Malnutrition in Sub – Saharan Africa: burden, causes and prospects

Malnutrition is estimated to contribute to more than one third of all child deaths, although it is rarely listed as the direct cause. Contributing to more than half of deaths in children worldwide; child malnutrition was associated with 54% of deaths in children in developing countries in 2001. Poverty remains the major contributor to this ill. The vicious cycle of poverty, disease and illness aggravates this situation. Grooming undernourished children causes children to start life at mentally sub optimal levels. This becomes a serious developmental threat. Lack of education especially amongst women disadvantages children, especially as far as healthy practices like breastfeeding and child healthy foods are concerned. Adverse climatic conditions have also played significant roles like droughts, poor soils and deforestation. Sociocultural barriers are major hindrances in some communities, with female children usually being the most affected. Corruption and lack of government interest and investment are key players that must be addressed to solve this problem. A multisectorial approach is vital in tackling this problem. Improvement in government  policy, fight against corruption, adopting a horizontal approach in implementing programmes at community level must be recognized. Genetically modified foods to increase food production and to survive adverse climatic conditions could be gateways in solving these problems. Socio cultural peculiarities of each community are an essential base line consideration for the implementation of any nutrition health promotion programs.Key words: Malnutrition, Sub–Saharan Africa, corruption, multisectorial approac

The subcutaneous movements of filarial infective larvae are impaired in vaccinated hosts in comparison to primary infected hosts

Our aim in this study was to observe the movements of filarial infective larvae following inoculation into the mammalian host and to assess the effect of vaccination on larval migration, in situ. Here we present recordings of larvae progressing through the subcutaneous tissues and inguinal lymph node of primary infected or vaccinated mice. We used the filaria Litomosoides sigmodontis in BALB/c mice that were necropsied 6 hours after the challenge inoculation of 200 larvae. Subcutaneous tissue sections were taken from the inoculation site and larvae were filmed in order to quantify their movements. Our analyses showed that the subcutaneous larvae were less motile in the vaccinated mice than in primary-infected mice and had more leucocytes attached to the cuticle. We propose that this reduced motility may result in the failure of a majority of larvae to evade the inflammatory reaction, thereby being a possible mechanism involved in the early vaccine-induced protection

HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

Histone deacetylases (HDACs) regulate the acetylation of histones in the control of gene expression. Many non-histone proteins are also targeted for acetylation, including TGF-ß signalling pathway components such as Smad2, Smad3 and Smad7. Our studies in mouse C3H10T1/2 fibroblasts suggested that a number of TGF-ß-induced genes that regulate matrix turnover are selectively regulated by HDACs. Blockade of HDAC activity with trichostatin A (TSA) abrogated the induction of a disintegrin and metalloproteinase 12 (Adam12) and tissue inhibitor of metalloproteinases-1 (Timp-1) genes by TGF-ß, whereas plasminogen activator inhibitor-1 (Pai-1) expression was unaffected. Analysis of the activation of cell signalling pathways demonstrated that TGF-ß induced robust ERK and PI3K activation with delayed kinetics compared to the phosphorylation of Smads. The TGF-ß induction of Adam12 and Timp-1 was dependent on such non-Smad signalling pathways and, importantly, HDAC inhibitors completely blocked their activation without affecting Smad signalling. Analysis of TGF-ß-induced Adam12 and Timp-1 expression and ERK/PI3K signalling in the presence of semi-selective HDAC inhibitors valproic acid, MS-275 and apicidin implicated a role for class I HDACs. Furthermore, depletion of HDAC3 by RNA interference significantly down-regulated TGF-ß-induced Adam12 and Timp-1 expression without modulating Pai-1 expression. Correlating with the effect of HDAC inhibitors, depletion of HDAC3 also blocked the activation of ERK and PI3K by TGF-ß. Collectively, these data confirm that HDACs, and in particular HDAC3, are required for activation of the ERK and PI3K signalling pathways by TGF-ß and for the subsequent gene induction dependent on these signalling pathways

In vivo evaluation of demyelination and remyelination in a nerve crush injury model

Nerves of the peripheral nervous system have, to some extent, the ability to regenerate after injury, particularly in instances of crush or contusion injuries. After a controlled crush injury of the rat sciatic nerve, demyelination and remyelination are followed with functional assessments and imaged both ex vivo and in vivo over the course of 4 weeks with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy. A new procedure compatible with live animal imaging is developed for performing histomorphometry of myelinated axons. This allows quantification of demyelination proximal and remyelination distal to the crush site ex vivo and in vivo respectively

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Light smoking at base-line predicts a higher mortality risk to women than to men; evidence from a cohort with long follow-up

BACKGROUND: There is conflicting evidence as to whether smoking is more harmful to women than to men. The UK Cotton Workers’ Cohort was recruited in the 1960s and contained a high proportion of men and women smokers who were well matched in terms of age, job and length of time in job. The cohort has been followed up for 42 years. METHODS: Mortality in the cohort was analysed using an individual relative survival method and Cox regression. Whether smoking, ascertained at baseline in the 1960s, was more hazardous to women than to men was examined by estimating the relative risk ratio women to men, smokers to never smoked, for light (1–14), medium (15–24), heavy (25+ cigarettes per day) and former smoking. RESULTS: For all-cause mortality relative risk ratios were 1.35 for light smoking at baseline (95% CI 1.07-1.70), 1.15 for medium smoking (95% CI 0.89-1.49) and 1.00 for heavy smoking (95% CI 0.63-1.61). Relative risk ratios for light smoking at baseline for circulatory system disease was 1.42 (95% CI 1.01 to 1.98) and for respiratory disease was 1.89 (95% CI 0.99 to 3.63). Heights of participants provided no explanation for the gender difference. CONCLUSIONS: Light smoking at baseline was shown to be significantly more hazardous to women than to men but the effect decreased as consumption increased indicating a dose response relationship. Heavy smoking was equally hazardous to both genders. This result may help explain the conflicting evidence seen elsewhere. However gender differences in smoking cessation may provide an alternative explanation

Intracellular mechanisms underlying the nicotinic enhancement of LTP in the rat dentate gyrus

We have previously shown that activation of nicotinic acetylcholine receptors (nAChRs) enhanced long-term potentiation (LTP) in the rat dentate gyrus in vitro via activation of α7 nAChR. In the present studies, mechanisms underlying the acute and chronic nicotinic enhancement of LTP were examined. In particular, the involvement of activation of intracellular kinases was examined using selective kinase antagonists, and the effects of enhancing cholinergic function with positive allosteric modulators of the α7 nAChR and with acetylcholinesterase (AChE) inhibitors were also investigated. Activation of extracellular signal-regulated kinase (ERK) and cAMP-dependent protein kinase (PKA) was found to be involved in the induction of the acute nicotinic enhancement of LTP, although not control LTP. In contrast, activation of the tyrosine kinase Src, Ca2+-calmodulin-dependent protein kinase II, Janus kinase 2 and p38 mitogen-activated protein kinase was not involved in the acute nicotinic enhancement of LTP, although Src activation was necessary for control LTP. Moreover, activation of phosphoinositide 3-kinase was involved in the acute nicotinic enhancement of LTP to a much lesser extent than in control LTP. Chronic nicotine enhancement of LTP was found to be dependent on PKA, ERK and Src kinases. Acute nicotinic enhancement of LTP was occluded by chronic nicotine treatment. The positive allosteric modulator PNU-120596 was found to strongly reduce the threshold for nicotinic enhancement of LTP, an affect mediated via the α7 nAChR as it was blocked by the selective antagonist methyllycaconitine. The AChE inhibitors tacrine and physostigmine enhanced control LTP

Mucosal Macrophages in Intestinal Homeostasis and Inflammation

Intestinal macrophages are essential for local homeostasis and in keeping a balance between commensal microbiota and the host. However, they also play essential roles in inflammation and protective immunity, when they change from peaceful regulators to powerful aggressors. As a result, activated macrophages are important targets for treatment of inflammatory bowel diseases such as Crohn's disease. Until recently, the complexity and heterogeneity of intestinal macrophages have been underestimated and here we review current evidence that there are distinct populations of resident and inflammatory macrophages in the intestine. We describe the mechanisms that ensure macrophages remain partially inert in the healthy gut and cannot promote inflammation despite constant exposure to bacteria and other stimuli. This may be because the local environment ‘conditions’ macrophage precursors to become unresponsive after they arrive in the gut. Nevertheless, this permits some active, physiological functions to persist. A new population of pro-inflammatory macrophages appears in inflammation and we review the evidence that this involves recruitment of a distinct population of fully responsive monocytes, rather than alterations in the existing cells. A constant balance between these resident and inflammatory macrophages is critical for maintaining the status quo in healthy gut and ensuring protective immunity when required

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

Reconsidering frameworks of Alzheimer’s dementia when assessing psychosocial outcomes

The purpose of this introductory article to the special issue on psychosocial outcome measures in Alzheimer’s & Dementia: Translational Research & Clinical Interventions is to outline new frameworks to more effectively capture and measure the full range of how people living with Alzheimer’s dementia and their family caregivers experience the disease process. Specifically, we consider the strengths and weaknesses of alternative perspectives, including person‐centered, strength‐based, and resilience‐focused approaches that may complement and extend the dominant deficit paradigm to reflect the entirety of the dementia experience. Our aim is to encourage innovative methods to measure psychosocial aspects of Alzheimer’s dementia and caregiving that have not yet received sufficient attention, including resources (e.g., services and supports) and positive caregiver and care recipient outcomes (e.g., positive mood and adaptation).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152840/1/trc2jtrci201902008.pd