Cluster analysis demonstrates co-existing sites of fragility fracture and associated comorbidities.

We undertook cluster analysis in 11,003 patients who had sustained ≥ 1 fragility fracture, to find associations between fracture sites and comorbidities. We identified three distinct groups of fracture sites and four clusters of fractures and comorbidities. Knowledge of factors associated with fracture sites will aid prophylaxis in at-risk patients. INTRODUCTION: Fragility fracture (FF) prevalence is increasing. Subsequent fractures lead to greater morbidity and mortality. Few data are available on the association between FF sites and comorbidities. OBJECTIVES: 1. Establish the most common sites of FF and clusters within patients. 2. Identify patterns of co-existing FF and associated comorbidities. METHODS: We retrospectively reviewed clinical records of patients undergoing bone mineral density estimation at a district hospital in North-West England, 2004-2016, identifying those who had sustained ≥ 1 FF. Demographics, FF site(s), comorbidities, and medications were recorded. Cluster analysis was performed on fracture sites alone, and sites and comorbidities, using Jaccard similarity coefficient. Results were plotted on a dendrogram and divided into clusters. RESULTS: Of 28,868 patients, 11,003 had sustained ≥ 1 FF, 84.6% female, with overall mean age 67.5 years and median T-score - 1.12 SD. FF of the forearm was more frequent (n = 5045), most commonly co-existing with tibia/fibula fractures. Three FF site clusters were identified: ankle and elbow; forearm, tibia/fibula, ribs and spine; and pelvis, femur and humerus. When including comorbidities, four clusters were identified: forearm, tibia/fibula, spine, associated with family history of FF, smoking, corticosteroids and bisphosphonates; pelvis associated with hyperparathyroidism, PMR, coeliac disease and HRT; femur and humerus associated with IBD and RA; and ribs associated with alcohol and hyperthyroidism. CONCLUSION: Cluster analysis demonstrated three fracture site clusters, and four subgroups of FF sites and comorbidities. Cluster analysis is a novel method to evaluate comorbidities associated with FF sites. Knowledge of factors associated with FF sites will aid prophylaxis in at-risk patients.

Ruling out Color Transparency in Quasielastic

Quasielastic ^{12}C(e,e^{'}p) scattering was measured at spacelike 4-momentum transfer squared Q^{2}=8, 9.4, 11.4, and 14.2 (GeV/c)^{2}, the highest ever achieved to date. Nuclear transparency for this reaction was extracted by comparing the measured yield to that expected from a plane-wave impulse approximation calculation without any final state interactions. The measured transparency was consistent with no Q^{2} dependence, up to proton momenta of 8.5 GeV/c, ruling out the quantum chromodynamics effect of color transparency at the measured Q^{2} scales in exclusive (e,e^{'}p) reactions. These results impose strict constraints on models of color transparency for protons.

Enantioseparation of ketoconazole and miconazole by capillary electrophoresis and a study on their inclusion interactions with ß-cyclodextrin and derivatives.

A chiral separation method coupled with capillary electrophoresis (CE) analysis for ketoconazole and miconazole enantiomers using chiral selectors such as ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-CD (HP-ß-CD) was developed in this study, which included the optimisation, validation and application of the method on the antifungal cream samples. The formation of inclusion complex between the hosts (ß-CD and HP-ß-CD) and guests (ketoconazole and miconazole) were compared and analysed using ultraviolet-visible spectrophotometry, nuclear magnetic resonance (NMR) spectroscopy and molecular docking methods. Results from the study showed that in a concentration that ranged between 0.25 and 50 mg L-1 , the linear calibration curves of each enantiomer had a high coefficient of regression (R2 > 0.999), low limit of detection (0.075 mg L-1 ) and low limit of quantification (0.25 mg L-1 ). The relative standard deviation (RSD) of the intraday and interday analyses ranged from 0.79% to 8.01% and 3.30% to 11.43%, respectively, while the recoveries ranged from 82.0% to 105.7% (RSD < 7%, n = 3). The most probable structure of the inclusion complexes was proposed based on the findings from the molecular docking studies conducted using the PatchDock server.

Probing the Deuteron at Very Large Internal Momenta.

We measure ^{2}H(e,e^{'}p)n cross sections at 4-momentum transfers of Q^{2}=4.5±0.5 (GeV/c)^{2} over a range of neutron recoil momenta p_{r}, reaching up to ∼1.0 GeV/c. We obtain data at fixed neutron recoil angles θ_{nq}=35°, 45°, and 75° with respect to the 3-momentum transfer q[over →]. The new data agree well with previous data, which reached p_{r}∼500 MeV/c. At θ_{nq}=35° and 45°, final state interactions, meson exchange currents, and isobar currents are suppressed and the plane wave impulse approximation provides the dominant cross section contribution. We compare the new data to recent theoretical calculations, where we observe a significant discrepancy for recoil momenta p_{r}>700 MeV/c.

Do we need to perform MRI of the whole spine in addition to MRI of the sacroiliac joints in suspected spondyloarthropathy?

AIM: To identify the incidence of spinal-only changes (including both acute inflammatory and chronic structural changes) in patients with suspected spondyloarthropathy (SpA) to determine whether MRI of the sacroiliac joints would be sufficient in the initial radiological work-up and whether the number of spinal magnetic resonance imaging (MRI) examinations performed could be reduced. MATERIALS AND METHODS: This was a retrospective study of patients with suspected SpA referred from the rheumatology department of a university teaching hospital undergoing MRI both of the whole spine and of the sacroiliac joints over a 3-year period. Imaging was assessed for the presence of acute inflammatory and chronic structural changes. RESULTS: Three hundred and sixty-five patients with suspected SpA undergoing both whole spine and sacroiliac joint MRI were identified. The majority (79.2%) had no spinal or sacroiliac joint inflammation. Spinal-only changes (acute inflammatory and/or chronic structural) were detected in only 0.8% (3/365) of cases. The majority of positive spinal cases had inflammatory changes involving the thoracic spine (21/24). The majority of positive sacroiliac joint cases were bilateral (51/73). CONCLUSION: The extremely low incidence of spinal-only inflammatory or structural change indicates that sacroiliac joint MRI may be sufficient for initial radiological work-up of SpA with spinal MRI reserved for instances where there is spinal symptomatology and uncertainty in the clinical diagnosis following interdisciplinary discussion or where a baseline is required.

Predictors of fracture risk in patients with systemic lupus erythematosus.

Objectives Bone loss in systemic lupus erythematosus is multifactorial. Recent studies demonstrate corticosteroids, previous fractures and increasing age decrease bone mineral density. The effect of body mass index and fat mass are less well characterized. We sought to determine fracture risk factors in patients undergoing dual-energy X-ray absorptiometry scanning at a district hospital in 2004-2015. Methods Standard dual-energy X-ray absorptiometry parameters were recorded, plus rheumatoid arthritis diagnosis, smoking status, alcohol consumption, family history of fractures, history of secondary operation and corticosteroid use. Data were analyzed using Fisher's exact test for categorical data and logistic regression for continuous data. Results One hundred and fifty patients (141 women, nine men) with SLE were included; 52 (34.6%) had sustained at least one fracture. Fracture risk increased with increased age, body mass index, fat mass and average tissue thickness, and decreased lean mass (adjusted for steroid use), as well as with smoking and rheumatoid arthritis. Increased femoral and vertebral bone mineral density conversely decreased fracture risk. Conclusion Our study suggests increased age, body mass index, fat mass, smoking and/or rheumatoid arthritis increase fracture risk in SLE patients. To our knowledge, this is the first demonstration of a correlation between increased fat mass, adjusted for steroid use and fracture risk, in adults, potentially indicating a differential effect of fat on bone metabolism and lessening of lean body mass.

Does plasticity enhance or dampen phenotypic parallelism? A test with three lake-stream stickleback pairs.

Parallel (and convergent) phenotypic variation is most often studied in the wild, where it is difficult to disentangle genetic vs. environmentally induced effects. As a result, the potential contributions of phenotypic plasticity to parallelism (and nonparallelism) are rarely evaluated in a formal sense. Phenotypic parallelism could be enhanced by plasticity that causes stronger parallelism across populations in the wild than would be expected from genetic differences alone. Phenotypic parallelism could be dampened if site-specific plasticity induced differences between otherwise genetically parallel populations. We used a common-garden study of three independent lake-stream stickleback population pairs to evaluate the extent to which adaptive divergence has a genetic or plastic basis, and to investigate the enhancing vs. dampening effects of plasticity on phenotypic parallelism. We found that lake-stream differences in most traits had a genetic basis, but that several traits also showed contributions from plasticity. Moreover, plasticity was much more prevalent in one watershed than in the other two. In most cases, plasticity enhanced phenotypic parallelism, whereas in a few cases, plasticity had a dampening effect. Genetic and plastic contributions to divergence seem to play a complimentary, likely adaptive, role in phenotypic parallelism of lake-stream stickleback. These findings highlight the value of formally comparing wild-caught and laboratory-reared individuals in the study of phenotypic parallelism.

