Asymptomatic bacteriuria (ASB) poses a serious health problem to pregnant women and fetuses. However, in most developing countries, routine screening for ASB and antimicrobial sensitivity test are rarely performed. This study, therefore, aimed to determine the best diagnostic method for routine screening of ASB and antimicrobial susceptibility pattern among pregnant women attending an antenatal clinic in the Ashanti Region of Ghana.

Urine samples from 412 pregnant women between the ages of 16 and 45 years-old attending antenatal clinic at Anglogold Ashanti Health Foundation Hospital and Ellolab Diagnostic Centre were screened for ASB by microscopy, dipstick urinalysis and bacteria culture. Susceptibility of the positive isolates were assessed against commonly used antimicrobial agents, adopting the disc diffusion test method.

Of the 412 pregnant women screened, 72 tested positive for ASB by the urine culture method, which translates into an overall prevalence of 17.5%. There was no association between age, marital status, occupation, parity, educational background nor duration of pregnancy with ASB (p > 0.05). Additionally, dipstick urinalysis was found to be a better diagnostic method than microscopy. The most isolated bacteria were Escherichia coli (62.5%) and Klebsiella pneumoniae (30.6%), and nitrofurantoin and nalidixic acid were the most effective antimicrobial agents.

Routine urine culture and antimicrobial susceptibility test should be carried out on all pregnant women attending antenatal clinic to detect possible ASB and prescribe appropriate drugs, such as nitrofurantoin and nalidixic acid, to prevent any related complications. However, in health centers that lack bacterial culture facilities, dipstick urinalysis should be the preferred screening option.

Regional anesthesia is the preferred modality for obstetric patients undergoing cesarean section due to the risks associated with general anesthesia in pregnant women. Single-shot spinal anesthesia is usually administered, which may be associated with post-block maternal hypotension, despite adequate intravenous fluid therapy. This is deleterious for the uteroplacental circulation, leading to poor outcomes in both the mother and fetus. There are several vasopressors which are used for treatment of these hypotensive episodes. Mephentermine is a sympathomimetic, having both direct and indirect actions. It has many side effects, however, including increased risks of arrhythmias, hypertension, central nervous system stimulation and abuse potential. Yet, it is still used in many developing countries, due to low cost and easy availability. We hereby report a case of rhythm disturbance with missed beats following use of mephentermine to counter hypotension after spinal anesthesia for cesarean section. The rhythm disturbance had a spontaneous resolution, with the patient maintaining hemodynamic stability during and after the episode.

Electromagnetic fields have been evaluated in multiple environments as a source of incidental exposure as well as a therapeutic treatment modality. At low levels and in specific therapies, electromagnetic fields have been found to be safe and may have positive effects on human physiology that improve disease course or alter the severity of some ailments. We conducted a study to investigate whether a commercial Federal Drug Administration-approved electromagnetic field generator device used for stress reduction and relaxation has the capability to impart a measurable impact on the cardiac autonomic nervous system.

This study was designed as a randomized double-blind, sham-stimulation controlled study in healthy subjects. The stimulation or treatment was the application of parasympathetic-targeted electromagnetic fields through the Federal Drug Administration-approved Resonator® device for 60 m. The primary measurements of treatment effect were heart rate variability (measured at baseline and every 15 m) and salivary cortisol (pre- and postapplication). The active treatment consisted of two sessions, 60 m in duration. The electromagnetic field algorithm applied was A160 (3.1 × 10−8 to 3.2 × 10−8 Gauss, frequency range of 0.857–0.859 Hz). All participants received both a sham and an active treatment session, the order of which was randomized.

A total of 28 patients completed both sessions. The measured difference in cortisol between the groups was not statistically significant (p = 0.66). There was a trend towards decreased cortisol levels over time in both groups (p = 0.09 for time trend). Measured heart rate variability showed a nonsignificant reduction in low frequency to high frequency ratio (low frequency/high frequency) at 60 m.

