Physiological and molecular insights into drought tolerance.

Water is a major limiting factor in world agriculture. In general, most crop plants are highly sensitive to even a mild dehydration stress. There are however, a few genera of plants unique to Southern Africa, called "resurrection plants" which can tolerate extreme water loss or desiccation. We have used Xerophyta viscosa, a representative of the monocotyledonous resurrection plants to isolate genes that are associated with osmotic stress tolerance. Several genes that are differentially expressed, and that confer functional sufficiency to osmotically-stressed Escherichia coli are being studied at the molecular and biochemical levels. In this review, we use this as a basis to discuss the physiological and molecular insights into drought tolerance

Treatment of Cancer‐Associated Venous Thromboembolism: 12‐month outcomes of the placebo versus rivaroxaban randomisation of the SELECT‐D Trial. (SELECT‐D: 12m)

Background The SELECT‐D trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared to dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation. Objectives To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months Patients/Methods In SELECT‐D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomisation to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomisation closed prematurely due to low recruitment when 92 of the planned 300 patients were recruited. Results 92 of 136 eligible patients were randomised to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomisation, was 14% with placebo and 4% with rivaroxaban (Hazard Ratio 0.32; 95% CI 0.06‐1.58). The major and clinically‐relevant non‐major bleeding rates were 0% and 0% with placebo; and 5% (95% CI 1‐18%) and 4% (95% CI 1‐17%) with rivaroxaban. In an exploratory analysis, 7 (15.2 %) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT‐negative cohort (P=0.03). Conclusion The SELECT‐D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence

Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting

BACKGROUND: Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-γ-inducible-10kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid. METHODS: We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis. Principal FINDINGS: Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed ∼20% of TB cases and mis-diagnosed ∼20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful. CONCLUSION: Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings

Evaluation of a new model of care for people with complications of diabetic retinopathy : The EMERALD Study

Objectives The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent and life-long follow-up, have markedly increased hospital demands. Resulting delays in the evaluation/treatment of patients are leading to sight loss. Strategies to increase capacity of medical retina clinics are urgently needed. EMERALD tested diagnostic accuracy, acceptability and costs of a new health care pathway for people with previously treated DME/PDR. Design Prospective, multicentric, case-referent, cross-sectional, diagnostic accuracy study, undertaken in 13 hospitals in the United Kingdom. Participants Adults with type 1 or 2 diabetes and previously successfully treated DME/PDR who, at the time of enrolment, had active or inactive disease. Methods A new health care pathway entailing multimodal imaging (spectral domain optical coherence tomography [SD-OCT] for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-wide-field fundus images [UWF] for PDR) interpreted by trained non-medical staff (ophthalmic graders) to detect re-activation of disease was compared with the current standard care (ophthalmologists face-to-face examination). Main outcome measures Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, with inadequate images/indeterminate findings. Results The new pathway had sensitivity of 97% (95% confidence interval [CI] 92-99%) and specificity of 31% (95% CI 23-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS (85%, 95% CI 77-91%; 48%; 95% CI 41-56%, respectively) or UWF (83%, 95% CI 75-89%; 54%; 95% CI 46-61%, respectively) were comparable. For detection of high risk PDR sensitivity and specificity were higher when using UWF images (87%, 95% CI 78-93%; 49% 95% CI 42-56%, respectively for UWF, versus 80%, 95% CI 69-88%; 40% CI 34-47%, respectively, for 7-field ETDRS). Participants preferred ophthalmologist’s assessments; in their absence, wished immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard care, the new pathway could save £1,390/100 DME visits and between £461-£1,189/100 PDR visits. Conclusion The new ophthalmic grader pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementatio

Collaborative care for the detection and management of depression among adults with hypertension in South Africa: study protocol for the PRIME-SA randomised controlled trial

Background: The high co-morbidity of mental disorders, particularly depression, with non-communicable diseases (NCDs) such as cardiovascular disease (CVD), is concerning given the rising burden of NCDs globally, and the role depression plays in confounding prevention and treatment of NCDs. The objective of this randomised control trial (RCT) is to determine the real-world effectiveness of strengthened depression identification and management on depression outcomes in hypertensive patients attending primary health care (PHC) facilities in South Africa (SA). Methods/design: The study design is a pragmatic, two-arm, parallel-cluster RCT, the unit of randomisation being the clinics, with outcomes being measured for individual participants. The 20 largest eligible clinics from one district in the North West Province are enrolled in the trial. Equal numbers of hypertensive patients (n = 50) identified as having depression using the Patient Health Questionnaire (PHQ-9) are enrolled from each clinic, making up a total of 1000 participants with 500 in each arm. The nurse clinicians in the control facilities receive the standard training in Primary Care 101 (PC101), a clinical decision support tool for integrated chronic care that includes guidelines for hypertension and depression care. Referral pathways available include referrals to PHC physicians, clinical or counselling psychologists and outpatient psychiatric and psychological services. In the intervention clinics, this training is supplemented with strengthened training in the depression components of PC101 as well as training in clinical communication skills for nurse-led chronic care. Referral pathways are strengthened through the introduction of a facility-based behavioural health counsellor, trained to provide structured manualised counselling for depression and adherence counselling for all chronic conditions. The primary outcome is defined as at least 50% reduction in PHQ-9 score measured at 6 months. Discussion: This trial should provide evidence of the real world effectiveness of strengtheneddepression identification and collaborative management on health outcomes of hypertensive patients withcomorbid depression attending PHC facilities in South Africa

