Combined Utilisation of Rapid Assessment Procedures for Loiasis (RAPLOA) and Onchocerciasis (REA) in Rain forest Villages of Cameroon

BACKGROUND: Individuals with high microfilarial loads of Loa loa are at increased risk of neurologic serious adverse (SAE) events following ivermectin treatment against onchocerciasis. RAPLOA (Rapid Assessment Procedure for loiasis), a newly developed rapid assessment procedure for loiasis that relates the prevalence of key clinical manifestation of loiasis (history of eye worm) to the level of endemicity of the infection (prevalence of high intensity), is a very useful tool to identify areas at potential risk of L. loa post ivermectin treatment encephalopathy. In a perspective of treatment decision making in areas of co-endemicity of loiasis/onchocerciasis, it would be advantageous (both in time and cost savings) for national onchocerciasis control programmes to use RAPLOA and the Rapid epidemiologic assessment for onchocerciasis (REA), in combination in given surveys. Since each of the two rapid assessment tools have their own specificities, the workability of combining the two methods needed to be tested. METHODS: We worked in 10 communities of a forest area presumed co-endemic for loiasis and onchocerciasis in the North-West Province of Cameroon where the mass-treatment with ivermectin had not been carried out. A four-step approach was used and comprised: (i) generating data on the prevalence and intensity of loiasis and onchocerciasis in an area where such information is scarce; (ii) testing the relationship between the L. loa microfilaraemia prevalence and the RAPLOA prevalence, (iii) testing the relationship between the O. volvulus microfiladermia prevalence and the REA prevalence, (iv) testing the workability of combining RAPLOA/REA by study teams in which a single individual can perform the interview for RAPLOA and the nodule palpation for REA. RESULTS: The microfilaraemia prevalence of loiasis in communities ranged from 3.6% to 14.3%. 6 (0.61%) individuals had L. loa microfilarial loads above 8000 mf/ml but none of them attained 30,000 mf/ml, the threshold value above which the risk of developing neurologic SAE after ivermectin treatment is very high. None of the communities surveyed had RAPLOA prevalence above 40%. All the communities had microfiladermia prevalence above 60%. The microfiladermia results could be confirmed by the rapid epidemiologic method (nodule palpation), with all the 10 communities having REA prevalence above 20%. For the first time, this study has demonstrated that the two rapid assessment procedures for loiasis and onchocerciasis can be carried out simultaneously by a survey team, in which a single individual can administer the questionnaire for RAPLOA and perform the nodule palpation for REA. CONCLUSION: This study has: (i) Revealed that the Momo valley of the North West province of Cameroon is hyperendemic for onchocerciasis, but is of lower level of endemicity for L. loa. (ii) Confirmed the previous relationships established between RAPLOA and the L. loa microfilaraemia prevalence in one hand and between the REA and the O. volvulus microfiladermia prevalence in another hand (iii) Shown that RAPLOA and REA could be used simultaneously for the evaluation of loiasis and onchocerciasis endemicity in areas targeted by the African Programme for onchocerciasis Control for community-directed treatment with ivermectin (CDTI).     

Slow oscillations as a probe of the dynamics of the locus coeruleus-frontal cortex interaction in anesthetized rats

Multiunit or single unit activity recorded simultaneously from frontal cortex (FC) and locus coeruleus (LC) under ketamine anesthesia revealed that both regions show slow oscillatory activity, together or separately. If, however, both regions are engaged in this oscillatory activity, there is a systematic relationship between their phases with peak LC firing always following FC firing by 200–400 ms. This was confirmed by cross-correlational analyses, which indicated that the two structures temporarily form a resonant system. The FC-LC resonant state is, however, loose enough to remain open to other intrinsic or extrinsic influences, keeping the measured frequencies of oscillations at each site slightly different, as demonstrated by a delailed analysis of the autocorrelograms. An injection of lidocaine at the frontal cortex site, while sharply reducing the prefrontal activity to essentially zero, leads to an increase of the LC activity and to a modification of the shape of the LC autocorrelogram, but does not change appreciably the phase relationship between the activity in the two structures during the diminishing activity in FC.     

Rates of nuclear and cytoplasmic mitochondrial DNA sequence divergence in mammals

Differential rates of nucleotide substitution among different gene segments and between distinct evolutionary lineages is well documented among mitochondrial genes and is likely a consequence of locus-specific selective constraints that delimit mutational divergence over evolutionary time. We compared sequence variation of 18 homologous loci (15 coding genes and 3 parts of the control region) among 10 mammalian mitochondrial DNA genomes which allowed us to describe different mitochondrial evolutionary patterns and to produce an estimation of the relative order of gene divergence. The relative rates of divergence of mitochondrial DNA genes in the family Felidae were estimated by comparing their divergence from homologous counterpart genes included in nuclear mitochondrial DNA (Numt, pronounced "new might"), a genomic fossil that represents an ancient transfer of 7.9 kb of mitochondrial DNA to the nuclear genome of an ancestral species of the domestic cat (Felis catus). Phylogenetic analyses of mitochondrial (mtDNA) sequences with multiple outgroup species were conducted to date the ancestral node common to the Numt and the cytoplasmic (Cymt) mtDNA genes and to calibrate the rate of sequence divergence of mitochondrial genes relative to nuclear homologous counterparts. By setting the fastest substitution rate as strictly mutational, an empirical "selective retardation index" is computed to quantify the sum of all constraints, selective and otherwise, that limit sequence divergence of mitochondrial gene sequences over time.      

Metabolomics approach to investigate phytotoxic effects of Wedelia trilobata leaves,litter and soil

Although release and accumulation of plant metabolites from plant into soil can influence allelopathy, little information is known about metabolite changes that occur in leaf, litter and soil. In this study, seed germination bioassay tests and metabolomics analysis were performed to investigate the phytotoxic effects and metabolic variations (measured as buckets) in the ethanolic extracts of leaf, leaf litter and soil of Wedelia trilobata. Increasing the ethanolic extracts concentration of all extracts significantly inhibited Lactuca sativa germination rate (GR), shoot height (SH) and root length (RL). Soil exerted the strongest inhibition but contained the lowest number of buckets relative to those of leaf and leaf litter extracts. An overlap overview on the metabolome revealed a poor bucket overlap and redundancy among the leaf, leaf litter and soil extracts. Canonical correspondence analysis concluded that the SH of L. sativa was more sensitive to leaf litter extract and the leaf extract exerted a strong influence on the GR and RL of L. sativa. Multivariate analysis suggested that the metabolome of the leaf, leaf litter and soil differ substantially. Finally, putative identification using MS/MS data demonstrated various plant metabolites with phytotoxic effects that can contribute to the allelopathy of W. trilobata.     

Ellagic acid mitigates arsenic‐trioxide‐induced mitochondrial dysfunction and cytotoxicity in SH‐SY5Y cells

In the current study, neuroprotective significance of ellagic acid (EA, a polyohenol) was explored by primarily studying its antioxidant and antiapoptotic potential against arsenic trioxide (As₂O₃)‐induced toxicity in SH‐SY5Y human neuroblastoma cell lines. The mitigatory effects of EA with particular reference to cell viability and cytotoxicity, the generation of reactive oxygen species, DNA damage, and mitochondrial dynamics were studied. Pretreatment of SH‐SY5Y cells with EA (10 and 20 μM) for 60 min followed by exposure to 2 μM As₂O₃ protected the SH‐SY5Y cells against the harmful effects of the second. Also, EA pre‐treated groups expressed improved viability, repaired DNA, reduced free radical generation, and maintained altered mitochondrial membrane potential than those exposed to As₂O₃ alone. EA supplementation also inhibited As₂O₃‐induced cytochrome c expression that is an important hallmark for determining mitochondrial dynamics. Thus, the current investigations are more convinced for EA as a promising candidate in modulating As₂O₃‐induced mitochondria‐mediated neuronal toxicity under in vitro system.     

A hassle a day may keep the doctor away: stress and the augmentation of immune function

Stress may be defined as a sequence of events, that begins witha stimulus (stressor), that is recognized by the brain (stressperception), and which results in the activation of physiologicfight/flight/fright systems within the body (stress response).Many evolutionary selection pressures are stressors, and oneof the primary functions of the brain is to perceive stress,warn the body of danger, and enable an organism to respond.We hypothesized that under acute conditions, just as the stressresponse prepares the cardiovascular and musculoskeletal systemsfor fight or flight, it may also prepare the immune system forchallenges (e.g., wounding) which may be imposed by a stressor(e.g., an aggressor). Initial studies showed that acute (2h)stress induced a significant trafficking of immune cells tothe skin. Since the skin is an organism's major protective barrier,we hypothesized that this leukocyte redistribution may serveto enhance skin immunity during acute stress. We tested thishypothesis using the delayed type hypersensitivity (DTH) reaction,which mediates resistance to various infectious agents, as amodel for skin immune function. Acute stress administered immediatelybefore antigen exposure significantly enhanced skin DTH. Adrenalectomy(ADX) eliminated the stress-induced enhancement of DTH whileadministration of physiological doses of corticosterone and/orepinephrine to ADX animals enhanced skin DTH in the absenceof stress. These studies showed that changes in leukocyte distributionand circulating stress hormones are systemic mediators of theimmunoenhancing effects of acute stress. We recently identifiedgamma interferon as a local cytokine mediator of a stress-inducedimmunoenhancement. Our results suggest that during acute stressthe brain sends preparatory warning signals to the immune systemjust as it does to other fight/flight systems of the body.     

