Effect Of Preventive Treatment Research Articles

Clinicopathological Features of Low-Grade Appendiceal Mucinous Neoplasms Confined to the Appendix.

ObjectiveTo investigate the clinicopathological features and follow-up of low-grade appendiceal mucinous neoplasms (LAMNs) confined to the appendix.MethodsThe clinicopathological features, pathological primary tumor (pT) staging and follow-up of 22 patients with LAMNs confined to the appendix were analyzed retrospectively.ResultsOf 22 patients with LAMNs, 14 were pTis (eight pTism and six pTisf), six were pT3, and two were pT4a. The appendiceal diameter was significantly larger for pTisf than for pTism. The interval between first symptoms and surgery was longer for pTisf than for pTism, but not significantly different. No significant differences were found between the pT stages and appendiceal diameter or in the interval between the first symptoms and surgery. Pathomorphologically, the epithelial structures were mainly flat (100%), undulating or scalloped (82%); a few showed filiform villous hyperplasia (46%), and seven (32%) had serrated lesions in the background. Diverticula may be associated with LAMNs, and the location of acellular mucin caused by diverticula affected the pT stage of the LAMNs. The immunohistochemistry information showed the same pattern with cytokeratin 7 (CK7) negative, cytokeratin 20 (CK20) positive and caudal type homeobox 2 (CDX-2) positive. No lymph node metastasis was found. The lack of treatment guidelines for LAMNs confined to the appendix and different acceptances of patients of preventive intervention led to varied clinical treatments. However, we found no short-term benefits of prophylactic extended resection or hyperthermic intraperitoneal chemotherapy.ConclusionLAMNs confined to the appendix are rare and must be differentiated from serrated lesions and diverticula. LAMNs with different pT stages have inert biological behavior. Determining the long-term effects of preventive treatment on survival and recurrence requires more data and a longer follow-up.

The new Epoch of Antithrombotic Therapy in the Long-Term Prevention of a non-Cardioembolic Stroke

This article presents current opinions on the role of antithrombotic therapy in secondary prevention of cardiovascular diseases (CVD) in patients after noncardioembolic stroke or a transient ischemic attack on the background of sinus rhythm. This review analytically analyses evidence-based data on antithrombotic drugs used for this secondary prevention. Despite the fact that acetylsalicylic acid (ASA) is still a "gold standard" for prevention of noncardioembolic stroke, the search for rational combinations of antithrombotic drugs to increase the effectiveness of preventive treatment is relevant. The question whether the rivaroxaban treatment as monotherapy or in combination with ASA is more effective than the ASA monotherapy for secondary prevention of cardiovascular complications (CVC) was addressed in the COMPASS study. In that study, three regimens of antithrombotic therapy were compared in patients with stable atherosclerotic CVD: rivaroxaban (2.5 mg twice a day) in combination with ASA (100 mg/day); rivaroxaban (5 mg twice a day); and ASA (100 mg/day). Risk for development of major CVC (death, stroke, myocardial infarction (IM)) was lower (p<0.001) in the rivaroxaban+ASA combination treatment group than in the ASA monotherapy group; however, the risk of major bleedings was somewhat higher. Total risk based on the definition of "pure clinical benefit" was lower for the rivaroxaban+ASA combination treatment than for the ASA monotherapy. The rivaroxaban monotherapy did not result in a significant decrease in the risk of major CVC compared to the ASA monotherapy but significantly increased the risk of major bleedings. Incidence of repeated ischemic stroke for a year was 1.1% for the combination therapy, 2.6% for the rivaroxaban therapy, and 3.4% for the ASA monotherapy with significant differences between the combination treatment group and the ASA monotherapy group (p<0.01). Relative risk of repeated stroke was 67% lower for the combination therapy group compared to the ASA monotherapy group. The combination of rivaroxaban (2.5 mg twice a day) and ASA (100 mg) opens a new epoch of antithrombotic treatment for primary and secondary prevention of stroke in patients with a stable atherosclerotic CVD and sinus rhythm.

Safety and medical cost effectiveness of preventive treatment of children with latent tuberculosis infection

The objective: to assess the safety and medical cost effectiveness of different LTBI treatment regimens in children and adolescents.Subjects and methods. 205 children in the age from 6 to 17 years old with latent tuberculosis infection were included in the study: The main (prospective) group included 31 children who were treated with isoniazid and rifapentine (HRpt). The comparison (retrospective) group included 174 pediatric patients: 128 patients received the regimen consisting of isoniazid and pyrazinamide (HZ), 14 patients received isoniazid and rifampicin (HR), and 32 patients received isoniazid and ethambutol (HE).Results. When using the HRpt regimen, the treatment was well tolerated; adverse events (eosinophilia) were documented in 6.5% of children. The medications were taken once a week and it allowed reducing the frequency of treatment interruptions for non-medical reasons. The overall cost per patient was lower with the HRpt regimen than with the other three LTBI treatment regimens.

PREVENTION OF MYCOSES OF AERIAL ORGANS OF REMONTANT RASPBERRIES USING BACTERIAL BIOAGENTS

The studies were carried out with the aim of assessing the preventive effect of treatment of remontant raspberries with strains of bacteria of the genus Bacillus against mycoses of aerial organs. The research was carried out during 2016–2018 while field experiments on production plantings of remontant raspberries of the agricultural artel “Sady Sibiri” (Novosibirsk region). Plants were treated in the budding phase and at the beginning of fruit filling by spraying the aboveground system with a working fluid containing a bioagent at a concentration of 1 · 104 CFU / ml. The presence of a protective preventive action of saprotrophic bacteria of the genus Bacillus of B. amyloliquefaciens strains VKPM B-10642, B. subtilis VKPM B-10641 and a mixed preparation Fitop 8.67 against gray rot of remontant raspberries with a biological efficiency of 40–46% under conditions of provocative background was revealed. In protection against purple spot and leaf septoria, the effect of strains B. amyloliquefaciens VKPM B-10642, B. subtilis VKPM B-10641, B. licheniformis VKPM B-10562 with a biological efficiency of up to 39–66% was proved. The formulation Fitop 8.67 reduced the level of development of purple spotting of stems by 1.2–1.6 times. Strains B. amyloliquefaciens VKPM B-10642, B. subtilis VKPM B-10641 and Fitop 8.67. The use of it is promising as an ecologically safe method for managing the phytosanitary state of plantations, exhibited an effective and stable protective effect against mycoses of the aerial organs of remontant raspberries.

Failure of preventive treatments in migraine: an observational retrospective study in a tertiary headache center

BackgroundAlthough the criteria for acute migraine treatment and prevention have been well described, there are still unmet needs, general underuse and low benefits of preventive drugs.The aim of the present study was to retrospectively observe the short-term effect of preventive treatment in a cohort of migraine patients attending a tertiary headache center, using data from electronic medical records.MethodsThis was an observational retrospective cohort study based on data collected in a tertiary headache center. Data were extracted from an electronic dataset collected from January 2009 to December 2019. The main selection criteria were as follows: age of 18–75 years; diagnosis of migraine without aura (MO), migraine with aura (MA) or chronic migraine (CM); a control visit 3 months after the first access; and prescription of preventive treatment with level of evidence 1 as reported by Italian guidelines. As the primary outcome, we considered the change in the frequency of headache at the follow-up visit. Then, as secondary outcome measures, we used disability scores, intensity of headache, and allodynia. As predictive factors, we considered age, migraine duration, sex, headache frequency, allodynia, anxiety and depression at baseline, and comorbidity with fibromyalgia.ResultsAmong the 6430 patients screened, 2800 met the selection criteria, 1800 returned to the follow-up visit, 550 withdrew because of adverse events, and 1100 were included the analysis. One hundred thirty-four patients had a frequency reduction of 50% or more. Flunarizine was used for less severe migraine, with a better effect compared to those of other drugs (odds ratio: 1.48; p: 0.022). Low headache frequency and absent or mild allodynia predicted a better outcome.ConclusionsThe mild effect of preventive drugs on migraine features and even the number of patients who were lost to follow-up or dropped out because of adverse events confirm that in severe and chronic patients, the first line of prevention can only delay a more focused therapeutic approach.

Latent tuberculosis infection among university students

Objective : to study the prevalence of latent tuberculosis infection (LTBI) among university students, to evaluate the effectiveness of preventive treatment in students with LTBI. Subjects and methods . In 2016-2019, the three-stage study was conducted that enrolled all university students in the city of Stavropol. In 2016-2017 during the first stage of the study, 4,139 students had tests with tuberculous recombinant allergen (TRA). At the second stage of the study, 141 medical files of students with positive results of TRA tests were retrospectively analyzed, all students were followed up and 133 of them underwent preventive treatment. In 2018-2019 at the third stage of the study, the long-term results of preventive treatment were evaluated. Results. Tests with TRA allowed detecting LTBI and defining indications for preventive treatment with anti-tuberculosis drugs. Among 133 students with LTBI who had preventive treatment, there were no cases of tuberculosis; sensitivity to TRA decreased, which manifested by a decreased induration size during the control test. Thus, in 36 months of follow-up over 83 patients with hyperergic reaction, it persisted only in 4 of them.

Do stickers indicating the use of forensic property marking prevent burglary? Results from a randomized controlled trial

This paper examines whether the posting of sticker decals indicating the use of forensic property marking deters burglary. The study is a randomized controlled trial (RCT). The sampling frame includes all (N = 6603) single-family houses in the municipality of Aarhus, Denmark, that were burgled once or more during the 4 years prior to the experiment. Houses were randomly assigned to treatment (n = 3378) and control (n = 3225). Treatment houses were offered a free forensic property marking kit and asked to post sticker decals around their front doors indicting their use of the product. Control households were not contacted. A process evaluation determined that only one-third (n = 1080) of the houses assigned to treatment requested property marking kits and posted stickers as instructed. An intention-to-treat (ITT) effect analysis was based on the full treatment group despite a low (32%) compliance rate. At the end of a 15½-month observation period, the full treatment group had experienced 21% fewer burglaries than the control group – a difference that is both substantively and statistically significant (χ2 = 5.305, p = 0.021 n = 6608). Analysis revealed that the preventive effect was limited to the beginning of the observation period and declined thereafter. It is therefore possible that some of the overall result may have been due to an “availability effect,” i.e., a heightened vigilance induced by the initial contact letter. The preventive effect of treatment seems incontestable. This said, the full pattern of results suggests that the reduction in burglary was likely due to a combination of treatment and availability effects.

Lowering Risk for Significant Behavior Problems Through Cognitive-Behavioral Intervention: Effects of the Tools for Getting Along Curriculum 2Years Following Implementation.

To address the needs of students at risk for significant behavior problems, educators need efficient, effective, and feasible preventive classroom interventions that increase students' ability to regulate their own behavior. Tools for Getting Along is a universally delivered cognitive-behavioral curriculum designed to address early emotional and behavioral risk among fourth and fifth grade students within the general classroom setting. We used latent growth model statistical methodology to investigate the effects of Tools for Getting Along 2years following treatment cessation on students who evidenced baseline risk relative to peers. We followed an average of 455 students across measure-specific baseline risk groups at pretest, posttest, 1-year post-treatment, and 2-years post-treatment. Growth models fit data for four (behavior regulation, metacognition, aggression, and behavioral adjustment) of the eight factors used to assess emotional and behavioral outcomes. Findings indicated a long-term positive treatment effect for students at baseline risk on behavior regulation and general behavioral adjustment. We discuss how findings related to long-term treatment benefits add to prior research on Tools for Getting Along and to the evaluation of preventive treatment effects on emotional and behavioral risk over time.

The prevalence of sarcopenia and dynapenia according to stage among Alzheimer-type dementia patients.

