Heterologous production of (-)-geosmin in Saccharomyces cerevisiae.

(-)-Geosmin has high demand in perfumes and cosmetic products for its earthy congenial aroma. The current production of (-)-geosmin is either by distillation of sun-baked soil or by inefficient chemical synthesis because of the presence of multiple chiral centers. Fermentation processes are not viable as the titers of the Streptomyces sp. based processes are low. This work presents an alternative route by the heterologous synthesis of (-)-geosmin in Saccharomyces cerevisiae. The enzyme involved is the bifunctional geosmin synthase that catalyzes the conversion of farnesyl diphosphate to germacradienol and germacradienol to geosmin. This study evaluated the activity of many orthologs of geosmin synthase when expressed heterologously in S. cerevisiae. When the well-characterized CAB41566 from Streptomyces coelicolor origin was tested, germacradienol and germacrene D were detected but no geosmin. Bioinformatic analysis based on high/low identities to N-terminal and C-terminal domains of CAB41566 was carried out to identify different orthologs of geosmin synthase proteins from different bacterial and fungal origins. ADO68918 of Stigmatella aurantiaca origin showed the best activity among the tested orthologs, not only in terms of geosmin production but also an order of magnitude higher total abundance of the products of geosmin synthase as compared to CAB41566. This study successfully demonstrated the production of (-)-geosmin in S. cerevisiae and offers an alternative, sustainable and environment-friendly approach to producing (-)-geosmin.

Comparison of Healthcare Resource Utilization and Costs between Rivaroxaban and Warfarin for Nonvalvular Atrial Fibrillation in a Skilled Nursing Facility Setting.

BACKGROUND: Use of direct-acting oral anticoagulants for patients with nonvalvular atrial fibrillation (NVAF) in skilled nursing facilities (SNFs) is increasing. Rivaroxaban is commonly used in this setting as an alternative to warfarin, based on comparable or increased efficacy in preventing stroke and a similar or lower risk of major bleeding. OBJECTIVE: The aim of this study was to compare healthcare resource utilization (HCRU) and costs between NVAF patients receiving rivaroxaban or warfarin in SNFs. METHODS: This retrospective study examined de-identified claims from Optum® Clinformatics® Extended Data Mart (1 January 2013-31 December 2017). Eligible patients had an AF diagnosis, were prescribed rivaroxaban or warfarin during an SNF stay, and had one or more such prescriptions filled in the 6 months preceding the stay. Patients were excluded if they received another oral anticoagulant or had evidence of valvular heart disease, mitral stenosis, or organ/tissue transplant. HCRU, mean number of events, and all-cause healthcare costs during the index SNF stay were reported. Results were also reported on a per-patient-per-month (PPPM) basis. Exploratory analyses at different time periods were also conducted. RESULTS: Overall, 4423 rivaroxaban patients and 22,796 warfarin patients were identified prior to inverse probability of treatment weighting adjustment. Index SNF stay was significantly shorter among rivaroxaban-treated patients (35.8 ± 35.8 days) versus warfarin (40.1 ± 46.3 days; p < 0.0001). During the SNF stay, overall HCRU was lower for the rivaroxaban cohort versus the warfarin cohort. All-cause total costs were significantly reduced for rivaroxaban ($6450 ± $10,379) versus warfarin ($7640 ± $16,556; p < 0.0001), and similar results were observed when calculated on a PPPM basis. During the 1-year post-index period, PPPM all-cause total costs were significantly lower with rivaroxaban versus warfarin ($4135 vs. $4561; p < 0.0001). CONCLUSION: In this SNF setting, HCRU and costs were lower among patients with NVAF who were experienced users of rivaroxaban compared with those who were experienced users of warfarin. These findings may help inform clinical decision making to reduce the economic burden of NVAF among older adults in SNFs.

Diagnosis, Treatment, and Prevention of Urinary Tract Infections in Post-Acute and Long-Term Care Settings: A Consensus Statement From AMDA's Infection Advisory Subcommittee.