TLR8 gene polymorphism and association in bacterial load in southern Punjab of Pakistan: an association study with pulmonary tuberculosis.

Only 5-10% of people infected with Mycobacterium tuberculosis develop active tuberculosis which suggests a role of genetic variation in host immunity. Genetic variants in TLRs are potential indicator for host susceptibility and outcome of several diseases. We explored the association of nonsynonymous genetic variants (Met1Val) with Toll-like receptor 8 in Pakistani population. Genotypic and allelic distribution of TLR8 polymorphism (rs3764880) in patients with TB and healthy donors from different areas of southern Punjab, Pakistan, was determined. Results provide that our population is highly influenced by TLR8 Met1Val SNP for TB, and G allele appeared to increase TB susceptibility. Mutant genotype GG or G/- and G allele was significantly higher among all the categories of cases than in controls. Among different levels of bacillary load and genotypes, GG or G/- and G allele significantly supports the incidence of 2 + class for bacterial load.

The prevalence of osteoporosis in an older population with very high body mass index: evidence for an association.

BACKGROUND: Studies have demonstrated the beneficial effect of normal and high body mass index (BMI) upon risk of osteoporosis (OP). No study has investigated the prevalence of OP in an older population with a very high BMI (higher than 40 kg/m(2) ). METHODS: Data of patients aged over 50 years that attended for a dual energy X-ray absorptiometry scan at a UK district general hospital were collated. The population was divided according to BMI increments of 5 kg/m(2) . The prevalence of OP for each BMI category was ascertained. Logistic regression analysis was used to investigate for significant associations between BMI and OP prevalence, adjusted for age, sex and number of OP risk factors. RESULTS: Data of 10,796 study subjects were collated. Mean age was 67.34 years. Decreasing prevalence of OP was associated with increasing BMI up to 40 kg/m(2) , above which increasing BMI was associated with increasing prevalence of OP. CONCLUSIONS: The protective effect of increasing BMI exists up to 40 kg/m(2) . A BMI higher than 40 kg/m(2) is associated with increased prevalence of OP. This finding may be attributable to reduced level of bone weight bearing in individuals with a very high BMI.

Assessment of the treat-to-target strategy in patients with refractory rheumatoid arthritis. A prospective study on efficacy and safety in a Saudi population.

AIM: The goal of the present study was to prospectively assess the long-term clinical outcome of biologic modifying drug therapy in a population of Saudi rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: This is the first prospective, long-term report on the efficacy and safety of biologic therapy in Saudi RA patients. It is a single center, observational study with a follow-up period of 3 years. Enrolled were 120 biologic naïve patients (94 women, 78.3 %; mean age 48.4 ± 17.9 years, mean disease duration 7.3 ± 3.9 years) with the diagnosis of RA (ACR/EULAR, 2010 criteria) who were inadequate responders to methotrexate and synthetic DMARDs. RESULTS: After 3 years, the mean Disease Activity Index-28 (DAS-28), Health Assessment Questionnaire (HAQ), Pain Score, ESR, and CRP values improved significantly. Of the 99 patients completing the 3-year follow-up, 35.3 % of patients achieved DAS-28 remission and 53.5 % achieved low disease activity, and 11.1 % of patients had moderate to high activity scores. At the 3-year follow-up, 80 % of patients had no evidence of significant radiographic progression (achieved < 0.5 of the mean total Sharp score). Infections were reported in 11.7 % and significantly correlated with conjugate use of oral prednisolone at doses above 5 mg/day, with chest infections being the most common type of infection (6.7 %). CONCLUSION: The results of this study can be understood as real-life clinical experience displaying the incremental benefit of biologic therapy in refractory disease when it is added to other optimal strategies. The study showed satisfying clinical and functional benefit with considerable safety.

New measurements of high-momentum nucleons and short-range structures in nuclei.

We present new measurements of electron scattering from high-momentum nucleons in nuclei. These data allow an improved determination of the strength of two-nucleon correlations for several nuclei, including light nuclei where clustering effects can, for the first time, be examined. The data also include the kinematic region where three-nucleon correlations are expected to dominate.

The prevalence and correlates of depressive symptoms from an Arabian setting: a wake up call.

It has been shown that medical students have a higher rate of depressive symptoms than the general population and age- and sex-matched peers. This study aimed to estimate the prevalence of depressive symptoms among the medical students of a large school following a traditional curriculum and its relation to personal background variables. A descriptive-analytic, cross-sectional study was conducted in a medical school in Riyadh, Saudi Arabia. The medical students of King Saud University in Riyadh, Saudi Arabia, were screened for depressive symptoms using the 21-item Beck Depression Inventory. A high prevalence of depressive symptoms (48.2%) was found, it was either mild (21%), moderate (17%), or severe (11%). The presence and severity of depressive symptoms had a statistically significant association with early academic years (p < 0.000) and female gender (p < 0.002). The high prevalence of depressive symptoms is an alarming sign and calls for remedial action, particularly for the junior and female students.

First confirmed report of outbreak of malignant ovine theileriosis among goats in Sudan.

An outbreak of malignant ovine theileriosis among goats was confirmed and documented. In this outbreak, 16 out of 22 (72.7%) goats died within 4 days showing clinical signs of malignant ovine theileriosis as well as in the postmortem findings. The goats were reared in a mixed flock with sheep in Atbara Town, Northern Sudan. The infection was detected microscopically and confirmed serologically by IFA test and molecularly by PCR technique using specific primer for Theileria lestoquardi. Hyalomma anatolicum was the most prevalent (dominant) tick species found in the farm. It is recommended to undertake future research on the role of goats on the epidemiology of malignant ovine theileriosis.

Scaling of the F2 structure function in nuclei and quark distributions at x>1.

We present new data on electron scattering from a range of nuclei taken in Hall C at Jefferson Lab. For heavy nuclei, we observe a rapid falloff in the cross section for x>1, which is sensitive to short-range contributions to the nuclear wave function, and in deep inelastic scattering corresponds to probing extremely high momentum quarks. This result agrees with higher energy muon scattering measurements, but is in sharp contrast to neutrino scattering measurements which suggested a dramatic enhancement in the distribution of the "superfast" quarks probed at x>1. The falloff at x>1 is noticeably stronger in 2H and 3He, but nearly identical for all heavier nuclei.

New measurements of the European Muon Collaboration effect in very light nuclei.

New Jefferson Lab data are presented on the nuclear dependence of the inclusive cross section from (2)H, (3)He, (4)He, (9)Be and (12)C for 0.3 < x < 0.9, Q(2) approximately 3-6 GeV(2). These data represent the first measurement of the EMC effect for (3)He at large x and a significant improvement for (4)He. The data do not support previous A-dependent or density-dependent fits to the EMC effect and suggest that the nuclear dependence of the quark distributions may depend on the local nuclear environment.

The Value of Spirometry in Subglottic Stenosis.

The diagnosis of subglottic stenosis (SGS) is usually made by clinical assessment and definitively by a direct endoscopic examination. This study aimed to evaluate different spirometric values in relation to anatomical grading and severity of subglottic stenosis cases of upper airway obstruction. Cases of SGS that underwent dilatational procedures endoscopically at the otolaryngology department of the King Saud University Medical City, Riyadh, Saudi Arabia, from June 2015 to October 2017 were collected. Pulmonary function test (PFT) pre- and postoperative parameters and the grades of subglottic stenosis were extracted. We compared different spirometric values to the severity of SGS and compared the pre- and postoperative results for each patient. There were 19 cases with a valid PFT study within 7 days preoperatively in addition to a documented intraoperative grading according to the Myer-Cotton grading system; 7 (36.8%) were grade 1, 8 (42.1%) were grade 2, and 4 (21.1%) were grade 3. The actual preoperative ratio of forced expiratory volume (FEV1) in 1 second to peak expiratory flow (PEF) for all 19 patients ranged from 7.34 to 21.40 mL/L/min. We found a significant improvement in all spirometric parameters postdilatation including PEF ( P < .001), FEV1 ( P < .001), FEV1/PEF ( P = .001), forced expiratory flow (FEF) from 25%, 50%, and 75% of vital capacity, respectively, FEF25 ( P < .001), FEF50 ( P = .001), FEF75 ( P = .048), and maximum mid-expiratory flow ( P = .002). We did not find any correlation between the severity of stenosis and spirometric values. This study revealed that spirometry is a useful marker in following up patients with subglottic stenosis and is also a good indicator to determine postairway surgery outcomes. However, these markers do not correlate with anatomical grading and the severity of subglottic stenosis.

