Cryptolepis sanguinolenta Root Tablets: Effect of Binder Type and Concentration on the Tablet Properties

ABSTRACT The objectives of the study were to formulate Cryptolepis sanguinolenta root powder into tablets and to evaluate the effect of different binders and binder concentrations on the properties of tablets. The tablets were formulated by the wet granulation method using gelatin and sodium carboxymethyl cellulose (SCMC) as binders at concentrations of 2%, 4%, 6% and 8%w/w. The tablets were evaluated using the relevant official and unofficial tests. Also the phytochemistry of the powdered root extract of C. sanguinolenta was evaluated. Phytochemical analysis showed that C. sanguinolenta root contains alkaloids, terpenoids, steroids, proteins, carbohydrate, resins, reducing sugars and glycosides. Tablets formulated with SCMC significantly exhibited higher disintegration times than those formulated with gelatin (p<0.05).Tablets hardness ranged from 3.51 ± 0.12 to 5.02 ± 0.10 kgf for A1 and A4 tablets formulated with 2 and 8% gelatin and 2.00 ± 0.11 to 5.00 ± 0.17 kgf for B1 and B4 tablets formulated with 2 and 8% SCMC. All the tablet batches exhibited friability of < 1% (p<0.05). Therefore the powdered root of C. sanguinolenta could be formulated as normal release tablets using gelatin and SCMC in order to standardize the preparation and also enhance patient's compliance

Intercomparison of methods of coupling between convection and large-scale circulation. 2: comparison over non-uniform surface conditions

As part of an international intercomparison project, the weak temperature gradient (WTG) and damped gravity wave (DGW) methods are used to parameterize large-scale dynamics in a set of cloud-resolving models (CRMs) and single column models (SCMs). The WTG or DGW method is implemented using a configuration that couples a model to a reference state defined with profiles obtained from the same model in radiative-convective equilibrium. We investigated the sensitivity of each model to changes in SST, given a fixed reference state. We performed a systematic comparison of the WTG and DGW methods in different models, and a systematic comparison of the behavior of those models using the WTG method and the DGW method. The sensitivity to the SST depends on both the large-scale parameterization method and the choice of the cloud model. In general, SCMs display a wider range of behaviors than CRMs. All CRMs using either the WTG or DGW method show an increase of precipitation with SST, while SCMs show sensitivities which are not always monotonic. CRMs using either the WTG or DGW method show a similar relationship between mean precipitation rate and column-relative humidity, while SCMs exhibit a much wider range of behaviors. DGW simulations produce large-scale velocity profiles which are smoother and less top-heavy compared to those produced by the WTG simulations. These large-scale parameterization methods provide a useful tool to identify the impact of parameterization differences on model behavior in the presence of two-way feedback between convection and the large-scale circulation

Critical management studies in South Africa

This book shows how Critical Management Studies (CMS) scholarship is starting to develop a character of its own in South Africa. It attests to CMS slowly gaining momentum and acquiring an identity of its own amongst South African scholars. However, management studies in South Africa is dominated by capitalist ideology and positivist methodology. Although Interpretive scholarship has gained some momentum, it still falls within the parameters of ‘mainstream’, capitalist thinking. Scholarship outside the domain of capitalist thinking, such as critical scholarship, remains sorely underexplored. Being entrenched in the positivist tradition is arguably a major Achilles’ Heel for the progression of management as a field of inquiry. CMS presents a vehicle for alternative epistemologies to be heard in the management discourse. With its focus on power imbalances, struggles for emancipation from oppression, and distrust of capitalism, CMS provides the peripheral point of view with a voice. CMS presents a space where scholars can engage with South African realities surrounding political, cultural, social, and historic contexts and issues in management. This book is promoting CMS to the scholarly community, to show that there are exciting possibilities being offered by a different approach to management scholarship. This book also forms part of a larger project of growing CMS in South Africa, and is a collection of original works by academics actively working in CMS, following various methodological approaches which can be categorised into two broad methodological categories, namely, conceptual work and empirical work following an Interpretive approach

