Nonalcoholic Fatty Liver Disease: Noninvasive Methods of Diagnosing Hepatic Steatosis

Hepatic steatosis is the buildup of lipids within hepatocytes. It is the simplest stage in nonalcoholic fatty liver disease (NAFLD). It occurs in approximately 30% of the general population and as much as 90% of the obese population in the United States. It may progress to nonalcoholic steatohepatitis, which is a state of hepatocellular inflammation and damage in response to the accumulated fat. Liver biopsy remains the gold standard tool to diagnose and stage NAFLD. However, it comes with the risk of complications ranging from simple pain to life-threatening bleeding. It is also associated with sampling error. For these reasons, a variety of noninvasive radiological markers, including ultrasound, computed tomography, magnetic resonance spectroscopy, and the controlled attenuation parameter using transient elastography and Xenon-133 scan have been proposed to increase our ability to diagnose NAFLD, hence avoiding liver biopsy. The aim of this review is to discuss the utility and accuracy of using available noninvasive diagnostic modalities for fatty liver in NAFLD.     

Improving Emergency Department Door to Doctor Time and Process Reliability: A Successful Implementation of Lean Methodology

The aim of this study is to determine the effectiveness of using lean management methods on improving emergency department door to doctor times at a tertiary care hospital.We performed a before and after study at an academic urban emergency department with 49,000 annual visits after implementing a series of lean driven interventions over a 20 month period. The primary outcome was mean door to doctor time and the secondary outcome was length of stay of both admitted and discharged patients. A convenience sample from the preintervention phase (February 2012) was compared to another from the postintervention phase (mid-October to mid-November 2013). Individual control charts were used to assess process stability.Postintervention there was a statistically significant decrease in the mean door to doctor time measure (40.0 minutes ± 53.44 vs 25.3 minutes ± 15.93 P < 0.001). The postintervention process was more statistically in control with a drop in the upper control limits from 148.8 to 72.9 minutes. Length of stay of both admitted and discharged patients dropped from 2.6 to 2.0 hours and 9.0 to 5.5 hours, respectively. All other variables including emergency department visit daily volumes, hospital occupancy, and left without being seen rates were comparable.Using lean change management techniques can be effective in reducing door to doctor time in the Emergency Department and improving process reliability.     

Bacterial RNA induces myocyte cellular dysfunction through the activation of PKR

Severe sepsis and the ensuing septic shock are serious life threatening conditions. These diseases are triggered by the host's over exuberant systemic response to the infecting pathogen. Several surveillance mechanisms have evolved to discriminate self from foreign RNA and accordingly trigger effective cellular responses to target the pathogenic threats. The RNA-dependent protein kinase (PKR) is a key component of the cytoplasmic RNA sensors involved in the recognition of viral double-stranded RNA (dsRNA). Here, we identify bacterial RNA as a distinct pathogenic pattern recognized by PKR. Our results indicate that natural RNA derived from bacteria directly binds to and activates PKR. We further show that bacterial RNA induces human cardiac myocyte apoptosis and identify the requirement for PKR in mediating this response. In addition to bacterial immunity, the results presented here may also have implications in cardiac pathophysiology.     

Binding of titanium dioxide nanoparticles to lactate dehydrogenase

Objective

Measurement of released lactate dehydrogenase (LDH) activity, a commonly used marker of lethal cell injury in both in vitro and in vivo screenings, has been used to assess the cytotoxicity of nanoparticles (NPs), chemical compounds, and environmental factors. We have recently demonstrated that titanium dioxide (TiO₂) particles bind to several serum proteins. In the present study we investigated the binding of TiO₂ NPs to LDH.

Methods

Purified LDH was incubated with TiO₂ NPs at 37°C for 1 h. The particles were then sedimented by centrifugation, and the activity and quantity of LDH in the supernatant and precipitated fraction were analyzed.

Results

Incubation with TiO₂ reduced the LDH activity in the supernatant in a dose-dependent manner, while LDH activity in the precipitated fraction increased in a dose-dependent manner. Moreover, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed a TiO₂ dose-dependent reduction in the quantity of LDH protein in the supernatant and an increase of LDH in particulate re-suspensions.

