Rejected

Neurotransmitters released at the neural synapse through vesicle exocytosis are spatiotemporally controlled by the action of neurotransmitter transporters. Integral membrane proteins of the solute carrier 6 (SLC6) family are involved in the sodium and chloride coupled uptake of biogenic amine neurotransmitters including dopamine, serotonin, noradrenaline and inhibitory neurotransmitters including glycine and γ-amino butyric acid. This ion-coupled symport works through a well-orchestrated gating of substrate through alternating-access, which is mediated through movements of helices that resemble a rocking-bundle. A large array of commercially prescribed drugs and psychostimulants selectively target neurotransmitter transporters thereby modulating their levels in the synaptic space. Drug-induced changes in the synaptic neurotransmitter levels can be used to treat depression or neuropathic pain whereas in some instances prolonged usage can lead to habituation. Earlier structural studies of bacterial neurotransmitter transporter homolog LeuT and recent structure elucidation of the dopamine transporter (dDAT) and human serotonin transporter (hSERT) have yielded a wealth of information in understanding the transport and inhibition mechanism of neurotransmitter transporters. Computational studies based on the structures of dDAT and hSERT have shed light on the dynamics of varied components of these molecular gates in affecting the uphill transport of neurotransmitters. This review seeks to address structural dynamics of neurotransmitter transporters at the extracellular and intracellular gates and the effect of inhibitors on the ligand-binding pocket. We also delve into the effect of additional factors including lipids and cytosolic domains that influence the translocation of neurotransmitters across the membrane.

Diabetes induces sensory symptoms of neuropathy as positive (hyperalgesia), negative (hypoalgesia), or both.

Abdominal pain is a common complaint in children and its differential diagnosis includes inflammatory bowel disease (IBD). The aim of the study was to assess the diagnostic accuracy of scintigraphy with 99mTechnetium Hexamethylpropyleneamine Oxime (99mTc-HMPAO) labeled leukocytes in children with suspected IBD.

Trichobezoar is a rare cause of bowel obstruction. In general, Trichobezoars are composed of hair and usually found incidentally in patients undergoing upper gastrointestinal endoscopy or imaging. Patients diagnosed with Trichobezoar may have psychiatric disorders.

To evaluate feasibility and acceptability of a sub-threshold exercise program with minimal in-person visits to treat youth with persistent sport-related concussion, and explore efficacy for improving concussive symptoms, health-related quality of life, and fear-avoidance. We conducted a pilot randomized controlled trial comparing a 6 week sub-threshold exercise program requiring only two in-person visits to active control (stretching) for 12-18 year old youth with persistent sport-related concussion. We measured moderate-to-vigorous physical activity pre- and post-intervention using accelerometry, and increased goals weekly via phone contact. We examined feasibility and acceptability using qualitative interviews. We used exponential regression to model differences in trajectory of concussive symptoms by experimental group, and linear regression to model differences in trajectory of health-related quality of life and fear-avoidance of pain by experimental group. Thirty-two subjects randomized, 30 completed the study ( = 11 control, = 19 intervention), 57 female. Youth and parents reported enjoying participating in the study and appreciated the structure and support, as well as the minimal in-person visits. Exponential regression modeling indicated that concussive symptoms declined more rapidly in intervention youth than control ( = 0.02). Health-related quality of life and fear-avoidance of pain improved over time, but were not significantly different by group. This study indicates feasibility and potential benefit of a 6 week subthreshold exercise program with minimal in-person visits for youth with persistent concussion. Potential factors that may play a role in improvement such as fear-avoidance deserve further study.

Excessive hindfoot pronation, talotarsal joint (TTJ) instability, has been attributed to an increase in medial knee compartment pathology. Advocacy for hindfoot realignment has been the subject of research. An internal solution for TTJ instability, extra-osseous talotarsal stabilization (EOTTS), exists but its effect on knee forces is unknown. This is the first study to measure the in vivo forces acting within the medial knee compartment before and after EOTTS. We hypothesized that following EOTTS there should be a reduction of force acting on the medial knee compartment.

Acute administration of remifentanil may lead to opioid-induced hyperalgesia (OIH). Studies in mice suggest that OIH is mediated by impaired anionic homeostasis in spinal lamina I neurons due to a down-regulation of the K-Cl co-transporter KCC2, which was reverted using acetazolamide (ACTZ), a carbonic anhydrase inhibitor. We propose that ACTZ prevents remifentanil-mediated OIH in humans.

Considering the heavy burden of migraine, it is essential to update insufficient and/or outdated clinical evidence supporting electroacupuncture (EA) in migraine therapy. In this study, a literature search of seven medical databases was performed. After data extraction and quality evaluation, 13 randomized controlled trials, including 1559 patients, were assessed in this analysis. Results demonstrated that EA was superior to control treatment (Western medicine, sham-EA, blank control, acupuncture, and acupoint catgut embedding) according to the visual analog scale (VAS) score, frequency of headache attack (Western medicine, sham-EA, blank control), self-rating anxiety scale (SAS [blank control]), self-rating depression score (SDS [Western medicine and blank control]), and clinical efficiency (Western medicine and sham-EA) after treatment (). Results of network meta-analysis (for VAS, SAS, and SDS) demonstrated statistically significant differences in VAS scores for EA compared with sham-EA, acupuncture with sham-EA, acupoint catgut embedding with sham-EA, and acupoint catgut embedding with blank control. Rank probability analysis of VAS, SAS, and SDS scores all demonstrated that EA ranked first. Most studies were symmetrically distributed on both sides of the midline in funnel plots for VAS, SAS, and SDS, which indicated a low likelihood of small sample effects. Sensitivity analysis confirmed the stability of the studies included in this research. EA is one of several effective treatments for migraine pain symptoms, and, to some extent, anxiety and depression. Nevertheless, multi-center studies with large sample sizes and/or well-designed randomized controlled trials (RCTs) will be needed in the future.

The objective of this work is to document the epidemiological, clinical, and etiological features of prurigo in children.

AKB48 is a designer drug belonging to the indazole synthetic cannabinoids class, illegally sold as herbal blend, incense, or research chemicals for their psychoactive cannabis-like effects. In the present study, we investigated the pharmacological and behavioral effects of AKB48 in male rats and measured the pharmacodynamic effects of AKB48 and simultaneously determined its plasma pharmacokinetic. AKB48 at low doses preferentially stimulated dopamine release in the nucleus accumbens shell (0.25 mg/kg) and impaired visual sensorimotor responses (0.3 mg/kg) without affecting acoustic and tactile reflexes, which are reduced only to the highest dose tested (3 mg/kg). Increasing doses (0.5 mg/kg) of AKB48 impaired place preference and induced hypolocomotion in rats. At the highest dose (3 mg/kg), AKB48 induced hypothermia, analgesia, and catalepsy; inhibited the startle/pre-pulse inhibition test; and caused cardiorespiratory changes characterized by bradycardia and mild bradipnea and SpO2 reduction. All behavioral and neurochemical effects were fully prevented by the selective CB receptor antagonist/inverse agonist AM251. AKB48 plasma concentrations rose linearly with increasing dose and were correlated with changes in the somatosensory, hypothermic, analgesic, and cataleptic responses in rats. For the first time, this study shows the pharmacological and behavioral effects of AKB48 in rats, correlating them to the plasma levels of the synthetic cannabinoid. AKB48 (PubChem CID: 57404063); AM251 (PubChem CID: 2125).