While the results were nonsignificant, the trend towards a reduction in low frequency/high frequency is suggestive of a delayed electromagnetic field effect. This study is hypothesis-generating since additional research is needed to either adjust the electromagnetic field treatment dose/duration during sessions or delay the final data collection of heart rate variability and salivary cortisol until hours after the active treatment.

Malaria and tuberculosis remain endemic in tropical regions and most often coexist, increasing the burden of malaria mortality due to unintended interactions of the co-administered drugs employed in the management of the infections. Rifampicin (RIF) and amodiaquine (ADQ) are likely to be administered concurrently in the treatment of patients with tuberculosis and malaria. The metabolism of ADQ is mediated principally by CYP2C8, while RIF is a known inducer of this enzyme. This study, therefore, investigated the effect of RIF on the disposition of ADQ, a major partner drug in the first-line treatment against uncomplicated malaria in line with the World Health Organization recommendations.

Sixteen healthy volunteers received oral 150 mg dose of RIF daily for 5 days with or without oral 600 mg single dose of ADQ on the fifth day (5th dose) with a 4-week wash out period, in a crossover fashion. Blood samples were collected at predetermined time intervals of 0, 1, 2, 4, 6, 8, 12, 24, 36 and 48 h. Plasma samples were analyzed for ADQ and its major metabolite desethylamodiaquine using a validated RP-high-performance liquid chromatography. Pharmacokinetic parameters were obtained using appropriate software and subjected to appropriate statistical analysis.

Coadministration of ADQ and RIF resulted in significant decreases in the critical pharmacokinetic parameters of ADQ, such as area under the curve (AUC0–∞) of about 66%, time to peak plasma concentration (Tmax) of about 10%, maximum plasma concentration of about 44%, and elimination half-life of about 55%, while the AUC0–∞ and Tmax of the main metabolite desethylamodiaquine increased about 2-fold and 3-fold respectively during the coadministration of RIF with ADQ. The metabolic ratio increased significantly, from 1.55 to 2.68. The AUC0–∞ and Tmax of the drug ADQ, as well as the maximum concentration of both the drug and its metabolite fell outside the point of estimates of the test/reference ratio of the geometric means of 80–125% of bioequivalence range.

An interaction was established during coadministration of RIF and ADQ, confirming RIF as a strong inducer of CYP2C8 in vivo, which may lead to malaria therapeutic failure or adverse drug reactions with ADQ and contribute to the rate at which resistance to ADQ develops.

Sterol regulator element binding proteins (SREBPs) are a family of transcription factors involved in the biogenesis of cholesterol, fatty acids and triglycerides. They also regulate physiological functions of many organs, such as thyroid, brain, heart, pancreas and hormone synthesis. Beside the physiological effects, SREBPs participate in some pathological processes, diabetes, endoplasmic reticulum stress, atherosclerosis and chronic kidney disease associated with SREBP expression changes. In the liver, SREBPs are involved in the pathogenesis of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatitis and hepatic cancer. There are several SREBP inhibitors that have potential for treating obesity, diabetes and cancer. This review assesses the recent findings about the roles of SREBPs in the physiology of organs’ function and pathogenesis of liver diseases.

Syphilitic hepatitis in adults is not frequently found in the population and is easily misdiagnosed. The incidence of viral hepatitis is increasing year by year, concomitantly increasing the importance of obtaining a systematic understanding of the clinical features and treatment strategies for this disease. There is, however, a lack of published definitive data regarding the clinical characteristics, diagnosis and standard treatment options for this disease. Searches were made using the MEDLINE database of PubMed and OVID for syphilitic hepatitis publications from 1951 to 2017 in an attempt to analyze and summarize the clinical characteristics.

