Can digital rectal examination be used to detect cauda equina compression in people presenting with acute cauda equina syndrome? A systematic review and meta-analysis of diagnostic test accuracy studies.

Background: Digital rectal examination (DRE) is a commonly used test to help identify people with cauda equina compression (CEC).

Objective: To determine the diagnostic accuracy of DRE in assessment of anal tone, squeeze, sensation and reflexes, as predictors of CEC.

Design: A systematic review to investigate the diagnostic accuracy of DRE to detect CEC compared with lumbar Magnetic Resonance Imaging (MRI).

Town-scale microbial sewer community and HS emissions response to common chemical and biological dosing treatments.

Controlling hydrogen sulfide (HS) odors and emissions using a single, effective treatment across a town-scale sewer network is a challenge faced by many water utilities. Implementation of a sewer diversion provided the opportunity to compare the effectiveness of magnesium hydroxide (Mg(OH)) and two biological dosing compounds (Bioproducts A and B), with different modes of action (MOA), in a field-test across a large sewer network. Mg(OH) increases sewer pH allowing suppression of HS release into the sewer environment while Bioproduct A acts to disrupt microbial communication through quorum sensing (QS), reducing biofilm integrity.

Discovery of trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as potent, orally bioavailable TGR5 (GPBAR1) agonists: structure-activity relationships, lead optimization, and chronic in vivo efficacy.

Activation of the G-protein coupled receptor (GPCR) Takeda G-protein receptor 5 (TGR5), also known as G-protein bile acid receptor 1 (GPBAR1), has been shown to play a key role in pathways associated with diabetes, metabolic syndrome, and autoimmune disease. Nipecotamide 5 was identified as an attractive starting point after a high-throughput screen (HTS) for receptor agonists. A comprehensive hit-to-lead effort culminated in the discovery of 45h as a potent, selective, and bioavailable TGR5 agonist to test in preclinical metabolic disease models.

Simple anatomical information improves the accuracy of locating specific spinous processes during manual examination of the low back.

The objective of the study was to test whether a teaching protocol including simple anatomical information on the surface anatomy of spinous processes, improves physiotherapy students' ability to accurately locate selected thoracic and lumbar spinal segments - T12 and L3. First year physiotherapy students were allocated to Group 1 (n=35) and Group 2 (n=34). Both groups were taught to identify spinous processes by counting up from the sacrum, but Group 2 received supplementary anatomical information on the shapes and vertical length of the tips of L5 to T12 spinous processes.

Synthesis and characterization of nonsteroidal glucocorticoid receptor modulators for multiple myeloma.

Structure-activity relationship studies centered around 3'-substituted (Z)-5-(2'-(thienylmethylidene))1,2-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinolines are described. A series of highly potent and efficacious selective glucocorticoid receptor modulators were identified with in vitro activity comparable to dexamethasone. In vivo evaluation of these compounds utilizing a 28 day mouse tumor xenograft model demonstrated efficacy equal to dexamethasone in the reduction of tumor volume.

5(Z)-benzylidene-1,2-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5H-1-aza-6-oxa-chrysenes as non-steroidal glucocorticoid receptor modulators.

A series of 5-benzylidene-1,2-dihydro-2,2,4-trimethyl-5H-1-aza-6-oxa-chrysenes was synthesized and profiled for their ability to act as selective glucocorticoid receptor modulators (SGRMs). The synthesis and structure-activity relationships for this series of compounds are presented.

Effects of 5'-alkyl-benzothiadiazides on (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor biophysics and synaptic responses.

Alkyl-substituted benzothiadiazides (BTDs) were tested for their effects on (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. In excised patches, the 5'-ethyl derivative "D1" blocked the desensitization of AMPA receptor currents during prolonged application of glutamate (EC(50), 36 microM), and it slowed deactivation of responses elicited by 1-ms glutamate pulses greater than 10-fold. [(3)H]Fluorowillardiine binding to rat synaptic membranes was increased by D1 by a factor of 3.

Total synthesis of dysiherbaine.

A convergent total synthesis of the marine natural product dysiherbaine was accomplished. The key steps of the synthesis are an alkylation at the gamma-carbon of a protected glutamate with a highly substituted pyran derived from mannose, which was followed by a ring-contraction cascade reaction, which simultaneously gave the tetrasubstituted carbon and the hexahydrofuro[3,2-b]pyran ring system of the natural product.

5'-alkyl-benzothiadiazides: a new subgroup of AMPA receptor modulators with improved affinity.

AMPA receptors form a major subdivision of the glutamate receptor family that mediates excitatory synaptic transmission in the brain. Currents through AMPA receptors can be up- or down-regulated by compounds that allosterically modulate receptor kinetics through binding sites distinct from that for glutamate. One of those modulators is the benzothiadiazide IDRA-21 which has been reported to enhance synaptic transmission and be effective in behavioral tests, but typically requires threshold concentrations of at least 100 microM to be active in vitro.