Prevalence,Associated Factors and Predictors of Depression among Adults in the Community of Selangor,Malaysia

Introduction

Depression is one of the most common mental health disorders and is an emerging public health problem. The objectives of this paper were to determine the prevalence of depression, its associated factors and the predictors of depression among adults in the community of Selangor.

Methods

A cross sectional study was conducted in three districts in Selangor, from 11th June to 30th December 2012. The sampling frame was obtained from the Department of Statistics Malaysia (DOS) in May 2012, using the National Population and Housing Census 2010. Adults aged 18 years and above, living in the selected living quarters were approached to participate in the study and requested to complete a set of questionnaires.

Results

A total of 1,556 out of 2,152 participants participated in this study, giving an overall study response rate of 61.90%. Patient Health Questionnaire 9 (PHQ-9) was used to determine the presence of depression. The prevalence of depression was 10.3%, based on the PHQ-9 cut off point of 10 and above. Based on multiple logistic regression analysis, the predictors of depression were presence of anxiety, serious problems at work, unhappy relationship with children, high perceived stress, domestic violence, unhappy relationship with spouse, low self-esteem, unhappy relationship with family, serious financial constraint and presence of chronic diseases. When reanalyzed after removing anxiety, high perceived stress and low self-esteem, additional predictors of depression were found to be serious marital problems and religiosity.

Conclusion

The prevalence of depression in this study is similar to that found in other studies. Findings from this study are being used as baseline data to develop an effective program to assist in the management of common mental health disorders in the community, in particular depression. The identification of predictors of depression in the community is important to identify the target population for the program.     

3D morphological and biophysical changes in a single tachyzoite and its infected cells using three‐dimensional quantitative phase imaging

Toxoplasma gondii is an apicomplexan parasite that causes toxoplasmosis in the human body and commonly infects warm‐blooded organisms. Pathophysiology of its diseases is still an interesting issue to be studied since T gondii can infect nearly all nucleated cells. Imaging techniques are crucial for studying its pathophysiology. In T gondii‐infected cells structural and biochemical alterations occurred. To study that modification, we use digital holotomography to investigate the structure and biochemical alteration of single tachyzoite and its infected cells in a label‐free and quantitative manner. Quantification analysis was done by measuring the refractive index distribution, which provides information about the concentration and dry mass of individual cells. This study showed that holotomography could be effectively used to identify the structural and biochemical alteration in tremendously different cells in supporting pathophysiological research in particular for T gondii‐caused diseases.     

Ecological cues, gestation length, and birth timing in African buffalo (Syncerus caffer)

We examined annual variation in the timing of conception andparturition in the African buffalo (Syncerus caffer) and thesynchrony of birth timing with resource cues, using 8 yearsof monthly birth, rainfall, and vegetation data, measured asNormalized Difference Vegetation Index (NDVI). Monthly birthshad the strongest significant correlations with NDVI and rainfalllevels 12 and 13 months in the past, respectively. In addition,the synchrony of current year births corresponds most stronglyto the synchrony of the previous year's NDVI distribution. Becausethe gestation period of buffalo has been estimated to be around11 months, these findings suggest that improved protein levels,occurring approximately a month after the first green flushof the wet season, are either a trigger for conception or conceptionhas evolved to be synchronous with correlated environmentalcues that ensure females enter a period of peak body conditionaround the time of conception and/or parturition. With a gestationperiod of approximately 340 days, parturition occurs to takeadvantage of the period when forage has its highest proteincontent. A comparative analysis of gestation periods withinthe subfamily Bovinae indicates that African buffalo have aprotracted gestation for their body size, which we suggest isan adaptation to their seasonal environment. We also found thatinterannual variation in the birth distribution suggests a degreeof plasticity in the date of conception, and variation in thenumber of calves born each year suggest further synchrony ata timescale longer than a single year.     

Long-term corticosteroid treatment but not chronic stress affects 11β-hydroxysteroid dehydrogenase type I activity in rat brain and peripheral tissues

Long-term treatment (21 days) of male rats with corticosterone in the drinking water caused a significant increase in the activity of the NADP-dependent form of 11β-hydroxysteroid dehydrogenase (11-HSD1) in the pituitary, thymus, and spleen, (marginally in the hippocampus, amygdala and lymph nodes), without having any effect in a number of other central and peripheral tissues. In contrast, repeated restraint stress, although increasing plasma corticosterone to the same level as that observed after its administration, failed to change the activity of this key regulatory enzyme, which allows aldosterone to exert its specific effects in the presence of a large excess of corticosterone. This resistance to elevation in 11-HSD activity was also observed in the thymuses of subordinate rats during social stratification in a visible burrow system. In both cases, the circulating levels of corticosterone were much higher in stressed rats than in control animals. Factors which might account for these differences in response are discussed and compared with the situation in intact cells where, unlike in tissue homogenates, the reduction of 11-dehydrocorticosterone to corticosterone (reductase activity) appears to predominate.