Neurogenic diabetes insipidus presenting in a patient with subacute liver failure: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, this is the first report in the literature of development of neurogenic diabetes insipidus in a patient with subacute liver failure.</p> <p>Case presentation</p> <p>A 25-year-old man presented with subacute liver failure. While awaiting a liver transplant, the patient developed cerebral edema, which resulted in neurogenic diabetes insipidus secondary to cerebral edema. The patient died before the liver transplantation could be carried out.</p> <p>Conclusion</p> <p>Neurogenic diabetes insipidus is well recognized in the neurosurgical population as a consequence of cerebral edema and increased intracranial pressure, both of which occur commonly in patients with subacute liver failure.</p

Acute bilateral simultaneous angle closure glaucoma after topiramate administration: a case report

<p>Abstract</p> <p>Introduction</p> <p>A case of severe acute bilateral angle closure glaucoma with complete visual loss after oral topiramate therapy.</p> <p>Case presentation</p> <p>A 34 year-old woman developed bilateral severe visual loss 2 days after doubling the dosage of topiramate. Her best-corrected visual acuity (BCVA) was counting fingers in both eyes (OU). Intraocular pressures were 49 mm and 51 mm of Hg in right and left eyes respectively, with conjunctival chemosis, corneal edema, shallow anterior chamber and closed angles on gonioscopy. B-scan ultrasound revealed annular peripheral choroidal effusions in both eyes.</p> <p>Conclusion</p> <p>Intraocular pressures and anterior chamber depth were normalized after discontinuation of topiramate and initiation of antiglaucoma therapy. Two weeks later, visual acuities improved to 20/25 in the right eye and 20/40 in the left eye. B-scan ultrasound showed resolution of choroidal effusion. Topiramate, an oral sulpha-derivative medication is known to cause ciliochoroidal effusions, which lead to forward rotation of the ciliary body and displacement of the lens-iris diaphragm, with resultant acute angle closure glaucoma and myopic shift.</p

Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria

BACKGROUND: Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone all individually reduce cardiovascular, kidney, and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known. METHODS: We used data from 2 SGLT2i trials (CANVAS [Canagliflozin Cardiovascular Assessment] and CREDENCE [Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation]), 2 ns-MRA trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease]), and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney, and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA, and ns-MRA in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE. RESULTS: Compared with conventional care, the combination of SGLT2i, GLP-1 RA, and ns-MRA was associated with a hazard ratio of 0.65 (95% CI, 0.55–0.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0–5.7), with a number needed to treat of 23 (95% CI, 18–33). For a 50-year-old patient commencing combination therapy, estimated major adverse cardiovascular event–free survival was 21.1 years compared with 17.9 years for conventional care (3.2 years gained [95% CI, 2.1–4.3]). There were also projected gains in survival free from hospitalized heart failure (3.2 years [95% CI, 2.4–4.0]), chronic kidney disease progression (5.5 years [95% CI, 4.0–6.7]), cardiovascular death (2.2 years [95% CI, 1.2–3.0]), and all-cause death (2.4 years [95% CI, 1.4–3.4]). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for major adverse cardiovascular events (2.4 years [95% CI, 1.1–3.5]), chronic kidney disease progression (4.5 years [95% CI, 2.8–5.9]), and all-cause death (1.8 years [95% CI, 0.7–2.8]). CONCLUSIONS: In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment of SGLT2i, GLP-1 RA, and ns-MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival

FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis

Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci) to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection

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Catalytic upgrading of refinery cracked products by trans-hydrogenation: a review

The production of high premium fuel is an issue of priority to every refinery. The trans-hydrogenation process is devised to convert two low valued refinery cracked products to premium products; the conversion processes involve the combination of dehydrogenation and hydrogenation reaction as a single step process. The paper reviews the recent literature on the use of catalysts to convert low value refinery products (i.e. alkanes and alkynes or alkadienes) to alkenes (olefins) by trans-hydrogenation. Catalysts based on VOx, CrOx and Pt all supported on alumina have been used for the process. However, further studies are still required to ascertain the actual reaction mechanism, mitigating carbon deposition and catalyst deactivation, and the role of different catalysts to optimize the reaction desired products

Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism

BACKGROUND: The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism. METHODS: This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99m Tc-MIBI scintigraphy- Intraoperative iPTH monitoring was routinely done. RESULTS: Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99m Tc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate. CONCLUSION: Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99m Tc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

Withaferin a-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species

Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast cancer cells in culture and MDA-MB-231 xenografts in vivo in association with apoptosis induction, but the mechanism of cell death is not fully understood. We now demonstrate, for the first time, that WA-induced apoptosis is mediated by reactive oxygen species (ROS) production due to inhibition of mitochondrial respiration. WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also resistant to WA-induced apoptosis. WA-mediated ROS production as well as apoptotic histone-associated DNA fragment release into the cytosol was significantly attenuated by ectopic expression of Cu,Zn-superoxide dismutase in both MDA-MB-231 and MCF-7 cells. ROS production resulting from WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity. Mitochondrial DNA-deficient Rho-0 variants of MDA-MB-231 and MCF-7 cells were resistant to WA-induced ROS production, collapse of mitochondrial membrane potential, and apoptosis compared with respective wild-type cells. WA treatment resulted in activation of Bax and Bak in MDA-MB-231 and MCF-7 cells, and SV40 immortalized embryonic fibroblasts derived from Bax and Bak double knockout mouse were significantly more resistant to WA-induced apoptosis compared with fibroblasts derived from wild-type mouse. In conclusion, the present study provides novel insight into the molecular circuitry of WA-induced apoptosis involving ROS production and activation of Bax/Bak. © 2011 Hahm et al

To be or not to be a pseudogene: a molecular epidemiological approach to the mclx genes and its impact in tuberculosis

Tuberculosis presents a myriad of symptoms, progression routes and propagation patterns not yet fully understood. Whereas for a long time research has focused solely on the patient immunity and overall susceptibility, it is nowadays widely accepted that the genetic diversity of its causative agent, Mycobacterium tuberculosis, plays a key role in this dynamic. This study focuses on a particular family of genes, the mclxs (Mycobacterium cyclase/LuxR-like genes), which codify for a particular and nearly mycobacterial-exclusive combination of protein domains. mclxs genes were found to be pseudogenized by frameshift-causing insertion(s)/deletion(s) in a considerable number of M. tuberculosis complex strains and clinical isolates. To discern the functional implications of the pseudogenization, we have analysed the pattern of frameshift-causing mutations in a group of M. tuberculosis isolates while taking into account their microbial-, patient- and disease-related traits. Our logistic regression-based analyses have revealed disparate effects associated with the transcriptional inactivation of two mclx genes. In fact, mclx2 (Rv1358) pseudogenization appears to be primarily driven by the microbial phylogenetic background, being mainly related to the Euro-American (EAm) lineage; on the other hand, mclx3 (Rv2488c) presents a higher tendency for pseudogenization among isolates from patients born on the Western Pacific area, and from isolates causing extra-pulmonary infections. These results contribute to the overall knowledge on the biology of M. tuberculosis infection, whereas at the same time launch the necessary basis for the functional assessment of these so far overlooked genes.This work was supported by Fundacao para a Ciencia e Tecnologia (FCT), Portugal, and cofunded by Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER), and from Projeto Estrategico - LA 26 - 2013-2014 (PEst-C/SAU/LA0026/2013). H.N.-G. received a personal FCT Grant (SFRH/BD/33902/2209). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript