Are the physicochemical properties of antibacterial compounds really different from other drugs?

Background: It is now widely recognized that there is an urgent need for new antibacterial drugs, with novel mechanisms of action, to combat the rise of multi-drug resistant bacteria. However, few new compounds are reaching the market. Antibacterial drug discovery projects often succeed in identifying potent molecules in biochemical assays but have been beset by difficulties in obtaining antibacterial activity.

Humanized mice efficiently engrafted with fetal hepatoblasts and syngeneic immune cells develop human monocytes and NK cells.

Background & Aims: Human liver chimeric mice are useful models of human hepatitis virus infection, including hepatitis B and C virus infections. Independently, immunodeficient mice reconstituted with CD34(+) hematopoietic stem cells (HSC) derived from fetal liver reliably develop human T and B lymphocytes. Combining these systems has long been hampered by inefficient liver reconstitution of human fetal hepatoblasts.

Nonalcoholic Fatty Liver Disease and Liver Transplantation.

Nonalcoholic fatty liver disease (NAFLD) is prevalent in the general population and a growing indication for liver transplant. Longer wait times and challenges with pretransplant survivorship are expected, underscoring the need for improved management of attendant comorbidities. Recognition with potential modification of obesity, sarcopenia, chronic kidney disease, and cardiovascular disease in patients with NAFLD may have important implications in the pretransplant and posttransplant periods.

Agreement Between HEDIS Performance Assessments in the VA and Medicare Advantage: Is Quality in the Eye of the Beholder?

Medicare Advantage (MA) plans and the Veterans Affairs (VA) health care system assess quality of care using standardized Healthcare Effectiveness Data and Information Set (HEDIS) performance measures. Little is known, however, about the relative accuracy of quality indicators for persons receiving care in more than one health care system. Among Veterans dually enrolled in an MA plan, we examined the agreement between MA and VA HEDIS assessments.

Protecting the Kidney in Liver Transplant Candidates: Practice-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common in patients awaiting liver transplantation, and both have a marked impact on the perioperative and long-term morbidity and mortality of liver transplant recipients. Consequently, we reviewed the epidemiology of AKI and CKD in patients with end-stage liver disease, highlighted strategies to prevent and manage AKI, evaluated the changing liver transplant waiting list's impact on kidney function, delineated important considerations in simultaneous liver-kidney transplant selection, and projected possible future transplant policy changes and outcomes. This review was assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice and Board of Directors and provides practice-based recommendations for preservation of kidney function in patients with end-stage liver disease.

A nanoporous gold membrane for sensing applications.

Design and fabrication of three-dimensionally structured, gold membranes containing hexagonally close-packed microcavities with nanopores in the base, are described. Our aim is to create a nanoporous structure with localized enhancement of the fluorescence or Raman scattering at, and in the nanopore when excited with light of approximately 600 nm, with a view to provide sensitive detection of biomolecules. A range of geometries of the nanopore integrated into hexagonally close-packed assemblies of gold micro-cavities was first evaluated theoretically.

Liver Transplantation for Alcoholic and Nonalcoholic Fatty Liver Disease: Pretransplant Selection and Posttransplant Management.

Alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease throughout the world. Although they have similar histologic features, a diagnosis of NAFLD requires the absence of significant alcohol use. ALD is seen commonly in patients with a long-standing history of excessive alcohol use, whereas NAFLD is encountered commonly in patients who have developed complications of obesity, such as insulin resistance, hypertension, and dyslipidemia.

Raised Intracellular Calcium Contributes to Ischemia-Induced Depression of Evoked Synaptic Transmission.

Oxygen-glucose deprivation (OGD) leads to depression of evoked synaptic transmission, for which the mechanisms remain unclear. We hypothesized that increased presynaptic [Ca2+]i during transient OGD contributes to the depression of evoked field excitatory postsynaptic potentials (fEPSPs). Additionally, we hypothesized that increased buffering of intracellular calcium would shorten electrophysiological recovery after transient ischemia.

On-treatment HCV RNA in patients with varying degrees of fibrosis and cirrhosis in the SOLAR-1 trial.

Background: In the Phase II SOLAR-1 study, 12 or 24 weeks of ledipasvir/sofosbuvir and ribavirin yielded high sustained virological response rates at 12 weeks (SVR12) in patients with chronic HCV infection and advanced liver disease, including untransplanted patients with decompensated cirrhosis and liver transplant recipients with all stages of liver disease.

Methods: We performed a post hoc analysis using data from this study to investigate associations between baseline characteristics and early on-treatment HCV RNA, and to determine the utility of early virological response (week 2 and 4) to predict SVR12. Serum HCV RNA was quantified using the Roche COBAS Ampliprep/Cobas TaqMan HCV Test, Version 2.

Disposable gold coated pyramidal SERS sensor on the plastic platform.

In this paper we investigate suitability of arrays of gold coated pyramids for surface-enhanced Raman scattering (SERS) sensing applications. Pyramidarrays composed of 1000 nm pit size with 1250 nm pitch lengthwerereplicated on a plastic substrate by roll-to-roll (R2R) ultraviolet (UV) embossing. The level of SERS enhancement, and qualitative performance provided by the new substrate is investigated by comparing Raman spectrum of benzenethiol (BTh) test molecules to the benchmark Klarite SERS substrate which comprises inverted pyramid arrays(1500 nm pit size with 2000 nm pitch length) fabricated on a silicon substrate.

An improved limit on the charge of antihydrogen from stochastic acceleration.

