Mapping Local and Global Liquid Phase Behavior in Living Cells Using Photo-Oligomerizable Seeds.

Liquid-liquid phase separation plays a key role in the assembly of diverse intracellular structures. However, the biophysical principles by which phase separation can be precisely localized within subregions of the cell are still largely unclear, particularly for low-abundance proteins. Here, we introduce an oligomerizing biomimetic system, "Corelets," and utilize its rapid and quantitative light-controlled tunability to map full intracellular phase diagrams, which dictate the concentrations at which phase separation occurs and the transition mechanism, in a protein sequence dependent manner. Surprisingly, both experiments and simulations show that while intracellular concentrations may be insufficient for global phase separation, sequestering protein ligands to slowly diffusing nucleation centers can move the cell into a different region of the phase diagram, resulting in localized phase separation. This diffusive capture mechanism liberates the cell from the constraints of global protein abundance and is likely exploited to pattern condensates associated with diverse biological processes. VIDEO ABSTRACT.

Patterns of drug use and polypharmacy burden in chronic kidney disease patients: An experience from a secondary care hospital in United Arab Emirates.

OBJECTIVE: To evaluate the patterns of drug use and polypharmacy burden in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: It was a prospective observational cohort study done in a secondary care hospital in Ras Al Khaimah, United Arab Emirates (UAE). 130 CKD patients admitted under the care of nephrology in-patient department including those undergoing regular maintenance hemodialysis were included in the study. Electronic patient case records of CKD patients were studied and analyzed to evaluate drug use pattern and medication burden. RESULTS: The majority of the study patients were in CKD stage G5 (82.3%, 107/130). The median number of different drugs prescribed per patient was found to be 11.0. Negative binomial regression analysis revealed that CKD patients with more than 4 comorbidities were prescribed 1.27 times more than patients with ≤ 4 comorbidities (IRR: 1.273, p = 0.017). Patients with dyslipidemia (IRR: 1.393, p < 0.001) and hyperphosphatemia (IRR: 1.189, p = 0.048) as comorbid conditions were more likely to be prescribed a higher number of drugs than patients without these comorbid conditions. With every 1-day increase in length of hospital stay, the likelihood of drug prescription also increased 1.01 times (IRR: 1.01, p = 0.040). Multivariate logistic regression analysis identified older age (OR:1.07, p = 0.004), higher number of comorbidities (OR: 9.58, p = 0.011), comorbid conditions like dyslipidemia (OR: 43.7, p = 0.001), and hyperphosphatemia (OR: 17.18, p = 0.044) as independent predictors of polypharmacy in our study population. CONCLUSION: The study represents the current drug use pattern among CKD patients in a secondary care hospital in UAE. Study findings highlight that medication burden in CKD patients was high, and the majority of them were on polypharmacy.

Comparison of Protocols to Reduce Diabetic Ketoacidosis in Patients With Type 1 Diabetes Prescribed a Sodium-Glucose Cotransporter 2 Inhibitor.

OBJECTIVE | Sodium-glucose cotransporter 2 (SGLT2) inhibitors are approved for type 1 diabetes in Europe and Japan, with off-label use in type 1 diabetes in the United States. Although there were no consistent approaches to risk mitigation in clinical trials of these agents, protocols have been developed to try to reduce the risk of diabetic ketoacidosis (DKA). However, a validated risk mitigation strategy does not exist. We reviewed available DKA risk mitigation protocols to better understand the various strategies currently in use. METHODS | We conducted a search of the published medical literature and other medical information sources, including conference presentations, for protocols. We then categorized the information provided into guidance on patient selection, initiation of SGLT2 inhibitors, ketone monitoring, necessary patient action in the event of ketosis or DKA, and inpatient treatment of ketosis or DKA. RESULTS | Patient selection is generally similar among the protocols, although some require a minimum BMI and insulin dose. All protocols advocate routine measurement of ketones, although some insist on blood ketone tests. Although action steps for ketosis varies, all protocols advocate rapid patient intervention. The importance of evaluating ketones and acid-base balance even in the absence of hyperglycemia is emphasized by all protocols, as is the need to continue administering insulin until ketosis has resolved. CONCLUSION | DKA risk mitigation must be pursued systematically in individuals with type 1 diabetes, although the best strategy remains to be determined. Given the ongoing need for adjunctive therapies in type 1 diabetes and current use of SGLT2 inhibitors for this purpose, additional education and research are crucial, especially in the hospital environment, where DKA may not be diagnosed promptly and treated appropriately.

Suppressing the Rayleigh-Plateau Instability in Field-Directed Colloidal Assembly.

Suspensions of superparamagnetic colloids that equilibrate in a toggled magnetic field undergo a Rayleigh-Plateau instability with a characteristic wavelength λ = 600 µm for the toggle frequency ν = 0.66 Hz. The instability is suppressed when the chamber length L in the field direction is less than 2λ. The final size of the magnetic domains perpendicular to the field, D, follows a power law relation of D ∼ L(0.71±0.07). These results demonstrate the structural differences of field-directed suspensions when confined to lengths scale set by the phase separation process and can potentially be used to create self-assembled colloidal crystals with well-defined size and shape.

Coarsening mechanics of a colloidal suspension in toggled fields.

Suspensions of paramagnetic colloids are driven to phase separate and self-assemble in toggled magnetic fields. At field strengths above 575 A/m and toggle frequencies between 0.66 and 2 Hz, an initial gel-like, arrested network collapses into condensed, ellipsoidal aggregates. The evolution to this equilibrium structure occurs via a Rayleigh-Plateau instability. The toggle frequency ν determines the fluidity of the breakup process. At frequencies between 0.66 and 1.5 Hz, the suspension breaks up similar to a viscous, Newtonian fluid. At frequencies ν > 1.5 Hz, the network ruptures like a viscoplastic material. The field strength alters the onset time of the instability. A power law relationship emerges as the scaled frequency and field strength can be used to predict the onset of breakup. These results further aid in understanding the mechanics and dynamics of the phase separation process of suspensions of polarizable colloids in toggled external fields.

Clinical Characteristics, Risk Factors for Severity and Pharmacotherapy in Hospitalized COVID-19 Patients in the United Arab Emirates.

Data on the clinical characteristics, severity and management of COVID-19 from the Middle East region, especially the United Arab Emirates (UAE), is very limited. We studied the clinical characteristics, laboratory biomarkers, risk factors for severity and pharmacotherapy of hospitalized COVID-19 patients in this single-center, analytical cross-sectional study conducted in a secondary care hospital of the UAE. A total of 585 patients were included in the study (median age, 49 years (IQR, 39−59); 66% male). Age > 45 years (OR = 2.07, 95% CI: 1.04−4.14, p = 0.040), male gender (OR = 3.15, 95% CI: 1.52−6.51, p = 0.002), presentation symptoms such as fever (OR = 3.68, 95% CI:1.34−10.11, p = 0.011) and shortness of breath/dyspnea (OR = 5.36, 95% CI: 2.69−10.67, p < 0.001), Hb < 13 g/dL (OR = 3.17, 95% CI: 1.51−6.65, p = 0.002), neutrophils > 7 × 103/mcL (OR = 4.89, 95% CI: 1.66−14.37, p=0.004), lymphocytes < 1 × 103/mcL (OR = 7.78, 95% CI: 1.01−60.19, p = 0.049), sodium < 135 mmol/L (OR = 5.42, 95% CI: 1.05−27.95, p = 0.044), potassium < 3.6 mmol/L (OR = 3.36, 95% CI: 1.03−11.01, p = 0.045), urea > 6.5 mmol/L (OR = 3.37, 95% CI: 1.69−6.73, p = 0.001) and LDH > 227 IU/L (OR = 6.26, 95% CI: 1.61−24.32, p = 0.008) were independent predictors of the severity of COVID-19. Antivirals (524, 89.6%) and corticosteroids (358, 61.2%) were prescribed for the management of COVID-19. In conclusion, older age, male gender, presentation symptoms such as fever and dyspnea, low hemoglobin, neutrophilia, lymphopenia, hyponatremia, hypokalemia, elevated levels of urea and lactate dehydrogenase were found to be independent risk factors for severe COVID-19. The pharmacotherapy of COVID-19 patients in our study was diverse, and the medications were prescribed based on the clinical condition of the patients.

Evaluation of Drug-Related Problems in Chronic Kidney Disease Patients.

Background Chronic kidney disease (CKD) is a challenging global health problem with increasing prevalence worldwide. Concurrence of CKD and comorbidities results in the use of multiple medications and exposing patients to polypharmacy. Polypharmacy in CKD is common across all the stages of the disease and leads to poor medication adherence, higher healthcare costs, and drug-related problems, such as drug-drug interactions (DDIs) and adverse drug reactions (ADRs). DDIs and ADRs in CKD patients may lower the quality of life, increase the length of hospital stay, and augment the risks of morbidity and mortality. Methodology This was a hospital-based, prospective, cross-sectional study conducted in a secondary care hospital. The study population comprised 130 adult CKD patients admitted to the nephrology department including those on maintenance hemodialysis. Study-related data were obtained from the electronic patient case records. Medications prescribed to the patients were analyzed for potential DDIs (pDDIs) using Portable Emergency and Primary Care Information Database (PEPID 12.1) drug interaction checker. All observed and reported suspected ADRs related to the prescribed drugs were evaluated for causality, severity, preventability, and predictability. Results Out of the 130 patients, majority were males (n = 71, 54.6%), in the age group of 61-70 years (n = 45, 34.6%), and belonged to CKD stage 5 (n = 105, 80.8%). The mean number of drugs prescribed was 11.1 ± 3.8 per patient. The prevalence of pDDIs was found to be 89.2%. Upon analysis by the PEPID database, 708 pDDIs with 215 different pairs of interacting drugs were identified. Polypharmacy (odds ratio (OR): 62.34, 95% confidence interval (CI): 7.97-487.64, p < 0.001) was identified as an independent predictor of the occurrence of pDDIs. Negative binomial regression analysis revealed that dyslipidemia (incidence rate ratio (IRR): 2.7, 95% CI 2.09-3.48, p < 0.001) and diabetes (IRR: 1.2, 95% CI 1.01-1.54, p = 0.040) increased the probability of occurrence of pDDI by 2.7 and 1.2 folds, respectively. Furthermore, the likelihood of pDDI increased with every one-day increase in the length of hospital stay (IRR: 1.02, 95% CI 1.00-1.03, p = 0.015) by 1.02 times and polypharmacy (IRR: 6.30, 95% CI 3.04-13.02, p < 0.001) by 6.3 times. The incidence of ADRs was found to be 10.7%. Majority of suspected ADRs were possible (n = 7, 50.0%), of mild and moderate severity (n = 7, 50.0%), and non-preventable (n = 8, 57.1%) type. Conclusions This study investigated two important drug-related problems, pDDIs, and ADRs, in the CKD population. High proportion of CKD patients in the study had pDDIs. Comorbid conditions such as dyslipidemia and diabetes mellitus, length of hospital stay, and polypharmacy were significantly associated with increased likelihood of pDDIs. Furthermore, there was a burden of ADRs in the study population, of which most ADRs were possible and of mild to moderate severity. Prevention, identification, and resolution of these problems in CKD patients is important and can be achieved through medication optimization, which requires a proactive interdisciplinary collaboration between clinicians, clinical pharmacists, and other healthcare professionals.

Prevalence and associations of moderately increased albuminuria in patients with type 2 diabetes in United Arab Emirates.

BACKGROUND AND AIMS: Our study sought to investigate the prevalence of moderately increased albuminuria in United Arab Emirates (UAE) nationals with type 2 diabetes, and to identify the associated factors. METHODS: This prospective cross-sectional study was conducted in two hundred and seven UAE nationals with type 2 diabetes mellitus attending the internal medicine department of a secondary care hospital. Moderately increased albuminuria was estimated in random spot urine samples and was defined as urinary albumin-to-creatinine ratio (UACR) of 3-30 mg/mmoL. Prevalence and associations of moderately increased albuminuria were evaluated. RESULTS: The study population had a mean UACR of 7.2 ± 10.2 mg/mmoL with mean eGFR of 94.5 ± 11.7 mL/min/1.73 m2. Prevalence of moderately increased albuminuria in our study population was found to be 44.0%. Multivariate logistic regression analysis showed that duration of diabetes (OR:1.72, 95% CI:1.34-2.19; p<0.001), presence of hypertension (OR:3.42, 95% CI:0.96-12.20; p=0.050) and neuropathy (OR:2.85, 95% CI:1.03-7.84; p=0.042), BMI (OR:1.08, 95% CI:1.01-1.16; p=0.019), HbA1c (OR:1.39, 95% CI:1.00-1.93; p=0.045), CRP (OR:1.10, 95% CI:1.00-1.22; p=0.035), serum creatinine (OR:1.04, 95% CI:1.02-1.06; p<0.001) and HDL-C (OR:0.10, 95% CI:0.01-0.28; p<0.001) were independently correlated with moderately increased albuminuria. Stepwise multiple linear regression analysis demonstrated that duration of diabetes, HbA1c, CRP and serum creatinine were independent predictors of UACR. CONCLUSION: We report a high prevalence of moderately increased albuminuria in UAE nationals with type 2 diabetes in a secondary care setting. Routine screening and timely management of moderately increased albuminuria in type 2 diabetes mellitus can lead to better patient outcomes.

Diabetes news.

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.

Seventh World congress on controversies to consensus in diabetes, obesity, and hypertension.

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.

Diabetes news.

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.

Health 2.0 2018.

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.

European Society of Cardiology 2018.

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.

European Association for the Study of Diabetes 2018.

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.

American Heart Association Scientific Sessions 2018.

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.

World Congress on Clinical Trials in Diabetes 2018.

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.

Diabetes news.

Ursula Biba, Rhea W. Teng, Martin J. Kurian, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Biba, Teng, Kurian, Carracher, and Close review the latest developments relevant to researchers and clinicians.

Practical ways to achieve targets in diabetes care conference.

Ursula Biba, Rhea W. Teng, Martin J. Kurian, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Biba, Teng, Kurian, and Close review the latest developments relevant to researchers and clinicians.

Use of Phosphate Binders in End-Stage Renal Disease: An Experience From a Secondary Care Hospital in United Arab Emirates.

OBJECTIVE: Hyperphosphatemia in end-stage renal disease (ESRD) is associated with many serious patient-level consequences including cardiovascular events and mortality. The purpose of this study was to investigate the use of phosphate binders in ESRD patients on maintenance hemodialysis. MATERIALS AND METHODS: The study was a prospective observational cohort study including adult ESRD patients undergoing hemodialysis at a secondary hospital in United Arab Emirates. Patient characteristics were compared as per type of phosphate binder used. Bivariate and multivariate multinomial logistic regression analyses were carried out to determine variables that were independently associated with use of different phosphate binders. RESULTS: Phosphate binders used at our study site were sevelamer, calcium carbonate, and a combination of sevelamer and calcium carbonate. Bivariate multinomial logistic regression analysis revealed that serum phosphorous (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.04-1.09, P = 0.047; OR: 0.10, 95% CI: 0.03-0.89, P = 0.042), calcium (OR: 0.11, 95% CI: 0.02-0.86, P = 0.041; OR: 0.22, 95% CI: 0.01-0.96, P = 0.012), and calcium-phosphorous product (OR: 0.20, 95% CI: 0.06-0.64, P = 0.008; OR: 0.16, 95% CI: 0.05-0.54, P = 0.003) levels were significantly lower in patients on sevelamer per se as well as in patients on combination therapy, respectively when compared to calcium carbonate per se. Multivariate multinomial logistic regression analysis revealed that in sevelamer and combination groups, cardiovascular diseases (OR: 0.12, 95% CI: 0.02-0.65, P = 0.022; OR: 0.10, 95% CI: 0.01-0.88, P = 0.038) were significantly lesser compared to calcium carbonate group after being adjusted for other variables in the model. CONCLUSION: We observed that hyperphosphatemia and related events in our study population were better controlled by sevelamer per se and combination therapy than calcium carbonate per se. Further large scale, multicenter studies are required to confirm and establish these findings.