Real-life efficacy of pregabalin for the treatment of peripheral neuropathic pain in daily clinical practice in Denmark:the NEP-TUNE study

OBJECTIVE: The aim of this study was to provide evidence regarding the real-life efficacy of pregabalin in the treatment of peripheral neuropathic pain (NeP) in Denmark. METHODS: In this prospective, observational, noninterventional study, pregabalin (Lyrica(®)) was prescribed following usual clinical practice. Compared with baseline, the primary study end points after 3 months of observation were changes in 1) the average level of pain during the past week, 2) the worst level of pain during the past week, and 3) the least level of pain during the past week. The Wilcoxon signed-rank test was used to perform paired analyses, and a multivariate regression analysis investigated factors driving change in pain. RESULTS: A total of 86 of the 128 patients included were regarded as efficacy evaluable (those completing 3 months of pregabalin treatment). Patients (59 years) were long-time sufferers of peripheral NeP, and 38% of them had comorbidities. The majority had previously been treated with tricyclic antidepressants or gabapentin. The average dose of pregabalin was 81.5 mg/d at baseline and 240 mg/d after 3 months. A clinically and statistically significant improvement of 2.2 points in the average level of pain intensity was found after 3 months. The higher the pain intensity at baseline, the higher was the reduction of the pain score. Positive results were also found for pain-related sleep interference, patients’ global impression of change, quality of life, and work and productivity impairment. Twenty-one patients reported 28 adverse events. CONCLUSION: This real-life study indicates that for some patients (two-thirds), addition of pregabalin for peripheral NeP helps to reduce their pain intensity significantly

Radiological findings in ancient Egyptian canopic jars: comparing three standard clinical imaging modalities (x-rays, CT and MRI)

© The Author(s) 2018 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background The aim of our study was to evaluate the potential and the limitations of standard clinical imaging modalities for the examination of ancient Egyptian canopic jars and the mummified visceral organs (putatively) contained within them. Methods A series of four ancient Egyptian canopic jars was imaged comparing the three standard clinical imaging modalities: x-rays, computed tomography (CT) and magnetic resonance imaging (MRI). Additionally, imaging-data-based volumetric calculations were performed for quantitative assessment of the jar contents. Results The image contrast of the x-ray images was limited by the thickness and high density of the calcite mineral constituting the examined jars. CT scans showed few artefacts and revealed hyperdense structures of organ-specific morphology, surrounded by a hypodense homogeneous material. The image quality of MRI scans was limited by the low amount of water present in the desiccated jar contents. Nevertheless, areas of pronounced signal intensity coincided well with hyperdense structures previously identified on CT scans. CT-based volumetric calculations revealed holding capacities of the jars of 626–1319 cm3 and content volumes of 206–1035 cm3. Conclusions CT is the modality of choice for non-invasive examination of ancient Egyptian canopic jars. However, despite its limitations, x-ray imaging will often remain the only practicable method for on-site investigations. Overall, the presented radiological findings are more compatible with contained small organ fragments rather than entire mummified organs, as originally expected, with consequent implications for envisioned future sampling for chemical and genetic analysis

The anatomical bases of the 3D digital facial approximation of the Zlatý kůň 1 woman (ca. 43,000 BP)

In 1950 on Mount Zlatý kůň (‘Golden Horse’) in modern-day Czech Republic a system of caves was discovered. During many years of research in this area, human and animal osteological remains have been excavated, among which the most interesting ones were nine fragments of a female skull, now dated to ca. 43,000 yrs BP which are one of the earliest known anatomically modern humans in Eurasia. The aim of this research was to use purely digital techniques to: (1) to reconstruct the skull based on the 3D data of preserved fragments, (2) to approximate the probable appearance of the female it belonged to, and (3) to analyze the calculated shape of the reconstructed mandible and volume of the neurocranium in the context of similarities and differences with other representatives of the genus Homo. Computer techniques used in this research constitute a new, original approach to the problem of 3D analyses and may be useful primarily in bioarchaeological sciences, where metric analyses of the most valuable bone artifacts are often severely limited due to the incompleteness of the material available for research. The digital techniques presented here may also contribute significantly to the field of surgery, with the possibility of being adapted for applications in cranial prosthetics and post-traumatic reconstructive surgery

Bitter gourd reduces elevated fasting plasma glucose levels in an intervention study among prediabetics in Tanzania

Ethnopharmacological relevance: Impaired glucose tolerance and diabetes mellitus have become major health issues even in non-industrialized countries. As access to clinical management is often poor, dietary interventions and alternative medicines are required. For bitter gourd, Momordica charantia L., antidiabetic properties have been claimed. Aim of the study: The main objective of the intervention study was to assess antidiabetic effects of daily bitter gourd consumption of 2.5 g powder over the course of eight weeks among prediabetic individuals. Materials and methods: In a randomized placebo-controlled single blinded clinical trial, 52 individuals with prediabetes were studied after consuming a bitter gourd or a cucumber juice. For reducing the impact of between subject differences in the study population, a crossover design was chosen with eight weeks for each study period and four weeks washout in between. Fasting plasma glucose was chosen as the primary outcome variable. Results: Comparing the different exposures, the CROS analysis (t=−2.23, p=0.031, r=0.326) revealed a significant difference in the change of FPG of 0.31 mmol/L (5.6 mg/dL) with a trend (R2=0,42387). The number of 44 finally complete data sets achieved a power of 0.82, with a medium-to-large effect size (Cohen's d 0.62). The effect was also proven by a general linear mixed model (estimate 0.31; SE: 0.12; p: 0.01; 95%CI: 0.08; 0.54). Not all participants responded, but the higher the initial blood glucose levels were, the more pronounced the effect was. No serious adverse effects were observed. Conclusions: Bitter gourd supplementation appeared to have benefits in lowering elevated fasting plasma glucose in prediabetes. The findings should be replicated in other intervention studies to further investigate glucose lowering effects and the opportunity to use bitter gourd for dietary self-management, especially in places where access to professional medical care is not easily assured

Systemic Immune Activation in HIV Infection Is Associated with Decreased MDC Responsiveness to TLR Ligand and Inability to Activate Naive CD4 T-Cells

HIV infection is characterized by ineffective anti-viral T-cell responses and impaired dendritic cell (DC) functions, including response to Toll-Like Receptor (TLR) ligands. Because TLR responsiveness may affect a host's response to virus, we examined TLR ligand induced Myeloid and Plasmacytoid DC (MDC and PDC) activation of naïve T-cells in HIV+ subjects.Freshly purified MDC and PDC obtained from HIV+ subjects and healthy controls were cultured in the presence and absence of TLR ligands (poly I∶C or R-848). We evaluated indices of maturation/activation (CD83, CD86, and HLA-DR expression), cytokine secretion (IFN-alpha and IL-6), and ability to activate allogeneic naïve CD4 T-cells to secrete IFN-gamma and IL-2.MDC from HIV+ subjects had increased spontaneous IL-6 production and increased CD83 and CD86 expression when compared to MDC of controls. MDC IL-6 expression was associated with plasma HIV level. At the same time, poly I∶C induced HLA-DR up-regulation on MDC was reduced in HIV+ persons when compared to controls. The latter finding was associated with impaired ability of MDC from HIV+ subjects to activate allogeneic naïve CD4 T-cells. PDC from HIV+ persons had increased spontaneous and TLR ligand induced IL-6 expression, and increased HLA-DR expression at baseline. The latter was associated with an intact ability of HIV PDC to activate allogeneic naïve CD4 T-cells.These results have implications for the ability of the HIV+ host to form innate and adaptive responses to HIV and other pathogens

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

A critical assessment on proposed outbreaks of plague and other epidemic diseases in Ancient Egypt

The current Covid-19 pandemic has brought back memories of past epidemics. Pharaonic Egypt has often been associated with epidemics and disasters through the ten plagues of the Bible. The study examines which epidemics and serious diseases can be effectively proven for Ancient Egypt in mummies and historical source texts. The biblical plagues cannot be proven because there is no agreement on the dating of the Exodus or the Exodus is a conglomeration of memories of different events. Other diseases such as malaria and schistosomiasis have been proven for ancient Egypt, while polio and smallpox are still uncertain. From the time of the middle 18th dynasty there are indications of a bubonic disease, but its exact nature cannot be extracted from source texts or mummies, as they are too vague

Epidemics and pandemics in the history of humankind and how governments dealt with them: A review from the Bronze Age to the Early Modern Age

This review offers an overview of several devastating historical epidemics and pandemics. The first pandemic ravaging the Middle East and Ancient Egypt was an unidentified “plague” in the late Bronze Age. The plague of Athens was apparently “only” a local epidemic but with fatal consequences for that ancient democracy. Great empires with well-developed trade routes seem to be very susceptible to rapid and devastating spreads as the Antonine Plague, the Plague of Cyprian and the Justinian Plague testify. The great Medieval plague wave in Europe was absolutely devastating, but for the first time it brought along with it substantial containment measures that are still being successfully used today (e.g. isolation, quarantine) as well as the seeds of the development of a new form of medical theory and practice. The blame game that can be observed in the current COVID-19 pandemic has also been seen in previous epidemics and pandemics. Particularly in the case of syphilis, its origin was often attributed to foreign countries. Finally, the paper comparatively stresses the historical importance of an early implementation of a lockdown-based approach as an effective form of controlling epidemic spreads