Antimatter continues to intrigue physicists because of its apparent absence in the observable Universe. Current theory requires that matter and antimatter appeared in equal quantities after the Big Bang, but the Standard Model of particle physics offers no quantitative explanation for the apparent disappearance of half the Universe. It has recently become possible to study trapped atoms of antihydrogen to search for possible, as yet unobserved, differences in the physical behaviour of matter and antimatter.

Practice patterns in NAFLD and NASH: real life differs from published guidelines.

Background: Management guidelines from the American Association for the Study of Liver Diseases/American College of Gastroenterology/American Gastroenterology Association published in 2012 for nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) recommend weight loss, vitamin E and pioglitazone as effective therapies for the treatment of biopsy-confirmed NASH. However, little is known about how physicians in the US diagnose NASH or whether published guidelines are being followed.

Methods: We assessed current diagnostic and treatment patterns of the management of NAFLD and NASH among academic gastroenterologists and hepatologists in the US using a standardized survey developed to collect information regarding respondents' practice environments, diagnostic techniques, and medication usage in patients with NAFLD/NASH.

Lipid-Induced Signaling Causes Release of Inflammatory Extracellular Vesicles From Hepatocytes.

Background & Aims: Hepatocyte cellular dysfunction and death induced by lipids and macrophage-associated inflammation are characteristics of nonalcoholic steatohepatitis (NASH). The fatty acid palmitate can activate death receptor 5 (DR5) on hepatocytes, leading to their death, but little is known about how this process contributes to macrophage-associated inflammation. We investigated whether lipid-induced DR5 signaling results in the release of extracellular vesicles (EVs) from hepatocytes, and whether these can induce an inflammatory macrophage phenotype.

Design and fabrication of a 3D-structured gold film with nanopores for local electric field enhancement in the pore.

Three-dimensionally structured gold membrane films with nanopores of defined, periodic geometries are designed and fabricated to provide the spatially localised enhancement of electric fields by manipulation of the plasmons inside nanopores. Square nanopores of different size and orientation relative to the pyramid are considered for films in aqueous and air environments, which allow for control of the position of electric fields within the structure. Designs suitable for use with 780 nm light were created.

A home-based comprehensive care model in patients with Multiple Sclerosis: A study pre-protocol.

Background Disability is prevalent in individuals with multiple sclerosis (MS), leading to difficulty in care access, significant caregiver burden, immense challenges in self-care and great societal burden.  Without highly coordinated, competent and accessible care, individuals living with progressive MS experience psychological distress, poor quality of life, suffer from life-threatening complications, and have frequent but avoidable healthcare utilizations. Unfortunately, current healthcare delivery models present severe limitations in providing easily accessible, patient-centered, coordinated comprehensive care to those with progressive MS.

Bridging the "green gap" of LEDs: giant light output enhancement and directional control of LEDs via embedded nano-void photonic crystals.

Green LEDs do not show the same level of performance as their blue and red cousins, greatly hindering the solid-state lighting development, which is the so-called "green gap". In this work, nano-void photonic crystals (NVPCs) were fabricated to embed within the GaN/InGaN green LEDs by using epitaxial lateral overgrowth (ELO) and nano-sphere lithography techniques. The NVPCs act as an efficient scattering back-reflector to outcouple the guided and downward photons, which not only boost the light extraction efficiency of LEDs with an enhancement of 78% but also collimate the view angle of LEDs from 131.

Hospital Characteristics Associated with Stage II/III Rectal Cancer Guideline Concordant Care: Analysis of Surveillance, Epidemiology and End Results-Medicare Data.

Background: Evidence suggests that high-volume facilities achieve better rectal cancer outcomes.

Methods: Logistic regression was used to evaluate association of facility type with treatment after adjusting for patient demographics, stage, and comorbidities. SEER-Medicare beneficiaries who were diagnosed with stage II/III rectal adenocarcinoma at age ≥66 years from 2005 to 2009 and had Parts A/B Medicare coverage for ≥1 year prediagnosis and postdiagnosis plus a claim for cancer-directed surgery were included.

Comparison of the Structure and Activity of Glycosylated and Aglycosylated Human Carboxylesterase 1.

Human Carboxylesterase 1 (hCES1) is the key liver microsomal enzyme responsible for detoxification and metabolism of a variety of clinical drugs. To analyse the role of the single N-linked glycan on the structure and activity of the enzyme, authentically glycosylated and aglycosylated hCES1, generated by mutating asparagine 79 to glutamine, were produced in human embryonic kidney cells. Purified enzymes were shown to be predominantly trimeric in solution by analytical ultracentrifugation.

Is Travel Time to Colonoscopy Associated With Late-Stage Colorectal Cancer Among Medicare Beneficiaries in Iowa?

Background: Colorectal cancer (CRC) screening has been shown to decrease the incidence of late-stage colorectal cancer, yet a substantial proportion of Americans do not receive screening. Those in rural areas may face barriers to colonoscopy services based on travel time, and previous studies have demonstrated lower screening among rural residents. Our purpose was to assess factors associated with late-stage CRC, and specifically to determine if longer travel time to colonoscopy was associated with late-stage CRC among an insured population in Iowa.

Congenital Methemoglobinemia Type II-Clinical Improvement with Short-Term Methylene Blue Treatment.

We report a case of prophylactic management with methylene blue (MB) in an almost 4-year-old male with congenital methemoglobinemia type II. He has a CYB5R3 compound heterozygote mutation, causing a cytochrome-b(5) reductase deficiency. Since the MB treatment regimen has commenced, his methemoglobin level has been significantly lower.

Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis.

Background: As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase.

Methods: We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks.