Engineering Saccharomyces cerevisiae to produce odd chain-length fatty alcohols.

Fatty aldehydes and alcohols are valuable precursors used in the industrial manufacturing of a myriad of specialty products. Herein, we demonstrate the de novo production of odd chain-length fatty aldehydes and fatty alcohols in Saccharomyces cerevisiae by expressing a novel biosynthetic pathway involving cytosolic thioesterase, rice α-dioxygenase and endogenous aldehyde reductases. We attained production titers of ∼20 mg/l fatty aldehydes and ∼20 mg/l fatty alcohols in shake flask cultures after 48 and 60 h respectively without extensive fine-tuning of metabolic fluxes. In contrast to prior studies which relied on bi-functional fatty acyl-CoA reductase to produce even chain-length fatty alcohols, our biosynthetic route exploits α-oxidation reaction to produce odd chain-length fatty aldehyde intermediates without using NAD(P)H cofactor, thereby conserving cellular resource during the overall synthesis of odd chain-length fatty alcohols. The biosynthetic pathway presented in this study has the potential to enable sustainable and efficient synthesis of fatty acid-derived chemicals from processed biomass.

Thiophene-containing Pechmann dyes and related compounds: synthesis, and experimental and DFT characterisation.

Attaching 2-thienyl residues to the Pechmann dye core chromophore (5,5-exo-dilactone situated around a C-C double bond) results in a novel magenta-coloured compound (UV/Vis spectroscopy λ(max) =570 nm in CHCl(3)), which can be rearranged to a yellow 6,6-endo-dilactone (λ(max) =462 nm in CHCl(3)). Single and double amidation results in pronounced redshift in the 5,5-exo series (violet, λ(max) =570 nm and blue, λ(max) =606 nm in CHCl(3), respectively) but pronounced blueshift in the 6,6-endo series (yellow, λ(max) =424 nm and pale yellow bordering on colourless, λ(max) =395 nm in CHCl(3), respectively). Incorporation of a 3-alkyl substituent on the thiophene ring allows for sharp increase of solubility in organic solvents concomitant with fine-tuning of the colour: a redshift in 5,5-exo-dilactones but a blueshift in 5,5-exo-dilactams. DFT computations demonstrate that both lactone classes are planar regardless of the presence of a 3-alkyl group. The lactam derivatives are non-planar: the thiophene-core chromophore dihedral angles increase on going from 5,5-exo to 6,6-endo and from thiophene to 3-alkyl thiophene. Depending on the core heteroatom (O vs. N-alkyl), ring junction (5,5-exo vs. 6,6-endo) and 3-thiophene substituent (H vs. alkyl), two, three, four or six conformers are possible. All of these conformers were characterised by DFT and were found to be very close in energy at both IEFPCM/B3LYP/DGDZVP and SMD/M06/DGDZVP levels of theory. Within each conformer set, the HOMO and LUMO energies were within 0.05 eV and the predicted λ(max) values (TD-DFT) within 10 nm, and this implies low sensitivity of the optical and electronic properties to conformation. Cyclic voltammetry measurements of selected compounds demonstrated good matching to the HOMO and LUMO energies from IEFPCM/B3LYP/DGDZVP computations. M06-2X was the best DFT functional for TD-DFT, giving predicted λ(max) values within about 20 nm.

Heroin in Malaysia and Singapore.

Clandestine heroin laboratories have been a feature of the Malaysian illicit drug scene since soon after the abuse of heroin emerged in 1972. The first few clandestine heroin laboratories which synthesised heroin via the acetylation of imported morphine were uncovered in 1973 and 1977. By the mid-1980s, this type of laboratory was replaced by heroin-cutting laboratories whereby imported high-grade heroin was cut to street heroin. This was to meet the rising demand for the drug owing to the rapid escalation of the number of drug users. Over the years, the most significant change in the composition of the street heroin is the decrease in its purity from 30%-50% to 3%-5%. Caffeine has remained the major adulterant and chloroquine is detected in virtually all recent seizures.

A new model for end-of-life care in nursing homes.

OBJECTIVES: This study aimed to promote quality end-of-life (EOL) care for nursing home residents, through the establishment of advance care plan (ACP) and introduction of a new care pathway. This pathway bypassed the emergency room (ER) and acute medical wards by facilitating direct clinical admission to an extended-care facility. DESIGN: An audit on a new clinical initiative that entailed the Community Geriatrics Outreach Service, ER, acute medical wards, and an extended-care facility during winter months in Hong Kong. METHODS: The participants were older nursing home residents enrolled in an EOL program. We monitored the ratio of clinical to emergency admissions, ACP compliance rate, average length of stay (ALOS) in both acute hospital and an extended-care facility, and mortality rates. RESULTS: A total of 76 patients were hospitalized from January to March 2013. Of them, 30 (39%) were directly admitted to the extended-care facility, either through the liaison of Community Geriatrics Outreach Service (group A, 19/76, 25%) or transferred from the ER (group B, 11/76, 14%). The remaining 46 patients (group C, 61%) were admitted via the ER to acute medical wards following the usual pathway, followed by transfer to an extended-care facility if indicated. The ACP compliance rate was nearly 100%. In the extended-care unit, groups A and C had similar ALOS of 11.8 and 11.1 days, respectively, whereas group B had a shorter stay of 7.6 days. The ALOS of group C in acute medical wards was 3.5 days. The in-hospital mortality rates were comparable in groups A and C of 26% and 28%, respectively, whereas group B had a lower mortality rate of 18%. CONCLUSIONS: Nearly 40% of EOL patients could be managed entirely in an extended-care setting without compromising the quality of care and survival. A greater number of patients may benefit from the EOL program by improving the collaboration between community outreach services and ER; and extending hours for direct clinical admission to an extended-care facility.

Improving the quality of end-of-life care in long-term care institutions.

PURPOSE: A knowledge transfer program was carried out to improve knowledge in end-of-life care staff at all levels in residential care homes for the elderly, using a model similar to that developed for a non-acute care hospital setting. METHODS: The program consisted of a series of seminars and on-site sharing sessions held in the hospital providing outreach support to residential care homes for the elderly (RCHEs), as well as case discussions in the RCHEs. Evaluation was carried out using a knowledge assessment questionnaire before and after the initiative, as well as recording RCHE staff feedback and in-depth interviews with selected residents and their family members. RESULTS: Knowledge gaps among RCHE staff existed in the areas of mortality relating to chronic diseases, pain and use of analgesics, feeding tubes, dysphagia, sputum management, and attitudes towards end-of-life care issues, which improved after the program. From the qualitative study, RCHE staff highlighted knowledge and service gaps, issues relating to use of feeding tubes and refusal to eat, lack of confidence in managing the dying process, application of Advance Care Plan (ACP) in the RCHE setting, and the need for training in these areas. Residents and family members highlighted the preference for death over suffering, planning for death, misconceptions about life-sustaining treatments and the advance directive (AD) document, and service gaps in advance care planning. CONCLUSION: Considerable knowledge and service gaps exist among staff and residents of RCHEs, which can be improved by the hospital geriatric team providing services to RCHEs.