Despite significant improvements in outcomes after liver transplantation, many patients continue to die on the waiting list, while awaiting an available organ for transplantation. Organ shortage is not only due to an inadequate number of available organs, but also the inability to adequately assess and evaluate these organs prior to transplantation. Over the last few decades, ex-vivo perfusion of the liver has emerged as a useful technique for both improved organ preservation and assessment of organs prior to transplantation. Large animal studies have shown the superiority of ex-vivo perfusion over cold static storage. However, these studies have not, necessarily, been translatable to human livers. Small animal studies have been essential in understanding and improving this technology. Similarly, these results have yet to be translated into clinical use. A few Phase 1 clinical trials have shown promise and confirmed the viability of this technology. However, more robust studies are needed before ex-vivo liver perfusion can be widely accepted as the new clinical standard of organ preservation. Here, we aimed to review all relevant large and small animal research, as well as human liver studies on normothermic ex-vivo perfusion, and to identify areas of deficiency and opportunities for future research endeavors.

Background and Aims: Sustained virologic response is evaluated by single-step reverse transcription (SRT) PCR assay, which assesses hepatitis C virus (HCV) clearance from plasma but not from tissues such as peripheral blood mononuclear cells (PBMCs). Persistence of HCV RNA in PBMCs beyond end of treatment (EOT) is associated with nonresponse. Our goal was to measure intra-PBMC HCV RNA levels during oral antiviral therapy according to the HCV therapy follow-up fractionation (CTF2) protocol.

Methods: Compensated chronic HCV patients (n = 2 78 SRT-PCR positive) were scheduled to receive oral antiviral therapy. Subjects were followed-up by SRT and intra-PBMCs HCV RNA PCR at the end of the 2nd, 6th, 10th, 14th, 18th and 24th weeks to evaluate virus clearance from plasma and PBMCs, respectively. The CTF2 protocol evaluated SRT and PBMC PCR status at each follow-up point for determining therapy continuation or interruption to address cost effectiveness.

Results: All patients tested negative by SRT PCR after therapy for 2 weeks. Application of the CTF2 protocol revealed: a) increasing HCV clearance rate from 75.9% at the end of 10th week to 90.3% at the end of 24th week (p < 0.00001); b) faster clearance of HCV from plasma compared to PBMCs at each point of follow-up until the 18th week (p < 0.05); c) higher viral elimination rates diagnosed by PBMC HCV RNA PCR(−) compared to PBMC HCV RNA PCR(+) from the 6th to 24th week of treatment (p < 0.0001); d) higher over-time increase curve of combined plasma and PBMC HCV RNA determined negativity compared to the decline in positivity curves by PBMC PCR at the 6th-18th week compared to the 24th week (p < 0.01)—these results validated treatment continuation; and e) solitary evaluation of EOT sustained HCV infection and relapses by PBMC HCV RNA (p < 0.001).

Conclusions: Early elimination of serum and tissue (PBMC) HCV infection by oral antiviral therapy can be achieved and evaluated during a cost-effective CTF2 protocol application.

Long QT syndrome (LQTS) is a rare primary cardiac electrophysiological disorder with characteristic symptoms of syncope, tachyarrhythmia and torsades-de-pointes. It is the outcome of mutations in genes encoding ion channels that function as voltage regulators. Heat shock protein (HSP) 90 is a molecular chaperone that plays vital roles in a variety of cellular processes, one of which is folding of nascent polypeptide chains into their native forms. The main objective of this study was to screen for HSP90 Q488H (C > G) polymorphism in patients with LQTS and identify its risk towards LQTS manifestation.

Allele-specific PCR was employed to genotype 49 LQTS patients, 71 first-degree relatives (FDRs) and 219 controls for the HSP90 Q488H polymorphism. The genotypes were statistically evaluated to assess their association with the risk of LQTS. Further, bioinformatic analysis was performed to validate the statistical findings.

Genotyping and statistical evaluation revealed a significant association of the CG genotype with LQTS, pointing towards a heterozygote disadvantage in the patients. The GG and CG genotypes showed a significant association with LQTS in the FDRs. Secondary pre-mRNA structure of the variant allele ‘G’ was found to be more stable than the wild-type structure.

Individuals harboring the heterozygous “CG” genotype are at increased risk for LQTS. In the FDRs, especially, the females harboring the “CG” and “GG” genotypes could transmit the risk allele to the future generation, giving rise to a disadvantage towards LQTS. It is imperative that all FDRs undergo carrier detection and/or prenatal diagnosis to prevent the recurrence of dominant-negative effect leading to sudden cardiac death events among the current and future generations.

The present study deals with a computational model of the transport and retention of drug within the arterial wall eluted from a drug-eluting stent, to enhance our understanding of the performance of this device. We considered a two-species model (free and bound) incorporating a reversible reaction to describe drug interactions with the constituents of the arterial wall. An axisymmetric model of drug delivery from a pair of stent struts has been developed, where the transport of free drug is modelled as an unsteady reaction-diffusion process, while the bound drug, assuming complete immobilization in the tissue, is modeled as an unsteady reaction process. The model also took into account a second-order binding process that describes a saturating reversible binding and time-dependent release kinetics of the drug-eluting stent. Considering that diffusion takes place over a tortuous path in a porous media, the effects of porosity and tortuosity on diffusion cannot be ruled out from this present investigation.

An explicit finite-difference scheme is leveraged to tackle numerically the governing equations of motion, together with the physiologically realistic boundary conditions.

The quantitative effects of significant factors, such as Peclet number (PeT), Damköhler number (Da), tortuosity, porosity, interstrut distance and time-dependent release kinetics of drug-eluting stent, on the distribution and retention of drug are determined graphically.

Predicted results are consistent with several existing results in the literature, which certainly validates the applicability of the model considered.

The CYP2C19*2 allele is associated with reduced clopidogrel bioactivation, increasing the risk of complications after percutaneous coronary intervention (PCI), particularly stent thrombosis. Recently published data suggests that CYP2C19*2 allele carriers have a higher risk for in-stent restenosis (ISR) after endovascular treatment. Very few studies have investigated the relationship between CYP2C19*2 and coronary ISR, with no significant association reported. The objective of this study was to assess the relationship between CYP2C19*2 allele carrier status and coronary ISR.

Patients with previous PCI with stenting and who were scheduled for elective PCI after coronary angiogram were recruited from the cardiac catheterization suite over a 12-month period. The angiography report of each patient was perused to identify patients requiring PCI due to ISR. For patients with angiography-confirmed ISR, date of previous PCI to the restenosed stent was noted. CYP2C19*2 genotyping was undertaken using a TaqMan® Drug Metabolism assay. The association between CYP2C19*2 allele carrier status and incidence of coronary ISR within 1 year was assessed using Fisher’s exact test (p < 0.05 significance) and by calculating the odds ratio (OR) with a 95% confidence interval (CI).

Of the 82 patients with previous PCI, 29 (35.4%) had angiography-confirmed ISR (12 carriers, 17 non-carriers of CYP2C19*2). In 13 (44.8%) of these patients, the restenosed stent was deployed within 1 year and the patients were on clopidogrel therapy at the time of repeat PCI (8 carriers, 5 non-carriers of CYP2C19*2). The association between CYP2C19*2 allele carrier status and ISR within 1 year was not statistically significant (Fisher’s exact p = 0.067; OR: 4.80, 95% CI: 0.98–23.54, p = 0.053).

