Investigating the Structure of Potential New Drug to Treat Sickle Cell Anemia through Inhibition of the Polymerization of Hemoglobin S​

Sickle cell anemia is a hematologic disorder impacting over 15 million people worldwide. It is caused by a single point mutation in the gene hemoglobin-Betha, where a glu group is replaced by val (GAG --- GTG) in the seventh codon (glu7val) of chromosome 1. In this study, we are comparing the anti-sickling properties of drugs in varied conditions in order to create a drug that is effective in an O2-independent manner and with a 1:1 stoichiometry for lower dosage purposes. We used Pymol and Jmol to compare the structures of the aldehydes GBT-440 and VZHE-039, which interact on the same binding site to treat sickle cell disease. GBT-440’s bulkiness allows it to have a 1:1 stoichiometry, while VZHE-039’s solubility is due to its interaction with the hemoglobin’s alpha cleft, allowing it to be O2-independent. We identified the pyridine and pyrazole structure from GBT-440 and the methyl hydroxy moite from VZHE-039 as key structures, and created a hypothetical new drug, a hybrid of VZHE-039 and GBT-440. The pose predicted would allow the drug to interact with the sickled hemoglobin in a 1 to 1 ratio and in an O2-independent manner.https://nsuworks.nova.edu/protein_modeling_reports/1002/thumbnail.jp

Cardiovascular Disease in Dialysis Patients

Cardiovascular disease (CVD) is highly prevalent in the dialysis population, affecting up to 60% of cohorts. Cardiovascular mortality rates are reported to be ~14 per 100 patient-years, which are 10- to 20-fold greater than those of age- and gender-matched controls. CVD is the primary cause of death in up to 40% of dialysis patients in Australia, New Zealand and the United States. Dialysis patients endure a greater burden of both traditional risk factors for CVD and risk factors related to loss of kidney function that may account for the higher CVD morbidity and mortality. Many cardiology guidelines include chronic kidney disease (CKD) and end-stage kidney disease (ESKD) as coronary heart disease (CHD) risk equivalents. It is therefore important for clinicians to both recognise and optimise the cardiovascular health of patients receiving maintenance dialysis. This chapter will focus on risk factor modification, screening and prevention of CVD in dialysis patients

Dissipative Analysis and Synthesis of Control for TS Fuzzy Markovian Jump Neutral Systems

This paper is focused on stochastic stability and strictly dissipative control design for a class of Takagi-Sugeno (TS) fuzzy neutral time delayed control systems with Markovian jumps. The main aim of this paper is to design a strictly dissipative controller such that the closed-loop TS fuzzy control system is stochastically stable, and also the disturbance rejection attenuation is obtained to a given level by means of the H∞ performance index. Intensive analysis is carried out to obtain sufficient conditions for the existence of desired dissipative controller which ensures both the stochastic stability and the strictly dissipative performance. The main advantage of the proposed technique is that it is possible to obtain the dissipative controller with less control effort and also, as special cases, robust H∞ control with the prescribed H∞ performance under given constraints and passivity control can be obtained for the considered systems. Also, the existence condition of the fuzzy dissipative controller can be obtained in terms of linear matrix inequalities. Finally, a practical example based on truck-trailer model is provided to demonstrate the effectiveness and feasibility of the proposed design technique

A coaching program to improve dietary intake of patients with CKD: ENTICE-CKD

The dietary self-management of CKD is challenging. Telehealth interventions may provide an effective delivery method to facilitate sustained dietary change.This pilot, randomized, controlled trial evaluated secondary and exploratory outcomes after a dietitian-led telehealth coaching intervention to improve diet quality in people with stage 3-4 CKD. The intervention group received phone calls every 2 weeks for 3 months (with concurrent, tailored text messages for 3 months), followed by 3 months of tailored text messages without telephone coaching, to encourage a diet consistent with CKD guidelines. The control group received usual care for 3 months, followed by nontailored, educational text messages for 3 months.Eighty participants (64% male), aged 62±12 years, were randomized to the intervention or control group. Telehealth coaching was safe, with no adverse events or changes to serum biochemistry at any time point. At 3 months, the telehealth intervention, compared with the control, had no detectable effect on overall diet quality on the Alternative Health Eating Index (3.2 points, 95% confidence interval, -1.3 to 7.7), nor at 6 months (0.5 points, 95% confidence interval, -4.6 to 5.5). There was no change in clinic BP at any time point in any group. There were significant improvements in several exploratory diet and clinical outcomes, including core food group consumption, vegetable servings, fiber intake, and body weight.Telehealth coaching was safe, but appeared to have no effect on the Alternative Healthy Eating Index or clinic BP. There were clinically significant changes in several exploratory diet and clinical outcomes, which require further investigation.Evaluation of Individualized Telehealth Intensive Coaching to Promote Healthy Eating and Lifestyle in CKD (ENTICE-CKD), ACTRN12616001212448

Outcomes of cinacalcet withdrawal in Australian dialysis patients

Background: Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacalcet. In Australia, cinacalcet was publicly funded for dialysis patients from 2009 to 2015 when funding was withdrawn following publication of the EVOLVE study, which resulted in most patients on cinacalcet ceasing therapy. We examined the clinical and biochemical outcomes associated with this change at Australian renal centres. Methods: We conducted a retrospective study of dialysis patients who ceased cinacalcet after August 2015 in 11 Australian units. Clinical outcomes and changes in biochemical parameters were assessed over a 24‐ and 12‐month period respectively from cessation of cinacalcet. Results: 228 patients were included (17.7% of all dialysis patients from the units). Patients were aged 63±15 years with 182 patients on haemodialysis and 46 on peritoneal dialysis. Over 24 months following cessation of cinacalcet, we observed 26 parathyroidectomies, 3 episodes of calciphylaxis, 8 fractures and 50 deaths. Seven patients recommenced cinacalcet, meeting criteria under a special access scheme. Biochemical changes from baseline to 12 months after cessation included increased levels of serum PTH from 54 (IQR 27‐90) pmol/L to 85 (IQR 41‐139) pmol/L (