The diagnosis and management of urinary tract infections (UTIs) among residents of post-acute and long-term care (PALTC) settings remains challenging. Nonspecific symptoms, complex medical conditions, insufficient awareness of diagnostic criteria, and unnecessary urine studies all contribute to the inappropriate diagnosis and treatment of UTIs in PALTC residents. In 2017, the Infection Advisory Subcommittee at AMDA-The Society for Post-Acute and Long-Term Care Medicine convened a workgroup comprised of experts in geriatrics and infectious diseases to review recent literature regarding UTIs in the PALTC population. The workgroup used evidence as well as their collective clinical expertise to develop this consensus statement with the goal of providing comprehensive guidance on the diagnosis, treatment, and prevention of UTIs in PALTC residents. The recommendations acknowledge limitations inherent to providing medical care for frail older adults, practicing within a resource limited setting, and prevention strategies tailored to PALTC populations. In addition, the consensus statement encourages integrating antibiotic stewardship principles into the policies and procedures used by PALTC nursing staff and by prescribing clinicians as they care for residents with a suspected UTI.

Healthcare resource utilization and costs among nonvalvular atrial fibrillation patients initiating rivaroxaban or warfarin in skilled nursing facilities: a retrospective cohort study.

Objective: Atrial fibrillation (AF) is present in up to 17% of patients in skilled nursing facilities (SNFs). This study compared healthcare resource utilization (HRU) and costs between AF patients initiating rivaroxaban or warfarin in SNFs.Methods: Using de-identified claims from Optum Clinformatics Extended Data Mart (1 January 2013 to 31 December 2017), this retrospective cohort study indexed AF patients with first SNF admission during which rivaroxaban or warfarin was initiated within 3 days of admission. To adjust for selection bias, inverse probability of treatment weighting (IPTW) was applied for baseline characteristics. Logistic regression and generalized linear models were used to compare HRU and costs.Results: 519 rivaroxaban and 1129 warfarin patients met inclusion criteria. After IPTW, the cohorts were well balanced for baseline characteristics. The average length of index SNF stay was 32.07 and 37.44 days for rivaroxaban and warfarin patients, respectively. During SNF stay, rivaroxaban patients had 27% lower odds of hospitalization (p < .0001), 2.7 fewer international normalized ratio (INR) tests per-patient-per-month (PPPM; p < .001), and 2.3 fewer pathology/laboratory encounters PPPM (p < .0001) than warfarin patients. All-cause healthcare costs were $2638 lower with rivaroxaban versus warfarin (p < .0001) during the index SNF stay, with lower medical costs (p < .0001) but higher pharmacy costs (p < .0001). Total all-cause healthcare costs 100 days post-index SNF were $8746 lower with rivaroxaban versus warfarin (p < .0001).Conclusions: In the SNF setting, AF patients treated with rivaroxaban had 5-day shorter length of stay, lower HRU, and lower all-cause total and medical costs compared to warfarin, despite higher treatment costs. These findings may help inform clinical decision-making to reduce economic burden.

Improving ethanol yields in sugarcane molasses fermentation by engineering the high osmolarity glycerol pathway while maintaining osmotolerance in Saccharomyces cerevisiae.

The ever-increasing demand of energy has made it imperative to increase the production of renewable fuels like ethanol. Many studies have reported increase in ethanol production by reducing fermentation by-products like glycerol. Deletion of structural genes like gpd1and gpd2 leads to an increase in ethanol by reducing glycerol; however, it makes the yeast osmosensitive that is not desirable for industrial strains. In this study, genes in the HOG pathway which regulates glycerol synthesis in Saccharomyces cerevisiae were targeted for improving ethanol yields in fermentation of sugarcane molasses. Deletion strains of ssk1, hot1, and smp1 were tested and they did not show osmosensitivity. Δssk1 and Δsmp1 recombinant strains showed consistent improved ethanol yields. As a result, a double-deletion strain, Δssk1Δsmp1, was also constructed, which showed a synergistic effect leading to 6% increase in ethanol yield and 35% decrease in glycerol yield. It was also observed that there was a significant decrease in acetic acid yields of all the recombinant strains. Overall, the study demonstrates an industrially viable technique of engineering the HOG pathway resulting in decrease of glycerol and no loss of osmotolerance. These S. cerevisiae strains showed a significant increase in ethanol yields.

Identifying safe practices for use of the urinary leg bag drainage system in the postacute and long-term care setting: An integrative review.

