Neuroprotective role of vitamin D3 in colchicine-induced Alzheimer’s disease in rats

Background: Alzheimer’s disease (AD) is a complex neurodegenerative disease characterized by progressive decline in memory, language and other cognitive functions. Recent studies provide convincing evidence on the role of vitamin D3 on the nervous system.Aim: To investigate the effect of the active form of vitamin D3 (1,25-dihydroxycholecalciferol) as a neuroprotective agent in experimentally induced AD in rats.Methods: 40 adult male Wistar (albino) rats weighing 180 to 200 g were included in this study. Rats were divided into four groups (each of 10 rats): Group I: normal healthy rats receiving intracerebroventricular injection (icv) of artificial cerebrospinal fluid (ACSF) and serving as a control group. Group II: rats with induced AD by icv colchicine injection of 15 lg/rat bilaterally and receiving no treatment. Group III: rats pre-treated with active form of vitamin D3 42 IU/kg/day subcutaneously (s.c.) for one week followed by induction of AD then post-treated with vitamin D3 in the same dose for 3 weeks. Group IV: rats with induced AD then post-treated with vitamin D3 for 3 weeks. The following parameters were evaluated in rats of all studied groups1- Behavioral assessment: Morris water maze and open field tasks were performed at days   13, 14 and 21 post-icv injection for assessing cognitive, gross behavioral and motor activities of studied groups.2- Biochemical tests: Hippocampal tissue levels of brain derived neurotrophic factor (BDNF), amyloid beta (Ab) peptide, and antioxidant system; glutathione reductase (GR) and glutathione peroxidase (GPX).Results: The present study revealed a significant increase in time latency of water maze test and hippocampal tissue level of Ab peptide concomitant with significant reduction of hippocampal tissue levels of BDNF, GR and GPX, in untreated AD rats (group II) versus control ACSF-injected rats (group I) and vitamin D3-treated AD rats (groups III and IV). However, group III (AD rats pre- and post-treated with vitamin D3) showed a significant decrease in time latency and Ab peptide, and a significant elevation of BDNF, GR and GPX, versus group IV (AD rats post-treated with vitamin D3).Conclusion: Prophylactic use of active form of vitamin D3 (1,25(OH)2D3) appears to possess a neuroprotective effect in AD involving various mechanisms. Hence, vitamin D3 or its analogues can be considered as promising agents for development of new prophylactic and therapeutic neuroprotectors

Introduction to the Workshop

Public health administrators are forced to consider efficiency as a criterion in their choice of preventive programs because of the numerous programs to choose from, restricted budgets, and declining caries experience in children. Interest in cost effectiveness in dental prevention has risen considerably since the initial conference on this issue at the University of Michigan in 1978. This article introduces the goals of the workshop, the nature of the work groups, and the data they will use.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66042/1/j.1752-7325.1989.tb02083.x.pd

Prevalence of Group A beta-haemolytic Streptococcus isolated from children with acute pharyngotonsillitis in Aden, Yemen.

OBJECTIVES: To estimate the prevalence of Group A beta-haemolytic streptococcus (GAS) and non-GAS infections among children with acute pharyngotonsillitis in Aden, Yemen, to evaluate the value of a rapid diagnostic test and the McIsaac score for patient management in this setting and to determine the occurrence of emm genotypes among a subset of GAS isolated from children with acute pharyngotonsillitis and a history of acute rheumatic fever (ARF) or rheumatic heart disease (RHD). METHODS: Group A beta-haemolytic streptococcus infections in school-aged children with acute pharyngotonsillitis in Aden, Yemen, were diagnosed by a rapid GAS antigen detection test (RADT) and/or GAS culture from a throat swab. The RADT value and the McIsaac screening score for patient management were evaluated. The emm genotype of a subset of GAS isolates was determined. RESULTS: Group A beta-haemolytic streptococcus pharyngotonsillitis was diagnosed in 287/691 (41.5%; 95% CI 37.8-45.3) children. Group B, Group C and Group G beta-haemolytic streptococci were isolated from 4.3% children. The RADT had a sensitivity of 238/258 (92.2%) and specificity of 404/423 (95.5%) against GAS culture. A McIsaac score of ≥4 had a sensitivity of 93% and a specificity of 82% for confirmed GAS infection. The emm genotypes in 21 GAS isolates from children with pharyngitis and a history of ARF and confirmed RHD were emm87 (11), emm12 (6), emm28 (3) and emm5 (1). CONCLUSION: This study demonstrates a very high prevalence of GAS infections in Yemeni children and the value of the RADT and the McIsaac score in this setting. More extensive emm genotyping is necessary to understand the local epidemiology of circulating strains

Osteoporosis and fracture as risk factors for self-harm and suicide: a systematic review and meta-analysis

This is the author accepted manuscript. The final version is available from the Royal College of General Practitioners via the DOI in this recordData Sharing Statement: Full search criteria for MEDLINE is included in Supplementary file 1.Background: Increase in presentations of self-harm to primary care, a risk factor of suicide has led to a growing interest in identifying at-risk populations. Aim: To examine whether osteoporosis or fractures are risk factors for self-harm, suicidal ideation, and suicide. Design and Setting: Systematic review of observational studies in adults (18> years) which had examined the role of osteoporosis and/or fractures in subsequent self-harm, suicidal ideation, and/or suicide. Method: Six databases were searched from inception to July 2019. Additional citation tracking of eligible studies was done in November 2022. Screening, data extraction and quality assessment of full-text articles were performed independently by at least two authors. Where possible, meta-analysis was run on comparable risk estimates. Results and Conclusion: Fifteen studies were included, two examined the outcome of self-harm, three suicidal ideation and 10 suicide. In approximately half of studies on osteoporosis, the risk of suicidal ideation and suicide remained significant. However, pooling of adjusted odds ratios from three studies indicated no association between osteoporosis and suicide (1.14(95% confidence interval 0.88-1.49)). Nine studies examined the risk of a mixture of fracture types across different outcomes, limiting comparisons. However, all studies examining vertebral fracture (n=3) reported a significant adjusted negative association for self-harm and suicide. In conclusion, Patients with vertebral fractures may benefit from case-finding for mood disorders in primary care, which are risk factors for suicide, and the subsequent management. However, due to the limited number and quality of studies and mixed findings, further examination of these associations is warranted.National Institute for Health and Care Research (NIHR

TLR2 and Nod2 Mediate Resistance or Susceptibility to Fatal Intracellular Ehrlichia Infection in Murine Models of Ehrlichiosis

Our murine models of human monocytic ehrlichiosis (HME) have shown that severe and fatal ehrlichiosis is due to generation of pathogenic T cell responses causing immunopathology and multi-organ failure. However, the early events in the liver, the main site of infection, are not well understood. In this study, we examined the liver transcriptome during the course of lethal and nonlethal infections caused by Ixodes ovatus Ehrlichia and Ehrlichia muris, respectively. On day 3 post-infection (p.i.), although most host genes were down regulated in the two groups of infected mice compared to naïve counterparts, lethal infection induced significantly higher expression of caspase 1, caspase 4, nucleotide binding oligomerization domain-containing proteins (Nod1), tumor necrosis factor-alpha, interleukin 10, and CCL7 compared to nonlethal infection. On day 7 p.i., lethal infection induced highly significant upregulation of type-1 interferon, several inflammatory cytokines and chemokines, which was associated with increased expression levels of Toll-like receptor-2 (TLR2), Nod2, MyD88, nuclear factor-kappa B (NF-kB), Caspase 4, NLRP1, NLRP12, Pycard, and IL-1β, suggesting enhanced TLR signals and inflammasomes activation. We next evaluated the participation of TLR2 and Nod2 in the host response during lethal Ehrlichia infection. Although lack of TLR2 impaired bacterial elimination and increased tissue necrosis, Nod2 deficiency attenuated pathology and enhanced bacterial clearance, which correlated with increased interferon-γ and interleukin-10 levels and a decreased frequency of pathogenic CD8+ T cells in response to lethal infection. Thus, these data indicate that Nod2, but not TLR2, contributes to susceptibility to severe Ehrlichia-induced shock. Together, our studies provide, for the first time, insight into the diversity of host factors and novel molecular pathogenic mechanisms that may contribute to severe HME. © 2013 Chattoraj et al

A meta-analysis of long-term effects of conservation agriculture on maize grain yield under rain-fed conditions

Conservation agriculture involves reduced tillage, permanent soil cover and crop rotations to enhance soil fertility and to supply food from a dwindling land resource. Recently, conservation agriculture has been promoted in Southern Africa, mainly for maize-based farming systems. However, maize yields under rain-fed conditions are often variable. There is therefore a need to identify factors that influence crop yield under conservation agriculture and rain-fed conditions. Here, we studied maize grain yield data from experiments lasting 5 years and more under rain-fed conditions. We assessed the effect of long-term tillage and residue retention on maize grain yield under contrasting soil textures, nitrogen input and climate. Yield variability was measured by stability analysis. Our results show an increase in maize yield over time with conservation agriculture practices that include rotation and high input use in low rainfall areas. But we observed no difference in system stability under those conditions. We observed a strong relationship between maize grain yield and annual rainfall. Our meta-analysis gave the following findings: (1) 92% of the data show that mulch cover in high rainfall areas leads to lower yields due to waterlogging; (2) 85% of data show that soil texture is important in the temporal development of conservation agriculture effects, improved yields are likely on well-drained soils; (3) 73% of the data show that conservation agriculture practices require high inputs especially N for improved yield; (4) 63% of data show that increased yields are obtained with rotation but calculations often do not include the variations in rainfall within and between seasons; (5) 56% of the data show that reduced tillage with no mulch cover leads to lower yields in semi-arid areas; and (6) when adequate fertiliser is available, rainfall is the most important determinant of yield in southern Africa. It is clear from our results that conservation agriculture needs to be targeted and adapted to specific biophysical conditions for improved impact

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA), updates in 2022-2023. Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease:Opportunities for therapy

This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age-related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid-related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA-related inflammation (CAA-ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid β (Aβ) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy

PhenoWorld : a new paradigm to screen rodent behavior

Modeling depression in animals has inherent complexities that are augmented by intrinsic difficulties to measure the characteristic features of the disorder. Herein, we describe the PhenoWorld (PhW), a new setting in which groups of six rats lived in an ethological enriched environment, and have their feeding, locomotor activity, sleeping and social behavior automatically monitored. A battery of emotional and cognitive tests was used to characterize the behavioral phenotype of animals living in the PhW and in standard conditions (in groups of six and two rats), after exposure to an unpredictable chronic mild stress paradigm (uCMS) and antidepressants. Data reveal that animals living in the PhW displayed similar, but more striking, behavioral differences when exposed to uCMS, such as increased behavioral despair shown in the forced swimming test, resting/sleep behavior disturbances and reduced social interactions. Moreover, several PhW-cage behaviors, such as spontaneous will to go for food or exercise in running wheels, proved to be sensitive indicators of depressive-like behavior. In summary, this new ethological enriched paradigm adds significant discriminative power to screen depressive-like behavior, in particularly rodent's hedonic behavior