In this study, the aim was to identify the prevalence of sarcopenia and dynapenia according to disease stage among Alzheimer-type dementia (AD) patients and collect data to suggest precautions related to reducing the disease load. The study was completed with 127 patients separated into stages according to Clinical Dementia Rating Scale (CDR) criteria and 279 healthy volunteers aged 18-39 years and 70-80 years abiding by the exclusion criteria who agreed to participate in the research. Our prospective and cross-sectional study applied the CDR and mini mental test (MMSE) to patients with disorder in more than one cognitive area and possible AD diagnosis according to NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) diagnostic criteria. The patient and control groups had skeletal muscle mass index (SMMI), muscle strength and physical performance assessed with sarcopenia diagnosis according to European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria. In our study, in parallel with the increase in disease stage of AD patients, the prevalence of sarcopenia (led by severe sarcopenia) and dynapenia was higher compared to a control group of similar age. In chronic, progressive diseases, like AD, identification of changes in parameters, like muscle mass and strength and reductions in physical performance in the early period, is important for identification and to take precautions in the initial stages considering the limitations of the preventive effects of treatment applied after diagnosis of AD.

Length of time periods in treatment effect descriptions and willingness to initiate preventive therapy: a randomised survey experiment

BackgroundCommon measures used to describe preventive treatment effects today are proportional, i.e. they compare the proportions of events in relative or absolute terms, however they are not easily interpreted from the patient’s perspective and different magnitudes do not seem to clearly discriminate between levels of effect presented to people.MethodsIn this randomised cross-sectional survey experiment, performed in a Swedish population-based sample (n = 1041, response rate 58.6%), the respondents, aged between 40 and 75 years were given information on a hypothetical preventive cardiovascular treatment. Respondents were randomised into groups in which the treatment was described as having the effect of delaying a heart attack for different periods of time (Delay of Event, DoE): 1 month, 6 months or 18 months. Respondents were thereafter asked about their willingness to initiate such therapy, as well as questions about how they valued the proposed therapy.ResultsLonger DoE:s were associated with comparatively greater willingness to initiate treatment. The proportions accepting treatment were 81, 71 and 46% when postponement was 18 months, 6 months and 1 month respectively. In adjusted binary logistic regression models the odds ratio for being willing to take therapy was 4.45 (95% CI 2.72–7.30) for a DoE of 6 months, and 6.08 (95% CI 3.61–10.23) for a DoE of 18 months compared with a DoE of 1 month. Greater belief in the necessity of medical treatment increased the odds of being willing to initiate therapy.ConclusionsLay people’s willingness to initiate preventive therapy was sensitive to the magnitude of the effect presented as DoE. The results indicate that DoE is a comprehensible effect measure, of potential value in shared clinical decision-making.

Effect of therapy on Quantiferon-Plus response in patients with active and latent tuberculosis infection

Lack of biomarkers for treatment monitoring is listed among the main requirements for next generation assays, as identified globally among tuberculosis (TB) researchers. In this study, we evaluated in a low TB endemic country such as Italy, the effect of preventive therapy on the results obtained in the QuantiFERON TB Plus (QFT-Plus), in a cohort of subjects with latent TB infection (LTBI) and active TB. We found that TB therapy significantly decreased IFN-γ values and number of responders to TB1- and TB2- peptides stimulation in both LTBI and active TB patients. Stratifying LTBI subjects according to the type of preventive TB therapy used, we found that INH treatment but not INH and RIF significantly decreased IFN-γ production. Stratifying the active TB patients according the microbiological status, we found that TB therapy significantly decreased IFN-γ response to antigen present in QFT-Plus test in patients with clinical diagnosis compared to those with a microbiological diagnosis. In conclusions, we demonstrated that TB therapy decreases IFN-γ level in response to antigen present in QFT-Plus test in LTBI and active TB patients. Future studies are needed to better characterize Mtb-specifc response as a potential marker for monitoring TB therapy and preventive treatment effects.

Intranasal administration of probiotic Lactobacillus rhamnosus GG prevents birch pollen-induced allergic asthma in a murine model.