Conclusions

These findings, although based on a purified form of LDH, suggest that TiO₂ NPs bind to LDH, and consequently, TiO₂ NP-induced toxicity could be underestimated by the LDH activity assay.     

Underestimating a serving size may lead to increased food consumption when using Canada's Food Guide

It is unclear whether Canadians accurately estimate serving sizes and the number of servings in their diet as intended by Canada's Food Guide (CFG). The objective of this study was to determine if participants can accurately quantify the size of 1 serving and the number of servings consumed per day. White, Black, South Asian, and East Asian adults (n = 145) estimated the quantity of food that constituted 1 CFG serving, and used CFG to estimate the number of servings that they consumed from their 24-h dietary recall. Participants estimated 1 serving size of vegetables and fruit (+43%) and grains (+55%) to be larger than CFG serving sizes (p?≤ 0.05); meat alternatives (-33%) and cheese (-31%) to be smaller than a CFG serving size (p?≤ 0.05); and chicken, carrots, and milk servings accurately (p?> 0.05). Serving size estimates were positively correlated with the amount of food participants regularly consumed at 1 meal (p?< 0.001). From their food records, all ethnicities estimated that they consumed fewer servings of vegetables and fruit (-15%), grains (-28%), and meat and alternatives (-14%) than they actually consumed, and more servings of milk and alternatives (+26%, p?≤ 0.05) than they actually consumed. Consequently, 68% of participants believed they needed to increase consumption by greater than 200?kcal to meet CFG recommendations. In conclusion, estimating serving sizes to be larger than what is defined by CFG may inadvertently lead to estimating that fewer servings were consumed and overeating if Canadians follow CFG recommendations without guidance. Thus, revision to CFG or greater public education regarding the dietary guidelines is warranted.     

Integration of evidence based medicine into the clinical years of a medical curriculum

Teaching Evidence Based Medicine (EBM) helps medical students to develop their decision making skills based on current best evidence, especially when it is taught in a clinical context. Few medical schools integrate Evidence Based Medicine into undergraduate curriculum, and those who do so, do it at the academic years only as a standalone (classroom) teaching but not at the clinical years. The College of Medicine at King Saud bin Abdulaziz University for Health Sciences was established in January 2004. The college adopted a four-year Problem Based Learning web-based curriculum. The objective of this paper is to present our experience in the integration of the EBM in the clinical phase of the medical curriculum. We teach EBM in 3 steps: first step is teaching EBM concepts and principles, second is teaching the appraisal and search skills, and the last step is teaching it in clinical rotations. Teaching EBM at clinical years consists of 4 student-centered tutorials. In conclusion, EBM may be taught in a systematic, patient centered approach at clinical rounds. This paper could serve as a model of Evidence Based Medicine integration into the clinical phase of a medical curriculum.     

5α-Reductase deficiency in patients with micropenis

The enzyme 5-reductase (5R), by virtue of its peripheral 5-reduction of testosterone (T) to dihydrotestosterone (DHT), is believed to play a major role in the differentiation and the subsequent growth of the penis. However, recent studies have reported 5R deficiency (5RD) in patients with isolated micropenis and hypothesized that 5RD is not invariably associated with genital ambiguity. In Egypt, 5RD has been reported frequently among intersex patients. The aim of this study was to assess the role of 5RD in the development of micropenis among Egyptian patients with abnormal sexual development. The study included 29 patients who were categorized into three groups (isolated micropenis, 9 patients; microphallus with genital ambiguity, 11 patients; genital ambiguity with normal-sized phallus, 9 patients). Activity of 5R was assessed by estimating T/DHT ratios in the basal state in pubertal subjects and following human chorionic gonadotropin (HCG) stimulation test in prepubertals.The results showed that the incidence of 5RD was much higher in cases of ambiguous genitalia with micropenis (5 families out of 10, 50%) than in those with isolated microphallus (1/9, 11·1%) or those with ambiguous genitalia and normal-sized phallus (1/8, 12.5%). In conclusion, the study showed that isolated micropenis is a heterogeneous disorder and that 5RD, despite its relative prevalence in Egypt, has a minimal role in the aetiology. On the other hand, 5RD seems to correlate with penile length in intersex cases.