of amyloid and tau protein by affecting their structure. Studies in animal models of cerebral ischemia have shown that curcumin reduces infarct volume, brain edema, blood-brain barrier permeability, apoptosis, neuroinflammation, glutamate neurotoxicity, inhibits autophagy and oxidative stress, and improves neurological and behavioral deficits. The available data suggest that curcumin may be a new therapeutic substance in both regenerative medicine and the treatment of neurodegenerative disorders such as post-ischemic neurodegeneration.

Maternal antioxidant treatment protects adult offspring against memory loss and hippocampal atrophy in a rodent model of developmental hypoxia.

Chronic fetal hypoxia is one of the most common outcomes in complicated pregnancy in humans. Despite this, its effects on the long-term health of the brain in offspring are largely unknown. Here, we investigated in rats whether hypoxic pregnancy affects brain structure and function in the adult offspring and explored underlying mechanisms with maternal antioxidant intervention. Pregnant rats were randomly chosen for normoxic or hypoxic (13% oxygen) pregnancy with or without maternal supplementation with vitamin C in their drinking water. In one cohort, the placenta and fetal tissues were collected at the end of gestation. In another, dams were allowed to deliver naturally, and offspring were reared under normoxic conditions until 4 months of age (young adult). Between 3.5 and 4 months, the behavior, cognition and brains of the adult offspring were studied. We demonstrated that prenatal hypoxia reduced neuronal number, as well as vascular and synaptic density, in the hippocampus, significantly impairing memory function in the adult offspring. These adverse effects of prenatal hypoxia were independent of the hypoxic pregnancy inducing fetal growth restriction or elevations in maternal or fetal plasma glucocorticoid levels. Maternal vitamin C supplementation during hypoxic pregnancy protected against oxidative stress in the placenta and prevented the adverse effects of prenatal hypoxia on hippocampal atrophy and memory loss in the adult offspring. Therefore, these data provide a link between prenatal hypoxia, placental oxidative stress, and offspring brain health in later life, providing insight into mechanism and identifying a therapeutic strategy.

Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial.

OBJECTIVE: To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. DESIGN: Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome. SETTING: KU Leuven, Belgium. SAMPLE: Twenty-four ewes. METHODS: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. MAIN OUTCOME MEASURES: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. RESULTS: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser-treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen-substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria. CONCLUSIONS: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. TWEETABLE ABSTRACT: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT.

Comparative Efficacy of Angiotensin II Type 1 Receptor Blockers Against Ventilator-Induced Diaphragm Dysfunction in Rats.

Mechanical ventilation (MV) is a life-saving intervention for many critically ill patients. Unfortunately, prolonged MV results in the rapid development of inspiratory muscle weakness due to diaphragmatic atrophy and contractile dysfunction (termed ventilator-induced diaphragm dysfunction (VIDD)). Although VIDD is a major risk factor for problems in weaning patients from MV, a standard therapy to prevent VIDD does not exist. However, emerging evidence suggests that pharmacological blockade of angiotensin II type 1 receptors (AT1Rs) protects against VIDD. Nonetheless, the essential characteristics of AT1R blockers (ARBs) required to protect against VIDD remain unclear. To determine the traits of ARBs that are vital for protection against VIDD, we compared the efficacy of two clinically relevant ARBs, irbesartan and olmesartan; these ARBs differ in molecular structure and effects on AT1Rs. Specifically, olmesartan blocks both angiotensin II (AngII) binding and mechanical activation of AT1Rs, whereas irbesartan prevents only AngII binding to AT1Rs. Using a well-established preclinical model of prolonged MV, we tested the hypothesis that compared with irbesartan, olmesartan provides greater protection against VIDD. Our results reveal that irbesartan does not protect against VIDD whereas olmesartan defends against both MV-induced diaphragmatic atrophy and contractile dysfunction. These findings support the hypothesis that olmesartan is superior to irbesartan in protecting against VIDD and are consistent with the concept that blockade of mechanical activation of AT1Rs is a required property of ARBs to shield against VIDD. These important findings provide a foundation for future clinical trials to evaluate ARBs as a therapy to protect against VIDD.

Grape Polyphenols Ameliorate Muscle Decline Reducing Oxidative Stress and Oxidative Damage in Aged Rats.

