Neuromodulation for the management of chronic pelvic pain syndromes: A systematic review.

BACKGROUND: Chronic pelvic pain is a burdensome condition that involves multiple medical sub-specialties and is often difficult to treat. Sacral stimulation for functional bladder disease has been well established, but little large-scale evidence exists regarding utilization of other neuromodulation techniques to treat chronic pelvic pain. Emerging evidence does suggest that neuromodulation is a promising treatment, and we aim to characterize the use and efficacy of such techniques for treating chronic pelvic pain syndromes. MATERIALS AND METHODS: A systematic review of the literature demonstrating the treatment of chronic pelvic pain syndromes with neuromodulation. Abstracts were reviewed and selected for inclusion, including case series, prospective studies, and randomized controlled trials (RCTs). Case studies and publications in abstract only were not included. The reporting for this systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed using MEDLINE, Embase, Cochrane Library, PubMed, CINAHL, and Scopus. RESULTS: A total of 50 studies were included in this review, three of which were randomized controlled trials, and the remaining were prospective and retrospective case series. The range of pelvic pain conditions treated included interstitial cystitis, peripheral neuralgia, pudendal neuralgia, gastrointestinal pain, urogenital pain, sacroiliac joint pain, and visceral chronic pelvic pain. We reported on outcomes involving pain, functionality, psychosocial improvement, and medication reduction. CONCLUSIONS: Neuromodulation is a growing treatment for various chronic pain syndromes. Peripheral nerve stimulation was the least studied form of stimulation. Posterior tibial nerve stimulation appears to offer short-term benefit, but long-term results are challenging. Sacral nerve stimulation is established for use in functional bladder syndromes and appears to offer pain improvement in these patients as well. Dorsal root ganglion stimulation and spinal cord stimulation have been used for a variety of conditions with promising results. Further studies of homogeneous patient populations are necessary before strong recommendations can be made at this time, although pooled analysis may also be impactful.

Library consultations and a global pandemic: An analysis of consultation difficulty during COVID-19 across multiple factors.

The purpose of this study is to examine the relationship between librarians' perception of the difficulty of patron consultations and a variety of factors that characterize these interactions in the context of an academic library at a large public university. The study also provides insight into how changes in library service operations due to the global COVID-19 pandemic have affected the perceived difficulty of library consultations. Data samples were drawn from a LibInsight dataset and limited to consultations from Fall 2019 and Spring 2020 (N = 3331). Statistical analysis was conducted using ordinal logistic regression to quantify the relationship between perceptions of difficulty and factors indicating pre/post-COVID-19 modifications, patron type, scheduling, question format, library department, consultation duration, semester, and campus. Most notably, results indicate a statistically significant (p < 0.001) increase in the perceived difficulty of consultations that followed the closure of the library's physical spaces due to COVID-19, even when controlling for other factors in multiple model formulations. These results, as well as insights pertaining to other factors associated with library consultations and perceptions of difficulty, have implications for how librarians frame, understand, and manage their workloads. Additionally, findings may provide library service managers with the evidence needed to better coordinate and evaluate library services.

Type 2 diabetes, socioeconomic status and life expectancy in Scotland (2012-2014): a population-based observational study.

AIMS/HYPOTHESIS: The aim of this study was to assess the role of socioeconomic status (SES) in the associations between type 2 diabetes and life expectancy in a complete national population. METHODS: An observational population-based cohort study was performed using the Scottish Care Information - Diabetes database. Age-specific life expectancy (stratified by SES) was calculated for all individuals with type 2 diabetes in the age range 40-89 during the period 2012-2014, and for the remaining population of Scotland aged 40-89 without type 2 diabetes. Differences in life expectancy between the two groups were calculated. RESULTS: Results were based on 272,597 individuals with type 2 diabetes and 2.75 million people without type 2 diabetes (total for 2013, the middle calendar year of the study period). With the exception of deprived men aged 80-89, life expectancy in people with type 2 diabetes was significantly reduced (relative to the type 2 diabetes-free population) at all ages and levels of SES. Differences in life expectancy ranged from -5.5 years (95% CI -6.2, -4.8) for women aged 40-44 in the second most-deprived quintile of SES, to 0.1 years (95% CI -0.2, 0.4) for men aged 85-89 in the most-deprived quintile of SES. Observed life-expectancy deficits in those with type 2 diabetes were generally greater in women than in men. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with reduced life expectancy at almost all ages and levels of SES. Elimination of life-expectancy deficits in individuals with type 2 diabetes will require prevention and management strategies targeted at all social strata (not just deprived groups).

Biocatalytic Stimuli-Responsive Asymmetric Triblock Terpolymer Membranes for Localized Permeability Gating.

The functionalization with phosphotriesterase of poly(isoprene-b-styrene-b-4-vinylpyridine)-based nanoporous membranes fabricated by self-assembly and nonsolvent induced phase separation (SNIPS) is shown to enable dynamically responsive membranes capable of substrate-specific and localized gating response. Integration of the SNIPS process with macroporous nylon support layers yields mechanically robust textile-type films with high moisture vapor transport rates that display rapid and local order-of-magnitude modulation of permeability. The simplicity of the fabrication process that is compatible with large-area fabrication along with the versatility and efficacy of enzyme reactivity offers intriguing opportunities for engineered biomimetic materials that are tailored to respond to a complex range of external parameters, providing sensing, protection, and remediation capabilities.

Complex Coacervate Core Micelles for the Dispersion and Stabilization of Organophosphate Hydrolase in Organic Solvents.

Organophosphate (OP) nerve agents are a class of chemical warfare agents (CWAs) that exist as bulk stocks in current and past war zones. Thus, a technology that can perform on-site decontamination in a safe and timely fashion is desirable. Here, complex coacervate core micelles (C3Ms) were used to encapsulate organophosphate hydrolase (OPH) and chemostabilize it to maintain activity after exposure to organophosphate simulants ethanol and dimethyl methylphosphonate (DMMP). C3Ms were formed by two polymers-poly(acrylic acid) (PAA) and poly(oligo(ethylene glycol) methacrylate)-b-poly(4-vinyl N-methylpyridyl iodide), (POEGMA-b-qP4VP). Complexes of the coacervate micelles with the enzyme OPH were investigated by small angle neutron scattering (SANS), dynamic light scattering (DLS), and transmission electron microscopy (TEM), demonstrating the formation of micellar structures in solution. The activity of OPH against methyl paraoxon in these C3Ms under aqueous conditions was assayed after heat treatment for 3 days at 37 °C. The OPH in C3Ms retained 88 ± 7% of its initial activity, as compared to the 48 ± 3% activity retained by OPH alone, indicating that the C3Ms were able to stabilize the enzyme to heat treatment. C3Ms transferred into the two organic solvents formed larger structures than inverse micelles formed by the block copolymer alone. The addition of OPH to the C3Ms in organic solvents did not significantly change their structure. The activity of OPH (again, against methyl paraoxon) after 24 h of incubation at 4 °C was measured and compared to that of OPH in C3Ms. While OPH alone retained less than 5% of its activity after this incubation in both solvents, OPH in C3Ms retained 35 ± 3% of its activity in DMMP and 26 ± 1% of its activity in ethanol.

Terminology and forensic gait analysis.

The use of appropriate terminology is a fundamental aspect of forensic gait analysis. The language used in forensic gait analysis is an amalgam of that used in clinical practice, podiatric biomechanics and the wider field of biomechanics. The result can often be a lack of consistency in the language used, the definitions used and the clarity of the message given. Examples include the use of 'gait' and 'walking' as synonymous terms, confusion between 'step' and 'stride', the mixing of anatomical, positional and pathological descriptors, and inability to describe appropriately movements of major body segments such as the torso. The purpose of this paper is to share the well-established definitions of the fundamental parameters of gait, common to all professions, and advocate their use in forensic gait analysis to establish commonality. The paper provides guidance on the selection and use of appropriate terminology in the description of gait in the forensic context. This paper considers the established definitions of the terms commonly used, identifies those terms which have the potential to confuse readers, and suggests a framework of terminology which should be utilised in forensic gait analysis.

The effect of frame rate on the ability of experienced gait analysts to identify characteristics of gait from closed circuit television footage.

Forensic gait analysis is increasingly being used as part of criminal investigations. A major issue is the quality of the closed circuit television (CCTV) footage used, particularly the frame rate which can vary from 25 frames per second to one frame every 4s. To date, no study has investigated the effect of frame rate on forensic gait analysis. A single subject was fitted with an ankle foot orthosis and recorded walking at 25 frames per second. 3D motion data were also collected, providing an absolute assessment of the gait characteristics. The CCTV footage was then edited to produce a set of eight additional pieces of footage, at various frame rates. Practitioners with knowledge of forensic gait analysis were recruited and instructed to record their observations regarding the characteristics of the subject's gait from the footage. They were sequentially sent web links to the nine pieces of footage, lowest frame rate first, and a simple observation recording form, over a period of 8 months. A sample-based Pearson product-moment correlation analysis of the results demonstrated a significant positive relationship between frame rate and scores (r=0.868, p=0.002). The results of this study show that frame rate affects the ability of experienced practitioners to identify characteristics of gait captured on CCTV footage. Every effort should therefore be made to ensure that CCTV footage likely to be used in criminal proceedings is captured at as high a frame rate as possible.

Genome-wide Single Nucleotide Polymorphism Analyses Reveal Genetic Diversity and Structure of Wild and Domestic Cattle in Bangladesh.

In spite of variation in coat color, size, and production traits among indigenous Bangladeshi cattle populations, genetic differences among most of the populations have not been investigated or exploited. In this study, we used a high-density bovine single nucleotide polymorphism (SNP) 80K Bead Chip derived from Bos indicus breeds to assess genetic diversity and population structure of 2 Bangladeshi zebu cattle populations (red Chittagong, n = 28 and non-descript deshi, n = 28) and a semi-domesticated population (gayal, n = 17). Overall, 95% and 58% of the total SNPs (69,804) showed polymorphisms in the zebu and gayal populations, respectively. Similarly, the average minor allele frequency value was as high 0.29 in zebu and as low as 0.09 in gayal. The mean expected heterozygosity varied from 0.42±0.14 in zebu to 0.148±0.14 in gayal with significant heterozygosity deficiency of 0.06 (F IS) in the latter. Coancestry estimations revealed that the two zebu populations are weakly differentiated, with over 99% of the total genetic variation retained within populations and less than 1% accounted for between populations. Conversely, strong genetic differentiation (FST = 0.33) was observed between zebu and gayal populations. Results of population structure and principal component analyses suggest that gayal is distinct from Bos indicus and that the two zebu populations were weakly structured. This study provides basic information about the genetic diversity and structure of Bangladeshi cattle and the semi-domesticated gayal population that can be used for future appraisal of breed utilization and management strategies.

Developing Crowdsourced Clinical Registry Studies.

ABSTRACT: Crowdsourced registries have been used to quickly gather information, especially during emerging public health concerns. Registries that began during the COVID-19 pandemic were used to rapidly answer key questions on coinfections, experimental treatments, and morbidity and mortality outcomes. Registries are also used more frequently to support clinical trials and track long-term outcomes in patient populations. This article reviews registry methodology, including the collection of data from crowdsourcing and real-world sources, that can be applied to nurse researcher and clinical research nurse skill sets. The authors illustrate a recently reported crowdsourced COVID-19 and cryptococcal disease registry that followed project management strategies and the Agency for Healthcare Research and Quality registry guidelines for planning, execution, and analysis of registries and other research methods.

Analysis of heterogeneity in nonspecific PEGylation reactions of biomolecules.

The compositional heterogeneity associated with polymer conjugation reactions of biomolecules is analyzed for the particular case of nonspecific PEGylation reactions. It is shown that the distribution of the number of PEG moieties grafted to biomolecules such as proteins is a binomial-type function of two parameters-the reaction efficiency as well as the number of binding sites per biomolecule. The nature of this distribution implies that uniform compositions are favored for increasing number of coupling sites per biomolecule as well as for increasing efficiency of the modification process. Therefore, the binomial distribution provides a rationale for the pronounced heterogeneity that is observed for PEGylated small enzyme systems even at high coupling efficiencies. For the particular case of PEGylated trypsin it is shown that the heterogeneity results in a broad distribution of deactivation times that is captured by a stretched exponential decay model. The presented analysis is expected to apply to general modification processes of compounds in which partial functionalization of a fixed number of reactive sites is achieved by means of a nonspecific coupling reaction.

Acute hypoglycemia decreases myocardial blood flow reserve in patients with type 1 diabetes mellitus and in healthy humans.

BACKGROUND: Hypoglycemia is associated with increased cardiovascular mortality, but the reason for this association is poorly understood. We tested the hypothesis that the myocardial blood flow reserve (MBFR) is decreased during hypoglycemia using myocardial contrast echocardiography in patients with type 1 diabetes mellitus (DM) and in healthy control subjects. METHODS AND RESULTS: Twenty-eight volunteers with DM and 19 control subjects underwent hyperinsulinemic clamps with maintained sequential hyperinsulinemic euglycemia (plasma glucose, 90 mg/dL [5.0 mmol/L]) followed by hyperinsulinemic hypoglycemia (plasma glucose, 50 mg/dL [2.8 mmol/L]) for 60 minutes each. Low-power real-time myocardial contrast echocardiography was performed with flash impulse imaging using low-dose dipyridamole stress at baseline and during hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia. In control subjects, MBFR increased during hyperinsulinemic euglycemia by 0.57 U (22%) above baseline (B coefficient, 0.57; 95% confidence interval, 0.38 to 0.75; P<0.0001) and decreased during hyperinsulinemic hypoglycemia by 0.36 U (14%) below baseline values (B coefficient, -0.36; 95% confidence interval, -0.50 to -0.23; P<0.0001). Although MBFR was lower in patients with DM at baseline by 0.37 U (14%; B coefficient, -0.37; 95% confidence interval, -0.55 to -0.19; P=0.0002) compared with control subjects at baseline, the subsequent changes in MBFR during hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia in DM patients were similar to that observed in control subjects. Finally, the presence of microvascular complications in the patients with DM was associated with a reduction in MBFR of 0.52 U (24%; B coefficient, -0.52; 95% confidence interval, -0.70 to -0.34; P<0.0001). CONCLUSIONS: Hypoglycemia decreases MBFR in both healthy humans and patients with DM. This finding may explain the association between hypoglycemia and increased cardiovascular mortality in susceptible individuals.

Hydrolase stabilization via entanglement in poly(propylene sulfide) nanoparticles: stability towards reactive oxygen species.

In the advancement of green syntheses and sustainable reactions, enzymatic biocatalysis offers extremely high reaction rates and selectivity that goes far beyond the reach of chemical catalysts; however, these enzymes suffer from typical environmental constraints, e.g. operational temperature, pH and tolerance to oxidative environments. A common hydrolase enzyme, diisopropylfluorophosphatase (DFPase, EC 3.1.8.2), has demonstrated a pronounced efficacy for the hydrolysis of a variety of substrates for potential toxin remediation, but suffers from the aforementioned limitations. As a means to enhance DFPase's stability in oxidative environments, enzymatic covalent immobilization within the polymeric matrix of poly(propylene sulfide) (PPS) nanoparticles was performed. By modifying the enzyme's exposed lysine residues via thiolation, DFPase is utilized as a comonomer/crosslinker in a mild emulsion polymerization. The resultant polymeric polysulfide shell acts as a 'sacrificial barrier' by first oxidizing to polysulfoxides and polysulfones, rendering DFPase in an active state. DFPase-PPS nanoparticles thus retain activity upon exposure to as high as 50 parts per million (ppm) of hypochlorous acid (HOCl), while native DFPase is observed as inactive at 500 parts per billion (ppb). This trend is also confirmed by enzyme-generated (chloroperoxidase (CPO), EC 1.11.1.10) reactive oxygen species (ROS) including both HOCl (3 ppm) and ClO(2) (100 ppm).

Neuregulin-1ß regulation of embryonic endothelial progenitor cell survival.

Endothelial progenitor cells (EPCs) are mobilized into the vascular space and home to damaged tissues, where they promote repair in part through a process of angiogenesis. Neuregulins (NRGs) are ligands in the epidermal growth factor family that signal through type I receptor tyrosine kinases in the erbB family (erbB2, erbB3, and erbB4) and regulate endothelial cell biology, promoting angiogenesis. Stimuli such as ischemia and exercise that promote EPC mobilization also induce cleavage and release of transmembrane NRG from cardiac microvascular endothelial cells (CMECs). We hypothesized that NRG/erbB signaling may regulate EPC biology. Using an embryonic (e)EPC cell line that homes to and repairs injured myocardium, we were able to detect erbB2 and erbB3 transcripts. Identical receptor expression was found in EPCs isolated from rat bone marrow and human whole blood. NRG treatment of eEPCs induces phosphorylation of kinases including Akt, GSK-3ß, and Erk1/2 and the nuclear accumulation and transcriptional activation of ß-catenin. NRG does not induce eEPC proliferation or migration but does protect eEPCs against serum deprivation-induced apoptosis. These results suggest a role for tissue-derived NRG in the regulation of EPC survival.

Does context matter for the relationship between deprivation and all-cause mortality? The West vs. the rest of Scotland.