Plaster cast versus functional brace for non-surgical treatment of Achilles tendon rupture (UKSTAR): a multicentre randomised controlled trial and economic evaluation

This is the final version. Available from Elsevier via the DOI in this record. Background Patients with Achilles tendon rupture who have non-operative treatment have traditionally been treated with immobilisation of the tendon in plaster casts for several weeks. Functional bracing is an alternative non-operative treatment that allows earlier mobilisation, but evidence on its effectiveness and safety is scarce. The aim of the UKSTAR trial was to compare functional and quality-of-life outcomes and resource use in patients treated non-operatively with plaster cast versus functional brace. Methods UKSTAR was a pragmatic, superiority, multicentre, randomised controlled trial done at 39 hospitals in the UK. Patients (aged ≥16 years) who were being treated non-operatively for a primary Achilles tendon rupture at the participating centres were potentially eligible. The exclusion criteria were presenting more than 14 days after injury, previous rupture of the same Achilles tendon, or being unable to complete the questionnaires. Eligible participants were randomly assigned (1:1) to receive a plaster cast or functional brace using a centralised web-based system. Because the interventions were clearly visible, neither patients nor clinicians could be masked. Participants wore the intervention for 8 weeks. The primary outcome was patient-reported Achilles tendon rupture score (ATRS) at 9 months, analysed in the modified intention-to-treat population (all patients in the groups to which they were allocated, excluding participants who withdrew or died before providing any outcome data). The main safety outcome was the incidence of tendon re-rupture. Resource use was recorded from a health and personal social care perspective. The trial is registered with ISRCTN, ISRCTN62639639. Findings Between Aug 15, 2016, and May 31, 2018, 1451 patients were screened, of whom 540 participants (mean age 48·7 years, 79% male) were randomly allocated to receive plaster cast (n=266) or functional brace (n=274). 527 (98%) of 540 were included in the modified intention-to-treat population, and 13 (2%) were excluded because they withdrew or died before providing any outcome data. There was no difference in ATRS at 9 months post injury (cast group n=244, mean ATRS 74∙4 [SD 19∙8]; functional brace group n=259, ATRS 72∙8 [20∙4]; adjusted mean difference –1∙38 [95% CI –4∙9 to 2∙1], p=0·44). There was no difference in the rate of re-rupture of the tendon (17 [6%] of 266 in the plaster cast group vs 13 [5%] of 274 in the functional brace group, p=0·40). The mean total health and personal social care cost was £1181 for the plaster cast group and £1078 for the functional bract group (mean between-group difference –£103 [95% CI –289 to 84]). Interpretation Traditional plaster casting was not found to be superior to early weight-bearing in a functional brace, as measured by ATRS, in the management of patients treated non-surgically for Achilles tendon rupture. Clinicians may consider the use of early weight-bearing in a functional brace as a safe and cost-effective alternative to plaster casting.UK National Institute for Health Research Health Technology Assessment Programm

Altered Esterase Activity Due To Pesticide Exposure In The Aquatic Snail Physa Acuta.

Presented at the first meeting of Federation of African Societies of Biochemistry & Molecular Biology in 1998.,The effect ofpesticides on the xenobiotic metabolising enzymes of the aquatic snail Physa acuta was studied. Adult snails reared in the laboratory were exposed daily for three days to the following pesticides: 2,4-dichlorophenoxyacetic acid, deltamethrin, endosulphan, malathion and pirimiphos-methyl. Cytosolic fractions prepared from the snails showed that pesticide exposure had no effect on the glutathione or glutathione dependent enzyme activities. General esterase activity using two different substrates was reduced significantly by exposure to the organophosphate pesticides malathion and pirimiphos. Exposure to the other pesticides did not cause any substantial changes in the esterases activities. The nature of this inhibition is not yet apparent. It is likely, however, that the changes are due to a competitive type inhibition by the pesticides for the active site of the enzyme.,Federation of African Societies of Biochemistry & Molecular Biology (FASBMB

Altered Esterase Activity Due To Pesticide Exposure In The Aquatic Snail Physa Acuta.

Presented at the first meeting of Federation of African Societies of Biochemistry & Molecular Biology in 1998.,The effect ofpesticides on the xenobiotic metabolising enzymes of the aquatic snail Physa acuta was studied. Adult snails reared in the laboratory were exposed daily for three days to the following pesticides: 2,4-dichlorophenoxyacetic acid, deltamethrin, endosulphan, malathion and pirimiphos-methyl. Cytosolic fractions prepared from the snails showed that pesticide exposure had no effect on the glutathione or glutathione dependent enzyme activities. General esterase activity using two different substrates was reduced significantly by exposure to the organophosphate pesticides malathion and pirimiphos. Exposure to the other pesticides did not cause any substantial changes in the esterases activities. The nature of this inhibition is not yet apparent. It is likely, however, that the changes are due to a competitive type inhibition by the pesticides for the active site of the enzyme.,Federation of African Societies of Biochemistry & Molecular Biology (FASBMB