Strain structure analysis of Mycobacterium tuberculosis circulating among HIV negative, positive and drug resistant TB patients attending chest clinics in Western Kenya.

BACKGROUND: Despite global tuberculosis (TB) interventions, the disease remains one of the major public health concerns. Kenya is ranked 15th among 22 high burden TB countries globally. METHODS: A cross-sectional study was conducted in Western Kenya, which comprises 10 counties. A multistage sampling method was used where a single sub-county was randomly selected followed by sampling two high volume health facility from each sub-county. Identification of spoligotype profiles and their family distribution and lineage level were achieved by comparison with SITVIT database. RESULTS: Lineage distribution pattern revealed that the most predominant lineage was CAS 220 (39.8%) followed by Beijing 128 (23.1%). The other lineages identified were T, LAM, H, X, S and MANU which were quantified as 87 (15.7%), 67 (12.1%), 16 (2.8%), 10 (1.8%), 8 (1.4%) and 5 (0.9%) respectively. CAS and Beijing strains were the most predominant lineage in both HIV negative and positive TB patients. The Beijing lineage was also the most predominant in resistant M. tuberculosis strains as compared to wild type. A total of 12 (2.0%) were orphaned M. tuberculosis strains which were spread across all the 10 counties of the study site. In multivariate logistic regression adjusting for potential cofounders three potential risk factors were significant. HIV status (OR = 1.52, CI = 0.29-3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43-3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49-3.87 and P value = 0.026). Most M. tuberculosis clinical isolates showed genetic clustering with multivariate logistic regression indicating three potential risk factors to clustering. HIV status (OR = 1.52, CI = 0.29-3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43-3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49-3.87 and P value = 0.026). CONCLUSION: There exist diverse strains of M. tuberculosis across the 10 counties of Western Kenya. Predominant distribution of clustered genotype points to the fact that most TB cases in this region are as a result of resent transmission other than activation of latent TB.

Promoting insect farming and household consumption through agricultural training and nutrition education in Africa: A study protocol for a multisite cluster-randomized controlled trial.

BACKGROUND: Edible insects are a sustainable source of high-quality animal protein. Insect farming is gaining interest globally, particularly in low-income countries, where it may provide substantial nutritional and economic benefits. To enhance insect farming practices in Africa, new farming systems are being developed. However, knowledge on how to best promote uptake of these systems is lacking. This study aims to fill this gap by investigating the effectiveness of educational interventions in promoting insect farming for household consumption in Africa. METHOD: The study is designed as a multi-site randomized controlled trial to evaluate the impacts of agricultural training alone or in combination with nutrition education on the adoption of insect farming in Ghana, Kenya and Uganda. In each of the three countries, ninety-nine villages are randomly assigned to one of three arms: two intervention arms and a control arm with no interventions. Focusing on production (P), the first intervention arm covers agricultural training on insect farming combined with provision of insect production starter kits. Focusing on both production and consumption (PC), the second intervention arm involves the same intervention components as treatment P plus additional nutrition education. The impacts of the interventions are measured by comparing baseline and endline data collected one year apart. Primary outcomes are adoption of insect farming and consumption of the farmed insects. DISCUSSION: Understanding the drivers and impacts of novel agricultural practices is crucial for transitioning to sustainable food systems. The current project is the first to investigate how educational interventions promote insect farming for household consumption in low-income countries. The results will contribute evidence-based knowledge to support sustainable development through insect farming in Africa. TRIAL REGISTRATION: The protocol is registered in the American Economic Association registry for randomized control trials with registration number AEARCTR-0009996. Initial registration date: 02 September 2022, last updated 17 May 2023.

In vitro assessment and comparison of quality of alcohol-based hand rubs, pre- and peri-COVID-19 pandemic outbreak in Kenya.