Detection of DNA by scraping the formalin-fixed paraffin-embedded tissue.

BACKGROUND: Pakistan is a developing country and most of the research laboratories have limited required infrastructures for the diagnosis of cancer at molecular level. The polymerase chain reaction (PCR) on formalin-fixed paraffin-embedded tissues is becoming a popular procedure in the research centres. The study was conducted to introduce two new methods of DNA extraction for the PCR from formalin-fixed paraffin-embedded sections of surgical pathology specimens. MATERIALS AND METHODS: Two methods of DNA detection were used. In method A the formalin-fixed tissues were grossed, proper sections were taken, processed in an automatic tissue processor, embedded in paraffin blocks, and microtomic sections were made. In method B, the procedure was the same until embedding in the paraffin blocks, after which the selected paraffin blocks were set on a black card paper (4 cm x 4 cm) and 1 mg of pure scraped tissue was obtained using a scalpel, manually without using microtone. RESULTS: DNA was successfully extracted but point mutation of p53 gene was not seen in SCP while it was determined in 96 and 93.75 per cent cases of SCC by method A and method B respectively. There was no statistical difference in the results by both methods (P = 0.359). CONCLUSION: Scraping of the tissue for DNA detection was a simple method and may be performed in any laboratory. The reliability, reproducibility, and quality assurance of the present results are consistent with the already established techniques of DNA extraction for PCR.

A role for interleukins in ochronosis in a chondrocyte in vitro model of alkaptonuria.

Alkaptonuria is a rare autosomal recessive condition resulting from inability to breakdown homogentisic acid (HGA), an intermediate in tyrosine degradation. The condition has a triad of clinical features, the most damaging of which is ochronotic osteoarthropathy. HGA is elevated from birth, but pigmentation takes many years. We hypothesise that interleukins play a role in initiation and progression of ochronotic osteoarthropathy. C20/A4 cells were cultured and maintained in 9-cm petri dishes containing either HGA at 0.33 mM, a single interleukin (IL-1ß, IL-6 or IL-10) at 1 ng/ml or a combination of HGA and a single interleukin. Statistical analysis of pigment deposits and cell viability was performed using analysis of variance with Newman-Keuls post-test. All cultures containing HGA showed a significant increase in pigment deposition compared to control and IL cultures alone. The cultures containing HGA and IL-6 showed a significant increase in pigment deposits compared to HGA alone. The cell viability counts across all cultures on day 10 demonstrated a significant decrease in cultures containing HGA compared to those which did not. There was no significant difference between cultures containing just HGA or those combined with an interleukin. This work demonstrates a role for cytokines present in the joint(s) in the pigmentation process, particularly IL-6, and that the presence of HGA in joint tissues appears more detrimental to chondrocytes than the presence of any of the interleukins found in response to joint injury, trauma and osteoarthritis (OA). This further supports the evidence that the arthropathy in alkaptonuria is much more severe and rapidly progressing.

Osteoarticular cells tolerate short-term exposure to nitisinone-implications in alkaptonuria.

Alkaptonuria (AKU) is a rare genetic disease resulting in severe, rapidly progressing, early onset multi-joint osteoarthropathy. A potential therapy, nitisinone, is being trialled that reduces the causative agent; homogentisic acid (HGA) and in a murine model has shown to prevent ochronosis. Little is currently known about the effect nitisinone has on osteoarticular cells; these cells suffer most from the presence of HGA and its polymeric derivatives. This led us to investigate nitisinone's effect on chondrocytes and osteoblast-like cells in an in vitro model. Human C20/A4 immortalized chondrocytes, and osteosarcoma cells MG63 cultured in DMEM, as previously described. Confluent cells were then plated into 24-well plates at 4 × 10(4) cells per well in varying concentrations of nitisinone. Cells were cultured for 7 days with medium changes every third day. Trypan blue assay was used to determine viability and the effect of nitisinone concentration on cells. Statistical analysis was performed using analysis of variance, and differences between groups were determined by Newman-Keuls post-test. Analysis of C20/A4 chondrocyte and MG63 osteoblast-like cell viability when cultured in different concentrations of nitisinone demonstrates that there is no statistically significant difference in cell viability compared to control cultures. There is currently no literature surrounding the use of nitisinone in human in vitro models, or its effect on chondrocytes or osteoblast like cells. Our results show that nitisinone does not appear detrimental to cell viability of chondrocytes or osteoblast-like cells, which adds to the evidence that this therapy could be useful in treating AKU.