Paediatric referrals in rural Tanzania: the Kilombero District Study – a case series

BACKGROUND: Referral is a critical part of appropriate primary care and of the Integrated Management of Childhood Illness (IMCI) strategy. We set out to study referrals from the aspect both of primary level facilities and the referral hospital in Kilombero District, southern Tanzania. Through record review and a separate prospective study we estimate referral rates, report on delays in reaching referral care and summarise the appropriateness of pediatric referral cases in terms of admission to the pediatric ward at a district hospital METHODS: A sample of patient records from primary level government health facilities throughout 1993 were summarised by age, diagnosis, whether a new case or a reattendance, and whether or not they were referred. From August 1994 to July 1995, mothers or carers of all sick children less than five years old attending the Maternal and Child Health (MCH) clinic or outpatient department (OPD) of SFDDH were interviewed using a standard questionnaire recording age, sex, diagnosis, place of residence, whether the child was admitted to the paediatric ward, and whether the child was referred. RESULTS: From record review, only 0.6% of children from primary level government facilities were referred to a higher level of care. At the referral hospital, 7.8 cases per thousand under five catchment population had been referred annually. The hospital MCH clinic and OPD were generally used by children who lived nearby: 91% (n = 7,166) of sick children and 75% (n = 607) of admissions came from within 10 km. Of 235 referred children, the majority (62%) had come from dispensaries. Almost half of the referrals (48%) took 2 or more days to arrive at the hospital. Severe malaria and anaemia were the leading diagnoses in referred children, together accounting for a total of 70% of all the referrals. Most referred children (167/235, 71%) were admitted to the hospital paediatric ward. CONCLUSIONS: The high admission rate among referrals suggests that the decision to refer is generally appropriate, but the low referral rate suggests that too few children are referred. Our findings suggest that the IMCI strategy may need to be adapted in sparsely-populated areas with limited transport, so that more children may be managed at peripheral level and fewer children need referral

Rupture by damage accumulation in rocks

The deformation of rocks is associated with microcracks nucleation and propagation, i.e. damage. The accumulation of damage and its spatial localization lead to the creation of a macroscale discontinuity, so-called "fault" in geological terms, and to the failure of the material, i.e. a dramatic decrease of the mechanical properties as strength and modulus. The damage process can be studied both statically by direct observation of thin sections and dynamically by recording acoustic waves emitted by crack propagation (acoustic emission). Here we first review such observations concerning geological objects over scales ranging from the laboratory sample scale (dm) to seismically active faults (km), including cliffs and rock masses (Dm, hm). These observations reveal complex patterns in both space (fractal properties of damage structures as roughness and gouge), time (clustering, particular trends when the failure approaches) and energy domains (power-law distributions of energy release bursts). We use a numerical model based on progressive damage within an elastic interaction framework which allows us to simulate these observations. This study shows that the failure in rocks can be the result of damage accumulation

Riluzole-Rasagiline Hybrids: Toward the Development of Multi-Target-Directed Ligands for Amyotrophic Lateral Sclerosis

Polypharmacology is a new trend in amyotrophic lateral sclerosis (ALS) therapy and an effective way of addressing a multifactorial etiology involving excitotoxicity, mitochondrial dysfunction, oxidative stress, and microglial activation. Inspired by a reported clinical trial, we converted a riluzole (1)-rasagiline (2) combination into single-molecule multi-target-directed ligands. By a ligand-based approach, the highly structurally integrated hybrids 3-8 were designed and synthesized. Through a target- and phenotypic-based screening pipeline, we identified hit compound 6. It showed monoamine oxidase A (MAO-A) inhibitory activity (IC50 = 6.9 mu M) rationalized by in silico studies as well as in vitro brain permeability. By using neuronal and non-neuronal cell models, including ALS-patient-derived cells, we disclosed for 6 a neuroprotective/neuroinflammatory profile similar to that of the parent compounds and their combination. Furthermore, the unexpected MAO inhibitory activity of 1 (IC50 = 8.7 mu M) might add a piece to the puzzle of its anti-ALS molecular profile

Kidins220/ARMS Is a Novel Modulator of Short-Term Synaptic Plasticity in Hippocampal GABAergic Neurons

Kidins220 (Kinase D interacting substrate of 220 kDa)/ARMS (Ankyrin Repeat-rich Membrane Spanning) is a scaffold protein highly expressed in the nervous system. Previous work on neurons with altered Kidins220/ARMS expression suggested that this protein plays multiple roles in synaptic function. In this study, we analyzed the effects of Kidins220/ARMS ablation on basal synaptic transmission and on a variety of short-term plasticity paradigms in both excitatory and inhibitory synapses using a recently described Kidins220 full knockout mouse. Hippocampal neuronal cultures prepared from embryonic Kidins220−/− (KO) and wild type (WT) littermates were used for whole-cell patch-clamp recordings of spontaneous and evoked synaptic activity. Whereas glutamatergic AMPA receptor-mediated responses were not significantly affected in KO neurons, specific differences were detected in evoked GABAergic transmission. The recovery from synaptic depression of inhibitory post-synaptic currents in WT cells showed biphasic kinetics, both in response to paired-pulse and long-lasting train stimulation, while in KO cells the respective slow components were strongly reduced. We demonstrate that the slow recovery from synaptic depression in WT cells is caused by a transient reduction of the vesicle release probability, which is absent in KO neurons. These results suggest that Kidins220/ARMS is not essential for basal synaptic transmission and various forms of short-term plasticity, but instead plays a novel role in the mechanisms regulating the recovery of synaptic strength in GABAergic synapses

Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development

The growth factor family of neurotrophins has major roles both inside and outside the nervous system. Here, we report a detailed histological analysis of key phenotypes generated by the ablation of the Kinase D interacting substrate of 220 kDa/Ankyrin repeat-rich membrane spanning (Kidins220/ARMS) protein, a membrane-anchored scaffold for the neurotrophin receptors Trk and p75NTR. Kidins220 is important for heart development, as shown by the severe defects in the outflow tract and ventricle wall formation displayed by the Kidins220 mutant mice. Kidins220 is also important for peripheral nervous system development, as the loss of Kidins220 in vivo caused extensive apoptosis of DRGs and other sensory ganglia. Moreover, the neuronal-specific deletion of this protein leads to early postnatal death, showing that Kidins220 also has a critical function in the postnatal brain

An update of malaria infection and anaemia in adults in Buea, Cameroon

<p>Abstract</p> <p>Background</p> <p>Anaemia is caused by many factors in developing countries including malaria. We compared anaemia rates in patients with malaria parasitaemia to that of patients without malaria parasitaemia.</p> <p>Findings</p> <p>A cross-sectional study was carried out from November 2007 to July 2008 in health units in Buea, Cameroon. Adult patients with fever or history of fever were included in the study. Information on socio-demographic variables and other variables was collected using a questionnaire. Malaria parasitaemia status was determined by microscopy using Giemsa stained thick blood smears. Haemoglobin levels were determined by the microhaematocrit technique.</p> <p>The study population consisted of 250 adult patients with a mean age of 29.31 years (SD = 10.63) and 59.44% were females. 25.60% of the patients had malaria parasitaemia while 14.80% had anaemia (haemoglobin < 11 g/dl). Logistic regression revealed that those with malaria parasitaemia had more anaemia compared to those without malaria parasitaemia(OR = 4.33, 95%CI = 1.21-15.43, p = 0.02) after adjusting for age, sex, rural residence, socioeconomic status, use of antimalarials, use of insecticide treated nets(ITN) and white blood cell count.</p> <p>Conclusions</p> <p>In adult patients with fever in this setting, malaria parasitaemia contributes to anaemia and is of public health impact. Our results also provide a baseline prevalence for malaria parasitaemia in febrile adults in health units in this setting.</p

Assessment of exposure to DDT and metabolites after indoor residual spraying through the analysis of thatch material from rural African dwellings

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.[Introduction] We report on the analysis of 4,4′-dichlorodiphenyltrichloroethane (4,4′-DDT) and its metabolites in thatch and branch samples constituting the wall materials of dwellings from South African subtropical areas. This approach was used to assess the exposure to DDT in the residents of the dwellings after indoor residual spraying (IRS) following recommended sanitation practices against malaria vectors.[Discussion] Examination of the distributions of DDT compounds (2,4′-DDT, 4,4′-DDT and its metabolites) in 43 dwellings from the area of Manhiça (Mozambique) has shown median concentrations of 19, 130, and 23 ng/g for 2,4′-DDT, 4,4′-DDT, and 4,4′-DDE, respectively, in 2007 when IRS implementation was extensive. The concentrations of these compounds at the onset of the IRS campaign (n = 48) were 5. 5, 47, and 2. 2 ng/g, respectively. The differences were statistically significant and showed an increase in the concentration of this insecticide and its metabolites. Calculation of 4,4′-DDT in the indoor air resulting from the observed concentrations in the wall materials led to the characteristic values of environments polluted with this insecticide. © 2011 The Author(s).Funding was received from MICINN (INMA G03/176, Consolider Ingenio GRACCIE, CSD2007-00067), CSIC (PIF06-053), and ArcRisk EU Project (FP7-ENV-2008-1-226534).Peer reviewe

Fuzzy Tandem Repeats Containing p53 Response Elements May Define Species-Specific p53 Target Genes

Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retinoblastoma-like 2 (Rbl2) gene to produce p130 in murine, but not human, cells. We found intronic fuzzy tandem repeats containing perfect p53 response elements to be important for this regulation. We next identified two other murine genes regulated by p53 via fuzzy tandem repeats: Ncoa1 and Klhl26. The repeats are poorly conserved in evolution, and the p53-dependent regulation of the murine genes is lost in humans. Our results indicate a role for the rapid evolution of tandem repeats in shaping differences in p53 regulatory networks between mammalian species

Inoculations with Arbuscular Mycorrhizal Fungi Increase Vegetable Yields and Decrease Phoxim Concentrations in Carrot and Green Onion and Their Soils

Background As one of the most widely used organophosphate insecticides in vegetable production, phoxim (C12H15N2O3PS) is often found as residues in crops and soils and thus poses a potential threat to public health and environment. Arbuscular mycorrhizal (AM) fungi may make a contribution to the decrease of organophosphate residues in crops and/or the degradation in soils, but such effects remain unknown. Methodology/Principal Findings A greenhouse pot experiment studied the influence of AM fungi and phoxim application on the growth of carrot and green onion, and phoxim concentrations in the two vegetables and their soil media. Treatments included three AM fungal inoculations with Glomus intraradices BEG 141, G. mosseae BEG 167, and a nonmycorrhizal control, and four phoxim application rates (0, 200, 400, 800 mg l−1, while 400 mg l−1 rate is the recommended dose in the vegetable production system). Carrot and green onion were grown in a greenhouse for 130 d and 150 d. Phoxim solution (100 ml) was poured into each pot around the roots 14d before plant harvest. Results showed that mycorrhizal colonization was higher than 70%, and phoxim application inhibited AM colonization on carrot but not on green onion. Compared with the nonmycorrhizal controls, both shoot and root fresh weights of these two vegetables were significantly increased by AM inoculations irrespective of phoxim application rates. Phoxim concentrations in shoots, roots and soils were increased with the increase of phoxim application rate, but significantly decreased by the AM inoculations. Soil phosphatase activity was enhanced by both AM inocula, but not affected by phoxim application rate. In general, G. intraradices BEG 141 had more pronounced effects than G. mosseae BEG 167 on the increase of fresh weight production in both carrot and green onion, and the decrease of phoxim concentrations in plants and soils. Conclusions/Significance Our results indicate a promising potential of AM fungi for enhancing vegetable production and reducing organophosphorus pesticide residues in plant tissues and their growth media, as well as for the phytoremediation of organophosphorus pesticide-contaminated soils

Spatio-Temporal Dynamics of Human Intention Understanding in Temporo-Parietal Cortex: A Combined EEG/fMRI Repetition Suppression Paradigm

Inferring the intentions of other people from their actions recruits an inferior fronto-parietal action observation network as well as a putative social network that includes the posterior superior temporal sulcus (STS). However, the functional dynamics within and among these networks remains unclear. Here we used functional magnetic resonance imaging (fMRI) and high-density electroencephalogram (EEG), with a repetition suppression design, to assess the spatio-temporal dynamics of decoding intentions. Suppression of fMRI activity to the repetition of the same intention was observed in inferior frontal lobe, anterior intraparietal sulcus (aIPS), and right STS. EEG global field power was reduced with repeated intentions at an early (starting at 60 ms) and a later (∼330 ms) period after the onset of a hand-on-object encounter. Source localization during these two intervals involved right STS and aIPS regions highly consistent with RS effects observed with fMRI. These results reveal the dynamic involvement of temporal and parietal networks at multiple stages during the intention decoding and without a strict segregation of intention decoding between these networks