Background: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended the use of alcohol-based hand rubs (ABHRs) to curb transmission, leading to increased production and use. This has posed a danger of production and use of poor-quality ABHRs. Methods: This study assessed and compared the quality of ABHRs in the Kenyan market that were produced before and after the outbreak of the COVID-19 pandemic in March 2020. Quality testing was carried out against European EN 1500:2013 and Kenyan EAS 789:2013 Standards and 20 samples analyzed for alcohol content by GC-FID. Results: The study found that 27.8% of the peri-COVID-19 pandemic sanitizers had less than 90% bactericidal reduction activity as compared to 12.5% manufactured pre-COVID-19 pandemic. Only 25% peri-COVID-19 pandemic ABHRs met the EAS 789:2013 acceptable limit of over 60% alcohol content. Product adulteration with methanol was found in 20 % of the samples with only 5% complying with FDA approval limit of <0.063% v/v methanol. Study found no correlation between the total alcohol content and the efficacy of ABHRs. Conclusions: The study found that more substandard products were produced during the pandemic. This raises a concern about possible emergence of alcohol resistant strains of microorganisms. The study therefore recommends an adequate quality monitoring system to curb against substandard products.

Household perception and infestation dynamics of bedbugs among residential communities and its potential distribution in Africa.

Bedbugs have experienced an extraordinary upsurge in the recent past across the world. This cross-sectional study aimed to explore the community perception of the pest outbreaks, the population dynamics, and dispersal patterns under different habitat systems. A survey was conducted within communities in nine counties in Kenya, where geographical coordinates of the sites of bedbug presence were recorded and maximum entropy distribution modelling (MaxEnt) was used to map and predict the potentially suitable habitat, while system thinking and system dynamics approach with Vensim PLE 8.0.9 software was applied to implement bedbug infestation dynamics. Our results indicated that majority of the respondents had ample knowledge on bedbugs and were concerned about the physico-psychologic and socio-economic health effects. Spatial distribution analysis showed regions in Kenya with optimal to suitable for bedbug occurrence in the whole country, and similar results were found at continental level across Africa. Furthermore, infestation dynamics results showed a rapid mobility of bedbug from one house to another. In terms of management strategies, the models showed that the combination of chemical with other control methods was considerably much more effective compared to the use of chemical approach only, appointing integrated pest management strategy as a better intervention approach in controlling the pest.

Development of Loop-Mediated Isothermal Amplification Combined with Lateral Flow Dipstick Assay for a Rapid and Sensitive Detection of Cystic Echinococcosis in Livestock in Kenya.

Background: Cystic echinococcosis is a zoonotic disease caused by the metacestode stage of Echinococcus granulosus and occurs worldwide, causing considerable economic losses and public health problems. The currently available methods for the diagnosis of animal hydatidosis are time-consuming and require well-equipped laboratories which make them incompatible with testing in resource-poor settings. This study developed and evaluated a rapid, more sensitive, and specific loop-mediated isothermal amplification combined with a lateral flow dipstick assay for the rapid and sensitive detection of cystic echinococcosis. Results: In this study, a specific primer set and FITC-labeled probe targeting the conserved region of the NADH-1 gene were designed. The LAMP reaction was performed at 60°C for 40 minutes, and the amplification products were successfully visualized by LFD strips. The analytical sensitivity of LAMP-LFD was determined using 10-fold serial dilutions of E. granulosus DNA. The minimal concentration detected was 10 fg/µl, and no cross-reactivity was observed with DNA extracted from Taenia solium, Taenia saginata, and Fasciola hepatica. The ability of the developed LAMP-LFD assay to detect cystic echinococcosis was further evaluated with 62 cyst samples from slaughtered cattle in Juja Abattoir, Kiambu County, Kenya. The LAMP-LFD was able to detect 59/62 (95.2%, 95% CI 0.87-0.98) as positive samples of E. granulosus compared to 53/62 (85.5%, 95% CI 0.75-0.92) by nested PCR assay. Conclusion: Our results indicated that the developed LAMP-LFD technique was more sensitive than the nested PCR assay, rapid, and easy to perform with a simple visual detection of products. Therefore, it could be an important point-of-care diagnostic tool for cystic echinococcosis.

Antiretroviral (ARV) Drug Resistance and HIV-1 Subtypes among Injecting Drug Users in the Coastal Region of Kenya.