There is an increasing interest in targeted application of probiotic bacteria for prevention and treatment of airway diseases, including allergies. Here, we investigated the beneficial effects of preventive intranasal treatment with probiotics Lactobacillus rhamnosus GG and L.rhamnosus GR-1 in a mouse model of allergic asthma. Lactobacillus rhamnosus was administered intranasally eight times on days 1-4 and 8-11 at 5×108 CFU/dose, followed by a 2-week asthma induction protocol with birch pollen extract on alternating days. Effects of preventive treatment were analyzed based on serum antibody levels, bronchoalveolar lavage cell counts, lung histology, lung cytokine levels, and airway hyperreactivity. Colonization and translocation of L.rhamnosus were assessed by bacterial cell counts in nasal mucosa, fecal samples, cervical lymph nodes, and blood. Binding of fluorescent L.rhamnosus to fixed murine nasal mucosal cells and airway macrophages was visualized by fluorescence microscopy. Transient colonization of the murine upper airways by L.rhamnosus GG was demonstrated and was approximately ten times higher compared to L.rhamnosus GR-1. Marked binding of fluorescent L.rhamnosus GG to murine nasal mucosal cells and airway macrophages was visualized. Preventive treatment with L.rhamnosus GG (but not L.rhamnosus GR-1) resulted in a significant decrease in bronchoalveolar lavage eosinophil counts, lung interleukin-13 and interleukin-5 levels, and airway hyperreactivity. A tendency toward a decrease in serum Bet v 1-specific immunoglobulin G1 was likewise observed. Intranasally administered L.rhamnosus GG prevents the development of cardinal features of birch pollen-induced allergic asthma in a strain-specific manner.

Neuroprotective effect of angiotensin II type 2 receptor stimulation in vincristine-induced mechanical allodynia.

Peripheral neuropathy is the major dose-limiting side effect of many currently used chemotherapies, such as vincristine (VCR). We recently demonstrated that candesartan, an angiotensin II type 1 receptor antagonist, was neuroprotective against resiniferatoxin-induced sensory neuropathy, and that this effect is mediated by stimulation of the angiotensin II type 2 receptor (AT2R). Thus, we evaluated the effect of preventive treatment with candesartan and a specific AT2R agonist, C21, on a mouse model of VCR-induced neuropathy. Vincristine was administered daily for 7 days to male Swiss mice. Treatment with candesartan and C21 was started on day 1, before VCR treatment, and continued until day 7. We evaluated the development of VCR-induced neuropathy and the effect of treatment by functional tests, immunohistochemical analyses of intraepidermal nerve fibers and dorsal root ganglia neurons, and ultrastructural analysis of the sciatic nerve. Mice treated with VCR showed high mechanical allodynia but no modifications of motor performance or mechanical/thermal nociception. Treatment with candesartan and C21 completely restored normal tactile sensitivity of VCR-treated mice. Both drugs prevented VCR-induced nonpeptidergic intraepidermal nerve fiber loss. Only C21 displayed neuroprotective effects against VCR-induced loss and enlargement of myelinated nerve fibers in the sciatic nerve. Our finding that candesartan and C21 are protective against VCR-induced neuropathic pain through AT2R stimulation favors evaluation of its therapeutic potential in patients receiving chemotherapy.

Efficacy and Acceptability of Interventions for Attenuated Positive Psychotic Symptoms in Individuals at Clinical High Risk of Psychosis: A Network Meta-Analysis.