BACKGROUND: A growing body of research emphasizes the importance of contextual factors on health outcomes. Using postcode sector data for Scotland (UK), this study tests the hypothesis of spatial heterogeneity in the relationship between area-level deprivation and mortality to determine if contextual differences in the West vs. the rest of Scotland influence this relationship. Research into health inequalities frequently fails to recognise spatial heterogeneity in the deprivation-health relationship, assuming that global relationships apply uniformly across geographical areas. In this study, exploratory spatial data analysis methods are used to assess local patterns in deprivation and mortality. Spatial regression models are then implemented to examine the relationship between deprivation and mortality more formally. RESULTS: The initial exploratory spatial data analysis reveals concentrations of high standardized mortality ratios (SMR) and deprivation (hotspots) in the West of Scotland and concentrations of low values (coldspots) for both variables in the rest of the country. The main spatial regression result is that deprivation is the only variable that is highly significantly correlated with all-cause mortality in all models. However, in contrast to the expected spatial heterogeneity in the deprivation-mortality relationship, this relation does not vary between regions in any of the models. This result is robust to a number of specifications, including weighting for population size, controlling for spatial autocorrelation and heteroskedasticity, assuming a non-linear relationship between mortality and socio-economic deprivation, separating the dependent variable into male and female SMRs, and distinguishing between West, North and Southeast regions. The rejection of the hypothesis of spatial heterogeneity in the relationship between socio-economic deprivation and mortality complements prior research on the stability of the deprivation-mortality relationship over time. CONCLUSIONS: The homogeneity we found in the deprivation-mortality relationship across the regions of Scotland and the absence of a contextualized effect of region highlights the importance of taking a broader strategic policy that can combat the toxic impacts of socio-economic deprivation on health. Focusing on a few specific places (e.g. 15% of the poorest areas) to concentrate resources might be a good start but the impact of socio-economic deprivation on mortality is not restricted to a few places. A comprehensive strategy that can be sustained over time might be needed to interrupt the linkages between poverty and mortality.

Application of non-contact scanning to forensic podiatry: A feasibility study.

Foot impression evidence recovered from crime scenes can be available in the form of barefoot prints, sock-clad footprints, or as impressions within footwear. In some cases, suspects leave their footwear at the scene of the crime, and the insoles from the footwear can be important in linking a person to the footwear. The application of 3D data-collecting technology is becoming more and more popular within forensic science and has been used to recover footwear impression evidence. The present study is a feasibility study to discover if 3D data capturing devices can be applied to insoles; to capture the footprint impression for measurement using the Gunn method (a method used in forensic podiatry casework). Three different methods of data capture were conducted; Adobe Photoshop, MeshLab, and calipers used directly on the insole. Paired t-tests and Intraclass Correlation Coefficient (ICC) were conducted for all three data capture methods. Seven measurements used in this study were significantly different across all three methods. ICC scores were moderate to excellent for the Photoshop method, poor to good for the 3D method, and moderate to excellent for the Direct method.

Sexing white 2D footprints using convolutional neural networks.

Footprints are left, or obtained, in a variety of scenarios from crime scenes to anthropological investigations. Determining the sex of a footprint can be useful in screening such impressions and attempts have been made to do so using single or multi landmark distances, shape analyses and via the density of friction ridges. Here we explore the relative importance of different components in sexing two-dimensional foot impressions namely, size, shape and texture. We use a machine learning approach and compare this to more traditional methods of discrimination. Two datasets are used, a pilot data set collected from students at Bournemouth University (N = 196) and a larger data set collected by podiatrists at Sheffield NHS Teaching Hospital (N = 2677). Our convolutional neural network can sex a footprint with accuracy of around 90% on a test set of N = 267 footprint images using all image components, which is better than an expert can achieve. However, the quality of the impressions impacts on this success rate, but the results are promising and in time it may be possible to create an automated screening algorithm in which practitioners of whatever sort (medical or forensic) can obtain a first order sexing of a two-dimensional footprint.

Understanding ligand distributions in modified particle and particlelike systems.

Chemical modification of nanoparticles or particlelike systems is ubiquitously being used to facilitate specific pharmaceutical functionalities or physicochemical attributes of nanocrystals, proteins, enzymes, or other particlelike systems. Often the modification process is incomplete and the functional activity of the product depends upon the distribution of functional ligands among the different particles in the system. Here, the distribution function describing the spread of ligands in particlelike systems undergoing partial modification reactions is derived and validated against a conjugated enzyme model system by use of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). The distribution function is shown to be applicable to describe the distribution of ligands in a wide range of particlelike systems (such as enzymes, dendrimers, or inorganic nanocrystals) and is used to establish guidelines for the synthesis of uniformly modified particle systems even at low reaction efficiencies.