BACKGROUND: In the postacute and long-term care setting, the practice of changing the indwelling urinary catheter large sterile drainage bag to a small-size leg drainage bag is intended to maintain a person's mobility, dignity, and comfort. There is scant evidence that assesses the impact of intermittent use of a leg bag on frequency of urinary tract infection since this breaks the closed urinary drainage system. METHODS: We reviewed research published between 1993 and 2014 for the answers to 20 practice questions developed by experts and long-term care clinicians on the risks and benefits, cleaning, connection, and storage of reusable leg bags. RESULTS: Seventeen of the 26 publications and studies provided varying advice on the risk of breaking the closed system and on practices for changing, disinfecting, and storing leg bags between uses. Thirteen of 20 practice questions were answered by ≥1 publications, few of which were evidence based. CONCLUSIONS: We identified the existence of low-level evidence that leg bags pose no evident, disproportionate risk of infection compared with maintaining a closed system. The lack of uniformity in evidence in the literature suggests aseptic technique should guide practice. Available evidence suggests that aseptic technique should guide practice.

Pneumococcal Vaccination Guidance for Post-Acute and Long-Term Care Settings: Recommendations From AMDA's Infection Advisory Committee.

Efforts at preventing pneumococcal disease are a national health priority, particularly in older adults and especially in post-acute and long-term care settings The Advisory Committee on Immunization Practices recommends that all adults ≥65 years of age, as well as adults 18-64 years of age with specific risk factors, receive both the recently introduced polysaccharide-protein conjugate vaccine against 13 pneumococcal serotypes as well as the polysaccharide vaccine against 23 pneumococcal serotypes. Nursing facility licensure regulations require facilities to assess the pneumococcal vaccination status of each resident, provide education regarding pneumococcal vaccination, and administer the appropriate pneumococcal vaccine when indicated. Sorting out the indications and timing for 13 pneumococcal serotypes and 23 pneumococcal serotypes administration is complex and presents a significant challenge to healthcare providers. Here, we discuss the importance of pneumococcal vaccination for older adults, detail AMDA-The Society for Post-Acute and Long-Term Care Medicine (The Society)'s recommendations for pneumococcal vaccination practice and procedures, and offer guidance to postacute and long-term care providers supporting the development and effective implementation of pneumococcal vaccine policies.

Sliding Scale Insulin vs Basal-Bolus Insulin Therapy in Long-Term Care: A 21-Day Randomized Controlled Trial Comparing Efficacy, Safety and Feasibility.

INTRODUCTION: Sliding scale insulin (SSI) therapy remains a common means of insulin therapy in long-term care (LTC) for the management of type 2 diabetes mellitus, despite current recommendations not supportive of the form of therapy today. Lack of randomized trial data on the efficacy and safety of basal-bolus insulin (B-BI) therapy in nursing home residents may have precluded this form of insulin administration in the LTC setting. Our study is a comparison of the efficacy of SSI (control) and B-BI (intervention) therapies during a 21-day intervention trial in older nursing home residents. METHODS: Fourteen LTC facilities in the US participated; 110 residents with type 2 diabetes volunteered to participate; 35 failed inclusion criteria, 75 signed informed written consent, and 11 were discharged to home/hospital or withdrew consent; data from 64 participants are reported. Recent fasting blood glucose (FBG), hemoglobin A1c, and chemistries were obtained. Four glucose readings (prior to breakfast, lunch, dinner, and bedtime), oral antiglycemic drug, and insulin doses and changes, and all adverse events/serious adverse events, both those related to glucose control [hypoglycemic (<70 mg/dL) and hyperglycemic (>200 mg/dL) episodes] and those unrelated, were recorded daily. Patients were randomized to either remain on SSI or be shifted to the B-BI group. RESULTS: Nursing home residents 80 ± 8 (standard deviation) years, 66% female participated; Control and Intervention participants had similar age, gender, race distributions, comorbidity, and 3-day average pretrial FBG levels (all P > .05). At study end, B-BI volunteers had significantly lower 3-day average FBG levels vs pretrial (P = .0231) while SSI participants had no change in 3-day average FBG (P > .05). During the trial, participants from both groups had similar rates of hypoglycemia, hyperglycemia, other adverse events, and hospitalizations (serious adverse events) unrelated to glucose control (all P > .05). CONCLUSIONS: B-BI therapy produced significantly lower average FBG levels after 21 days compared with SSI therapy; both groups had similar rates of hypo- and hyperglycemia. Switching to B-BI therapy is feasible, safe, and effective in the LTC setting.