HIV-1 genetic diversity results into the development of widespread drug-resistant mutations (DRMs) for the first-line retroviral therapy. Nevertheless, few studies have investigated the relationship between DRMs and HIV-1 subtypes among HIV-positive injecting drug users (IDUs). This study therefore determined the association between HIV-1 genotypes and DRMs among the 200 IDUs. Stanford HIV Drug Resistance Database was used to interpret DRMs. The five HIV-1 genotypes circulating among the IDUs were A1 (25 (53.2%)), A2 (2 (4.3%)), B (2 (4.3%)), C (9 (19.1%)), and D (9 (19.1%)). The proportions of DRMs were A1 (12 (52.2%)), A2 (1 (4.3%)), B (0 (0.0%)), C (5 (21.7%)), and D (5 (21.7%)). Due to the large proportion of drug resistance across all HIV-1 subtypes, surveillance and behavioral studies need to be explored as IDUs may be spreading the drug resistance to the general population. In addition, further characterization of DRMs including all the relevant clinical parameters among the larger population of IDUs is critical for effective drug resistance surveillance.

Clinical heterogeneity of low flow spinal arteriovenous fistulas; a case series.

BACKGROUND: Spinal AVF (SAVF), a potentially treatable cause of myelopathy, remains a challenging diagnosis. Its rarity and non-specific imaging findings often result in misdiagnosis despite a high index of clinical suspicion. The classically described high T2 signal in the spinal cord or prominent vascular flow voids in the intradural space were not infrequently missed on initial imaging, only to be picked up at follow-up imaging after progression of symptoms. Additionally, small sized fistulas(< 1 mm) and SAVF involving less frequent locations like the craniocervical junction in a patient presenting with paraplegia further complicates the diagnosis. On rare occasions, acute atypical presentation following a surgery adds to the conundrum. Definite diagnosis with spinal angiography, the gold-standard modality requires the expertise of highly skilled interventionists which may otherwise lead to false negative findings. We describe four SAVF patients with unconventional presentations, highlighting less described clinical findings. CASE PRESENTATION: First was a 50-year-old man presented with spastic paraparesis and was found to have an AVF at the cervical region arising from the vertebral artery. Second, a 45-year-old man with acute paraplegia post-operatively, initially treated for a transverse myelitis before lumbar region AVF was detected. Thirdly, a 27-year-old man presented with subacute lower thoracic myelopathy and deteriorated after corticosteroid treatment. The last patient, who initially appeared to have conus medullaris/cauda equina syndrome had a SAVF at the mid thoracic level. Presentation varied with some exhibiting acute deterioration mimicking other spinal cord pathology such as inflammatory disorders. All patients eventually underwent endovascular treatment with successful embolization of SDAVF. None of them exhibited further neurological deterioration after embolization. CONCLUSION: Successful treatment of SAVF is possible provided the diagnosis is made early, allowing timely intervention. Certain clues may aid the diagnosis. Firstly, arteriovenous fistula can be located distant to the clinical localization of myelopathy resulting in the unexpected longitudinally extensive spinal cord signal change. This clinical-radiological discrepancy can be a useful clue in diagnosing SAVF. Secondly, an acute myelopathic presentation immediately post-surgery may be related to SAVF. Other SAVF feature of note includes progressive myelopathy mimicking immune-mediated myelitis among young adults below 30 years of age refractory to immune therapy.

Carica papaya Leaf Extract Silver Synthesized Nanoparticles Inhibit Dengue Type 2 Viral Replication In Vitro.

The current global occurrence of dengue infection annually is approximately 400 million, with a case fatality rate of 2.5%. However, there are no antiviral agents. Carica papaya leaf extract is known for its medicinal value, due to the presence of organic compounds that possess antimicrobial, anti-inflammatory, and antioxidant activities. This study determined the anti-dengue effect of C. papaya leaf extract silver synthesized nanoparticles. In this study, aqueous and non-aqueous extractions were carried out, followed by the synthesis of silver nanoparticles as well as characterization through Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy. The in vitro anti-dengue effect was evaluated using a focus reduction neutralization test on kidney Vero E2 cell lines. In silico studies involved molecular docking to determine the potential interactions between the bioactive compounds in C. papaya leaf extract and the viral NS5 protein. C. papaya leaf methanol extract silver synthesized nanoparticle was the most promising with an IC50 of 9.20 µg/mL. Molecular docking showed 5,7 dimethoxycoumarin as the best ligand, with binding energy of -7.75 kcal/mol, indicating high affinity for the NS5 protein. These results highlight that C. papaya leaf methanol extract silver synthesized nanoparticles could be used to inhibit dengue virus type 2 viral replication. However, we recommend further studies to determine their toxicity and the safety profiles.

A cautionary case: osteoporotic femur fracture after robotic-assisted total knee arthroplasty.

Osteoporosis is a disease of low bone mass which leads to an increased risk of fracture. The prevalence of osteoporosis is greatest amongst postmenopausal women who also form a large portion of patients with osteoarthritis presenting for total knee arthroplasty. We present a case of a 77-year-old female with knee osteoarthritis and osteoporosis on denosumab who underwent robotic-assisted total knee arthroplasty. Postoperatively, she suffered an atraumatic midshaft femur fracture at the pin site associated with the use of intraoperative robotic technology. This is a unique complication related to the use of robotics which requires additional skeletal fixation versus standard arthroplasty surgical technique. We recommend caution and further study regarding the use of robotics in total knee arthroplasty in the setting of osteoporosis and denosumab use.

Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people.

Does dissemination of guidelines alone increase the use of palliative single-fraction radiotherapy? Initial report of a longitudinal change management campaign at a provincial cancer program.

Background: Despite level 1 evidence demonstrating the equivalence of single-fraction radiotherapy (sfrt) and multiple-fraction radiotherapy (mfrt) for the palliation of painful bone metastases, sfrt remains underused. In 2015, to encourage the sustainable use of palliative radiation oncology resources, CancerCare Manitoba disseminated, to each radiation oncologist in Manitoba, guidelines from Choosing Wisely Canada (cwc) that recommend sfrt. We assessed whether dissemination of the guidelines influenced sfrt use in Manitoba in 2016, and we identified factors associated with mfrt. Methods: All patients treated with palliative radiotherapy for bone metastasis in Manitoba from 1 January 2016 to 31 December 2016 were identified from the provincial radiotherapy database. Patient, treatment, and disease characteristics were extracted from the electronic medical record and tabulated by fractionation schedule. Univariable and multivariable logistic regression analyses were performed to identify risk factors associated with mfrt. Results: In 2016, 807 patients (mean age: 70 years; range: 35-96 years) received palliative radiotherapy for bone metastasis, with 69% of the patients having uncomplicated bone metastasis. The most common primary malignancies were prostate (27.1%), lung (20.6%), and breast cancer (15.9%). In 62% of cases, mfrt was used-a proportion that was unchanged from 2015. On multivariable analysis, a gastrointestinal [odds ratio (or): 5.3] or lung primary (or: 3.3), complicated bone metastasis (or: 4.3), and treatment at a subsidiary site (or: 4.4) increased the odds of mfrt use. Conclusions: Dissemination of cwc recommendations alone did not increase sfrt use by radiation oncologists in 2016. A more comprehensive knowledge translation effort is therefore warranted and is now underway to encourage increased uptake of sfrt in Manitoba.

A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2-/- phenotype.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of end-stage renal failure in humans and results from germline mutations in PKD1 or PKD2. Despite the recent approval of tolvaptan, safer and more effective alternative drugs are clearly needed to slow disease progression. As a first step in drug discovery, we conducted an unbiased chemical screen on zebrafish pkd2 mutant embryos using two publicly available compound libraries (Spectrum, PKIS) totalling 2,367 compounds to identify novel treatments for ADPKD. Using dorsal tail curvature as the assay readout, three major chemical classes (steroids, coumarins, flavonoids) were identified from the Spectrum library as the most promising candidates to be tested on human PKD1 cystic cells. Amongst these were an androgen, 5α-androstane 3,17-dione, detected as the strongest enhancer of the pkd2 phenotype but whose effect was found to be independent of the canonical androgen receptor pathway. From the PKIS library, we identified several ALK5 kinase inhibitors as strong suppressors of the pkd2 tail phenotype and in vitro cyst expansion. In summary, our results identify ALK5 and non-canonical androgen receptors as potential therapeutic targets for further evaluation in drug development for ADPKD.