Critical management studies in South Africa

This book shows how Critical Management Studies (CMS) scholarship is starting to develop a character of its own in South Africa. It attests to CMS slowly gaining momentum and acquiring an identity of its own amongst South African scholars. However, management studies in South Africa is dominated by capitalist ideology and positivist methodology. Although Interpretive scholarship has gained some momentum, it still falls within the parameters of ‘mainstream’, capitalist thinking. Scholarship outside the domain of capitalist thinking, such as critical scholarship, remains sorely underexplored. Being entrenched in the positivist tradition is arguably a major Achilles’ Heel for the progression of management as a field of inquiry. CMS presents a vehicle for alternative epistemologies to be heard in the management discourse. With its focus on power imbalances, struggles for emancipation from oppression, and distrust of capitalism, CMS provides the peripheral point of view with a voice. CMS presents a space where scholars can engage with South African realities surrounding political, cultural, social, and historic contexts and issues in management. This book is promoting CMS to the scholarly community, to show that there are exciting possibilities being offered by a different approach to management scholarship. This book also forms part of a larger project of growing CMS in South Africa, and is a collection of original works by academics actively working in CMS, following various methodological approaches which can be categorised into two broad methodological categories, namely, conceptual work and empirical work following an Interpretive approach

SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms

Pharmacologic inhibition of the renal sodium/glucose cotransporter-2 induces glycosuria and reduces glycemia. Given that SGLT2 inhibitors (SGLT2i) reduce mortality and cardiovascular risk in type 2 diabetes, improved understanding of molecular mechanisms mediating these metabolic effects is required. Treatment of obese but nondiabetic mice with the SGLT2i canagliflozin (CANA) reduces adiposity, improves glucose tolerance despite reduced plasma insulin, increases plasma ketones, and improves plasma lipid profiles. Utilizing an integrated transcriptomic-metabolomics approach, we demonstrate that CANA modulates key nutrient-sensing pathways, with activation of 5\u2032 AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR), independent of insulin or glucagon sensitivity or signaling. Moreover, CANA induces transcriptional reprogramming to activate catabolic pathways, increase fatty acid oxidation, reduce hepatic steatosis and diacylglycerol content, and increase hepatic and plasma levels of FGF21. Given that these phenotypes mirror the effects of FGF21 to promote lipid oxidation, ketogenesis, and reduction in adiposity, we hypothesized that FGF21 is required for CANA action. Using FGF21-null mice, we demonstrate that FGF21 is not required for SGLT2i-mediated induction of lipid oxidation and ketogenesis but is required for reduction in fat mass and activation of lipolysis. Taken together, these data demonstrate that SGLT2 inhibition triggers a fasting-like transcriptional and metabolic paradigm but requires FGF21 for reduction in adiposity

CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC’s functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing >3200 variants in >470 genes from >3100 publications

Anti-neutrophil cytoplasmic autoantibody-associated vasculitis in the very elderly: a 90-year-old iron lady

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are characterized by blood vessel inflammation resulting in organ dysfunction or in the patient\u2019s death. The peak of incidence was observed in patients over 75 years of age. We describe an unusual ANCA vasculitis presentation in a 90-year old patient admitted to the emergency room for severe dyspnea, oliguria and a recent onset cutaneous purple rush. Plain chest radiography disclosed pulmonary edema and diffuse bilateral reticulonodular infiltrates. Creatinine was 7.3 mg/dl, azotemia 202 mg/dl, hemoglobin 6.8 g/dl. CPAP (continuous positive airway pressure), furosemide 20 ml/h, nitroglycerin 8\u3b3/kg/min, blood transfusions and i.v. methylprednisolone 60 mg/day were administered. On day 1 a femoral venous catheter was placed and hemodialysis (HD) treatment started for acute renal failure. The patient underwent 13 HD sessions without heparin (EVAL dialyzer). On day 7 renal function had still not recovered and a new plain chest radiogram was unchanged. Proteinase 3(PR3) ANCA were 81 IU/ml (ELISA), C-reactive protein (CRP) was 18 mg/dl, C3 42 mg/dl, C4 5 mg/dl. A high resolution computed tomography considering that the 53% of cases were managed with glucocorticoids alone. Nonetheless, Walsh et al\u2019s metanalysis showed that patients who received a course of glucocorticoid therapy for more than 12 months suffered fewer relapses of ANCA vasculitis. In patients older than 80 years any immunosuppressive therapy is associated with a significantly lower risk of ESRD and death, but the rate of infections is higher than in younger patients. In our patient the CY dose related to the body surface area was reduced to 200 mg in view of age, risk of infection and renal failure, but glucocorticoid therapy was maintained. During the 2 year follow-up no infections were reported, the Birmingham vasculitis score was lower than 10 and reached the 50% reduction of the initial disease activity score recommended. A good outcome was obtained and it seems to be related both to CY and to the long-term maintenance therapy with glucocorticoids

Associations between sleep disturbances and diabetes mellitus among blacks with metabolic syndrome: Results from the Metabolic Syndrome Outcome Study (MetSO)

Introduction. The association between sleep disturbances and cardiometabolic diseases has been understudied in blacks with metabolic syndrome. Methods. This study is a cross-sectional analysis of the Metabolic Syndrome Outcome Study (MetSO) trial. We assessed insomnia symptoms, sleep duration, and risk for sleep apnea. Multivariate logistic regression models evaluated the association between sleep disturbances with diabetes mellitus (DM) and the combined outcomes of DM and hypertension as well as DM and dyslipidemia. Results. The sample consisted of 1,013 participants, mean age of 62 ± 14 years and 61% female. DM was diagnosed in 60% of the sample. Sleep apnea risk was observed in 48% of the sample, while 10% had insomnia symptoms and 65% reported short sleep duration (< 6 hours). Sleep apnea risk, but not insomnia or sleep duration, was associated with DM (OR 1.66; 95% CI 1.21-2.28), adjusting for age, sex, income, obesity (BMI ≥ 30 kg/m 2 ), tobacco use, alcohol use, hypertension, dyslipidemia, and depression. In fully adjusted models, sleep apnea risk was associated with the combined outcome of DM-hypertension (OR 1.95; 95% CI 1.42-2.69), but not with diabetes-dyslipidemia. Conclusion. We observed a strong association between sleep apnea risk and diabetes mellitus among blacks with metabolic syndrome

The use of idealised experiments in testing a new convective parameterization: performance of CoMorph-A

CoMorph is a new mass-flux convection parameterization under development at the Met Office designed for use within the Unified Model and its successor model, LFRic. Use of a three-dimensional idealised model enables controlled tests of the performance of the scheme across different regimes. This includes the interaction between the physical parametrizations and the resolved dynamics, allowing study of the emergent organisation of convection on the resolved scale. A selection of well-known cases is revisited here, with the purpose of documenting the extent to which CoMorph captures a range of important, but challenging behaviour such as the diurnal cycle and sensitivity to tropospheric moisture. Simulations using CoMorph-A, a new physics package, that has been demonstrated to perform well at NWP and climate scales, are compared against the current global atmosphere configuration and high-resolution results. In addition to an entirely new convection scheme, the package of changes includes significant changes to the cloud, microphysics, and boundary layer parametrizations. Recognising that CoMorph-A is the first version of a scheme that will continue to be substantially developed and to obtain good performance, compromises in tuning have had to be made. These idealised tests therefore show what works well in this configuration, and what areas will require further work. As such, it is quite a demanding testbed and could be viewed as some of the equipment required for a 'convective playground'