Antimicrobial activities of pomegranate rind extracts: enhancement by addition of metal salts and vitamin C

Background

Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course.

Methods/Design

The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis.

Discussion

This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia.

Trial registration

Current Controlled Trials ISRCTN01897462.     

Actin and myosin isoforms in gallbladder smooth muscle following cholesterol feeding in prairie dogs

Gallbladder smooth muscle contractility decreases after high-cholesterol feeding in prairie dogs. This decrease is not associated with alterations in the total amounts of the contractile proteins actin and myosin. The present study was designed to determine if cholesterol feeding results in alterations in the isoforms of actin and/or myosin heavy chain in gallbladder smooth muscle. Control prairie dogs were fed a trace-cholesterol diet and test animals were fed a high (1.2%)-cholesterol diet for 8 days. Although the proportion of beta-actin was unchanged, the proportion of alpha-actin in the gallbladder was less in the animals fed the high-cholesterol diet (32.6% +/- 1.5% in the control animals and 24.6% +/- 0.4% in the diet animals). On the other hand, the proportion of gamma-actin was significantly greater in the cholesterol-fed animals. There were no significant differences in the proportions of the myosin heavy-chain isoforms between the two groups. Also, there was no change in the volume fraction of smooth muscle in the gallbladders from the two groups. Thus, cholesterol feeding induces a shift in actin isoforms at the same time that there is a decrease in contractility. Whether the altered pattern of actin isoforms is related to the functional changes remains to be determined.     

A Monte Carlo approach for improving transient dopamine release detection sensitivity

Current methods using a single PET scan to detect voxel-level transient dopamine release—using F-test (significance) and cluster size thresholding—have limited detection sensitivity for clusters of release small in size and/or having low release levels. Specifically, simulations show that voxels with release near the peripheries of such clusters are often rejected—becoming false negatives and ultimately distorting the F-distribution of rejected voxels. We suggest a Monte Carlo method that incorporates these two observations into a cost function, allowing erroneously rejected voxels to be accepted under specified criteria. In simulations, the proposed method improves detection sensitivity by up to 50% while preserving the cluster size threshold, or up to 180% when optimizing for sensitivity. A further parametric-based voxelwise thresholding is then suggested to better estimate the release dynamics in detected clusters. We apply the Monte Carlo method to a pilot scan from a human gambling study, where additional parametrically unique clusters are detected as compared to the current best methods—results consistent with our simulations.     

Increased permeability of sheep lung vessels to proteins after Pseudomonas bacteremia

To see whether lung transvascular protein sieving occurred during the period of increased microvascular permeability in response to Pseudomonas bacteremia, we measured lung lymph flow and concentrations of eight protein fractions with molecular radii from 36–96 Å during steady state base line periods and during periods of steady state increased permeability after Pseudomonas infusion in five unanesthetized sheep. Lymph clearance (lymph flow × lymph-plasma concentration ratio) for all of the proteins was markedly increased after Pseudomonas, but, as during base line, clearance still decreased with increasing molecular size. We conclude that Pseudomonas bacteremia causes a marked increase in filtration through lung exchanging vessels. The changes in vessel walls result in decreasing passage of protein molecules with increasing molecular size from 36–96 Å.     

Design, synthesis, and biological activity of peptides which release growth hormone in vitro

Experimental observations showed that the analogs [D-Trp2]- and [D-Phe2]methionine enkephalin amide were weakly active in releasing GH from rat pituitary in vitro. These observations were used to design more active GH-releasing factors. Conformational energy calculations were carried out, and energetically favored conformations of these polypeptides were found. Structural similarities as well as structural differences between active and inactive analogs were examined, and new sequences were predicted. Progressively more active analogs were designed, then synthesized, and tested. This cycle of steps was repeated, each time using structural and chemical concepts as design guides, until a series of very active analogs resulted. The most active analog to date, Tyr-D-Trp-Ala-Trp-D-Phe-NH2, was shown to release GH in vitro at 10-30 ng/ml medium, which is approximately 10(3) times more active than the two starting enkephalin-based analogs. From the structure-activity data, a mechanism for binding at the receptors is formulated, and a comparison is made between the structural relationships of the GH-releasing peptide analogs and the GH inhibitor, somatostatin.     

Selection of Deep Brain Stimulation Candidates in Private Neurology Practices: Referral May Be Simpler than a Computerized Triage System

Objective: The objective of this study is to compare a computerized deep brain stimulation (DBS) screening module (Comparing Private Practice vs. Academic Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX, USA) with traditional triage by a movement disorders specialized neurologist as the gold standard. Methods: The COMPRESS consists of a combination of the Florida Surgical Questionnaire for Parkinson disease (FLASQ‐PD), a cognitive assessment battery provided by MindStreams® (NeuroTrax Corp.), and the Geriatric Depression Scale and the Zung Anxiety Self‐Assessment Scale. COMPRESS resulted in the classification of patients into three categories: “optimal candidate,”“probable candidate,” and “not a good candidate.” Similar categorical ratings made by a referring private practice neurologist and by a trained movement disorders specialist were compared with the ratings generated by COMPRESS. Results: A total of 19 subjects with Parkinson's disease were enrolled from five private neurological practices. The clinical impressions of the private practice neurologist vs. those of the movement disorders specialist were in agreement approximately half the time (10/19 cases). The movement disorders specialist and COMPRESS agreed on 15/19 cases. A further comparison between outcomes from the entire COMPRESS module and the FLASQ‐PD questionnaire by itself resulted in high agreement (18/19 cases in agreement). Conclusions: The COMPRESS agreed with an in‐person evaluation by a movement disorders neurologist approximately 80% of the time. The computerized COMPRESS did not provide any screening advantage over the short FLASQ‐PD paper questionnaire. Larger studies will be needed to assess the utility and cost effectiveness of this computerized triage method for DBS.     

Greater improvement in quality of life following unilateral deep brain stimulation surgery in the globus pallidus as compared to the subthalamic nucleus

While deep brain stimulation (DBS) surgery is a well-accepted treatment for Parkinson disease (PD) that improves overall quality of life (QoL), its effects across different domains of QoL are unclear. The study reported here directly compared the effects of unilateral DBS in subthalamic nucleus (STN) or globus pallidus (GPi) on QoL in 42 non-demented patients with medication-refractory PD. Patients were enrolled in the COMPARE trial, a randomized clinical trial of cognitive and mood effects of STN versus GPi DBS conducted at the University of Florida Movement Disorders Center. Patients underwent motor, mood, verbal fluency and QoL (Parkinson disease questionnaire: PDQ-39) measures before and 6 months following surgery. Groups experienced motor and mood improvements that did not differ by target. Patients with STN DBS evidenced a slight decrement on letter fluency. On average, all patients endorsed better overall QoL after surgery. However, despite similar motor and mood improvements, GPi patients improved more than STN patients (38 vs. 14%, respectively; P = 0.03). Patients reported better QoL on subscales of mobility, activities of daily living (ADLs), emotional well-being, stigma, cognition and discomfort, but not on those of social support and communication. Improvements on the mobility, ADLs, stigma and social support subscales were greater amongst GPi patients. In regression analyses, only depression changes independently predicted changes in overall QoL as well as emotional well-being and social support changes. Within the STN group only, declining category fluency scores correlated with poorer QoL on the communication subscale. Unilateral DBS in both STN and GPi improved QoL overall and in disparate domains 6 months after surgery. Patients receiving GPi DBS reported greater improvements that cannot be explained by differential mood or motor effects; however, verbal fluency changes may have partially contributed to lesser QoL improvements amongst STN patients.     