Cooperative Communications Based on Deep Learning Using a Recurrent Neural Network in Wireless Communication Networks

In recent years, cooperative communication (CC) technology has emerged as a hotspot for testing wireless communication networks (WCNs), and it will play an important role in the spectrum utilization of future wireless communication systems. Instead of running node transmissions at full capacity, this design will distribute available paths across multiple relay nodes to increase the overall throughput. The modeling WCNs coordination processes, as a recurrent mechanism and recommending a deep learning-based transfer choice, propose a recurrent neural network (RNN) process-based relay selection in this research article. This network is trained according to the joint receiver and transmitter outage likelihood and shared knowledge, and without the use of a model or prior data, the best relay is picked from a set of relay nodes. In this study, we make use of the RNN to do superdimensional (high-layered) processing and increase the rate of learning and also have a neural network (NN) selection testing to study the communication device, find out whether or not it can be used, find out how much the system is capable of, and look at how much energy the network needs. In these simulations, it has been shown that the RNN scheme is more effective on these targets and allows the design to keep converged over a longer period of time. We will compare the accuracy and efficiency of our RNN processed-based relay selection methods with long short-term memory (LSTM), gated recurrent units (GRU), and bidirectional long short-term memory (BLSTM),which are all acronyms for long short-term memory methods

An update on bone imaging and markers in chronic kidney disease

Introduction: Bone disorders in chronic kidney disease ( CKD) are associated with heightened risks of fractures, vascular calcification, poor quality of life and mortality compared to the general population. However, diagnosis and management of these disorders in CKD are complex and appreciably limited by current diagnostic modalities

The impact of fibroblast growth factor-23 on the cardiovascular system in chronic kidney disease

Chronic kidney disease is associated with an accelerated risk of cardiovascular (CV) mortality. Seminal work over the last decade has identified abnormal bone metabolism as an important modulator of the increased CV burden in this cohort. In particular, FGF23, a phosphaturic hormone with serum levels found to be markedly elevated in chronic kidney disease, is independently associated with increased risks of all-cause mortality and CV events. This editorial will discuss the proposed mechanisms linking FGF23 to CV disease in chronic kidney disease, namely, direct cardiac myocyte toxicity, endothelial dysfunction and vascular calcification

Energy Efficiency Maximization In Cognitive Radio Channels Using Modified Water Filling Algorithm

In this paper, we present a novel and computationally efficient water filling algorithm for multiuser in cognitive radio network (CRN). This algorithm is based on the multiuser water filling theorem and persuades the subcarrier allocation for a multiple access system. This approach exaggerates the total bit rate under the constraints of user-individual power budgets. Acquiring Energy Efficiency (EE) is very troublesome for wireless communication systems exclusively for CRN. The analysis here is with the mean EE maximization problem for secondary user (SU) with both primary user (PU) and SUs. The solution to the problem starts by examining both the peak and mean transmit power constraints for the SUs and outage probability constraint for the PUs. The problem here is nontrivial.nbsp The results attestnbsp that the efficiency of the system is enhanced with the proposed water filling algorithm and also it has been observed that the outage probability is reduced. Further, there is enhancementnbsp in the capacity of a MIMO system

Antimicrobial susceptibility, risk factors and prevalence of bla cefotaximase, temoneira, and sulfhydryl variable genes among Escherichia coli in community-acquired pediatric urinary tract infection

INTRODUCTION: The emergence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has become an important challenge among pediatric patients with community-acquired urinary tract infection (UTI). OBJECTIVES: The aim of this study was to assess the antimicrobial susceptibility patterns, associated risk factors and to survey the frequency of bla cefotaximase (CTX-M), bla temoneira (TEM), and bla sulfhydryl variable (SHV) genotypes in ESBL-producing E. coli isolated from children with community-acquired UTI. METHODS: This was a prospective study conducted from November 2012 to March 2016 in a tertiary care center. E. coli isolated in urine cultures from children aged ≤18 years was identified and confirmed for ESBL production. ESBL-positive strains were screened for ESBL encoding genes. Chi-square test and Fisher’s exact test were used to compare the difference in antibiotic susceptibility with respect to ESBL positive and negative, and binary logistic regression was used to identify the risk factors associated with ESBL production. RESULTS: Among 523 E. coli isolates, 196 (37.5%) were ESBL positive, >90% were resistant to cephalosporins, and 56% were resistant to fluoroquinolones. Least resistance was observed for imipenem, netilmicin, and nitrofurantoin (2%, 8.6%, 15.3%). Association between ESBL production and drug resistance was significant for ceftazidime (P < 0.001), cefixime (P < 0.001), cefotaxime (P = 0.010), ceftazidime-clavulanic acid (P < 0.001), levofloxacin (P = 0.037), and gentamicin (P = 0.047) compared to non-ESBL E. coli. CTX-M gene was the most prevalent (87.5%), followed by TEM (68.4%) and SHV (3.1%). Previous history of UTI and intake of antibiotics were the common risk factors. CONCLUSION: ESBL-producing E. coli from community-acquired pediatric UTI carries more than one type of beta-lactamase coding genes correlating their increased antibiotic resistance. Aggressive infection control policy, routine screening for detecting ESBL isolates in clinical samples, and antimicrobial stewardship are the keys to prevent their dissemination in community settings