High sustained virologic response rates, regardless of race or socioeconomic class, in patients treated with chronic hepatitis C in community practice using a specialized pharmacy team.

Approved direct-acting antiviral (DAA) regimens against hepatitis C virus (HCV) can cure nearly all patients; however, socioeconomic disparities may impact access and outcome. This study assesses socioeconomic factors, differences in insurance coverage and the drug prior authorization process in HCV-infected patients managed in community practices partnered with a dedicated pharmacy team with expertise in liver disease. This Institutional Review Board-approved, ongoing study captures data on a cohort of 2480 patients from community practices.

Oxidative Stability and Genotoxic Activity of Vegetable Oils Subjected to Accelerated Oxidation and Cooking Conditions.

The oxidative stability and genotoxicity of coconut, rapeseed and grape seed oils were evaluated. Samples were submitted to different treatments: 10 days at 65 °C, 20 days at 65 °C (accelerated storage) and 90 min at 180 °C. Peroxide values and thiobarbituric acid reactive substances values were altered as a function of storage time, but their greatest changes were recorded in samples subjected to 180 °C.

Green, HF-Free Synthesis of MXene Quantum Dots and their Photocatalytic Activity for Hydrogen Evolution.

A general methodology to prepare MXene quantum dots (MxQDs) with yields over 20% by liquid-phase laser ablation of the MAX phase is reported. Mechanical and thermal shock by 532 nm laser pulses (7 ns fwhp, 50 mJ × pulse , 1 Hz pulse frequency) produces MAX etching and exfoliation to form MXene QDs, avoiding the use of HF. The process can be followed by absorption and emission spectroscopy and by dynamic laser scattering and it appears to be general, being applied to Ti AlC , Ti AlC, Nb AlC, and V AlC MAX phases.

Range-wide persistence of the endangered arroyo toad () for 20+ years following a prolonged drought.

Prolonged drought due to climate change has negatively impacted amphibians in southern California, U.S.A.

Real-world observational experience with direct-acting antivirals for hepatitis C: baseline resistance, efficacy, and need for long-term surveillance.

The aim of this study was to obtain real-world, US, observational data on the effect of baseline resistance-associated substitutions (RASs) on achieving sustained virologic response (SVR) in hepatitis C (HCV) patients treated with direct-acting antiviral (DAA) regimens; the need for long-term follow-up in post-SVR patients.It is uncertain if the presence of RASs limits efficacy to DAAs. Once SVR is achieved, society guidelines recommend long-term surveillance for hepatocellular carcinoma in certain patients.

Persistent Taenia solium Cysticercosis In the State of Morelos, Mexico: Human and Porcine Seroprevalence.

Serological tests are needed to estimate the prevalence of Taenia solium cysticercosis in endemic rural areas. The predictive value of serum antibody levels to diagnose porcine cysticercosis and human neurocysticercosis (NC) was herein assessed by ELISA using serum samples from 247 backyard pigs (141 without cysticercosis and 106 with cysticercosis) and 183 human subjects (116 non-NC subjects and 67 NC patients) in central Mexico diagnosed by necropsy and computed tomography, respectively. A sensitivity of 77.

Successional convergence in experimentally disturbed intertidal communities.

Determining the causes of variation in community assembly is a central question in ecology. Analysis of β-diversity can provide insight by relating the extent of regional to local variation in diversity, allowing inference of the relative importance of deterministic versus stochastic processes. We investigated the effects of disturbance timing on community assembly at three distinct regions with varying environmental conditions: Northern Portugal, Azores and Canaries.

Human Metapneumovirus Infection in Chronic Obstructive Pulmonary Disease: Impact of Glucocorticosteroids and Interferon.

Background: Human metapneumovirus (hMPV) infection is implicated in exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Research into the pathogenesis of infection is restricted to animal models, and information about hMPV replication and inflammatory and immune responses in human disease is limited.

Methods: Human primary bronchial epithelial cells (PBECs) from healthy and asthmatic subjects and those with COPD were infected with hMPV, with or without glucocorticosteroid (GCS) exposure.

Gastrointestinal Mucormycosis Resulting in a Catastrophic Outcome in an Immunocompetent Patient.

We present a case of a middle-aged female who was admitted to the hospital with a respiratory infection and subsequently developed an acute surgical abdomen secondary to a perforated viscous. She was found to have mucormycosis of the intestinal tract and eventually succumbed to the sequelae of the infection.

Extended release potassium salts overdose and endoscopic removal of a pharmacobezoar: A case report.

Background: Reported cases of potassium overdoses have shown that this condition could generate several morbidities, mainly related to cardiac dysrhythmias even with fatal outcomes in some cases. Potassium salts in extended release tablets could form pharmacobezoars if a large amount is ingested. In relation to the above, when the patient has a pharmacobezoar, clinical findings may be delayed and may persist.

Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations.

We used CDK4/hTERT-immortalized normal human bronchial epithelial cells (HBEC) from several individuals to study lung cancer pathogenesis by introducing combinations of common lung cancer oncogenic changes (p53, KRAS, and MYC) and followed the stepwise transformation of HBECs to full malignancy. This model showed that: (i) the combination of five genetic alterations (CDK4, hTERT, sh-p53, KRAS(V12), and c-MYC) is sufficient for full tumorigenic conversion of HBECs; (ii) genetically identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation; (iii) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; (iv) high levels of KRAS(V12) are required for full malignant transformation of HBECs, however, prior loss of p53 function is required to prevent oncogene-induced senescence; (v) overexpression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRAS(V12); (vi) growth of parental HBECs in serum-containing medium induces differentiation, whereas growth of oncogenically manipulated HBECs in serum increases in vivo tumorigenicity, decreases tumor latency, produces more undifferentiated tumors, and induces epithelial-to-mesenchymal transition (EMT); (vii) oncogenic transformation of HBECs leads to increased sensitivity to standard chemotherapy doublets; (viii) an mRNA signature derived by comparing tumorigenic versus nontumorigenic clones was predictive of outcome in patients with lung cancer. Collectively, our findings show that this HBEC model system can be used to study the effect of oncogenic mutations, their expression levels, and serum-derived environmental effects in malignant transformation, while also providing clinically translatable applications such as development of prognostic signatures and drug response phenotypes.

Linoleic acid increases adhesion, chemotaxis, granule release, intracellular calcium mobilisation, MAPK phosphorylation and gene expression in bovine neutrophils.

Neutrophils are critical to the innate immune response; therefore, the proper function of neutrophils is critical to avoid the development of certain diseases. Linoleic acid, a polyunsaturated long-chain fatty acid, is one of the most abundant long-chain fatty acids found in the plasma of cows after giving birth. In this study, we evaluated the effects of linoleic acid treatment on bovine neutrophil adhesion, chemotaxis, metalloproteinase (MMP)-9 release, CD11b expression, intracellular calcium mobilisation, mitogen-activating protein kinase (MAPK) phosphorylation and COX-2 and IL-8 expression.

siRNA against the G gene of human metapneumovirus.

Background: Human metapneumovirus (hMPV) is a significant viral respiratory pathogen of infants and children, the elderly and immunocompromised individuals. Disease associated with hMPV infection resembles that of human respiratory syncytial virus (RSV) and includes bronchiolitis and pneumonia. The glycosylated G attachment protein of hMPV is required for viral entry in vivo and has also been identified as an inhibitor of innate immune responses.

Mannose binding lectin is required for alphavirus-induced arthritis/myositis.

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease.

The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling.

Background: Although it is known that stress elevates the levels of pro-inflammatory cytokines and promotes hyper-excitable central conditions, a causal relationship between these two factors has not yet been identified. Recent studies suggest that increases in interleukin 6 (IL-6) levels are specifically associated with stress. We hypothesized that IL-6 acutely and directly induces cortical hyper-excitability by altering the balance between synaptic excitation and inhibition.

Determining the burden of neurological disorders in populations living in tropical areas: who would be questioned? Lessons from a Mexican rural community.

Background: The best approach to determine the burden of neurological disorders in developing countries is to perform population-based studies. Our objectives were to determine the prevalence of neurological disorders in a Mexican rural community and assess the usefulness of a household screening questionnaire.

Methods: The survey took place in a Mexican rural community of Puebla State in Mexico.

Treatment of acute colonic pseudo-obstruction with tegaserod.

Acute colonic pseudo-obstruction is characterized by symptoms, signs and radiologic appearance of large bowel obstruction in the absence of a true mechanical obstruction. Several pharmacologic treatments have been proposed. We present a case of a patient with Guillain-Barré syndrome complicated by acute colonic pseudo-obstruction, who had a clinical response to tegaserod, a partial 5-hydroxytryptamine type-4 agonist.

Cutaneous melanoma metastatic to the eyelid and periocular skin.

Purpose: To report the clinical and histopathologic features in 6 patients with cutaneous melanoma metastatic to the eyelid and periocular skin.

Methods: Clinical records and radiographic features of all consecutive patients treated by the principal investigator between January 2005 and October 2007 with the diagnosis of cutaneous melanoma metastatic to the eyelid and periocular skin.

Results: Six patients ranged in age from 26 to 84 years old (median, 55 years).

H-ras expression in immortalized keratinocytes produces an invasive epithelium in cultured skin equivalents.

Background: Ras proteins affect both proliferation and expression of collagen-degrading enzymes, two important processes in cancer progression. Normal skin architecture is dependent both on the coordinated proliferation and stratification of keratinocytes, as well as the maintenance of a collagen-rich basement membrane. In the present studies we sought to determine whether expression of H-ras in skin keratinocytes would affect these parameters during the establishment and maintenance of an in vitro skin equivalent.

EGFR signaling is required for TGF-beta 1 mediated COX-2 induction in human bronchial epithelial cells.

Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins and thromboxanes from free arachidonic acid. Increasing evidence suggests that COX-2 plays a role in tumorigenesis. A variety of stimuli induce COX-2 and it is overexpressed in many tumors, including non-small cell lung cancer (NSCLC).

Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokers.

Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChR) on bronchial epithelial cells, can regulate cellular proliferation and apoptosis via activating the Akt pathway. Delineation of nAChR subtypes in non-small-cell lung cancers (NSCLC) may provide information for prevention or therapeutic targeting. Expression of nAChR subunit genes in 66 resected primary NSCLCs, 7 histologically non-involved lung tissues, 13 NSCLC cell lines, and 6 human bronchial epithelial cell lines (HBEC) was analyzed with quantitative PCR and microarray analysis.

Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus.

Eosinophils are recruited to the lungs in response to respiratory syncytial virus (RSV) infection; however, their role in promoting antiviral host defense remains unclear. Here, we demonstrate that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after single-stranded RNA (ssRNA) stimulation of the TLR-7-MyD88 pathway, and provide host defense against RSV that is MyD88 dependent. In contrast to wild-type mice, virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice.