An elderly gentleman with chronic lower back and bilateral knee pain was found to have clinical and radiographic findings consistent with alkaptonuria. Diagnosis was confirmed by the detection of elevated homogentisic acid level in the urine using gas chromatography-mass spectrometry.
Herpotrichiellaceae spp. are known to be opportunistic human pathogens. Here, we report the ~28.46-Mb draft genome of Herpotrichiellaceae sp. UM 238, isolated from human skin scraping. The UM 238 genome was found to contain many classes of protective genes that are responsible for fungal adaptation under adverse environmental conditions.
Contact pressure in the knee joint is a key element in the mechanisms of knee pain and osteoarthritis. Assessing the contact pressure in tibiofemoral joint is a challenging mechanical problem due to uncertainty in material properties. In this study, a sensitivity analysis of tibiofemoral peak contact pressure to the material properties of the soft tissue was carried out through fractional factorial and Box-Behnken designs. The cartilage was modeled as linear elastic material, and in addition to its elastic modulus, interaction effects of soft tissue material properties were added compared to previous research. The results indicated that elastic modulus of the cartilage is the most effective factor. Interaction effects of axial/radial modulus with elastic modulus of cartilage, circumferential and axial/radial moduli of meniscus were other influential factors. Furthermore this study showed how design of experiment methods can help designers to reduce the number of finite element analyses and to better interpret the results.
BACKGROUND: Pulmonary arterial systolic pressure (PASP) can be estimated with transthoracic echocardiography. However, the significance of raised PASP on routine echocardiography is uncertain. In this study, we evaluated the mortality and hospitalization rates of subjects with raised PASP in a cohort of patients referred directly by their general practitioners for routine outpatient (open access) echocardiography for further analysis of suspected heart failure.
RESULTS: A total of 485 subjects were referred for open access echocardiography at our hospital in 2002. A cohort of 209/485 (43%) consecutive subjects with measurable tricuspid regurgitation were followed for a minimum of five years investigating hospitalization rates and survival. Some 62 of 209 (30%) subjects had pulmonary hypertension (PH). Subjects with PH were significantly more likely to have four or more hospital admissions (22% vs. 8%; P < 0.01) and > 30 days of cumulative hospital stay over five years (29% vs. 13%; P < 0.01). PH was significantly associated with mortality (P = 0.003), while moderate to severe PH was an independent predictor of mortality (hazard ratio: 4.31; 95% confidence interval (95% CI): 1.51-12.30). Records from the Office of National Statistics revealed that subjects with PH were more likely to have chronic lung diseases recorded as immediate or contributory causes of death (50% vs. 14%; P < 0.05).
CONCLUSIONS: PASP ≥ 36 mmHg on routine echocardiography is associated with recurrent hospital admissions, prolonged hospitalizations and increased cause of mortality. Therefore, the diagnosis of PH on echocardiography deserves further clinical evaluation, with future studies designed at defining a suitable diagnostic strategy.
KEYWORDS: Chronic lung disease; Dyspnoea; Heart failure; Pulmonary hypertension; Transthoracic echocardiography
Study site: Sunderland Royal Hospital, United Kingdom
Polymer supported dichlorophosphate (PEG-OPOCl(2)) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis(indolyl) methanes with short reaction time, at room temperature. The synthesized compounds and their anti-cancer activity are evaluated.
Protein-protein interactions (PPIs) play a major role in many biological processes and they represent an important class of targets for therapeutic intervention. However, targeting PPIs is challenging because often no convenient natural substrates are available as starting point for small-molecule design. Here, we explored the characteristics of protein interfaces in five non-redundant datasets of 174 protein-protein (PP) complexes, and 161 protein-ligand (PL) complexes from the ABC database, 436 PP complexes, and 196 PL complexes from the PIBASE database and a dataset of 89 PL complexes from the Timbal database. In all cases, the small molecule ligands must bind at the respective PP interface. We observed similar amino acid frequencies in all three datasets. Remarkably, also the characteristics of PP contacts and overlapping PL contacts are highly similar.
BACKGROUND: Genital human papillomavirus (HPV) infection is the most common sexually transmitted viral disease in the world. HPV infection of the genital epithelium is associated with genital warts and malignancies of the lower genital tract.
OBJECTIVES: To describe the distribution, phenotypic appearance and HPV type associated with genital warts in women.
METHODS: This was a prospective observational study of all women with genital warts who attended the Colposcopy Clinic, Groote Schuur Hospital, Cape Town, South Africa, during 2010 and fulfilled the inclusion and exclusion criteria. One hundred and thirteen women were tested for HPV using the Roche Linear Array HPV genotyping kit to determine the HPV genotypes causing genital warts.
RESULTS: The median age of the women was 27 years (range 15 - 53); 90 (79.6%) were HIV-positive, and two-thirds were on antiretroviral treatment. Treatment involved ablation with topical agents, cauterisation or carbon dioxide laser. At 3 months' follow-up after treatment, 56.6% of the women, the majority of whom were HIV-positive, had recurrent/persistent disease. In both HIV-positive and HIV-negative women, HPV was detected in over 90% of cases. However, over half the HIV-positive women as opposed to 2/18 of the HIV-negative women were infected with multiple HPV genotypes. The commonest HPV genotypes in HIV-positive and HIV-negative women were types 11, 6, 89, 61, 55 and 62 and types 11 and 6, respectively.