Despite a higher proportion of CYP2C19*2 allele carriers exhibiting ISR within 1 year compared to non-carriers, the association was not statistically significant. This result may be attributed to the small sample size, and larger prospective studies are recommended to further assess this association.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide. Curative resection is frequently limited in Hong Kong by hepatitis B virus-related cirrhosis, and liver transplantation is the treatment of choice. Liver transplantation has been shown to produce superior oncological benefits, when compared to hepatectomy for HCC. New developments in the context of patient selection criteria, modification of organ allocation, bridging therapy, salvage liver transplantation and pharmaceutical breakthrough have improved the survival of HCC patients. In this article, we will share our experience in transplanting hepatitis B virus-related HCC patients in Hong Kong and discuss the recent progress in several areas of liver transplantation.

Since the beginning of the century, viral infection has become a widespread problem to public health globally. Recently, the latest newcomer of the Flaviviridae family, the Zika virus, has emerged as a potential global threat to human health. Due to lack of sufficient data at present, Zika infection has become a major cause of Zika fever, central nervous system malformations such as microcephaly, severe neuroimmunopathology, fetal abnormalities, and recently Guillain-Barre syndrome. The lack of genomic as well as proteomic information keeps the Zika virus under examination by a multitude of researchers. The rapid increase in Zika viral infections has been classified as a public health emergency by the World Health Organization. Neither preventive antiviral drugs nor effective vaccines are available on the market for combating Zika infection. Urgent innovative research is necessary to facilitate the development of protective and fruitful therapeutic agents, to improve lifespan of individuals throughout the world. Thus, we present this review to summarize the current research findings for Zika viral infection and to highlight the importance of computational drug discovery in the development of potent antiviral inhibitors against the Zika virus. We also anticipate that the information in this review will present a valuable opportunity for the prediction of efficient novel therapeutic remedies for controlling Zika.

Spontaneous or intended conversion of atrial fibrillation (AF) to sinus rhythm is associated with a short-term increase from baseline risk of clinical thromboembolism. Guidelines suggest performing cardioversion without prior execution of trans esophageal echo (TEE) if the patient has completed a month of anticoagulation with warfarin (in the therapeutic international normalized ratio range) or non-vitamin K antagonist oral anticoagulants (NOACs).

We performed TEE echo in 100 consecutive patients taking NOACs or warfarin for 1 month or more, to see if there was evidence of left arterial appendage thrombi or extremely low flow velocity (<40 cm/s) that can increase risk of ischemic events after cardioversion.

Even in patients with correct anticoagulation therapy, thrombi can be found in the left atrial appendage. For this reason, until further data are present, we suggest executing TEE before direct current cardioversion. Moreover, NOAC was shown to be safe for use before cardioversion. The only exception was with rivaroxaban, so we suggest further analysis with larger samples to determine the mechanisms underlying this finding.

Even if cardioversion can be performed without prior TEE after 1 month of anticoagulation therapy, we think that (except in patients with very low risk of thrombosis) it is preferable to execute this exam before trying to restore sinus rhythm.

Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

Tight junction and cell polarity proteins are paramount to epithelial cell polarity and transport. In vivo studies have shown the differential expression of tight junctions in colorectal cancer, with little to no human data to corroborate those findings. We investigated whether tight junction genes were differentially expressed in human colon cancer versus normal controls.

Total RNA was extracted from fresh frozen tumor tissues and normal adjacent tissues of 6 patients who were diagnosed with primary colon cancer as well as from normal mucosa of 5 unrelated polyp-free individuals. We used the Qiagen RT2 Profiler PCR array to determine the expression of 84 genes in the tight junction pathway. Student’s t-test was used to compare gene expression levels between cancer tissues and normal mucosa using normalized gene expression data.

Compared with normal mucosa, significant up-regulation of the claudin 1 (CLDN1) gene (fold-change = 16, p = 0.001) but down-regulation of the AMOTL1, CLDN5, JAM2 and TIAM1 genes (fold-change > 2, p < 0.05) were seen in colon cancer tissue.

We observed the differential expression of CLDN, AMOTL1, JAM2 and TIAM1 in colon cancer versus normal mucosa. Further larger studies are warranted to investigate the role of tight junction and cell polarity proteins in the progression of human colon tumors.