Assessing Ethnic Minority Representation in Fibromyalgia Clinical Trials: A Systematic Review of Recruitment Demographics.

The under-representation of non-White participants in Western countries in clinical research has received increased attention, due to recognized physiological differences between ethnic groups, which may affect the efficacy and optimal dosage of some treatments. This review assessed ethnic diversity in pharmaceutical trials for fibromyalgia, a poorly understood chronic pain disorder. We also investigated longitudinal change to non-White participant proportions in trials and non-White participants' likelihood to discontinue with fibromyalgia research between trial stages (retention). First, we identified relevant trials conducted in the United States and Canada between 2000 and 2022, by searching PubMed, Web of Science, Scopus, and the Cochrane Library databases. In trials conducted both across the United States and Canada, and exclusively within the United States, approximately 90% of participants were White. A longitudinal analysis also found no change in the proportion of non-White participants in trials conducted across the United States and Canada between 2000 and 2022. Finally, we found no significant differences in trial retention between White and non-White participants. This review highlights the low numbers of ethnic minorities in fibromyalgia trials conducted in the United States and Canada, with no change to these proportions over the past 22 years. Furthermore, non-White participants were not more likely to discontinue with the fibromyalgia research once they were recruited.

Impact of heterotopic ossification following lumbar total disk replacement: a systematic review.

BACKGROUND CONTEXT: Lumbar total disc replacement (TDR) is an alternative to lumbar fusion in the treatment of lower back pain and reduces the risk of adjacent segment degeneration. Heterotopic ossification (HO) has been identified as a common complication following lumbar TDR. PURPOSE: This systematic review aims to determine the prevalence, risk factors and clinical and radiological impact of HO following lumbar TDR. STUDY DESIGN: Systematic Review. METHODS: MEDLINE, Scopus, PubMed and Cochrane Central were searched for articles that referred to lumbar TDR and HO. The hits were assessed against inclusion and exclusion criteria. Data from each included study was extracted and analysed with respect to the study aims. RESULTS: Twenty-six studies were included in this review and the pooled prevalence of HO was estimated to be between 13.2% (participants) and 15.3% (vertebral levels). TDR clinical outcomes were not found to be reduced by HO and there was insufficient data to identify a given impact upon radiological outcomes. Age and follow up time were identified as potential risk factors for HO. CONCLUSIONS: This review was hampered by inconsistencies in the reporting of HO across the studies. We therefore recommend that a set of guidelines should be produced to aid future researchers and reduce the risk of bias.

Comparing the use of conventional and three-dimensional printing (3DP) in mandibular reconstruction.

BACKGROUND: There are a number of clinical disorders that require mandibular reconstruction (MR). Novel three-dimensional (3D) printing technology enables reconstructions to be more accurate and beneficial to the patient. However, there is currently no evidence identifying which techniques are better suited for MR, based on the type of clinical disorder the patient has. In this study, we aim to compare 3D techniques with conventional techniques to identify how best to reconstruct the mandible based on the clinical cause that necessitates the reconstructive procedure: cancerous or benign tumours, clinical disorders, infection or disease and trauma or injury. METHODS: PubMed, Scopus, Embase and Medline were searched to identify relevant papers that outline the clinical differences between 3D and conventional techniques in MR. Data were evaluated to provide a clear outline of suitable techniques for surgery. RESULTS: 20 of 2749 papers met inclusion criteria. These papers were grouped based on the clinical causes that required MR into four categories: malignant or benign tumour resection; mandibular trauma/injury and other clinical disorders. CONCLUSIONS: The majority of researchers favoured 3D techniques in MR. However, due to a lack of standardised reporting in these studies it was not possible to determine which specific techniques were better for which clinical presentations.

Effects of short-term administration of melatonin before gonadectomy on oxidative stress, cortisol and sex hormones in male dogs.

The aim of this study was to investigate gonadectomy stress, steroid hormones and serotonin in male dogs treated with melatonin before gonadectomy. Twenty-five mixed breed adult dogs were divided into five equal groups. The melatonin and melatonin + gonadectomized groups received melatonin treatment (3 mg/10 Kg, PO, TID) the day before gonadectomy; the gonadectomized and anaesthesia groups did not receive melatonin; and the control group just received the melatonin vehicle. Blood sampling was performed before melatonin administration (day -1) and on days 0 (gonadectomy), 1, 3 and 6 after gonadectomy. Superoxide dismutase and glutathione peroxidase concentrations decreased significantly in gonadectomized dogs compared with dogs treated with melatonin before gonadectomy and intact dogs. Gonadectomy led to a significant decrease in catalase concentration in gonadectomized dogs compared with other study groups. Malondialdehyde levels increased significantly in gonadectomized dogs compared with other groups. Melatonin administration before gonadectomy led to decreased malondialdehyde concentration in gonadectomized and intact dogs compared to the control group. Cortisol concentration increased significantly in gonadectomized dogs compared to the control dogs. Serotonin levels decreased in gonadectomized dogs, but melatonin treatment increased serotonin concentration in gonadectomized and intact dogs. Melatonin treatment before gonadectomy suppressed oxidative stress and the cortisol but increased serotonin level.

Socio-Economic Disparities in Access to Diagnostic Neuroimaging Services in the United Kingdom: A Systematic Review.

Socio-economic factors affecting health care can lead to delays in diagnosis of neurological conditions, consequentially affecting treatment and morbidity rates. This inequality in health care can leave patients from lower socio-economic backgrounds more vulnerable to a poorer quality of care from health care providers in the United Kingdom (U.K.). AIMS: In this systematic review, we assess the impact of socio-economic status on the use of diagnostic neuroimaging in the U.K., measured by the timeliness, accessibility and appropriate use of computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, electroencephalography (EEG) and single-photon emission computed tomography (SPECT). We specifically evaluate the non-surgical use of neuroimaging techniques as this relies on the judgment of primary care-givers (e.g., doctors and radiologists), where health disparities are most common. This study includes the analysis of diagnostic imaging used for dementia, minor head injury, stroke, cancer, epilepsy, chronic inflammatory demyelinating polyneuropathy and Parkinson's disease. With this study, we aim to assess the health inequalities at disease diagnosis. METHODS: Using Medline (via Ovid), PubMed and Web of Science databases as sources of information, we critically appraise existing studies on neuroimaging use in the U.K. health care system, published between January 2010 and February 2021. FINDINGS: A total of 18 studies were included in this research, revealing that there was an increase in patients of Black and Asian communities diagnosed with dementia and at an earlier age. There was little evidence to suggest that a lack of access to diagnostic imaging is associated with socio-economic status. However, there are data to suggest that people of a lower socio-economic background require more specialist services with diagnostic neuroimaging tools. In addition, there is evidence to suggest that diagnostic neuroimaging techniques could be utilised more effectively by health care workers to prevent unnecessary delays in diagnosis for patients in lower socio-economic areas.

Assessing demographic access to hip replacement surgery in the United Kingdom: a systematic review.

Persisting evidence suggests significant socioeconomic and sociodemographic inequalities in access to medical treatment in the UK. Consequently, a systematic review was undertaken to examine these access inequalities in relation to hip replacement surgery. Database searches were performed using MEDLINE, PubMed and Web of Science. Studies with a focus on surgical need, access, provision and outcome were of interest. Inequalities were explored in the context of sociodemographic characteristics, socioeconomic status (SES), geographical location and hospital-related variables. Only studies in the context of the UK were included. Screening of search and extraction of data were performed and 482 articles were identified in the database search, of which 16 were eligible. Eligible studies consisted of eight cross-sectional studies, seven ecological studies and one longitudinal study. Although socioeconomic inequality has somewhat decreased, lower SES patients and ethnic minority patients demonstrate increased surgical needs, reduced access and poor outcomes. Lower SES and Black minority patients were younger and had more comorbidities. Surgical need increased with age. Women had greater surgical need and provision than men. Geographical inequality had reduced in Scotland, but a north-south divide persists in England. Rural areas received greater provision relative to need, despite increased travel for care. In all, access inequalities remain widespread and policy change driven by research is needed.

Silica-copper catalyst interfaces enable carbon-carbon coupling towards ethylene electrosynthesis.

Membrane electrode assembly (MEA) electrolyzers offer a means to scale up CO2-to-ethylene electroconversion using renewable electricity and close the anthropogenic carbon cycle. To date, excessive CO2 coverage at the catalyst surface with limited active sites in MEA systems interferes with the carbon-carbon coupling reaction, diminishing ethylene production. With the aid of density functional theory calculations and spectroscopic analysis, here we report an oxide modulation strategy in which we introduce silica on Cu to create active Cu-SiOx interface sites, decreasing the formation energies of OCOH* and OCCOH*-key intermediates along the pathway to ethylene formation. We then synthesize the Cu-SiOx catalysts using one-pot coprecipitation and integrate the catalyst in a MEA electrolyzer. By tuning the CO2 concentration, the Cu-SiOx catalyst based MEA electrolyzer shows high ethylene Faradaic efficiencies of up to 65% at high ethylene current densities of up to 215 mA cm-2; and features sustained operation over 50 h.

Anti-inflammatory activity of emu oil-based nanofibrous scaffold through downregulation of IL-1, IL-6, and TNF-α pro-inflammatory cytokines.

Background Inflammation is one of the most important responses of the body against infection or disease, and it protects tissues from injury; however, it causes redness, swelling, pain, fever and loss of function. The aim of this present study was to evaluate the anti-inflammatory activity of emu oil (Eu) formulated nanofibrous scaffold in HFFF2 fibroblast cells. Materials and methods Eu was formulated successfully in nanofibers through the electrospinning method. Besides, the morphological and structural properties of Eu nanofibres were evaluated using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) was performed to evaluate the HFFF2 fibroblast cells' viability. Also, real-time polymerase chain reaction (PCR) was used to evaluate the anti-inflammatory signaling pathway in treated HFFF2 cells with Eu nanofiber. Results Our study showed that the Eu nanofiber increased the viability of fibroblast HFFF2 cells (p < 0.05). Also, the expression of interleukin1 (IL1), IL6 and tumor necrosis factor- alpha (TNF-α) pro-inflammatory cytokines genes were significantly decreased in treated HFFF2 cells with Eu nanofiber (p < 0.05). Conclusions In conclusion, Eu nanofiber scaffold potentially can reduce the inflammation process through downregulation of IL-1, IL-6 and TNF-α cytokines.

The effectiveness of foot orthoses in the treatment of medial knee osteoarthritis: A systematic review.

BACKGROUND: Knee osteoarthritis is a disease of the joint causing decreased function and pain. Currently, treatments range from medication to surgery, with the use of different insoles and footwear recommended. These methods are effective by either correcting the position of the knee or providing shock absorption. However, there is little understanding of the effective characteristics of these devices. RESEARCH QUESTION: This paper aims to investigate this question and provide future areas of research to help better define treatment guidelines. Foot orthoses are an example of non-pharmacological conservative treatments mentioned in National Institute for Health and Care Excellence (NICE) guidelines to treat knee osteoarthritis (OA). These include lateral wedge insoles (LWI), developed with the intention of load reduction of the knee. Different footwear has also been shown to affect pain, biomechanical and functional outcomes in knee OA patients. METHODS: To address what features of LWIs and footwear make them effective in the treatment of knee OA, scientific databases were used to search for papers on this topic and then selected to be included based on pre-defined criteria. Data were extracted and analysed from these studies to provide a basis for possible areas for future development of these foot orthoses, and research required to improve clinical treatment guidelines. Databases used were PubMed, Scopus and Web of Science. RESULTS AND SIGNIFICANCE: Thirty-four out of 226 papers were included after application of inclusion and exclusion criteria. Regarding LWIs, the characteristics showing the most beneficial effect on either biomechanical, functional or pain outcomes were customisation, full-length, 5° elevation, shock absorption and arch support. For footwear, barefoot mimicking soles produced the most favourable biomechanics. Results also showed that insoles work in correcting the position of the knee, but it may or may not affect patients' pain and function.

Nephrotic syndrome is associated with increased plasma K+ concentration, intestinal K+ losses, and attenuated urinary K+ excretion: a study in rats and humans.

The present study tested the hypotheses that nephrotic syndrome (NS) leads to renal K+ loss because of augmented epithelial Na+ channel (ENaC) activity followed by downregulation of renal K+ secretory pathways by suppressed aldosterone. The hypotheses were addressed by determining K+ balance and kidney abundance of K+ and Na+ transporter proteins in puromycin aminonucleoside (PAN)-induced rat nephrosis. The effects of amiloride and angiotensin II type 1 receptor and mineralocorticoid receptor (MR) antagonists were tested. Glucocorticoid-dependent MR activation was tested by suppression of endogenous glucocorticoid with dexamethasone. Urine and plasma samples were obtained from pediatric patients with NS in acute and remission phases. PAN-induced nephrotic rats had ENaC-dependent Na+ retention and displayed lower renal K+ excretion but elevated intestinal K+ secretion that resulted in less cumulated K+ in NS. Aldosterone was suppressed at day 8. The NS-associated changes in intestinal, but not renal, K+ handling responded to suppression of corticosterone, whereas angiotensin II type 1 receptor and MR blockers and amiloride had no effect on urine K+ excretion during NS. In PAN-induced nephrosis, kidney protein abundance of the renal outer medullary K+ channel and γ-ENaC were unchanged, whereas the Na+-Cl- cotransporter was suppressed and Na+-K+-ATPase increased. Pediatric patients with acute NS displayed suppressed urine Na+-to-K+ ratios compared with remission and elevated plasma K+ concentration, whereas fractional K+ excretion did not differ. Acute NS is associated with less cumulated K+ in a rat model, whereas patients with acute NS have elevated plasma K+ and normal renal fractional K+ excretion. In NS rats, K+ balance is not coupled to ENaC activity but results from opposite changes in renal and fecal K+ excretion with a contribution from corticosteroid MR-driven colonic secretion.

Macrophage repolarization using emu oil-based electrospun nanofibers: possible application in regenerative medicine.

In the regenerative medicine therapies, the availability of engineered scaffolds that modulate inflammatory states is highly required. The aim of this study was to evaluate the efficiency of electrospun nanofibrous scaffolds containing natural substances with anti-inflammatory properties such as Emu oil (EO) to control inflammation and re-polarization of macrophages toward M2 anti-inflammatory phonotype. For this purpose, bead free and smooth EO-blended PCL/PEG electrospun nanofibrous mats were successfully fabricated and characterized using FE-SEM, FTIR, and Universal Testing Machine. GC/MS findings of pure EO revealed the fatty acids composition. MTT results showed that macrophage viability on EO-PCL/PEG nanofibres was higher than on PCL/PEG nanofibres and control (p ≤ .05). Additionally, the presence of EO into nanofibres was found to influence on macrophage morphologies, using FE-SEM. qPCR results showed a reduction in iNOS-2 and an increase in Arg-1 levels of macrophages seeded on EO-PCL/PEG nanofibres, indicating the successfully polarization of the macrophages to M2 phenotype. The change in macrophage phenotype on EO-based nanofibres could suppress the inflammation in LPS/IFN-γ stimulated macrophages as evidenced by a major reduction in pro-inflammatory cytokine levels TNF-α, IL-1ß, and IL-6. Conclusively, the results demonstrated that EO-based nanofibres efficiently modulated RAW264.7 macrophage polarity toward an anti-inflammatory M2 phenotype.

The use of fluoroscopic guided percutaneous pedicle screws in the upper thoracic spine (T1-T6): Is it safe?

PURPOSE: This study analysed the accuracy and safety of the fluoroscopic guided percutaneous screws in the upper thoracic vertebrae (T1-T6). METHODS: Computed tomography scans from 74 patients were retrospectively evaluated between January 2008 and December 2012. Pedicle perforations were classified by two types of grading systems. For medial, lateral, superior and inferior perforations: grade 0 - no violation; grade 1 - <2 mm; grade 2 - 2-4 mm and grade 3 - >4 mm. For anterior perforations: grade 0 - no violation; grade 1 - <4 mm; grade 2 - 4-6 mm and grade 3 - >6 mm. RESULTS: There were 35 (47.3%) male and 39 (52.7%) female patients with a total 260 thoracic pedicle screws (T1-T6) analysed. There were 32 screw perforations which account to a perforation rate of 12.3% (11.2% grade 1, 0.7% grade 2 and 0.4% grade 3). None led to pedicle screw-related complications. The perforation rate was highest at T1 (33.3%, all grade 1 perforations), followed by T6 (14.5%) and T4 (14.0%). CONCLUSION: Fluoroscopic guided percutaneous pedicle screws of the upper thoracic spine (T1-T6) are technically more demanding and carry potential risks of serious complications. Extra precautions need to be taken when fluoroscopic guided percutaneous pedicle screws are placed at T1 and T2 levels, due to high medial pedicular angulation and obstruction of lateral fluoroscopic images by the shoulder girdle and at T4-T6 levels, due to smaller pedicular width.

A comparison of feasibility and safety of percutaneous fluoroscopic guided thoracic pedicle screws between Europeans and Asians: is there any difference?

