Bisphosphonate's and Intermittent Parathyroid Hormone's Effect on Human Spinal Fusion: A Systematic Review of the Literature.

There has been a conscious effort to address osteoporosis in the aging population. As bisphosphonate and intermittent parathyroid hormone (PTH) therapy become more widely prescribed to treat osteoporosis, it is important to understand their effects on other physiologic processes, particularly the impact on spinal fusion. Despite early animal model studies and more recent clinical studies, the impact of these medications on spinal fusion is not fully understood. Previous animal studies suggest that bisphosphonate therapy resulted in inhibition of fusion mass with impeded maturity and an unknown effect on biomechanical strength. Prior animal studies demonstrate an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. The purpose of this study was to determine if bisphosphonates and intermittent PTH treatment have impact on human spinal fusion. A systematic review of the literature published between 1980 and 2015 was conducted using major electronic databases. Studies reporting outcomes of human subjects undergoing 1, 2, or 3-level spinal fusion while receiving bisphosphonates and/or intermittent PTH treatment were included. The results of relevant human studies were analyzed for consensus on the effects of these medications in regards to spinal fusion. There were nine human studies evaluating the impact of these medications on spinal fusion. Improved fusion rates were noted in patients receiving bisphosphonates compared to control groups, and greater fusion rates in patients receiving PTH compared to control groups. Prior studies involving animal models found an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. No significant complications were demonstrated in any study included in the analysis. Bisphosphonate use in humans may not be a deterrent to spinal fusion. Intermittent parathyroid use has shown early promise to increase fusion mass in both animal and human studies but further studies are needed to support routine use

Reliable microsatellite genotyping of the Eurasian badger (Meles meles) using faecal DNA

The potential link between badgers and bovine tuberculosis has made it vital to develop accurate techniques to census badgers. Here we investigate the potential of using genetic profiles obtained from faecal DNA as a basis for population size estimation. After trialling several methods we obtained a high amplification success rate (89%) by storing faeces in 70% ethanol and using the guanidine thiocyanate/silica method for extraction. Using 70% ethanol as a storage agent had the advantage of it being an antiseptic. In order to obtain reliable genotypes with fewer amplification reactions than the standard multiple-tubes approach, we devised a comparative approach in which genetic profiles were compared and replication directed at similar, but not identical, genotypes. This modified method achieved a reduction in polymerase chain reactions comparable with the maximumlikelihood model when just using reliability criteria, and was slightly better when using reliability criteria with the additional proviso that alleles must be observed twice to be considered reliable. Our comparative approach would be best suited for studies that include multiple faeces from each individual. We utilized our approach in a well-studied population of badgers from which individuals had been sampled and reliable genotypes obtained. In a study of 53 faeces sampled from three social groups over 10 days, we found that direct enumeration could not be used to estimate population size, but that the application of mark–recapture models has the potential to provide more accurate results

A comparison between three conditioning factors dataset for landslide prediction in the sajadrood catchment of iran

This study investigates the effectiveness of three datasets for the prediction of landslides in the Sajadrood catchment (Babol County, Mazandaran Province, Iran). The three datasets (D1, D2 and D3) are constructed based on fourteen conditioning factors (CFs) obtained from Digital Elevation Model (DEM) derivatives, topography maps, land use maps and geological maps. Precisely, D1 consists of all 14 CFs namely altitude, slope, aspect, topographic wetness index (TWI), terrain roughness index (TRI), distance to fault, distance to stream, distance to road, total curvature, profile curvatures, plan curvature, land use, steam power index (SPI) and geology. D2, on the other hand, is a subset of D1, consisting of eight CFs. This reduction was achieved by exploiting the Variance Inflation Factor, Gini Importance Indices and Chi-Square factor optimization methods. Dataset D3 includes only selected factors derived from the DEM. Three supervised classification algorithms were trained for landslide prediction namely the Support Vector Machine (SVM), Logistic Regression (LR), and Artificial Neural Network (ANN). Experimental results indicate that D2 performed the best for landslide prediction with the SVM producing the best overall accuracy at 82.81%, followed by LR (81.71%) and ANN (80.18%). Extensive investigations on the results of factor optimization analysis indicate that the CFs distance to road, altitude, and geology were significant contributors to the prediction results. Land use map, slope, total-, plan-, and profile curvature and TRI, on the other hand, were deemed redundant. The analysis also revealed that sole reliance on Gini Indices could lead to inefficient optimization

Effect of a multicomponent intervention on antihypertensive medication intensification in rural South Asia: post-hoc analysis of a cluster RCT

BACKGROUND: Inadequate treatment of hypertension is a widespread problem, especially in South Asian countries where cardiovascular disease mortality rates are high. We aimed to explore the effect of a multicomponent intervention (MCI) on antihypertensive medication intensification among rural South Asians with hypertension. METHODS: A post-hoc analysis of a two-year cluster-randomized controlled trial including 2645 hypertensives aged≥ 40 years from 30 rural communities, 10 each, in Bangladesh, Pakistan, and Sri Lanka. Independent assessors collected information on participants' self-reports and physical inspection of medications. The main outcomes were the changes from baseline to 24 months in the following: 1) the therapeutic intensity score (TIS) for all (and class specific) antihypertensive medications; 2) the number of antihypertensive medications in all trial participants. RESULTS: At 24 months, the mean increase in the TIS score of all antihypertensive medications was 0.11 in the MCI group and 0.03 in the control group, with a between-group difference in the increase of 0.08 (95% CI (0.03, 0.12); P=0.002). In MCI compared to controls, a greater increase in the TIS of renin angiotensin-aldosterone system blockers (0.05; 95% CI (0.02, 0.07); P<0.001) and calcium channel blockers (0.03; 95% CI (0.00, 0.05);p=0.031) , and in the number of antihypertensive medications (0.11, 95% CI (0.02, 0.19);P=0.016) was observed. CONCLUSIONS: In rural communities in Bangladesh, Pakistan, and Sri Lanka, MCI led to a greater increase in antihypertensive medication intensification compared to the usual care among adults with hypertension. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02657746

An assessment of the usefulness of a rapid immuno-chromatographic test, "Determine™ malaria pf" in evaluation of intervention measures in forest villages of central India

BACKGROUND: Plasmodium falciparum malaria, is a major health problem in forested tribal belt of central India. Rapid and accurate methods are needed for the diagnosis of P. falciparum. We performed a blinded evaluation of the recently introduced Determine™ malaria pf test (Abbott, Laboratories, Japan) compared with microscopy and splenomegaly in children in epidemic prone areas of district Mandla to assess the impact of intervention measures. METHODS: Children aged 2–10 yrs with and without fever were examined for spleen enlargement by medical specialist by establishing a mobile field clinic. From these children thick blood smears were prepared from finger prick and read by a technician. Simultaneously, rapid tests were performed by a field lab attendant. The figures for specificity, sensitivity and predictive values were calculated using microscopy as gold standard. RESULTS: In all 349 children were examined. The sensitivity and specificity for Determine rapid diagnostic test were 91 and 80% respectively. The positive predictive values (PPV), negative predictive values (NPV) and accuracy of the test were respectively 79, 91 and 85%. On the contrary, the sensitivity and specificity of spleen in detecting malaria infection were 57 and 74 % respectively with PPV of 73%, NPV 59 % and an accuracy of 65%. CONCLUSIONS: Determine™ malaria rapid diagnostic test is easier and quicker to perform and has other advantages over microscopy in not requiring prior training of personnel or quality control. Thus, highlighting the usefulness of a rapid antigen test in assessing prevailing malaria situation in remote areas

Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer

In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa

Physical inactivity is associated with chronic musculoskeletal complaints 11 years later: results from the Nord-Trøndelag Health Study

Background Physical inactivity is associated with several diseases, but studies evaluating the association between chronic musculoskeletal complaints (MSCs) and physical exercise have shown conflicting results. The aim of this large-scale prospective population-based study was to investigate the association between self-reported physical exercise at baseline and the prevalence of chronic musculoskeletal complaints (MSCs) 11 years later. Methods The results are based upon two consecutive public health studies conducted within the county of Nord-Trøndelag, Norway (The HUNT studies). A total of 39,520 (83%) out of 47,556 adults who participated in HUNT 1 and HUNT 2 responded to questions about physical exercise at baseline in 1984–86, and to questions about musculoskeletal complaints 11 years later (1995–97). Chronic MSCs was defined as MSCs ≥ 3 months during the past year, and chronic widespread MSCs such as pain ≥ 15 days during the last month from the axial region, above the waist, and below the waist. Associations were assessed using multiple logistic regression, estimating prevalence odds ratio (OR) with 95% confidence intervals (CIs). All the final analyses were adjusted for age, gender, body mass index, smoking and education level. Results At follow-up 20,223 (51%) reported chronic MSCs, and among these 2,318 (5.9%) reported chronic widespread MSCs. Individuals who exercised at baseline were less likely to report chronic MSCs 11 years later (OR 0.91, 95% CI 0.85–0.97) than inactive persons. Among individuals who exercised more than three times per week, chronic widespread MSCs were 28% less common (OR 0.72, 95% CI 0.59–0.88) compared to inactive individuals. Conclusion In this large-scale population-based study, physical exercise was associated with lower prevalence of chronic MSCs, in particular chronic widespread MSCs. Future studies should try to clarify whether chronic MSCs are a cause or a consequence of inactivity

The Clinical Correlations between Diabetes, Cigarette Smoking and Obesity on Intervertebral Degenerative Disc Disease of the Lumbar Spine

Study DesignRetrospective analysis of a nationwide private insurance database. Chi-square analysis and linear regression models were utilized for outcome measures.PurposeThe purpose of this study was to investigate any relationship between lumbar degenerative disc disease, diabetes, obesity and smoking tobacco.Overview of LiteratureDiabetes, obesity, and smoking tobacco are comorbid conditions known to individually have effect on degenerative disc disease. Most studies have only been on a small populous scale. No study has yet to investigate the combination of these conditions within a large patient cohort nor have they reviewed the combination of these conditions on degenerative disc disease.MethodsA retrospective analysis of insurance billing codes within the nationwide Humana insurance database was performed, using PearlDiver software (PearlDiver, Inc., Fort Wayne, IN, USA), to identify trends among patients diagnosed with lumbar disc degenerative disease with and without the associated comorbidities of obesity, diabetes, and/or smoking tobacco. Patients billed for a comorbidity diagnosis on the same patient record as the lumbar disc degenerative disease diagnosis were compared over time to patients billed for lumbar disc degenerative disease without a comorbidity. There were no sources of funding for this manuscript and no conflicts of interest.ResultsThe total number and prevalence of patients (per 10,000) within the database diagnosed with lumbar disc degenerative disease increased by 241.4% and 130.3%, respectively. The subsets of patients within this population who were concurrently diagnosed with either obesity, diabetes, tobacco use, or a combination thereof, was significantly higher than patients diagnosed with lumbar disc degenerative disease alone (p <0.05 for all). The number of patients diagnosed with lumbar disc degenerative disease and smoking rose significantly more than patients diagnosed with lumbar disc degenerative disease and either diabetes or obesity (p <0.05). The number of patients diagnosed with lumbar disc degenerative disease, smoking and obesity rose significantly more than the number of patients diagnosed with lumbar disc degenerative disease and any other comorbidity alone or combination of comorbidities (p <0.05).ConclusionsDiabetes, obesity and cigarette smoking each are significantly associated with an increased diagnosis of lumbar degenerative disc disease. The combination of smoking and obesity had a synergistic effect on increased rates of lumbar degenerative disc disease. Patient education and preventative care is a vital goal in prevention of degenerative disc disease within the general population