Background: Attenuated positive psychotic symptoms represent the defining features of the clinical high-risk for psychosis (CHR-P) criteria. The effectiveness of each available treatment for reducing attenuated positive psychotic symptoms remains undetermined. This network meta-analysis (NMA) investigates the consistency and magnitude of the effects of treatments on attenuated positive psychotic symptoms in CHR-P individuals, weighting the findings for acceptability.Methods: Web of Science (MEDLINE), PsycInfo, CENTRAL and unpublished/gray literature were searched up to July 18, 2017. Randomized controlled trials in CHR-P individuals, comparing at least two interventions and reporting on attenuated positive psychotic symptoms at follow-up were included, following PRISMA guidelines. The primary outcome (efficacy) was level of attenuated positive psychotic symptoms at 6 and 12 months; effect sizes reported as standardized mean difference (SMD) and 95% CIs in mean follow-up scores between two compared interventions. The secondary outcome was treatment acceptability [reported as odds ratio (OR)]. NMAs were conducted for both primary and secondary outcomes. Treatments were cluster-ranked by surface under the cumulative ranking curve values for efficacy and acceptability. Assessments of biases, assumptions, sensitivity analyses and complementary pairwise meta-analyses for the primary outcome were also conducted.Results: Overall, 1,707 patients from 14 studies (57% male, mean age = 20) were included, representing the largest evidence synthesis of the effect of preventive treatments on attenuated positive psychotic symptoms to date. In the NMA for efficacy, ziprasidone + Needs-Based Intervention (NBI) was found to be superior to NBI (SMD = −1.10, 95% CI −2.04 to −0.15), Cognitive Behavioral Therapy-French and Morrison protocol (CBT-F) + NBI (SMD = −1.03, 95% CI −2.05 to −0.01), and risperidone + CBT-F + NBI (SMD = −1.18, 95% CI −2.29 to −0.07) at 6 months. However, these findings did not survive sensitivity analyses. For acceptability, aripiprazole + NBI was significantly more acceptable than olanzapine + NBI (OR = 3.73; 95% CI 1.01 to 13.81) at 12 months only. No further significant NMA effects were observed at 6 or 12 months. The results were not affected by inconsistency or evident small-study effects, but only two studies had an overall low risk of bias.Conclusion: On the basis of the current literature, there is no robust evidence to favor any specific intervention for improving attenuated positive psychotic symptoms in CHR-P individuals.

34. IMPROVING THE DETECTION OF INDIVIDUALS AT RISK OF PSYCHOSIS

Overall : Research findings from the past two decades have opened new opportunities for ameliorating outcomes of psychosis through indicated primary prevention in individuals at clinical high risk for psychosis (CHR-P), which can result in delayed or prevented onset of first episode.To optimize these benefits, available research has mostly focused on improving the prognostic accuracy and the effectiveness of preventive treatments for individuals at CHR-P.However, research evidence published in the recent years indicates that despite the prominence of the CHR state, difficulty remains in identifying all individuals who may later develop psychosis. In particular, there is converging evidence indicating that most individuals who will develop a first episode are not currently benefiting from indicated prevention. There is thus a pressing and urgent need to enhance our ability to detect the individuals who are at risk. Identifying at-risk individuals who will later develop psychosis (true positives) is particularly challenging. This symposium acknowledges these challenges by reviewing the empirical validity of the CHR-P construct for detecting individuals at risk of psychosis. At the same time, the symposium suggests specific and differential strategies for overcoming these challenges in secondary mental health care, primary care, or the community.The first speaker (Dr. Shah) will discuss the relevance of the CHR-P construct for identifying individuals at risk for psychosis. Dr. Shah found that over half of the first episode cases in a catchment area had experienced CHR-P like features prior to their illness onset, while a substantial minority of first episode cases had not. This indicates that not all the first episode cases did pass through a CHR-P like stage, thereby providing an initial estimate of what proportion of first episode cases could be prevented through interventions at the CHR-P stage.The second speaker (Dr. Fusar-Poli) will discuss the effectiveness of current CHR-P detection strategies in secondary mental health care. Dr. Fusar-Poli found that only a tiny minority (5%) of first episode cases accessing secondary mental health were detected by the local CHR-P service that had been fully established in the Trust. This study developed and validated an individualised risk calculator that can improve the detection of individuals at risk of psychosis in secondary mental health care.The third speaker (Dr. Perez) will discuss how to improve detection of individuals at risk for psychosis within primary care. Dr. Perez will present a cluster-randomised controlled trial assessing whether increased specific liaison with primary care improves the clinical effectiveness and cost-effectiveness of detection of people at high risk of developing a first psychotic illness. This study showed that intensive outreach to improve liaison with primary care is clinically and cost effective for improving the detection of at risk cases.The fourth speaker (Dr. Calkins) will discuss the importance of investigating psychosis risk as a dynamic developmental process. Dr. Calkins will present a neurodevelopment prospective study evaluating subclinical symptoms in the community. This study showed that an integrated and multidimensional evaluation of youths with early psychotic-like experiences can enrich our ability to detect individuals at risk of psychosis in the general public.These findings will be then appraised and critically integrated by the discussant, prof. Craig Morgan.

The Neuroprotective Effects of Long-Term Repetitive Transcranial Magnetic Stimulation on the Cortical Spreading Depression-induced Damages in Rat's Brain.

Introduction:Cortical Spreading Depression (CSD) is a propagating wave of neural and glial cell depolarization with important role in several clinical disorders. Repetitive Transcranial Magnetic Stimulation (rTMS) is a potential tool with preventive treatment effects in psychiatric and neuronal disorders. In this paper, we study the effects of rTMS on CSD by using behavioral and histological approaches in hippocampus and cortical regions.Methods:Twenty-four rats were divided into four groups. A group of control rats were kept in their home cage during the experiment. The CSD group received four CSD inductions during 4 weeks with 1 week intervals. The CSD-rTMS group were treated with rTMS stimulation (figure-eight coils, 20 Hz, 10 min/d) for 4 weeks. The fourth group, i.e. rTMS group received rTMS stimulation similar to the CSD-rTMS group without CSD induction.Results:Long-term rTMS application in treated groups significantly reduced production of dark neurons, increased the mean volume of normal neurons, and decreased the number of apoptotic neurons in cortical regions compared to the control group. The protective effects of long-term treatment by rTMS in the hippocampal regions were also studied. It was effective in some regions; however, rTMS effects on hippocampal regions were lower than cortical ones.Conclusion:Based on the study results, rTMS has significant preventive and protective effects in CSD-induced damages in cortical and hippocampal regions of the rat’s brain.

Palivizumab Prophylaxis in Preterm Infants and Subsequent Recurrent Wheezing. Six-Year Follow-up Study.

Respiratory syncytial virus (RSV) induces not only infantile recurrent wheezing but also potentially atopic asthma. To test the effect of RSV infection on development of subsequent atopic asthma, we evaluated whether palivizumab, an anti-RSV monoclonal antibody, by preventing severe RSV disease in the first year of life, could impact subsequent recurrent wheezing and atopic asthma at 6 years of age. During the 2007 to 2008 RSV season, the decision to administer palivizumab was made based on standard medical practice and an observational prospective multicenter (n = 52) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed from 0 to 3 years (preceding Committee on Recurrent Wheezing study). The 52 investigators at hospitals then followed these subjects until 6 years of age, reported here (Effects of Preventive Treatment for Respiratory Syncytial [RS] Virus Infection During Infancy on Later Atopic Asthma in Preterm Infants; Scientific Committee for Elucidation of Infantile Asthma). Parents of study subjects reported the infants' physicians' assessment of recurrent wheezing, using a report card and a novel mobile phone-based reporting system using the Internet. The primary endpoint was the incidence of atopic asthma. Of 444 preterm infants enrolled, 349 received palivizumab during the first year of life. At 6 years, atopic asthma was not different in the groups: 15.3 and 18.2% of infants in the treated and untreated groups, respectively (P = 0.57). On the other hand, physician-diagnosed recurrent wheezing was observed in 15.3 and 31.6% in the treated and untreated groups, respectively (P = 0.003). Palivizumab prophylaxis administered to preterm infants did not suppress the onset of atopic asthma but resulted in a significantly lower incidence of recurrent wheezing during the first 6 years. Clinical trial registered with www.clinicaltrials.gov (NCT 01545245).

Effect of preventive treatment in EAE mouse model transplanted with DN T cells transformed from CD4 T cells

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has long served as an animal model for human MS. Both diseases are characterized by inflammation and demyelination of the CNS. Lots of study confirmed that Th1 and Th17 cells could aggravate the illness, while Foxp3+ regulatory T cells (Treg cells) could inhibit the autoimmune reaction and limit disease progression. However, it has been studied that both the number and immune suppression function of Treg cells were reduced in EAE mice, and although myelin specific Treg cells accumulated in the CNS, it failed to control autoimmune inflammation. Based on that, promoting immune regulation by other regulatory cells may be a new strategy to restore immune homeostasis and control EAE. Many studies have demonstrated that in peripheral lymphoid tissues of normal mice and healthy humans, 1% to 3% of T cell receptor positive T cells are double negative T cells (DN T cells), which capable of down regulating immune responses. We have identified a new differentiation pathway for the conversion of CD4 T cells to DN T cells, which could large amount DN T cells in vitro in a short time. We have showed that the converted DN T cells retained a stable phenotype and expressed a unique set of cell surface markers and gene profiles. These cells were highly potent in suppressing allo- and auto-immune responses both in vitro and in vivo in an antigen specific manner. Adoptive cell therapy using these antigen specific DN T cells could prevent and cure autoimmune diabetes and promote islet allograft survival in NOD mice. In a ConA mediated liver injury model, CD4 T cell converted DN T cells exerted significant protection against immune mediated liver injury and maintained the homeostasis of the immune system. Up to now, there is no report on the role of these converted DNT cells in mouse EAE model. In this study, we further explored the protection and its mechanism of DN T cells on EAE. CD4 T cells were converted to antigen specific DN T cells in vitro with MOG35–55 stimulation. Then we adoptive transferred these antigen specific DN T cells to mice before EAE immunization. Time of disease onset, EAE score, mouse weight, lymphocyte infiltration were compared between EAE control group and DNT pre-treatment group, the inhibitory function of DN T cells on pathogenic CD4 T cells from EAE model were further explored. Our data showed that a single adoptive transfer of MOG35–55 primed DN T cells significantly lowered the EAE score, prevented the weight loss and reduced lymphocytes infiltration in brain tissue. DN T cells pre-treatment group contained lower plasma IL-2 and IL-4 levels compared to EAE control group. In vitro suppression assays showed DN T cells significantly suppressed the proliferation of inflammatory CD4 T cells from EAE mice. Our data suggests that DN T cells can significantly reduce the EAE severity. This preventive effect is partly due to DN T cells’ suppression on the proliferation and cytokine production of inflammatory CD4 T cells. DN T cells may have a potential clinical application in the prevention and treatment of MS.

Neuroprotective Effects of Electroacupuncture Preventive Treatment in Senescence-Accelerated Mouse Prone 8 Mice

To investigate the preventive treatment effects of electroacupuncture (EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8 (SAMP8) mice. The 5-month-old male SAMP8 and age-matched homologous normal aging mice (SAMR1) were adopted in this study. EA stimulation at Baihui (GV 20) and Yintang (EX-HN 3) was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β (A β) expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, A β expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting A β-containing aggregates.

A new approach for investigating neurodegenerative disorders in mice based on DSC

In this work, we develop a new approach based on differential scanning calorimetry (DSC) for diagnostics and characterization of the changes in the brain at molecular and supramolecular level associated with drug-induced neurodegenerative disorders. In order to test the DSC potential, we used an experimental animal model of scopolamine-induced dementia of Alzheimer’s disease (AD) type. The DSC measurements taken on supernatants of brain tissue homogenates isolated from healthy animals and animals with scopolamine-induced dementia showed that heat capacity curves for animals with scopolamine-induced dementia strongly differ from the respective curves for healthy animals. The effects of preventive treatments with various substances and their combinations expected to have protective effect and hinder the development of AD (myrtenal, ellagic acid, lipoic acid, ascorbic acid) are also clearly displayed in the calorimetric scans. These measurements show that DSC is an appropriate method for detection and characterization of the compositional changes taking place in affected by dementia brain tissues.