A large number of studies have demonstrated the implication of oxidative stress (OxS) in the pathogenesis of ageing-related muscle decline and atrophy. The key mechanism is related to the OxS-induced production of free radicals, with the consequent increase in oxidative damage, resulting in affected muscle quality and strength. The present study aimed to evaluate the efficacy of a grape polyphenol-based nutraceutical formulation (Taurisolo®) in reducing the OxS in muscle of aged rats. A group of 16 aged (20 months) rats were orally administered with Taurisolo® (n = 8; 100 mg/kg Taurisolo®) or placebo (n = 8; 50 mg/kg maltodextrin); an additional group of eight young (three months) rats were also treated with placebo. All the treatments were orally administered for 30 days. The activities of antioxidant enzymes, the levels of malondialdehyde (MDA) and nitrotyrosine (N-Tyr) and the expression of OxS- and inflammation-related genes were evaluated on the gastrocnemius muscle. In muscle samples of the treated-group, increased activity of antioxidant enzymes, reduced MDA and N-Tyr levels and increased expression of antioxidant and anti-inflammatory genes were observed in respect to the placebo. Data herein presented suggest that the chronic treatment with Taurisolo® significantly reduces oxidative damage and improves muscle performance in aged rats.

Efficacy and safety of plasma gel as a new modality in treatment of atrophic acne scars.

BACKGROUND: Postacne scarring is an unfortunate and frequent complication of acne, with varied morphological forms and associated significant psychological distress to patients. AIM OF THE WORK: To evaluate the efficacy and safety of plasma gel injection alone and in combination with microneedling in treatment of atrophic postacne scars. PATIENTS AND METHODS: Sixty patients with atrophic postacne scars were enrolled in this single blinded randomized controlled study. The patients were divided into three groups with 20 patients being treated with intradermal injection of plasma gel, 20 patients treated with dermaroller, and 20 patients subjected to combined plasma gel and dermaroller. Patients received four sessions at monthly intervals and were evaluated by clinical, histopathological, and immunohistochemical analysis. RESULTS: There was statistically significant improvement in postacne scars after treatment in all studied groups with variable degrees; the combined technique showed the best clinical improvement in postacne scars. There was an increase in newly formed collagen and elastic fibers with more organized and condensed bundles after the end of treatment. CONCLUSION: Plasma gel showed a remarkable improvement for most patients after one session, providing a quick and easy solution for acne scars. The combination of dermaroller and plasma gel potentiated its effect with more improvement in scars.

Platelet-rich plasma in noninvasive procedures for atrophic acne scars: A systematic review and meta-analysis.

BACKGROUND: The use of platelet-rich plasma (PRP) combined with noninvasive, nonenergy procedures for atrophic acne scars has shown promise. To date, there has not been a systematic review or meta-analysis of the effectiveness of this therapy. AIMS: To use meta-analysis to compare Goodman and Baron qualitative scores, patient satisfaction outcomes, and adverse effects in patients undergoing combination procedures with PRP, combination procedures without PRP, and noninvasive monotherapy without PRP in the treatment of patients with atrophic acne scars. PATIENTS/METHODS: The Pubmed and Cochrane library databases were searched for relevant studies published before May 1, 2019. PRISMA guidelines were utilized. Studies that compared the use of PRP in combination with a noninvasive procedure and therapies without PRP for the treatment of atrophic acne scars were included. Cochrane's handbook was utilized to assess the individual biases of the included studies. Publication bias was assessed. RESULTS: A total of 311 participants (153 whole-face participants and 158 split-face participants) were reviewed across eight included studies. Quantitative analysis of 241 participants across six included studies showed a statistically significant reduction in scar severity scores in favor of microneedling or subcision with PRP (P < .001). Combination therapy with intradermal or topical PRP was significantly more effective than monotherapy alone and combination therapy with an adjunct other than PRP (P < .001 and .001, respectively). CONCLUSION: This systematic review and meta-analysis demonstrated that microneedling or subcision with PRP produced statistically significant improvement in validated outcomes over microneedling or subcision alone.

Treatment of atrophic acne scars using autologous platelet-rich plasma vs combined subcision and autologous platelet-rich plasma: A split-face comparative study.