Prostate-specific Antigen Bounce After Stereotactic Body Radiotherapy for Prostate Cancer: A Pooled Analysis of Four Prospective Trials.

AIMS: We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored. MATERIALS AND METHODS: The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis. RESULTS: In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS. CONCLUSION: The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.

Enalapril-Induced Angioedema: Two Case Reports in a Rural Health Facility in Kenya.

Tolerability, a good safety profile, affordability, and a preponderance to afford cardio-renal protection in patients with diabetes make enalapril one of the most commonly prescribed angiotensin-converting enzyme (ACE) inhibitors. However, there is low awareness of enalapril/ACE inhibitor-induced angioedema among medical personnel. This is because the diagnosis presents an ongoing challenge, particularly when the presentation is delayed following long-term therapy with ACE inhibitors. Here, we present two cases: a 58-year-old female and a 55-year-old male who presented to the outpatient department of Nyakach County Hospital, Pap Onditi village, Kenya, with progressive swelling of the face and upper and lower lips and stridor of 11 and 10 hours, respectively, after their usual dose of enalapril. Case 1 resolved following the administration of stat doses of intravenous (IV) hydrocortisone 200 mg and IV chlorpheniramine 20 mg as well as thrice daily peroral doses of chlorpheniramine 8 mg, and tapered peroral doses of prednisolone: 40 mg thrice daily for five days, 20 mg thrice daily for five days, 10 mg thrice daily for five days, and 5 mg thrice daily for five days. Case 2 resolved following the administration of a stat dose of IV dexamethasone, a twice daily peroral dose of cetrizine 10 mg, and tapered peroral doses of prednisolone: 20 mg thrice daily for five days, 10 mg thrice daily for five days, and 5 mg thrice daily for five days.

Correlated Dynamics in a Synthetic Lattice of Momentum States.

We study the influence of atomic interactions on quantum simulations in momentum-space lattices (MSLs), where driven transitions between discrete momentum states mimic transport between sites of a synthetic lattice. Low-energy atomic collisions, which are short ranged in real space, relate to nearly infinite-ranged interactions in momentum space. However, the added exchange energy between atoms in distinguishable momentum states leads to an effectively attractive, finite-ranged interaction between atoms in momentum space. In this Letter, we observe the onset of self-trapping driven by such interactions in a momentum-space double well, paving the way for more complex many-body studies in tailored MSLs. We consider the types of phenomena that may result from these interactions, including the formation of chiral solitons in zigzag flux lattices.

Adding a PECS II block for proximal arm arteriovenous access - a randomised study.

BACKGROUND: Brachial plexus block is often utilised for proximal arm arteriovenous access creation. However, the medial upper arm and axilla are often inadequately anaesthetised, requiring repeated, intraoperative local anaesthetic supplementation, or conversion into general anaesthesia. We hypothesised that the addition of a PECS II block would improve anaesthesia and analgesia for proximal arm arteriovenous access surgery. METHODS: In this prospective, double-blinded, randomised proof-of-concept study, 36 consenting adults with end-stage renal disease aged between 21 and 90 years received either a combined supraclavicular and PECS II block (Group PECS, n = 18), or combined supraclavicular and sham block (Group SCB, n = 18) for proximal arm arteriovenous access surgery. Primary outcome was whether patients required intraoperative local anaesthetic supplementation by the surgeon. RESULTS: In Group PECS, 33.3% (6/18) needed local anaesthetic supplementation vs. 100% (18/18) in Group SCB. Group SCB had three times (RR 3.0, 95% CI 1.6-5.8; P < 0.001) the risk of requiring intraoperative local anaesthetic supplementation. Group PECS required lower volume of supplemental local anaesthetic compared to Group SCB (0.0 ml, IQR 0.0-6.3 ml vs. 15.0 ml, IQR 7.4-17.8 ml; P < 0.001). Group SCB had twice [RR 2.2, 95% CI 1.1-4.4; (P = 0.019)] the risk of needing additional sedation or analgesia. There were no significant differences between the groups with respect to postoperative visual analogue scale pain scores, time to first rescue analgesia or patient satisfaction. CONCLUSION: The results suggest that adding a PECS II block to a supraclavicular block improves regional anaesthesia for patients with end-stage renal disease undergoing proximal arm arteriovenous access surgery.

