Fast and Sensitive Real-Time PCR Detection of Major Antiviral-Drug Resistance Mutations in Chronic Hepatitis B Patients by Use of a Predesigned Panel of Locked-Nucleic-Acid TaqMan Probes.

We developed a novel real-time PCR assay that simultaneously evaluates 11 major nucleos(t)ide antiviral (NA) drug resistance mutations (mt) in chronic hepatitis B patients (CHB), including L180M, M204I/V, and V207M (lamivudine [LMV] resistance), N/H238A/T (adefovir [ADF] resistance), which are circulating in Vietnam; and T184G/L, S202I, and M250V (entecavir [ETV] resistance) and A194T (tenofovir resistance), which have been recently reported in several studies across the globe. We detected drug-resistant mt in hepatitis B virus (HBV) samples using our predesigned panel of allele-specific locked-nucleic acid (LNA) probes. Our assay had a high sensitivity of 5% in a low-HBV DNA population of ≥5 × 103 IU/ml and was validated in a cohort of 130 treatment-naive children and 98 NA-experienced adults with CHB. Single-point mt for LMV and ADF resistance were detected in 57.7% and 54.1% of the child and adult samples, respectively, with rtV207M (children, 42.3%; adults, 36.7%) and rtN238T/A (children, 15.4%; adults, 16.3%) being the most frequent mt in these populations. Multiple-point mt, including rtL180M-rtM204V- rtN238A and rtL180M-rtM204I, were identified in only two children, resulting in LMV-ADF resistance and reduced ETV susceptibility. In conclusion, this assay accurately identified the mt profile of children (98.4%) and adults (91.2%) with CHB, which is comparable to established methods. This fast and sensitive screening method can be used for the detection of major NA-resistant mt circulating in developing countries, as well as providing a model for the development of similar mt-detection assays, especially for use in nonhospitalized patients who need their results within half a day, before starting treatment.

Problem solving skills and deficits among homeless veterans with serious mental illness.

Few interventions train homeless consumers in housing-related independent living skills. To inform the development of such interventions for the Department of Veterans Affairs' Supported Housing consumers with serious mental illness, we examined these consumers' problem-solving skills and deficits. We performed semistructured interviews and cognitive tests with 20 consumers who retained housing for ≥1 year ("stayers") and 20 consumers who lost housing in <1 year ("exiters"). Salient types of problems were identified in the qualitative data; we categorized problem-solving approaches by complexity level and identified differences in problem-solving complexity by consumers' housing outcomes. Instrumental (e.g., money management), interpersonal, and health-related problems were prominent in consumers' narratives. Cognition was poor among stayers and exiters. Problem-solving approaches were highly relevant to day-to-day functioning in supported housing. There was a trend toward greater problem-solving complexity in stayers versus exiters. These data explore potential challenges faced in supported housing and help inform the development of a Veterans Affairs-based housing-focused skills training intervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer.

Flowers of the hop plant provide both bitterness and "hoppy" flavor to beer. Hops are, however, both a water and energy intensive crop and vary considerably in essential oil content, making it challenging to achieve a consistent hoppy taste in beer. Here, we report that brewer's yeast can be engineered to biosynthesize aromatic monoterpene molecules that impart hoppy flavor to beer by incorporating recombinant DNA derived from yeast, mint, and basil. Whereas metabolic engineering of biosynthetic pathways is commonly enlisted to maximize product titers, tuning expression of pathway enzymes to affect target production levels of multiple commercially important metabolites without major collateral metabolic changes represents a unique challenge. By applying state-of-the-art engineering techniques and a framework to guide iterative improvement, strains are generated with target performance characteristics. Beers produced using these strains are perceived as hoppier than traditionally hopped beers by a sensory panel in a double-blind tasting.

Chemo-immunotherapy versus chemotherapy in acute myeloid leukemia. Preliminary results.

Since November 1974, 44 patients with acute myeloid leukemia, in first remission were randomized between chemotherapy alone and chemotherapy plus BCG. There were 8 relapses and 7 deaths with chemotherapy, 7 relapses and 3 deaths with chemotherapy plus BCG. The survival of both groups is not, at the time, significantly different.