PURPOSE: To directly compare the safety of fluoroscopic guided percutaneous thoracic pedicle screw placement between Caucasians and Asians. METHODS: This was a retrospective computerized tomography (CT) evaluation study of 880 fluoroscopic guided percutaneous pedicle screws. 440 screws were inserted in 73 European patients and 440 screws were inserted in 75 Asian patients. Screw perforations were classified into Grade 0: no violation; Grade 1: <2 mm perforation; Grade 2: 2-4 mm perforation; and Grade 3: >4 mm perforation. For anterior perforations, the pedicle perforations were classified into Grade 0: no violation, Grade 1: <4 mm perforation; Grade 2: 4-6 mm perforation; and Grade 3: >6 mm perforation. RESULTS: The inter-rater reliability was adequate with a kappa value of 0.83. The mean age of the study group was 58.3 ± 15.6 years. The indications for surgery were tumor (70.3 %), infection (18.2 %), trauma (6.8 %), osteoporotic fracture (2.7 %) and degenerative diseases (2.0 %). The overall screw perforation rate was 9.7 %, in Europeans 9.1 % and in Asians 10.2 % (p > 0.05). Grade 1 perforation rate was 8.4 %, Grade 2 was 1.2 % and Grade 3 was 0.1 % with no difference in the grade of perforations between Europeans and Asians (p > 0.05). The perforation rate was the highest in T1 (33.3 %), followed by T6 (14.5 %) and T4 (14.0 %). Majority of perforations occurred medially (43.5 %), followed by laterally (25.9 %), and anteriorly (23.5 %). There was no statistical significant difference (p > 0.05) in the perforation rates between right-sided pedicle screws and left-sided pedicle screws (R: 10.0 %, L: 9.3 %). CONCLUSIONS: There were no statistical significant differences in the overall perforation rates, grades of perforations, direction of perforations for implantation of percutaneous thoracic pedicle screws insertion using fluoroscopic guidance between Europeans and Asians. The safety profile for this technique was comparable to the current reported perforation rates for conventional open pedicle screw technique.

Ultrastructural and immunohistochemical localization of plasma membrane Ca2+-ATPase 4 in Ca2+-transporting epithelia.

Plasma membrane Ca(2+)-ATPases (PMCAs) participate in epithelial Ca(2+) transport and intracellular Ca(2+) signaling. The Pmca4 isoform is enriched in distal nephron isolates and decreased in mice lacking the epithelial transient receptor potential vanilloid 5 Ca(2+) channel. We therefore hypothesized that Pmca4 plays a significant role in transcellular Ca(2+) flux and investigated the localization and regulation of Pmca4 in Ca(2+)-transporting epithelia. Using antibodies directed specifically against Pmca4, we found it expressed only in the smooth muscle layer of mouse and human intestines, whereas pan-specific Pmca antibodies detected Pmca1 in lateral membranes of enterocytes. In the kidney, Pmca4 showed broad localization to the distal nephron. In the mouse, expression was most abundant in segments coexpressing the epithelial ransient receptor potential vanilloid 5 Ca(2+) channel. Significant, albeit lower, expression was also evident in the region encompassing the cortical thick ascending limbs, macula densa, and early distal tubules as well as smooth muscle layers surrounding renal vessels. In the human kidney, a similar pattern of distribution was observed, with the highest PMCA4 expression in Na(+)-Cl(-) cotransporter-positive tubules. Electron microscopy demonstrated Pmca4 localization in distal nephron cells at both the basolateral membrane and intracellular perinuclear compartments but not submembranous vesicles, suggesting rapid trafficking to the plasma membrane is unlikely to occur in vivo. Pmca4 expression was not altered by perturbations in Ca(2+) balance, pointing to a housekeeping function of the pump in Ca(2+)-transporting epithelia. In conclusion, Pmca4 shows a divergent expression pattern in Ca(2+)-transporting epithelia, inferring diverse roles for this isoform not limited to transepithelial Ca(2+) transport.

Polarity-driven polytypic branching in cu-based quaternary chalcogenide nanostructures.

An appropriate way of realizing property nanoengineering in complex quaternary chalcogenide nanocrystals is presented for Cu2CdxSnSey(CCTSe) polypods. The pivotal role of the polarity in determining morphology, growth, and the polytypic branching mechanism is demonstrated. Polarity is considered to be responsible for the formation of an initial seed that takes the form of a tetrahedron with four cation-polar facets. Size and shape confinement of the intermediate pentatetrahedral seed is also attributed to polarity, as their external facets are anion-polar. The final polypod extensions also branch out as a result of a cation-polarity-driven mechanism. Aberration-corrected scanning transmission electron microscopy is used to identify stannite cation ordering, while ab initio studies are used to show the influence of cation ordering/distortion, stoichiometry, and polytypic structural change on the electronic band structure.