IFNL3/4 genotype is associated with altered immune cell populations in peripheral blood in chronic hepatitis C infection.

Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals. Genotype-associated differences were seen in the ratio of CD4CD45RO+ to CD4CD45RO-; CD8CD45RO+ to CD8CD45RO-, NK CD56 dim to bright and monocyte numbers and percentages. Whole blood expression levels of IFNL3, IFNLR1 (interferon lambda receptor 1), IFNLR1-mem (a membrane-associated receptor), IFNLR1-sol (a truncated soluble receptor), MxA and T- and NK (natural killer) cell transcription factors TBX21, GATA3, RORC, FOXP3 and EOMES in two subjects were also determined. CHC patients demonstrated endogenous IFN activation with higher levels of MxA, IFNLR1, IFNLR1-mem and IFNLR1-sol, and IFNL3 genotype-associated differences in transcription factors. Taken together, these data provide evidence of an IFNL3 genotype association with differences in monocyte, T- and NK cell levels in the peripheral blood of patients with CHC. This could underpin genotype associations with spontaneous and treatment-induced HCV clearance and hepatic necroinflammation.

Treatment of bone disorders with parathyroid hormone: success and pitfalls.

Bone diseases such as osteoporosis, osteoarthritis, bone tumours and bone fractures are rather common and not just in the elderly. Parathyroid hormone (PTH) is responsible for maintaining calcium homeostasis, increasing bone mineral density (BMD), increasing cortical and trabecular bone thickness and thus increasing bone strength. Teriparatide (PTH 1-34) has the same effects as endogenous PTH and is pharmacologically used to treat bone diseases such as osteoporosis, osteoarthritis, bone fractures and bone tumours. This review discusses how PTH 1-34 plays a role in managing bone diseases. Clinical studies have shown that short or intermittent dosing of PTH 1-34 has minimal adverse effects, while long-term dosing (over two years) has been linked to de novo osteoarthritis and bone deformation. Currently PTH therapy is only approved in the treatment of post-menopausal osteoporosis, however it is also proven to have effects in treating osteoarthritis, bone tumours and bone fractures. If the patient undergoing therapy is closely monitored, the major pitfalls are very unlikely to take place, thus it is highly recommended that patients be closely monitored by a medical practitioner.

TIA, stroke and orthostatic hypotension: a disease spectrum related to ageing vasculature?

AIMS: We sought to identify the determinants of orthostatic hypotension (OH) among patients referred to the transient ischaemic attack (TIA) clinic. METHODS: We conducted a retrospective analysis of prospectively collected data on patients who attended the TIA clinic in a UK hospital between January 2006 and September 2009. Each patient had their supine and standing or sitting blood pressure measured. Logistic regression was used to estimate the univariate and multivariate odds of OH for the subgroups of patients based on their diagnosis. A 10% significance level for the univariate analysis was used to identify variables in the multivariate model. RESULTS: A total of 3222 patients were studied of whom 1131 had a TIA, 665 a stroke and 1426 had other diagnoses. The prevalence of either systolic or diastolic OH in the TIA, stroke and patients with other diagnoses was similar being 22% (n = 251), 24% (n = 162) and 20% (n = 292), respectively. Multivariate analyses showed age, prior history of TIA, and diabetes were independently significantly associated with systolic OH alone or diastolic OH alone or either systolic or diastolic OH [ORs 1.03 (1.02-1.05); 1.56 (1.05-2.31); 1.65 (1.10-2.47), respectively]. Among the patients with the diagnosis of stroke, peripheral vascular disease (PVD) was significantly associated with increased odds of OH (3.56, 1.53-8.31), whereas male gender had a significantly lower odds of OH (0.61, 0.42-0.88). In patients with other diagnoses, age (1.04, 1.02-1.05) and diabetes (1.47, 1.04-2.09) were associated with OH, whereas male gender was (0.76, 0.58-1.00) not associated with OH. CONCLUSION: Orthostatic hypotension is prevalent among patients presenting to TIA clinic. Previous history of vascular disease (prior TIA/stroke/PVD) appears to be a significant associate of OH in this patient population.