Chemosensing of fat digestion by the expression pattern of GPR40, GPR120, CD36 and enteroendocrine profile in sheep.

Gastrointestinal tract (GIT) epithelial cells detect nutrients in the lumen via G-protein coupled receptors (GPRs) located in the gut epithelial cells especially in enteroendocrine cells. Dietary free fatty acids (FFA) are the major energy source and also acts as signalling molecules for FFA receptors. Long chain fatty acids (LCFA) activate LCFA receptors, GPR40/FFAR1 and GPR120/FFAR4 which trigger intracellular signalling and release gut hormones or modifies gene expression that facilitate fat digestion and absorption. However, there is a paucity of information on chemosensing of nutrients and digestion in ruminants. Hence, present study was aimed to evaluate chemosensing of fat digestion and absorption by the expression pattern of GPR40, GPR120, chylomicron forming genes, fatty acid translocase (CD36/FAT), microsomal triglyceride transfer protein (MTTP) and apolipoprotein B (APOB) in the various segments of GIT in sheep supplemented with calcium salts of long chain fatty acids (CSLCFAs) along with the secretory patterns of gut peptides cholecystokinin (CCK) and peptide tyrosine tyrosine (PYY). The study was carried out for a period 60 days with eighteen adult ewes of 8-12 months of age and they were divided into three groups with six animals each as group-I, group-II and group-III. All the experimental animals were stall fed with a basal diet and maintained as per animal husbandry standards. Group-II and group-III were supplemented additionally with 3% and 5% CSLCFAs, respectively on dry matter intake. The results from the study indicated that the supplementation of CSLCFAs upregulated (P < 0.05) the relative mRNA expression of GPR40 and GPR120 in the various segments of GIT of sheep in correspondence to level of dietary fat. Abundance of mRNA expression of CD36, MTTP and APOB increased (P < 0.05) in the GIT of sheep in accordance to quantity of LCFAs in the diet where these genes facilitate fatty acid uptake. Feeding of CSLCFAs enhanced (P < 0.05) pre-feeding level of CCK from day 15 onwards, whereas, post-feeding CCK and PYY increased in all the experimental sheep. However, the increase was higher (P < 0.05) in sheep supplemented with CSLCFAs by 10.80 ± 1.45% and 14.25 ± 1.17%, respectively in comparison to group-I. The comprehensive results of the study concluded that feeding of additional CSLCFAs upregulated the expression of GPR40, GPR120, CD36, and chemosensing of LCFAs by these genes triggered the signalling transduction that enhanced CCK and PYY levels to facilitate fat digestion and absorption in accordance with quantity of dietary fat. This was further evident from the significant upregulation of MTTP and APOB in the various segments of GIT supported the high content of dietary fat at cellular fat metabolism in the gut that regulates the fatty acid uptake.

A randomized open label efficacy clinical trial of oral guava leaf decoction in patients with acute infectious diarrhoea.

BACKGROUND: Diarrhoea is amongst the first ten causes of death and its treatment faces an increased threat of drug resistance. Previous studies on the guava leaf decoction (GLD) revealed its suitability for use in infectious diarrhoea of unknown etiology. OBJECTIVE: The objective of this trial was to establish efficacy, dose and safety of GLD prepared from the Indian Sardar variety in adults with acute infectious diarrhoea. METHODS: The current trial was an open efficacy randomized 5-day, parallel group multi-arm interventional study. Amongst 137 adults (18-60 years) suffering with acute diarrhoea, 109 were included (57% females, 43% males). Three doses of GLD (6-leaf, 10-leaf and 14-leaf) were compared with controls receiving oral rehydration solution. Decrease in stool frequency and improvement in consistency were the outcomes measured. The data was analyzed using ANOVA, Tukey's post-hoc test, Kruscal-Wallis test and Chi-Square test where applicable. RESULTS: The trial showed that the 14-leaf (7.4 g) decoction was the most effective. Administration of the decoction, thrice daily helped the patients regain normalcy in 72 h as opposed to 120 h in controls. Safety of the intervention was reflected by normal levels of haemoglobin, liver and kidney parameters. No adverse events were reported. CONCLUSION: The 14 leaves decoction was a safe treatment for adult acute uncomplicated diarrhoea of unknown etiology. Moreover due to component synergy and divergent mechanisms of action, it could possibly combat the generation of drug resistance and destruction of gut microbiota. Hence GLD has the potential for development as a first line treatment for diarrhoea. TRIAL REGISTRATION: Trial was registered with Clinical Trials Registry - India (CTRI registration number: CTRI/2016/07/007095). The trial was retrospectively registered.

Simulating human sleep spindle MEG and EEG from ion channel and circuit level dynamics.

BACKGROUND: Although they form a unitary phenomenon, the relationship between extracranial M/EEG and transmembrane ion flows is understood only as a general principle rather than as a well-articulated and quantified causal chain. METHOD: We present an integrated multiscale model, consisting of a neural simulation of thalamus and cortex during stage N2 sleep and a biophysical model projecting cortical current densities to M/EEG fields. Sleep spindles were generated through the interactions of local and distant network connections and intrinsic currents within thalamocortical circuits. 32,652 cortical neurons were mapped onto the cortical surface reconstructed from subjects' MRI, interconnected based on geodesic distances, and scaled-up to current dipole densities based on laminar recordings in humans. MRIs were used to generate a quasi-static electromagnetic model enabling simulated cortical activity to be projected to the M/EEG sensors. RESULTS: The simulated M/EEG spindles were similar in amplitude and topography to empirical examples in the same subjects. Simulated spindles with more core-dominant activity were more MEG weighted. COMPARISON WITH EXISTING METHODS: Previous models lacked either spindle-generating thalamic neural dynamics or whole head biophysical modeling; the framework presented here is the first to simultaneously capture these disparate scales. CONCLUSIONS: This multiscale model provides a platform for the principled quantitative integration of existing information relevant to the generation of sleep spindles, and allows the implications of future findings to be explored. It provides a proof of principle for a methodological framework allowing large-scale integrative brain oscillations to be understood in terms of their underlying channels and synapses.

Steady state and induced auditory gamma deficits in schizophrenia.

Steady state auditory evoked potentials (SSAEPs) in the electroencephalogram (EEG) and magnetoencephalogram (MEG) have been reported to be reduced in schizophrenia, most consistently to frequencies in the gamma range (40 Hz and greater). The current study evaluated the specificity of this deficit over a broad range of stimulus frequencies and harmonics, the relationship between phase locking and signal power, and whether induced 40 Hz activity was also affected. SSAEPs to amplitude modulated tones from 5 to 50 Hz were obtained from subjects with schizophrenia (SZ) and healthy control subjects in 5 Hz steps. Time-frequency spectral analysis was used to differentiate EEG activity synchronized in phase across trials using Phase Locking Factor (PLF) and Mean Power (MP) change from baseline activity. In the SSAEP frequency response condition, patients with SZ showed broad band reductions in both PLF and MP. In addition, the control subjects showed a more pronounced increase in PLF with increases in power compared to SZ subjects. A noise pulse embedded in 40 Hz stimuli resulted in a transient reduction of PLF and MP at 40 Hz in control subjects, while SZ showed diminished overall PLF. Finally, induced gamma (around 40 Hz) response to unmodulated tone stimuli was also reduced in SZ, indicating that disturbances in this oscillatory activity are not confined to SSAEPs. In summary, SZ subjects show impaired oscillatory responses in the gamma range across a wide variety of experimental conditions. Reduction of PLF along with reduced MP may reflect abnormalities in the auditory cortical circuits, such as a reduction in pyramidal cell volume, spine density and alterations in GABAergic neurons.

Insights into linear and nonlinear cochlear transduction: application of a new system-identification procedure on transient-evoked otoacoustic emissions data.

Transient-evoked otoacoustic emissions (TEOAE) were used to characterize linear and nonlinear cochlear transduction using a new system-identification procedure. In this technique, a computational model of the system is first developed. From the measured stimulus and response records, spectral-density functions and multiple coherence functions are calculated. The coherence functions allow the characterization of linear/nonlinear processes as a function of frequency. Summations of linear and nonlinear coherences provide a goodness-of-fit of the chosen model. Finite impulse response pulses with a bandwidth of 1-8 kHz were used to evoke otoacoustic emissions. Eleven adults with normal hearing served as subjects. Third- and fifth-order polynomial models were used to model the data, and the results indicate that the fifth-order model is a better fit to the TEOAE data. The results of this study suggest that this system-identification procedure can be successfully applied to model cochlear transduction using a broadband stimulus. Most importantly, coherence functions provide useful insights into linear and nonlinear cochlear processes and have the potential to be developed as a clinical measure for monitoring changes in cochlear status.

The effects of subcortical lesions on evoked potentials and spontaneous high frequency (gamma-band) oscillating potentials in rat auditory cortex.

Functional subdivisions of auditory cortex in the rat were identified based on the distribution of temporal components of the mid-latency auditory evoked potential (MAEP) recorded with a multichannel epipial electrode array. Spontaneous data collected from the same location exhibited spindle-shaped bursts of oscillations in the gamma-band (20-40 Hz) whose location and spatial distribution were similar to that of the MAEP complex in that the bursts were localized to primary and secondary auditory cortex, the principle targets of thalamocortical projections. This suggested that the neural generators of these electrophysiological events may be similar. However, ablation of the medial geniculate nucleus (MG) of the thalamus revealed that while this nucleus is required for the generation of MAEPs, it is not required for the generation of spontaneous gamma-band oscillations. Ablation of subcortical cholinergic nuclei revealed that cholinergic input via the thalamus or the basal forebrain is not necessary for the generation of either MAEPs or spontaneous gamma-band oscillations recorded in this study. These results indicated that there may be networks of cells in sensory cortical areas endowed with an intrinsic capacity to oscillate independently of sensory or cholinergic input, but that may be modulated by this input.

Nasal scarring by joss stick burns.

Vasomotor rhinitis is a common condition in Malaysia. Patients' dissatisfaction with medical treatment of this recurring condition leads them to seek other forms of traditional cures. This paper highlights the complications in such patients who seek traditional cures for their chronic condition.