BACKGROUND: Multiple therapeutic approaches are usually required when treating atrophic acne scars. Subcision was reported to be of value in improving rolling scars. Autologous platelet-rich plasma (PRP) has recently been proposed as an adjuvant treatment option for atrophic acne scars with few reports evaluating its efficacy. OBJECTIVE: Our objective was to compare the effect of intradermal injection of PRP vs combined PRP and subcision in the treatment of atrophic acne scars. METHODS: Thirty patients with bilateral atrophic acne scars were enrolled. Each patient received three monthly sessions. Each side of the face was randomly treated either with intradermal PRP alone or with combined treatment with subcision followed by PRP injection. Patients were assessed at 3 and 6 months following the last treatment session. Evaluation of serial photographs was performed by two blinded investigators. RESULTS: Platelet-rich plasma alone showed a better response, fewer side effects, and shorter downtime compared to combined subcision and PRP. CONCLUSION: Autologous PRP injection can be a therapeutic option in the treatment of atrophic acne scars, with fewer complications and better tolerability than combined subcision and autologous PRP.

Nexrutine® preserves muscle mass similar to exercise in prostate cancer mouse model.

Muscle loss is a debilitating side effect to prostate cancer (PCa) experienced by nearly 60% of men. The purpose of this study was to test the hypothesis that Nexrutine® , a bark extract from the Phellodendrum amurense, can protect against prostate cancer induced muscle loss in a similar manner as exercise, using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Forty-five, 8- to 10-week old TRAMP mice were randomized to either control, Nexrutine® (600 mg/kg pelleted in chow) or exercise (voluntary wheel running). Mice were serially sacrificed at weeks 4, 8, 12, and 20, at which time either the left or right gastrocnemius muscle was harvested, weighted, and frozen. Proteolysis inducing factor (PIF), ubiquitin, and NF-κB concentrations were quantified using ELISA kits. Nexrutine® and exercise were equally able to protect TRAMP mice against PCa-induced muscle loss (P = 0.04). Both interventions decreased intramuscular PIF concentrations at 20 weeks compared to control (P < 0.05). A treatment effect was also observed when all time points were combined with exercise significantly lowering PIF concentrations (P < 0.01). Exercise significantly lowered intramuscular ubiquitin concentrations in weeks 4, 8, and 20 compared to control mice (P < 0.001). A treatment effect was also observed with exercise significantly lowering ubiquitin compared to control mice (P < 0.001). No significant changes were observed for NF-κB. The results of this investigation demonstrate that PCa-induced muscle loss can be attenuated with the herbal supplement Nexrutine® . This investigation provides preliminary evidence to support continued research into Nexrutine® as a potential exercise analog in protecting against muscle loss.

Combination therapy using subcision, needling, and platelet-rich plasma in the management of grade 4 atrophic acne scars: A pilot study.

BACKGROUND: Multimodality therapies including minimally invasive modalities are increasingly used in atrophic scarring. OBJECTIVE: To evaluate the role of platelet-rich plasma (PRP) as adjunctive therapy to a combined subcision and needling treatment in severe (grade 4) atrophic acne scarring. METHODS: A total of 30 patients with grade 4 acne scars were randomly divided into two groups, 15 patients each: Group A underwent three sequential treatments of subcision and needling while Group B, three sequential treatments of subcision, needling, and topical application of PRP that were performed at 3-week intervals. Scar grading was assessed 3 months following the final session. Participant's assessment of treatment response was registered. RESULTS: Scar improvement ≥50% was reported significantly more often by Group B than Group A patients (P = 0.025). Regarding physician-based assessment of scar grading post-therapy (number of patients with two grades improvement vs one grade or no improvement), there was a trend toward more improvement in Group B (P = 0.195). Physician's evaluation of acne scar improvement correlated with the patient's assessment of improvement: 60% of Group A and 66.6% of Group B patients appreciated an improvement of 25%-49% and 50%-74%, respectively. Mean duration of postprocedure erythema/edema was shorter among Group B than Group A patients (16.1 vs 32.9 hours, respectively). Overall, substantial improvement was noticed in rolling and boxcar scars with only a mild change in icepick scars. CONCLUSION: Platelet-rich plasma appears to add to the improvement of grade 4 atrophic acne scars when combined with needling and subcision. These findings require further evaluation by future studies.