Middle Meningeal Artery Embolization Using Combined Particle Embolization and n-BCA with the Dextrose 5% in Water Push Technique for Chronic Subdural Hematomas: A Prospective Safety and Feasibility Study

BACKGROUND AND PURPOSE:Embolization of the middle meningeal artery for treatment of refractory or recurrent chronic subdural hematomas has gained momentum during the past few years. Little has been reported on the use of the n-BCA liquid embolic system for middle meningeal artery embolization. We present the technical feasibility of using diluted n-BCA for middle meningeal artery embolization.MATERIALS AND METHODS:We sought to examine the safety and technical feasibility of the diluted n-BCA liquid embolic system for middle meningeal artery embolization. Patients with chronic refractory or recurrent subdural hematomas were prospectively enrolled from September 2019 to June 2020. The primary outcome was the safety and technical feasibility of the use of diluted n-BCA for embolization of the middle meningeal artery. The secondary end point was the efficacy in reducing hematoma volume.RESULTS:A total of 16 patients were prospectively enrolled. Concomitant burr-hole craniotomies were performed in 12 of the 16 patients. Two patients required an operation following middle meningeal artery embolization for persistent symptoms. The primary end point was met in 100% of cases in which there were no intra- or postprocedural complications. Distal penetration of the middle meningeal artery branches was achieved in all the enrolled cases. A 7-day post–middle meningeal artery embolization follow-up head CT demonstrated improvement (>50% reduction in subdural hematoma volume) in 9/15 (60%) patients, with 6/15 (40%) showing an unchanged or stable subdural hematoma. At day 21, available CT scans demonstrated substantial further improvement (>75% reduction in subdural hematoma volume).CONCLUSIONS:Embolization of the middle meningeal artery using diluted n-BCA and ethiodized oil (1:6) is safe and feasible from a technical standpoint. The use of a dextrose 5% bolus improves distal penetration of the glue.

Despite traditional treatment with surgical evacuation, chronic subdural hematomas (cSDHs) tend to have an indolent course with frequent recurrences.¹ In recent years, embolization of the middle meningeal artery (MMA) for treatment of refractory or recurrent cSDH has gained momentum, with recent literature showing a significant reduction in the size of the cSDH as well as lower rates of recurrence.² The primary endovascular techniques used to date have involved the use of polyvinyl alcohol particles (PVA) and Onyx liquid embolic (ethylene-vinyl alcohol dissolved in dimethyl-sulfoxide; Medtronic). Another commonly used liquid embolic agent in the neurointerventional area is n-BCA, which is a liquid adhesive that polymerizes rapidly on contact with ionic substances and can be injected to achieve permanent vessel occlusion. The rates of polymerization and flow and the penetration depth can be modified using varying amounts of ethiodized oil as well as concurrent infusion of dextrose 5% in water (D5W) during n-BCA (Trufill, Cordis Neurovascular) injection (D5W-push technique).³ Data on the use of n-BCA as an embolic agent in cases of cSDH are extremely limited. Herein, we sought to study the safety and technical feasibility of using diluted n-BCA for embolization of the MMA for cSDHs.     

Does preoperative needle localization lead to an increase in local breast cancer recurrence?

Between 1978 and 1981, 74 women with nonpalpable breast cancer underwent surgery after localization guides were placed. In 72 patients, guides were introduced parallel to the chest wall; in two the needle was positioned anteroposteriorly under computed tomographic guidance. Fifty-six cases (76%) were infiltrating cancer; 13 (17%), intraductal cancers; two (3%), inflammatory; and three (4%), lobular carcinoma in situ. Surgery was not used to treat the latter five patients. In the remaining 69 women, 42 (61%) were treated by means of modified radical mastectomy; six (9%), total mastectomy; 12 (17%), local excision and radiation therapy; and seven (10%), local excision alone; exact therapy for two women (3%) was unknown. At a minimum follow-up of 5 years, none of the 67 women in whom the parallel approach was used had a local recurrence. The authors conclude that preoperative placement of guides parallel to the chest wall does not appear to increase the risk of local breast cancer recurrence.