CONCLUSIONS: The majority of the patients were HIV-positive and had multiple HPV infections. While this did not alter the phenotypic appearance of the warts, recurrence/persistence after treatment was more common.
BACKGROUND: Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis represents an important cause of morbidity in people with beta-thalassaemia and its pathogenesis is multifactorial. Factors include bone marrow expansion due to ineffective erythropoiesis, resulting in reduced trabecular bone tissue with cortical thinning; endocrine dysfunction secondary to excessive iron loading, leading to increased bone turnover; and lastly, a predisposition to physical inactivity due to disease complications with a subsequent reduction in optimal bone mineralization.A number of therapeutic strategies have been applied to treat osteoporosis in people with beta-thalassaemia, which include bisphosphonates, with or without, hormone replacement therapy. There are various forms of bisphosphonates, such as clodronate, pamidronate, alendronate and zoledronic acid. Other treatments include calcitonin, calcium, zinc supplementation, hydroxyurea and hormone replacement therapy for preventing hypogonadism.
OBJECTIVES: To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 04 February 2016.
SELECTION CRITERIA: Randomised, placebo-controlled trials in people with thalassaemia with a bone mineral density z score of less than -2 standard deviations for: children less than 15 years old; adult males (15 to 50 years old); and all pre-menopausal females above 15 years and a bone mineral density t score of less than -2.5 standard deviations for post-menopausal females and males above 50 years old.
DATA COLLECTION AND ANALYSIS: Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and completed the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate.
MAIN RESULTS: Four trials (with 211 participants) were included; three trials investigated the effect of bisphosphonate therapies and one trial investigated the effect of zinc supplementation. Only one trial was judged to be of good quality (low risk of bias); the remaining trials had a high or unclear risk of bias in at least one key domain.One trial (data not available for analysis) assessing the effect of neridronate (118 participants) reported significant increases in favour of the bisphosphonate group for bone mineral density at the lumbar spine and hip at both six and 12 months. For the femoral neck, a significant difference was noted at 12 months only. A further trial (25 participants) assessed the effect of alendronate and clodronate and found that after two years, bone mineral density increased significantly in the alendronate and clodronate groups as compared to placebo at the lumbar spine, mean difference 0.14 g/cm(2) (95% confidence interval 0.05 to 0.22) and at the femoral neck, mean difference 0.40 g/cm(2) (95% confidence interval 0.22 to 0.57). One 12-month trial (26 participants) assessed the effects of different doses of pamidronate (30 mg versus 60 mg) and found a significant difference in bone mineral density in favour of the 60 mg dose at the lumbar spine and forearm, mean difference 0.43 g/cm(2) (95% CI 0.10 to 0.76), mean difference 0.87 g/cm(2) (95% CI 0.23 to 1.51), respectively, but not at the femoral neck.In a zinc sulphate supplementation trial (42 participants), bone mineral density increased significantly compared to placebo at the lumbar spine after 12 months (37 participants), mean difference 0.15 g/cm(2) (95% confidence interval 0.10 to 0.20) and after 18 months (32 participants), mean difference 0.34 g/cm(2) (95% confidence interval 0.28 to 0.40). The same was true for bone mineral density at the hip after 12 months, mean difference 0.15 g/cm(2) (95% confidence interval 0.11 to 0.19) and after 18 months, mean difference 0.26 g/cm(2) (95% confidence interval 0.21 to 0.31).Fractures were not observed in one trial and not reported in three trials. There were no major adverse effects reported in two of the bisphosphonate trials; in the neridronate trial there was a reduction noted in the use of analgesic drugs and in the reported back pain score in favour of bisphosphonate treatment. Adverse effects were not reported in the trial of different doses of pamidronate or the zinc supplementation trial.
AUTHORS' CONCLUSIONS: There is evidence to indicate an increase in bone mineral density at the femoral neck, lumbar spine and forearm after administration of bisphosphonates and at the lumbar spine and hip after zinc sulphate supplementation. The authors recommend that further long-term randomised control trials on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia and osteoporosis are undertaken.
Breaking bad news is a process of delivering news, which may negatively affect a patient's view of the future, however is an essential skill for doctors. There are a multitude of benefits if doctors can execute this task well, and will improve the disease journey for the patient. There are several published models including the SPIKES and ABCDE models to help guide the doctor to break bad news effectively. This important skill can be taught through various methods but the most effective may be actually observing a session by senior clinicians.
Smoking problem is considered as one of the hot topics for many years. In spite of overpowering facts about the dangers, smoking is still a bad habit widely spread and socially accepted. Many people start smoking during their gymnasium period. The discovery of the dangers of smoking gave a warning sign of danger for individuals. There are different statistical methods used to analyze the dangers of smoking. In this study, we apply an algebraic statistical method to analyze and classify real data using Markov basis for the independent model on the contingency table. Results show that the Markov basis based classification is able to distinguish different date elements. Moreover, we check our proposed method via information theory by utilizing the Shannon formula to illustrate which one of these alternative tables is the best in term of independent.
Medication non-adherence is one of the major challenges in treating patients with depression. This systematic review aims to determine the clinical and economic outcomes of non-adherence in depression.