Proof of concept: Exposing the myth of urethral atrophy after artificial urinary sphincter via assessment of circumferential recovery after capsulotomy and intraoperative pressure profiling of the pressure regulating balloon.

Purpose: Rate of continence after artificial urinary sphincter (AUS) placement appears to decline with time. After appropriate workup to exclude inadvertent device deactivation, development of urge or overflow incontinence, and fluid loss, many assume recurrent stress urinary incontinence (rSUI) to be secondary to nonmechanical failure, asserting urethral atrophy as the etiology. We aimed to characterize the extent of circumferential urethral recovery following capsulotomy and that of pressure regulating balloon (PRB) material fatigue in men undergoing AUS revision for rSUI. Materials and Methods: Retrospective review of a single surgeon database was performed. Cases of AUS removal/replacement for rSUI involving ventral subcuff capsulotomy and intraoperative PRB pressure profile assessments were identified. Results: The described operative approach involving capsulotomy was applied in 7 patients from November 2015 to September 2017. Mean patient age was 75 years. Mean time between AUS placement and revision was 103 months. Urethral circumference increased in all patients after capsulotomy (mean increase 1.1 cm; range 0.5-2.5 cm). Cuff size increased, remained the same, and decreased in 2, 3, and 2 patients, respectively. Six of 7 patients underwent PRB interrogation. Four of these 6 PRBs (66.7%) demonstrated pressures in a category below the reported range of the original manufacturer rating. Conclusions: Despite visual appearance to suggest urethral atrophy, subcuff capsulotomy results in increased urethral circumference in all patients. Furthermore, intraoperative PRB profiling demonstrates material fatigue. Future multicenter efforts are warranted to determine if capsulotomy, with or without PRB replacement, may simplify surgical management of rSUI with reductions in cost and/or morbidity.

Does attentional dysfunction and thalamic atrophy predict decline in dementia with Lewy bodies?

INTRODUCTION: To evaluate the clinical characteristics of DLB subjects who died within 1 year of assessment compared to those who survived and investigate their patterns of in vivo regional thalamic atrophy using structural MRI. METHODS: Seventy subjects (35 DLB, 35 aged controls) underwent 3 T T1-weighted MR scanning as well as clinical and cognitive assessments, including a computerised assessment of attention. All subjects were contacted after 12 months for reassessment. For both hemispheres, using FSL FIRST, the thalamus was automatically segmented followed by inter-subject vertex-wise analyses involving group comparisons and behavioural correlates. RESULTS: There was significant bilateral atrophy in the ventral-dorsal and pulvinar regions in DLB relative to controls (pcorrected < 0.05). The DLB group was then re-categorised based on 12-month mortality data: DLB-a (n = 26) and DLB-d (n = 9) (a = alive, d = death within 12 months of study assessment). Compared to controls, significant attentional dysfunction and bilateral atrophy of the pulvinar, ventral and dorsal nuclei were observed in DLB-d (pcorrected < 0.05), whereas in DLB-a, atrophy was far less extensive. CONCLUSIONS: Distinct patterns of thalamic atrophy occur in DLB that may relate to the attentional dysfunction and cognitive fluctuations that characterise this disorder. Relative to controls, the extent of attentional impairment and pattern of thalamic degeneration differ in those patients who died within 12 months of assessment, despite having an otherwise similar level of dementia severity. These findings may provide insight into the neurobiological changes underpinning important clinical characteristics and disease heterogeneity.

Selective verbal recognition memory impairments are associated with atrophy of the language network in non-semantic variants of primary progressive aphasia.

Primary progressive aphasia (PPA) is clinically defined by an initial loss of language function and preservation of other cognitive abilities, including episodic memory. While PPA primarily affects the left-lateralized perisylvian language network, some clinical neuropsychological tests suggest concurrent initial memory loss. The goal of this study was to test recognition memory of objects and words in the visual and auditory modality to separate language-processing impairments from retentive memory in PPA. Individuals with non-semantic PPA had longer reaction times and higher false alarms for auditory word stimuli compared to visual object stimuli. Moreover, false alarms for auditory word recognition memory were related to cortical thickness within the left inferior frontal gyrus and left temporal pole, while false alarms for visual object recognition memory was related to cortical thickness within the right-temporal pole. This pattern of results suggests that specific vulnerability in processing verbal stimuli can hinder episodic memory in PPA, and provides evidence for differential contributions of the left and right temporal poles in word and object recognition memory.

