Original Article Gum Arabic in treatment of functional constipation in children in Sudan

Background: Constipation represents a common problem in children. The worldwide prevalence of functional constipation in children varies from 0.7% to 29.6%.Objective: The aim of this study is to assess the response to Gum Arabic in addition to laxative in management of functional constipation.Methods: All children less than 16 years old who suffered from constipation and attended Gaafar Ibnaouf Specialized Children Hospital and  gastroenterology private clinic of one pediatric gastroenterologist between June 2011 and May 2012 were included in this study. Patients were considered having functional constipation according to Rome III criteria. They were divided randomly into two similar groups. Children in the first group were treated with laxative (lactulose), and those in the second group were treated with Gum Arabic in addition to laxative (lactulose), children in both groups were educated about the process of developing constipation, defecation process and approach to toilet training. All children were seen after 1month and 3 months after treatment, they were rated as successfully treated when they had .3 bowel movements per week, soft stool, no soiling or abdominal pain in the last 3weeks of treatment.Results: A total of 150 children suffered from constipation were seen. (81males), the age was divided into three groups, the majority 96 (64 %) aged between 1-5years, and the least were 12 (8%) aged less than 1year. 133 children (88.7%) had functional constipation, while the remaining 17 children (11.3%) had an associated organic disorders, among them 12 children (8%) had Hirschsprungfs disease, 2 children (1.3%) had hypothyroidism, 2 children (1.3%) had celiac disease, and 1child (0.7%) had cerebral palsy. The main clinical characteristic of functional constipation were faecal impaction presented in 59.4% of patients, straining in 43%, withholding behavior in 32.3%, soiling in 16.5%, abdominal pain in12% of patients. In those who were treated with Gum Arabic, 41/63 (65%) showed improvement at 1st month of treatment and 59/63 (93.6%) at 3rd month of treatment, while those who were treated with laxative alone showed that 34/60(56.66%) improved at 1month of treatment and 48/60 (80%) at 3rd month, with p value <0.025Conclusions: Functional constipation is the most cause of constipation in Sudanese children. Gum Arabic achieved better results than laxative alone in treatment of functional constipation.Keywords: Hirschsprungfs disease, hypothyroidism, faecal impaction

Pattern and clinical presentation of constipation in children in Sudan

Background: Constipation represents a common problem in children. The worldwide prevalence of functional constipation in children varies from 0.7% to 29.6%. The aim of this study is to identify common causes of childhood constipation, clinical profiles of functional constipation.Methods: all children less than 16years old who suffered from constipation and attended Gaafar Ibnaouf specialized children hospital and gastroenterology private clinic of one pediatric gastroenterologist between June 2011 and May 2012 were included in this study. Patients wereconsidered having functional constipation if there were no objective evidences of pathological condition, and the rest were termed as organic constipation.Results: a total of 150 children suffered from constipation were seen. (81males), the age was divided into three groups, the majority 96 (64 %) aged between 1-5years, and the least were 12 (8%) aged less than 1year.133 children (88.7%) had functional constipation, while the remaining 17 children (11.3%) had an associated organic disorders, among them 12 children (8%) had Hirschsprung’s disease, 2children (1.3%) had hypothyroidism, 2 children (1.3%) had celiac disease,and 1child (0.7%) had cerebral palsy. The main clinical characteristic of functional constipation were faecal impaction presented in 59.4% of patients, straining in 43%, withholding behavior in 32.3%, soiling in 16.5%, abdominal pain in12% of patients.Conclusions: Functional constipation is the most common cause of constipation in Sudanese children.Keywords: functional constipation, hypothyroidism, Hirschsprung

Threshold photoelectron photoion coincidence spectroscopy of trichloroethene and tetrachloroethene

The threshold photoelectron, the threshold photoelectron photoion coincidence and ion breakdown spectra of trichloroethene and tetrachloroethene have been recorded from 9 – 22 eV. Comparisons with the equivalent data for the three dichloroethene molecules and theoretical calculations highlight the nature of the orbitals involved during photoionisation in this energy range. The ground electronic state of C$_2$HCl$_3^+$ (C$_2$Cl$_4^+$) is bound, with excited valence states dissociating to C$_2$HCl$_2^+$ (C$_2$Cl$_3^+$) and C$_2$HCl$^+$ (C$_2$Cl$_2^+$). Appearance energies suggest that C$_2$HCl$^+$ forms from C$_2$HCl$_3^+$ by loss of two chlorine atoms, whereas C$_2$Cl$_2^+$ forms from C$_2$Cl$_4^+$ by loss of a Cl$_2$ molecule. The translational kinetic energy release into C$_2$HCl$_2^+$ (C$_2$Cl$_3^+$) + Cl is determined as a function of energy. In both cases, the fraction of the available energy released into translational energy of the two products decreases as the photon energy increases

The photoionization dynamics of the three structural isomers of dichloroethene

Using tunable vacuum-UV radiation from a synchrotron, the threshold photoelectron spectrum, threshold photoelectron photoion coincidence spectrum and ion breakdown diagram of the 1,1, cis-1,2 and trans-1,2 isomers of C$_2$H$_2$Cl$_2$ have been recorded in the range 9-23 eV. The energies of the peaks in the threshold photoelectron spectrum are in good agreement with outer-valence Greens function caculations. The major difference between the isomers, both predicted and observed experimentally is that the F and G states of C$_2$H$_2$Cl$_2^+$ are approximately degenerate for 1,1 and trans-1,2, but well separated for the cis-1,2 isomer. The ground and low-lying valence states of C$_2$H$_2$Cl$_2^+$ are bound, with higher-lying states dissociating to C$_2$H$_2$Cl$^+$ or C$_2$H$_2^+$. The translational kinetic energy release into C$_2$H$_2$Cl$^+$ + Cl is determined as a function of energy. Isolated-state behaviour for the low-lying electronic states of C$_2$H$_2$Cl$_2^+$ becomes more statistical as the energy increases

Simulation of the deflected cutting tool trajectory in complex surface milling

Since industry is rapidly developing, either locally or globally, manufacturers witness harder challenges due to the growing competitivity. This urges them to better consider the four factors linked to production and output: quality, quantity, cost and price, quality being of course the most important factor which constitutes their main concern. Efforts will be concentrated—in this research—on improving the quality and securing more accuracy for a machined surface in ball-end milling. Quality and precision are two essential criteria in industrial milling. However, milling errors and imperfections, duemainly to the cutting tool deflection, hinder the full achieving of these targets. Our task, all along this paper, consists in studying and realizing the simulation of the deflected cutting tool trajectory, by using the methods which are available. In a future stage, and in the frame of a deeper research, the simulation process will help to carry out the correction and the compensation of the errors resulting from the tool deflection. The corrected trajectory which is obtained by the method mirror will be sent to the machine. To achieve this goal, the next process consists—as a first step—in selecting a model of cutting forces for a ball-end mill. This allows to define—later on—the behavior of this tool, and the emergence of three methods namely the analytical model, the finite elements method, and the experimental method. It is possible to tackle the cutting forces simulation, all along the tool trajectory, while this latter is carrying out the sweeping of the part to be machined in milling and taking into consideration the cutting conditions, as well as the geography of the workpiece. A simulation of the deflected cutting tool trajectory dependent on the cutting forces has been realized

Open complete dislocation of trapezium with a vertically split fracture: a case report

Open complete dislocation of the trapezium is an extraordinarily rare injury with only a few cases reported so far in literature. The association of a vertically split fracture makes this injury even rare and hence worth reporting. A 14 year old Kashmiri boy presented to us with a history of massive trauma to the non dominant left hand sustained as a result of a blow from a heavy hammer. The thenar area was burst out and the trapezium was vertically split apart into two halves which were dislocated from the articular surfaces of the scaphoid as well as the first metacarpal. The mechanism of injury as in other such reported cases was a massive direct force localized over the carpal bone which causes its enucleation and fracture. Although some authors have recommended excision of the dislocated trapezium, open reduction of the fracture dislocation and fixation with K wires was carried out under General anesthesia. At the end of one year although there was some functional deficit in the affected thumb, especially in opposition, the patient was quite satisfied with the outcome as this was the non dominant hand

Selective Modulation of α5 GABAA Receptors Exacerbates Aberrant Inhibition at Key Hippocampal Neuronal Circuits in APP Mouse Model of Alzheimer’s Disease

Selective negative allosteric modulators (NAMs), targeting α5 subunit-containing GABAA receptors (GABAARs) as potential therapeutic targets for disorders associated with cognitive deficits, including Alzheimer’s disease (AD), continually fail clinical trials. We investigated whether this was due to the change in the expression of α5 GABAARs, consequently altering synaptic function during AD pathogenesis. Using medicinal chemistry and computational modeling, we developed aqueous soluble hybrids of 6,6-dimethyl-3-(2-hydroxyethyl) thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophene-4(5H)-one, that demonstrated selective binding and high negative allosteric modulation, specifically for the α5 GABAAR subtypes in constructed HEK293 stable cell-lines. Using a knock-in mouse model of AD (APPNL−F/NL−F), which expresses a mutant form of human amyloid-β (Aβ), we performed immunofluorescence studies combined with electrophysiological whole-cell recordings to investigate the effects of our key molecule, α5-SOP002 in the hippocampal CA1 region. In aged APPNL−F/NL−F mice, selective preservation of α5 GABAARs was observed in, calretinin- (CR), cholecystokinin- (CCK), somatostatin- (SST) expressing interneurons, and pyramidal cells. Previously, we reported that CR dis-inhibitory interneurons, specialized in regulating other interneurons displayed abnormally high levels of synaptic inhibition in the APPNL−F/NL−F mouse model, here we show that this excessive inhibition was “normalized” to control values with bath-applied α5-SOP002 (1 μM). However, α5-SOP002, further impaired inhibition onto CCK and pyramidal cells that were already largely compromised by exhibiting a deficit of inhibition in the AD model. In summary, using a multi-disciplinary approach, we show that exposure to α5 GABAAR NAMs may further compromise aberrant synapses in AD. We, therefore, suggest that the α5 GABAAR is not a suitable therapeutic target for the treatment of AD or other cognitive deficits due to the widespread neuronal-networks that use α5 GABAARs

Diazepam-induced loss of inhibitory synapses mediated by PLCδ/ Ca²⁺/calcineurin signalling downstream of GABAA receptors

Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABA_{A}Rs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effects of benzodiazepines in patients. However, extended benzodiazepine treatments lead to development of tolerance, a process which, despite its important therapeutic implications, remains poorly characterised. Here we report that prolonged exposure to diazepam, the most widely used benzodiazepine in clinic, leads to a gradual disruption of neuronal inhibitory GABAergic synapses. The loss of synapses and the preceding, time- and dose-dependent decrease in surface levels of GABA_{A}Rs, mediated by dynamin-dependent internalisation, were blocked by Ro 15-1788, a competitive benzodiazepine antagonist, and bicuculline, a competitive GABA antagonist, indicating that prolonged enhancement of GABA_{A}R activity by diazepam is integral to the underlying molecular mechanism. Characterisation of this mechanism has revealed a metabotropic-type signalling downstream of GABA_{A}Rs, involving mobilisation of Ca²⁺ from the intracellular stores and activation of the Ca²⁺/ calmodulin-dependent phosphatase calcineurin, which, in turn, dephosphorylates GABA_{A}Rs and promotes their endocytosis, leading to disassembly of inhibitory synapses. Furthermore, functional coupling between GABA_{A}Rs and Ca²⁺ stores was sensitive to phospholipase C (PLC) inhibition by U73122, and regulated by PLCδ, a PLC isoform found in direct association with GABA_{A}Rs. Thus, a PLCδ/Ca²⁺/ calcineurin signalling cascade converts the initial enhancement of GABA_{A}Rs by benzodiazepines to a long-term downregulation of GABAergic synapses, this potentially underpinning the development of pharmacological and behavioural tolerance to these widely prescribed drugs

Identifying the favored mutation in a positive selective sweep.

Most approaches that capture signatures of selective sweeps in population genomics data do not identify the specific mutation favored by selection. We present iSAFE (for "integrated selection of allele favored by evolution"), a method that enables researchers to accurately pinpoint the favored mutation in a large region (∼5 Mbp) by using a statistic derived solely from population genetics signals. iSAFE does not require knowledge of demography, the phenotype under selection, or functional annotations of mutations