BioSimulators: a central registry of simulation engines and services for recommending specific tools.

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations.

Datanator: an integrated database of molecular data for quantitatively modeling cellular behavior.

Integrative research about multiple biochemical subsystems has significant potential to help advance biology, bioengineering and medicine. However, it is difficult to obtain the diverse data needed for integrative research. To facilitate biochemical research, we developed Datanator (https://datanator.info), an integrated database and set of tools for finding clouds of multiple types of molecular data about specific molecules and reactions in specific organisms and environments, as well as data about chemically-similar molecules and reactions in phylogenetically-similar organisms in similar environments. Currently, Datanator includes metabolite concentrations, RNA modifications and half-lives, protein abundances and modifications, and reaction rate constants about a broad range of organisms. Going forward, we aim to launch a community initiative to curate additional data. Datanator also provides tools for filtering, visualizing and exporting these data clouds. We believe that Datanator can facilitate a wide range of research from integrative mechanistic models, such as whole-cell models, to comparative data-driven analyses of multiple organisms.

RunBioSimulations: an extensible web application that simulates a wide range of computational modeling frameworks, algorithms, and formats.

Comprehensive, predictive computational models have significant potential for science, bioengineering, and medicine. One promising way to achieve more predictive models is to combine submodels of multiple subsystems. To capture the multiple scales of biology, these submodels will likely require multiple modeling frameworks and simulation algorithms. Several community resources are already available for working with many of these frameworks and algorithms. However, the variety and sheer number of these resources make it challenging to find and use appropriate tools for each model, especially for novice modelers and experimentalists. To make these resources easier to use, we developed RunBioSimulations (https://run.biosimulations.org), a single web application for executing a broad range of models. RunBioSimulations leverages community resources, including BioSimulators, a new open registry of simulation tools. These resources currently enable RunBioSimulations to execute nine frameworks and 44 algorithms, and they make RunBioSimulations extensible to additional frameworks and algorithms. RunBioSimulations also provides features for sharing simulations and interactively visualizing their results. We anticipate that RunBioSimulations will foster reproducibility, stimulate collaboration, and ultimately facilitate the creation of more predictive models.

Hybrid Surgical Hot Clinic (HSHC): Evaluation of Surgical Hot Clinic Services during COVID-19 Lockdown.

BACKGROUND: Surgical Hot Clinic (SHC) is an acute, ambulatory service for management provided on an outpatient basis. Following the start of global Novel Coronavirus (COVID-19) pandemic and as per the statement released by the Association of Surgeons of Great Britain and Ireland (ASGBI), we also modified our services to hybrid SHC (HSHC) by mainly providing telephonic follow-up with an occasional face-to-face (F2F) service. We conducted a service evaluation to assess the effectiveness and serviceability of HSHC during a pandemic. METHODS: This service evaluation was conducted from 30th March till 26th May 2020. The pathway was developed to mostly telephonic consultation with selective face-to-face consultation at a designated area in the medical ambulatory unit. The analysis then performed using SPSS version 21. RESULTS: As the overall attendance fell in hospital, 149 patients, including 54(36.2%) male, and 95(63.8%) females, attended SHC during COVID-19 lockdown. Out of these 149, 87(58.3%) were referred from Accident & Emergency (A&E), 2(1.3%) from GP, 9(6.04%) after scan through radiology department, while 51(34.2%) after discharge from hospital. Out of those who have telephonic consultation (n = 98), 12 patients were called in for review with either blood tests or further clinical examination. In total, only 10 out of 149 patients required admission to the hospital, for either intervention or symptomatic treatment. CONCLUSION: Hybrid Surgical Hot Clinic (HSHC) with both telephonic & face-to-face consultation, as per requirement, is flexible, effective and safe patient-focused acute surgical service during COVID-19 like crisis.

Role of renin-angiotensin system antagonists in the prevention of bevacizumab- and sunitinib-mediated cardiac dysfunction.

Although anticancer systemic therapy agents clearly lead to improved survival in patients with cancer, these can come at the cost of serious complications including cardiotoxicity. Two types of targeted systemic therapies currently in use for colorectal cancer (CRC) and renal cell cancer (RCC), respectively, include the vascular endothelial growth factor inhibitor bevacizumab (BVZ) and the tyrosine kinase inhibitor sunitinib (SNT). Despite the beneficial effects of BVZ and SNT in improving clinical outcomes in the settings of CRC and RCC, there is an increased risk of cardiac dysfunction. The aim of the present study was to determine whether prophylactic administration of renin-angiotensin system (RAS) inhibitors would attenuate the cardiotoxic side effects of BVZ or SNT in a chronic in vivo murine model. A total of 194 wild-type C57Bl/6 male mice received: 1) 0.9% saline, 2) BVZ (10 mg·kg-1·wk-1), or 3) SNT (40 mg·kg-1·day-1) for 4 wk. Within each arm, mice received daily prophylactic treatment with hydralazine (0.05 mg/ml), aliskiren (50 mg/kg), perindopril (4 mg/kg), or valsartan (2 mg/kg). Although hydralazine effectively lowered blood pressure in BVZ- or SNT-treated mice, it did not prevent left ventricular systolic dysfunction. Prophylactic administration of aliskiren, perindopril, or valsartan prevented adverse cardiovascular remodeling in mice treated with either BVZ or SNT. The addition of RAS antagonists also downregulated expression of phosphorylated p38 and Bcl-2-like 19-kDa interacting protein 3 in SNT-treated mice. In our chronic in vivo murine model, RAS antagonists partially attenuated the development of BVZ- or SNT-mediated cardiac dysfunction. Future clinical studies are warranted to investigate the cardioprotective effects of prophylactic treatment with RAS inhibitors in the settings of CRC and RCC. NEW & NOTEWORTHY In the evolving field of cardio-oncology, bevacizumab and sunitinib improve clinical outcomes in the settings of metastatic colorectal cancer and renal cell cancer, respectively. These anticancer drugs, however, are associated with an increased risk of cardiotoxicity. The prophylactic administration of renin-angiotensin system antagonists is partially cardioprotective against bevacizumab- and sunitinib-mediated cardiac dysfunction.

The role of renin angiotensin system antagonists in the prevention of doxorubicin and trastuzumab induced cardiotoxicity.

BACKGROUND: Cardio-Oncology is an evolving discipline that focuses on the management of cancer patients who develop cardiovascular complications as a result of their treatment. Although the current combination of surgical resection, radiation, and chemotherapy may lead to a cure in cancer patients, the administration of anti-cancer drugs, in particular Doxorubicin (DOX) and Trastuzumab (TRZ), is associated with an increased risk of cardiotoxicity. Little is known on the potential cardioprotective role of renin angiotensin system (RAS) antagonists in the prevention of DOX+TRZ mediated cardiotoxicity. OBJECTIVE: The aim of the study was to determine whether RAS antagonists would be useful in attenuating DOX+TRZ induced cardiotoxicity. METHODS: A total of 240 C57Bl/6 mice were randomized to prophylactic treatment with placebo, Aliskiren, Perindopril, or Valsartan for a total of 13 weeks. Within each arm, mice received treatment with either DOX, TRZ, or the combination of both drugs. Serial murine echocardiography was performed weekly to characterize the degree of cardiovascular remodeling within each group. RESULTS: In wild-type (WT) mice treated with DOX+TRZ, LV end diastolic internal diameter (LVID) increased from 3.1 ± 0.2 mm at baseline to 4.6 ± 0.3 mm at week 13 (p < 0.05) and the LV fractional shortening (FS) decreased from 52 ± 2% at baseline to 26 ± 2% at week 13 (p < 0.05). Prophylactic treatment with Aliskiren, Perindopril, or Valsartan attenuated the degree of LV cavity dilatation with LVID dimensions of 3.9 ± 0.2 mm, 4.1 ± 0.2 mm, and 4.2 ± 0.1 mm at week 13, respectively (p < 0.05). Similarly, prophylactic treatment with Aliskiren, Perindopril, or Valsartan was partially cardioprotective with FS of 40 ± 1%, 32 ± 1%, and 33 ± 2% at week 13, respectively (p < 0.05). As compared to WT mice receiving DOX+TRZ, prophylactic treatment with RAS inhibition was also associated with improved survival, corroborating the echocardiographic findings. CONCLUSION: The cardiotoxic effects of DOX+TRZ were partially attenuated by the prophylactic administration of RAS antagonists in a chronic murine model of chemotherapy induced cardiac dysfunction.

BpForms and BcForms: a toolkit for concretely describing non-canonical polymers and complexes to facilitate global biochemical networks.

Non-canonical residues, caps, crosslinks, and nicks are important to many functions of DNAs, RNAs, proteins, and complexes. However, we do not fully understand how networks of such non-canonical macromolecules generate behavior. One barrier is our limited formats for describing macromolecules. To overcome this barrier, we develop BpForms and BcForms, a toolkit for representing the primary structure of macromolecules as combinations of residues, caps, crosslinks, and nicks. The toolkit can help omics researchers perform quality control and exchange information about macromolecules, help systems biologists assemble global models of cells that encompass processes such as post-translational modification, and help bioengineers design cells.

Recent advances in the management of diabetic retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the leading cause of vision loss in people with diabetes. The current treatments do not target early stages of disease or impede disease progression. Therefore, the identification of new therapeutic targets, the development of novel therapies targeting early stages of the disease and accurate models that simulate pathological characteristics of this disorder are crucial. This review provides an overview of the pathological mechanisms underlying the development of DR, highlighting the recent advances in current and emerging treatments for DR.

Salts and energy balance: A special role for dietary salts in metabolic syndrome.

BACKGROUND: Dietary salts sodium (Na+), potassium (K+), magnesium (Mg2+), and calcium (Ca2+) are important in metabolic diseases. Yet, we do not have sufficient understanding on the salts global molecular network in these diseases. In this systematic review we have pooled information to identify the general effect of salts on obesity, insulin resistance and hypertension. AIMS: To assess the roles of salts in metabolic disorders by focusing on their individual effect and the network effect among these salts. METHODS: We searched articles in PubMed, EMBASE and Google Scholar. We selected original laboratory research, systematic reviews, clinical trials, observational studies and epidemiological data that focused on dietary salts and followed the preferred reporting items for systematic review in designing the present systematic review. RESULTS: From the initial search of 2898 studies we selected a total of 199 articles that met our inclusion criteria and data extraction. Alterations in metabolic pathways associated with the sensitivity of sodium, potassium, magnesium and calcium may lead to obesity, hypertension, and insulin resistance. We found that the results of most laboratory research, animal studies and clinical trials are coherent but some research outcome are either inconsistent or inconclusive. CONCLUSION: Important of salts in metabolic disorder is evident. In order to assess the effects of dietary salts in metablic diseases, environmental factors, dietary habits, physical activity, and the microbiome, should be considered in any study. Although interest in this area of research continues to grow, the challenge is to integrate the action of these salts in metabolic syndrom.

Serum creatine phosphokinase as prognostic indicator in the management of electrical burn.

OBJECTIVE: To determine the mean difference of serum creatine phosphokinase according to the extent of tissue damage and prognosis of the patients suffering from electrical burn injuries. STUDY DESIGN: A case series study. PLACE AND DURATION OF STUDY: Department of Burns, Liaquat University Hospital, Hyderabad, from September 2005 to August 2006. PATIENTS AND METHODS: During the study period, 38 patients with electrical burn injuries were enrolled. Victims of electrical burns with evidence of myocardial injury were excluded. Following admission, serum creatine phosphokinase was measured serially on 10 consecutive occasions. The data was later analyzed statistically using SPSS-10.0. RESULTS: Of the 38 patients, the mean age of the victims was 28 years, with males dominating the study population (82%). A statistically significant association was found between the level of serum creatine phosphokinase and likelihood of death (p=0.000). It was also found that serial monitoring of this enzyme can be used as prognostic indicator in the management of electrical burns injury. CONCLUSION: The level of creatine phosphokinase increased with the degree of tissue injuries in patients with electrical burns. This prognostic value is of great importance in the local setup, where sophisticated investigations to detect extent of injuries are not available.

Diabetic Ketoacidosis and the Domino Effect.

BACKGROUND Severe hypertriglyceridemia is a well-known cause of acute pancreatitis. Mild elevations of triglyceride levels are common in patients presenting with diabetic ketoacidosis (DKA). Rarely, DKA can be accompanied by an elevation of serum triglyceride level severe enough to lead to AP. CASE REPORT We report one such case of a young diabetic male who presented with DKA that was complicated by hypertriglyceridemia-induced acute pancreatitis (HTGAP). We were able to treat the condition with a slightly prolonged infusion of intravenous (IV) regular insulin in an efficient and cost-effective manner with a good outcome. CONCLUSIONS From our experience, DKA-associated HTGAP can be rapidly, efficiently, and cost-effectively treated with IV regular insulin and close biochemical monitoring. A high index of suspicion for acute pancreatitis is necessary in patients with DKA, especially with co-existing hypertriglyceridemia; and all efforts should be made to diagnose it in a timely manner to prevent subsequent complications.

Shigella sonnei Bacteremia Presenting with Profound Hepatic Dysfunction.

Worldwide, Shigellosis is a significant public health issue, associated with nearly one million deaths annually. About half a million cases of Shigella infection are reported annually in the United States. Shigella bacteremia is uncommon and generally seen in children and immunocompromised adults. We present a case of a Shigella sonnei bacteremia with marked hepatic derangement in a 27-year-old previously healthy homosexual male with history of Roux-en-Y gastric bypass, who presented to the emergency room with a 4-day history of loose watery stool, abdominal cramps, nausea and vomiting, and yellow skin of 2-day duration. He reports similar diarrhea illness in two close contacts in preceding days. On examination, he was fully oriented but dehydrated, icteric, and febrile. Laboratory data revealed WBC of 2200/µL, elevated AST and ALT (201 IU/L, 73 IU/L resp.), normal alkaline phosphatase, elevated total and direct bilirubin of 8.2 mg/dL and 4.4 mg/dL, albumin of 3.2 g/dL, INR of 2.9, prothrombin time of 31.7, and platelet of 96,000/µL. Workup for infectious, autoimmune and medication-induced hepatitis, Wilson's disease, and hemochromatosis was negative. Abdominal ultrasound and computed tomography of the abdomen showed hepatic steatosis and right-sided colitis. Stool and blood cultures were positive for Shigella sonnei. He was treated with ciprofloxacin with improvement in liver function. Follow-up blood test 4 months later was within normal limits.

Severe Enteropathy From Mycophenolate Mofetil.

The adverse effects of mycophenolate mofetil on the colon are well known. However, isolated small intestinal involvement resulting in diarrhea and severe weight loss is infrequently reported in the literature. We present the case of a 45-year-old woman on mycophenolate mofetil following renal transplant, who presented with abdominal pain and weight loss. An esophagogastroduodenoscopy and colonoscopy with biopsies were normal. A small bowel capsule study revealed extensive enteropathy of jejunum and ileum that was confirmed on a push enteroscopy with biopsies. Her symptoms completely resolved after being switched to enteric-coated mycophenolic acid.

An Unusual Case of Crimean Congo Hemorrhagic Fever: Prolonged Bleeding with Successful Recovery.

Crimean Congo Hemorrhagic Fever (CCHF) is a tick-borne viral disease with a major reservoir in both domestic and wild animals. In Pakistan, it is endemic largely in rural areas and most cases occur in spring and autumn. Recently, cases are being reported throughout the year, including winter months, with some even from urban areas. Death from CCHF is most likely to occur during the hemorrhagic phase. We report a case presenting from an urban locality in December. Clinical presentation was characterized by a prolonged hemorrhagic phase and a delayed normalization of platelet counts.

Calcitriol-mediated hypercalcemia in a patient with bilateral adrenal non-Hodgkin's B-cell lymphoma case report.

Calcitriol-mediated hypercalcemia is a frequent manifestation of hematological malignancies. However, there are a few reports of cases presenting with increased angiotensin-converting enzyme (ACE) level, which suggests a possible mechanism similar to that of granulomatous diseases. We present a patient with hypercalcemia, normal parathyroid hormone, and parathyroid hormone-related protein levels but high calcitriol and ACE levels that, after further investigation, was diagnosed with bilateral adrenal non-Hodgkin's B-cell lymphoma. Primary adrenal lymphoma represents only 1% of all non-Hodgkin's lymphomas and is usually asymptomatic but should be considered by clinicians among the malignancies that cause calcitriol-mediated hypercalcemia.

Impending aortic aneurysm rupture - a case report and review of the warning signs.

Abdominal aortic aneurysm (AAA) may present with subtle clinical findings. Recognition of the imaging features of an impending rupture is key for timely diagnosis. This report reviews the classic computed tomography findings of impending AAA rupture and presents a recent case which illustrates the key features.

Addison's Disease and Dilated Cardiomyopathy: A Case Report and Review of the Literature.

Addison's disease is often accompanied by a number of cardiovascular manifestations. We report the case of a 30-year-old man who presented with a new onset dilated cardiomyopathy due to Addison's disease. The clinical presentation, treatment, and outcomes of this rare hormone mediated cardiac disorder are reviewed.