B‐Type Natriuretic Peptide Levels Predict Ventricular Arrhythmia Post Left Ventricular Assist Device Implantation

B‐type natriuretic peptide (BNP) levels have been shown to predict ventricular arrhythmia (VA) and sudden death in patients with heart failure. We sought to determine whether BNP levels before left ventricular assist device (LVAD) implantation can predict VA post LVAD implantation in advanced heart failure patients. We conducted a retrospective study consisting of patients who underwent LVAD implantation in our institution during the period of May 2009–March 2013. The study was limited to patients receiving a HeartMate II or HeartWare LVAD. Acute myocardial infarction patients were excluded. We compared between the patients who developed VA within 15 days post LVAD implantation to the patients without VA. A total of 85 patients underwent LVAD implantation during the study period. Eleven patients were excluded (five acute MI, four without BNP measurements, and two discharged earlier than 13 days post LVAD implantation). The incidence of VA was 31%, with 91% ventricular tachycardia (VT) and 9% ventricular fibrillation. BNP remained the single most powerful predictor of VA even after adjustment for other borderline significant factors in a multivariate logistic regression model (P < 0.05). BNP levels are a strong predictor of VA post LVAD implantation, surpassing previously described risk factors such as age and VT in the past.     

Development and course of heart failure after a myocardial infarction in younger and older people

Background Acute myocardial infarction （AMI） is a common cause of heart failure （HF）, which can develop soon after AMI and may persist or resolve or develop late. HF after an MI is a major source of mortality. The cumulative incidence, prevalence and resolution of HF after MI in different age groups are poorly described. This study describes the natural history of HF after AMI according to age. Methods Patients with AMI during 1998 were identified from hospital records. HF was defined as treatment of symptoms and signs of HF with loop diuretics and was considered to have resolved if loop diuretic therapy could be stopped without recurrence of symptoms. Patients were cate- gorised into those aged 〈 65 years, 65-75 years, and 〉 75 years. Results Of 896 patients, 311,297 and 288 were aged 〈 65, 65-75 and 〉75 years and of whom 24%, 57% and 82% had died respectively by December 2005. Of these deaths, 24 （8%）, 68 （23%） and 107 （37%） oc- curred during the index admission, many associated with acute HF. A further 37 （12%）, 63 （21%） and 82 （29%） developed HF that persisted until discharge, of whom 15, 44 and 62 subsequently died. After discharge, 53 （24%）, 55 （40%） and 37 （47%） patients developed I-IF for the first time, of whom 26%, 62% and 76% subsequently died. Death was preceded by the development of HF in 35 （70%）, 93 （91%） and 107 （85%） in aged 〈 65 years, 65-75 years and 〉75 years, respectively. Conclusions The risk of developing HF and of dying after an MI in- creases progressively with age. Regardless of age, most deaths after a MI are preceded by the development of HF.     

IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist

The functional role of IL-1 family member 10, recently renamed IL-38, remains unknown. In the present study we aimed to elucidate the biological function of IL-38 and to identify its receptor. Heat-killed Candida albicans was used to stimulate memory T-lymphocyte cytokine production in freshly obtained human peripheral blood mononuclear cells from healthy subjects. The addition of recombinant IL-38 (152 amino acids) inhibited the production of T-cell cytokines IL-22 (37% decrease) and IL-17 (39% decrease). The reduction in IL-22 and IL-17 caused by IL-38 was similar to that caused by the naturally occurring IL-36 receptor antagonist (IL-36Ra) in the same peripheral blood mononuclear cells cultures. IL-8 production induced by IL-36γ was reduced by IL-38 (42% decrease) and also was reduced by IL-36Ra (73% decrease). When human blood monocyte-derived dendritic cells were used, IL-38 as well as IL-36Ra increased LPS-induced IL-6 by twofold. We screened immobilized extracellular domains of each member of the IL-1 receptor family, including the IL-36 receptor (also known as "IL-1 receptor-related protein 2") and observed that IL-38 bound only to the IL-36 receptor, as did IL-36Ra. The dose-response suppression of IL-38 as well as that of IL-36Ra of Candida-induced IL-22 and IL-17 was not that of the classic IL-1 receptor antagonist (anakinra), because low concentrations were optimal for inhibiting IL-22 production, whereas higher concentrations modestly increased IL-22. These data provide evidence that IL-38 binds to the IL-36R, as does IL-36Ra, and that IL-38 and IL-36Ra have similar biological effects on immune cells by engaging the IL-36 receptor.     

The Efficacy of Gabapentin versus Stabilization Splint in Management of Sleep Bruxism

Purpose : This study aimed to determine if the use of gabapentin is more efficacious than a stabilization splint with regard to the intensity of masseter muscle contractions and/or sleep quality for patients experiencing sleep bruxism (SB). Materials and Methods : Twenty patients with SB participated in this clinical study. They were randomly divided into two treatment groups: stabilization splint group (n = 10) and gabapentin group (n = 10). The first polysomnographic examination was performed before the beginning of the experiment for all the participants. At the end of a 2‐month period of stabilization splint therapy or gabapentin usage, a second polysomnographic recording was made. Results : Statistically significant reductions in the number of SB episodes per hour and per night, bruxism time index, total duration of SB episodes per night and number of SB episodes in stages NR I and NR II (p < 0.05) were observed in both groups after treatment. Both treatments significantly reduced the mean intensity of masseter muscle contractions during SB episodes. Moreover, the participants treated with gabapentin showed a significant improvement in total sleep time, slow wave sleep (stage III), and sleep efficiency (p < 0.05). Conclusions : Gabapentin could be an effective treatment modality in SBs, especially in those with poor sleep quality.     

Discovery of 4-(2-(dimethylamino)ethoxy)benzohydrazide derivatives as prospective microtubule affinity regulating kinase 4 inhibitors

Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase, considered as a potential drug target for cancer, diabetes and neurodegenerative diseases. Due to its significant role in the development and progression of cancer, different in-house libraries of synthesized small molecules were screened to identify potential MARK4 inhibitors. A small library of hydrazone compounds showed a considerable binding affinity to MARK4. The selected compounds were further scrutinized using an enzyme inhibition assay and finally two hydrazone derivatives (H4 and H19) were selected that show excellent inhibition (nM range). These compounds have a strong binding affinity for MARK4 and moderate binding with human serum albumin. Anticancer studies were performed on MCF-7 and A549 cells, suggesting H4 and H19 selectively inhibit the growth of cancer cells. The IC₅₀ value of compound H4 and H19 was found to be 27.39 μM and 34.37 μM for MCF-7 cells, while for A549 cells it was 45.24 μM and 61.50 μM, respectively. These compounds inhibited the colonogenic potential of cancer cells and induced apoptosis. Overall findings reflect that hydrazones/hydrazone derivatives could be exploited as potential lead molecules for developing effective anticancer therapies via targeting MARK4.

Inhibition studies of MARK4 with selected hydrazone derivatives.     

Tarlov Cyst and Infertility

Background/Objective: Tarlov cysts or spinal perineurial cysts are uncommon lesions. These are mostly incidental findings on magnetic resonance imaging or myelograms. The objectives of this study were to describe Tarlov cysts of the sacral region as a potential cause for retrograde ejaculations and review available management options.

Methods: Case report and literature review.

Results: A 28-year-old man presented with back pain and retrograde ejaculations resulting in infertility. After microsurgical excision of large perineurial cysts, back pain resolved, but semen quality showed only marginal improvement. Later, the couple successfully conceived by intrauterine insemination. To the best of our knowledge, this is the first reported case of Tarlov cyst associated with retrograde ejaculation and infertility.

Conclusions: Despite being mostly asymptomatic and an incidental finding, Tarlov cyst is an important clinical entity because of its tendency to increase in size with time. Tarlov cysts of the sacral and cauda equina region may be a rare underlying cause in otherwise unexplained retrograde ejaculations and infertility. Microsurgical excision may be a good option in a select group of patients.     

Median nerve compression by a large cephalic vein aneurysm—a case report

The term aneurysm is derived from the Greek word aneurysma, meaning “a widening.” In current vascular surgery practice, an aneurysm is defined as a permanent localized dilatation of any vessel, having at least a 50 % increase in diameter compared with the expected normal diameter (Suggested standards for reporting on arterial aneurysms; Johnston et al., J Vasc Surg, 13: 452–458, 1991). Generally, this term is used for arteries as it is more common in them, but it can also be used for veins which are extremely rare presentation. In our case, a middle-aged female presented with complaints of swelling over the right mid-forearm flexor aspect with difficulty in flexing her wrist and paraesthesia over the right index finger and thumb. The patient was examined and diagnosed as a case of cephalic vein aneurysm compressing the median nerve. She underwent surgical resection of the involved segment of the cephalic vein. Venous aneurysm is a rare disorder and till date only few cases have been reported in English literature; however, its possibility should be kept when dealing with a subcutaneous mass in upper limb.     

Structure modeling and docking study of HCV NS5B-3a RNA polymerase for the identification of potent inhibitors

Homology modeling in combination with molecular docking studies has been applied to predict the binding modes of the Hepatitis C virus (HCV) NS5B-3a inhibitors within the pocket of NS5B polymerase of HCV genotype 3a. Structure modeling and docking using Genetic Optimization for Ligand Docking (GOLD) were carried out to understand the ligand binding properties of NS5B-3a and to identify a potent inhibitor against it. The three-dimensional homology model of Pakistani strain is not available and was built based on the HCV-J4 NS5B polymerase structure. Compound 1 possessing high GOLD fitness score of 62.17 with IC50 value of 0.04 μM was selected as the potent inhibitor. The docking analysis depicted that hydrogen bonding, ionic and hydrophobic interactions contributed significantly for its ligand binding and the amino acid residues Arg442 and His403 seemed to be the anchor residues for receptor recognition. For developing a connection between the experimental bioactivities and GOLD fitness scores, a squared correlation coefficient was calculated and found as acceptable with the value of r ² = 0.67. These findings may act as potent lead in designing effective NS5B-3a inhibitors.