Mango leaf extract improves central pathology and cognitive impairment in a type 2 diabetes mouse model.

Epidemiological studies reveal that metabolic disorders, and specifically type 2 diabetes (T2D), are relevant risk factors to develop Alzheimer's disease (AD) and vascular dementia (VaD), the most common causes of dementia. AD patients are in a tremendous need of new therapeutic options because of the limited success of available treatments. Natural polyphenols, and concretely Mangifera indica Linn extract (MGF), have been reported to have antiinflammatory, antioxidant and antidiabetic activities. The role of MGF in central complications associated with T2D, after long-term treatment of db/db mice with MGF was analyzed. Metabolic parameters (body weight, glucose and insulin levels) as well as central complications including brain atrophy, inflammatory processes, spontaneous bleeding, tau phosphorylation and cognitive function in db/db mice treated with MGF for 22 weeks were assessed. MGF limits body weight gain in obese db/db mice. Insulin and C-peptide levels, indicative of pancreatic function, were longer maintained in MGF-treated animals. MGF reduced central inflammation by lowering microglia burden, both in the cortex and the hippocampus. Likewise, central spontaneous bleeding was significantly reduced in db/db mice. Cortical and hippocampal atrophy was reduced in db/db mice and tau hyperphosphorylation was lower after MGF treatment, resulting in partial recovery of learning and memory disabilities. Altogether, the data suggested that MGF treatment may provide a useful tool to target different aspects of AD and VaD pathology, and could lead to more effective clinical therapies for the prevention of metabolic related central complications associated with AD and VaD.

When the Wedding March becomes sad: Semantic memory impairment for music in the semantic variant of primary progressive aphasia.

Music can induce particular emotions and activate semantic knowledge. In the semantic variant of primary progressive aphasia (svPPA), semantic memory is impaired as a result of anterior temporal lobe (ATL) atrophy. Semantics is responsible for the encoding and retrieval of factual knowledge about music, including associative and emotional attributes. In the present study, we report the performance of two individuals with svPPA in three experiments. NG with bilateral ATL atrophy and ND with atrophy largely restricted to the left ATL. Experiment 1 assessed the recognition of musical excerpts and both patients were unimpaired. Experiment 2 studied the emotions conveyed by music and only NG showed impaired performance. Experiment 3 tested the association of semantic concepts to musical excerpts and both patients were impaired. These results suggest that the right ATL seems essential for the recognition of emotions conveyed by music and that the left ATL is involved in binding music to semantics. They are in line with the notion that the ATLs are devoted to the binding of different modality-specific properties and suggest that they are also differentially involved in the processing of factual and emotional knowledge associated with music.

GLP-2 Prevents Intestinal Mucosal Atrophy and Improves Tissue Antioxidant Capacity in a Mouse Model of Total Parenteral Nutrition.

We investigated the effects of exogenous glucagon-like peptide-2 (GLP-2) on mucosal atrophy and intestinal antioxidant capacity in a mouse model of total parenteral nutrition (TPN). Male mice (6-8 weeks old) were divided into three groups (n = 8 for each group): a control group fed a standard laboratory chow diet, and experimental TPN (received standard TPN solution) and TPN + GLP-2 groups (received TPN supplemented with 60 µg/day of GLP-2 for 5 days). Mice in the TPN group had lower body weight and reduced intestinal length, villus height, and crypt depth compared to the control group (all p < 0.05). GLP-2 supplementation increased all parameters compared to TPN only (all p < 0.05). Intestinal total superoxide dismutase activity and reduced-glutathione level in the TPN + GLP-2 group were also higher relative to the TPN group (all p < 0.05). GLP-2 administration significantly upregulated proliferating cell nuclear antigen expression and increased glucose-regulated protein (GRP78) abundance. Compared with the control and TPN + GLP-2 groups, intestinal cleaved caspase-3 was increased in the TPN group (all p < 0.05). This study shows GLP-2 reduces TPN-associated intestinal atrophy and improves tissue antioxidant capacity. This effect may be dependent on enhanced epithelial cell proliferation, reduced apoptosis, and upregulated GRP78 expression.