Vaccination barriers and drivers in Romania: a focused ethnographic study.

BACKGROUND: In 2016-18, a large measles outbreak occurred in Romania identified by pockets of sub-optimally vaccinated population groups in the country. The aim of the current study was to gain insight into barriers and drivers from the experience of measles vaccination from the perspectives of caregivers and their providers. METHODS: Data were collected by non-participant observation of vaccination consultations and individual interviews with health workers and caregivers in eight Romanian clinics with high or low measles vaccination uptake. Romanian stakeholders were involved in all steps of the study. The findings of this study were discussed during a workshop with key stakeholders. RESULTS: Over 400 h of observation and 161 interviews were conducted. A clear difference was found between clinics with high and low measles vaccination uptake which indicates that being aware of and following recommended practices for both vaccination service delivery and conveying vaccine recommendations to caregivers may have an impact on vaccine uptake. Barriers identified were related to shortcomings in following recommended practices for vaccination consultations by health workers (e.g. correctly assessing contraindications or providing enough information to allow an informed decision). These observations were largely confirmed in interviews with caregivers and revealed significant knowledge gaps. CONCLUSIONS: The identification of key barriers provided an opportunity to design specific interventions to improve vaccination service delivery (e.g. mobile vaccination clinics, use of an electronic vaccination registry system for scheduling of appointments) and build capacity among health workers (e.g. guidance and supporting materials and training programmes).

A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain.

OBJECTIVE: To evaluate the efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Seventy-nine US and Canadian centers. SUBJECTS: Patients aged ≥ 18 years with OIC, defined as <3 spontaneous bowel movements (SBMs) per week. METHODS: Patients received lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary endpoint was change from baseline in SBM frequency at week 8. RESULTS: Among randomized patients (N=418; lubiprostone, N=210; placebo, N=208), most completed the study (lubiprostone, 67.1%; placebo, 69.7%). The safety and efficacy (intent-to-treat) populations included 414 (lubiprostone, N=208; placebo, N=206) and 413 (lubiprostone, N=209; placebo, N=204) patients, respectively. The mean (standard deviation) age was 50.4 (10.9) years; most patients were female (64.4%) and white (77.7%). Changes from baseline in SBM frequency rates were significantly higher at week 8 (P=0.005) and overall (P=0.004) in patients treated with lubiprostone compared with placebo. Pairwise comparisons showed significantly greater overall improvement for abdominal discomfort (P=0.047), straining (P<0.001), constipation severity (P=0.007), and stool consistency (P<0.001) with lubiprostone compared with placebo. Moreover, patients rated the effectiveness of lubiprostone as significantly (P<0.05) better than placebo for 11 of 12 weeks. The most common treatment-related adverse events (AEs) with lubiprostone and placebo were nausea (16.8% vs 5.8%, respectively), diarrhea (9.6% vs 2.9%), and abdominal distention (8.2% vs 2.4%). No lubiprostone-related serious AEs occurred. CONCLUSION: Lubiprostone effectively relieved OIC and associated signs and symptoms and was well tolerated in patients with chronic noncancer pain (http://clinicaltrials.gov/ct2/show/NCT00595946).

First bioanthropological evidence for Yamnaya horsemanship.

The origins of horseback riding remain elusive. Scientific studies show that horses were kept for their milk ~3500 to 3000 BCE, widely accepted as indicating domestication. However, this does not confirm them to be ridden. Equipment used by early riders is rarely preserved, and the reliability of equine dental and mandibular pathologies remains contested. However, horsemanship has two interacting components: the horse as mount and the human as rider. Alterations associated with riding in human skeletons therefore possibly provide the best source of information. Here, we report five Yamnaya individuals well-dated to 3021 to 2501 calibrated BCE from kurgans in Romania, Bulgaria, and Hungary, displaying changes in bone morphology and distinct pathologies associated with horseback riding. These are the oldest humans identified as riders so far.

The Influence of Diet and Physical Activity on Oxidative Stress in Romanian Females with Osteoarthritis.

Osteoarthritis (OA) is the most prevalent chronic joint disease, increases in prevalence with age, and affects most individuals over 65. The present study aimed to assess the oxidative status in relation to diet and physical activity in patients with OA. We used a cross-sectional study applied to 98 females with OA. Blood samples were collected to determine oxidative stress markers: malonyl dialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSH/GSSG. Diet was estimated with a standardized food frequency questionnaire. We used the International Physical Activity Questionnaire (IPAQ) to assess the females' physical activity. Multiple regression analyses were executed to determine the association between the oxidative markers and the intake of vegetables and fruit. The study showed that most patients were overweight or obese (88.8%). The level of physical activity was above the recommended level for adults, mainly based on household activities. The intake of vegetables and fruit was low. The MDA marker was inversely, statistically significantly associated with the consumption of vegetables (p < 0.05). Public health policies must address modifiable risk factors to reduce energy intake and obesity and increase the intake of vegetables and fruit. Higher consumption of vegetables and fruit may provide natural antioxidants that can balance oxidative compounds.

A model-based method for estimating Ca2+ release fluxes from linescan images in Xenopus oocytes.

We propose a model-based method of interpreting linescan images observed in Xenopus oocytes with the use of Oregon Green-1 as a fluorescent dye. We use a detailed modeling formalism based on numerical simulations that incorporate physical barriers for local diffusion, and, by assuming a Gaussian distribution of release durations, we derive the distributions of release Ca(2+) amounts and currents, fluorescence amplitudes, and puff widths. We analyze a wide set of available data collected from 857 and 281 events observed in the animal and the vegetal hemispheres of the oocyte, respectively. A relatively small fraction of events appear to involve coupling of two or three adjacent clusters of Ca(2+) releasing channels. In the animal hemisphere, the distribution of release currents with a mean of 1.4 pA presents a maximum at 1.0 pA and a rather long tail extending up to 5 pA. The overall distribution of liberated Ca(2+) amounts exhibits a dominant peak at 120 fC, a smaller peak at 375 fC, and an average of 166 fC. Ca(2+) amounts and release fluxes in the vegetal hemisphere appear to be 3.6 and 1.6 times smaller than in the animal hemisphere, respectively. Predicted diameters of elemental release sites are approximately 1.0 microm in the animal and approximately 0.5 microm in the vegetal hemisphere, but the side-to-side separation between adjacent sites appears to be identical (approximately 0.4 microm). By fitting the model to individual puffs we can estimate the quantity of liberated calcium, the release current, the orientation of the scan line, and the dimension of the corresponding release site.

Spectroscopic and Spectrometric Methods Used for the Screening of Certain Herbal Food Supplements Suspected of Adulteration.

Purpose: This study was carried out in order to find a reliable method for the fast detection of adulterated herbal food supplements with sexual enhancement claims. As some herbal products are advertised as "all natural", their "efficiency" is often increased by addition of active pharmaceutical ingredients such as PDE-5 inhibitors, which can be a real health threat for the consumer. Methodes: Adulterants, potentially present in 50 herbal food supplements with sexual improvement claims, were detected using 2 spectroscopic methods - Raman and Fourier Transform Infrared - known for reliability, reproductibility, and an easy sample preparation. GC-MS technique was used to confirm the potential adulterants spectra. Results: About 22% (11 out of 50 samples) of herbal food supplements with sexual enhancement claims analyzed by spectroscopic and spectrometric methods proved to be "enriched" with active pharmaceutical compounds such as: sildenafil and two of its analogues, tadalafil and phenolphthalein. The occurence of phenolphthalein could be the reason for the non-relevant results obtained by FTIR method in some samples. 91% of the adulterated herbal food supplements were originating from China. Conclusion: The results of this screening highlighted the necessity for an accurate analysis of all alleged herbal aphrodisiacs on the Romanian market. This is a first such a screening analysis carried out on herbal food supplements with sexual enhancement claims.

Lewy bodies in the amygdala: increase of alpha-synuclein aggregates in neurodegenerative diseases with tau-based inclusions.

BACKGROUND: Increased attention has been given to alpha-synuclein aggregation in nonsynucleinopathies because alpha-synuclein-containing Lewy bodies (LBs) influence symptoms. However, the spectrum of disorders in which secondary inclusions are likely to occur has not been defined. Amygdala neurons commonly develop large numbers of secondary LBs, making it a practical region for studying this phenomenon. OBJECTIVE: To characterize the spectrum of diseases associated with LB formation in the amygdala of neurodegenerative disease and control cases. DESIGN: An autopsy series of 101 neurodegenerative disease and 34 aged control cases. Using immunohistochemistry studies, we examined the amygdala for alpha-synuclein aggregates. RESULTS: Lewy bodies were often abundant in classic Pick disease, argyrophilic grain disease, Alzheimer disease, and dementia with LBs but not in cases with amygdala degeneration lacking tau-based inclusions, control cases, preclinical disease carriers, or degenerative diseases lacking pathologic involvement of the amygdala. The exposed alpha-synuclein epitopes were similar in all cases containing LBs. CONCLUSIONS: Abnormal alpha-synuclein aggregation in the amygdala is disease selective, but not restricted to disorders of alpha-synuclein and beta-amyloid. Our data are compatible with the notion that tau aggregates predispose neurons to develop secondary LBs.

Diffusion-convection effects on drug distribution at the cell membrane level in a patch-clamp setup.

We present a model-based method for estimating the effective concentration of the active drug applied by a pressure pulse to an individual cell in a patch-clamp setup, which could be of practical use in the analysis of ligand-induced whole-cell currents recorded in patch-clamp experiments. Our modelling results outline several important factors which may be involved in the high variability of the electric response of the cells, and indicate that with a pressure pulse duration of 1s and diameter of the perfusion tip of 600 µm, elevated amounts of drug can accumulate locally between the pipette tip and the cell. Hence, the effective agonist concentration at the cell membrane level can be consistently higher than the initial concentration inside the perfusion tubes. We performed finite-difference and finite-element simulations to investigate the diffusion/convection effects on the agonist distribution on the cell membrane. Our model can explain the delay between the commencement of acetylcholine application and the onset of the whole-cell current that we recorded on human rhabdomyosarcoma TE671 cells, and reproduce quantitatively the decrease of signal latency with the concentration of agonist in the pipette. Results also show that not only the geometry of the bath chamber and pipette tip, but also the transport parameters of the diffusive and convective phenomena in the bath solution are determinant for the amplitude and kinetics of the recorded currents and have to be accounted for when analyzing patch-clamp data.

Direct observation of protein motion during the photochemical reaction cycle of bacteriorhodopsin.

Platinum-coated, conductive atomic force microscope cantilevers were used to deposit electrophoretically purple membranes from Halobacterium salinarum on the bottom part of the cantilevers. By illuminating the bacteriorhodopsin-containing purple membranes, the protein goes through its photochemical reaction cycle, during which a conformational change happens in the protein, changing its shape and size. The size change of the protein acts upon the cantilever by causing its deflection, which can be monitored by the detection system of the atomic force microscope. The shape of the signal, the action spectrum of the deflection amplitude, and the blue light inhibition of the deflection all prove that the origin of the signal is the conformational change arising in the bacteriorhodopsin during the photocycle. From the size of the signal, the magnitude of the protein motion could be estimated. Using polarized light, the orientation of the motion was determined, relative to the transition moment of the retinal.

Treatment of Guillain-Barré syndrome induced by cyclosporine in a lung transplant patient.

We report the case of a 58-year-old man with severe chronic obstructive pulmonary disease who developed acute quadriparesis during the post-operative period following bilateral lung transplantation after receiving cyclosporine for immunosuppression. Electromyography with nerve conduction study and cerebrospinal fluid analysis supported a diagnosis of Guillain-Barré Syndrome, which improved upon the discontinuation of cyclosporine, replacement with tacrolimus, and initiation of plasmapheresis. We propose the discontinuation of cyclosporine and initiation of plasmapheresis as a treatment for cyclosporine-associated Guillain-Barré syndrome.

Reflex sympathetic dystrophy.

Reflex sympathetic dystrophy (RSD) is composed of five major features: pain, swelling, autonomic dysregulation, movement disorders, and atrophy and dystrophy. RSD is caused by an injury to a specific nerve or the C- and A-delta fibers that innervate the involved tissue. It is a progressive illness that spreads with time and may encompass the entire body. There is no psychological disposition to the problem, but all patients are severely depressed because of the constant pain, lack of sleep, and complete disruption of their lifestyle. The continuing pain is usually secondary to the process of central sensitization. The autonomic dysregulation has a major central nervous system component. Atrophy and dystrophy are partly due to loss of nutritive blood supply to the affected tissues. The movement disorder is partly due to deficiency of GABAergic mechanisms; the tremor is an exaggeration of the normal physiologic tremor. Treatment consists of decreasing the afferent pain, maintaining barrage from the underlying defect, and blocking the sympathetic component of the process. New developments include the use of neurotrophic factors to reverse the phenotypic changes that occur in the dorsal horn and the use of pharmacologic agents to block the activity-dependent NMDA channels that appear to be instrumental in maintaining central sensitization.