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Aims The aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery. Patients and Methods A single-centre, interventional, two arm, parallel group randomised controlled trial was undertaken, involving 407 patients who underwent elective spinal surgery. For 203 patients, the skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). The primary outcome measure was contamination of the wound determined by aerobic and anaerobic bacterial growth from samples taken after disinfection. Results The detection of viable bacteria in any one of the samples taken after disinfection (culture-positive) was significantly lower in the group treated with both PVI and CHG than in the group treated with PVI alone (59 (29.1%) versus 85 (41.7%), p = 0.009; odds ratio 0.574; 95% confidence interval, 0.380 to 0.866). Conclusions Antisepsis of the skin with the sequential application of PVI and CHG more effectively reduces the contamination of a surgical wound than PVI alone. Cite this article: Bone Joint J 2017;99-B:1354–65.

Abstract As the part of a study to develop buparvaquone (BPQ) formulations for the treatment of cutaneous leishmaniasis, the topical delivery of BPQ and one of its prodrugs from a range of formulations was evaluated. In previous studies, BPQ and its prodrugs were shown to be potent antileishmanials in-vitro, with ED50 values in the nanomolar range. 3-Phosphono-oxymethyl-buparvaquone (3-POM-BPQ) was the most potent antileishmanial and was chosen, together with the parent drug, for further investigation. The ability of the parent and prodrug formulations to cross human and murine skin was tested in-vitro using the Franz diffusion cells. Formulations intended for topical application containing either BPQ or 3-POM-BPQ were developed using excipients that were either acceptable for topical use (GRAS or FDA inactive ingredients) or currently going through the regulatory process. BPQ was shown to penetrate both human epidermal membranes and full thickness BALB/c skin from a range of formulations (gels, emulsions). Similarly, 3-POM-BPQ penetrated full-thickness BALB/c skin from several gel formulations. In-vitro binding studies showed that BPQ bound melanin in a dose-dependent manner and preferably bound to delipidized skin over untreated BALB/c skin (on a weight to weight basis). The results confirm that BPQ and its prodrug 3-POM-BPQ can penetrate the skin from several formulations, making them potentially interesting candidates for further investigation of topical formulations using in-vivo models of cutaneous leishmaniasis.

Cholesta-5,7,9(11)-trien-3β-ol and its oleate ester were incorporated into human low-density lipoprotein and reconstituted high-density lipoprotein. The unesterified sterol was more efficient than its ester in quenching tryptophan fluorescence, especially in low-density lipoprotein. The results, which indicate that in such lipoproteins unesterified sterols are more closely associated with peptide than are esterified sterols, are used to assess possible structures for the lipoproteins.

Abstract: Five groups of NMRI mice were fed ethanol or sucrose in a nutritionally adequate liquid diet for 9 days. The dietary fat consisted of olive oil with the fatty acid composition 18:1 77%, 18:2 10%, 18:0 and 16:0 12%. The ethanol treated groups received 5% w/v ethanol (E) or isocaloric sucrose (S). Two groups (S‐ and E‐) received the diet without supplement. In two groups (S+ and E +) 7% of the fat was exchanged for arachidonic acid (20:4). In a fifth group (IE +) treated with ethanol and arachidonic acid the diet also contained indomethacin (10 mg/1). The mean intake of ethanol was about 20 g/kg/day. After 9 days animals were killed and liver lipids analyzed after Folch extraction. The post mortem accumulation of prostaglandin E2 in the kidney was measured by GC‐MS. Dietary 20:4 was found to protect mice against fatty liver caused both by a high fat diet alone and in combination with ethanol. The liver triglycerides were 30.7 + 4.3 (S ‐), 46.1+6.9 (E ‐), 6.8 + 0.4 (S +) and 19.4 ±1.8 (E +). Prostaglandin levels in the kidney were depressed by ethanol treatment. Indomethacin gave variable degrees of PG synthesis inhibition. The degree of liver triglyceride accumulation in the IE+ group was inversely propotional to the degree of PG synthesis. The data suggest a role for liver 20:4 cyclooxyganase metabolites in fatty liver caused by high fat diets and ethanol.

Abstract Background Polylactic acid (PLA), a biodegradable polymer, has the potential to replace (at least partially) traditional petroleum-based plastics, minimizing “white pollution”. However, cost-effective production of optically pure L-lactic acid is needed to achieve the full potential of PLA. Currently, starch-based glucose is used for L-lactic acid fermentation by lactic acid bacteria. Due to its competition with food resources, an alternative non-food substrate such as cellulosic biomass is needed for L-lactic acid fermentation. Nevertheless, the substrate (sugar stream) derived from cellulosic biomass contains significant amounts of xylose, which is unfermentable by most lactic acid bacteria. However, the microorganisms that do ferment xylose usually carry out heterolactic acid fermentation. As a result, an alternative strain should be developed for homofermentative production of optically pure L-lactic acid using cellulosic biomass. Results In this study, an ethanologenic Escherichia coli strain, SZ470 (ΔfrdBC ΔldhA ΔackA ΔpflB ΔpdhR ::pflBp6-acEF-lpd ΔmgsA), was reengineered for homofermentative production of L-lactic acid from xylose (1.2 mole xylose = > 2 mole L-lactic acid), by deleting the alcohol dehydrogenase gene (adhE) and integrating the L-lactate dehydrogenase gene (ldhL) of Pediococcus acidilactici. The resulting strain, WL203, was metabolically evolved further through serial transfers in screw-cap tubes containing xylose, resulting in the strain WL204 with improved anaerobic cell growth. When tested in 70 g L-1 xylose fermentation (complex medium), WL204 produced 62 g L-1 L-lactic acid, with a maximum production rate of 1.631 g L-1 h-1 and a yield of 97% based on xylose metabolized. HPLC analysis using a chiral column showed that an L-lactic acid optical purity of 99.5% was achieved by WL204. Conclusions These results demonstrated that WL204 has the potential for homofermentative production of L-lactic acid using cellulosic biomass derived substrates, which contain a significant amount of xylose.

In 2015, an estimated 429,000 deaths and 212 million cases of malaria occurred worldwide, while 70% of the deaths occurred in children under five years old. Changes in climatic exposure such as temperature and precipitation makes malaria one of the most climate sensitive outcomes. Using a global malaria mortality dataset for 105 countries between 1980 and 2010, we estimate that the global optimal temperature maximizing all-age malaria mortality is 20.6, lower than previously predicted in the literature. While in the case of child mortality, a significantly lower optimum temperature of 19.3° is estimated. Our results also suggest that in Africa and Asia, the continents where malaria is most prevalent malaria, mortality is maximized at 28.4 and 26.3, respectively. Furthermore, we estimate that child mortality (ages 0-4) is likely to increase by up to 20 percent in some areas due to climate change by the end of the 21st century.

AbstractObjectives:  Little is known about the clinical significance of acute ethanol coingestion around the time of acetaminophen (paracetamol) overdose. This study prospectively examined the effect of acute ethanol coingestion on risk of hepatotoxicity among patients admitted to hospital for N‐acetylcysteine (NAC) therapy after deliberate acetaminophen overdose.Methods:  This was a prospective observational study and included sequential patients who presented within 24 hours of acute acetaminophen ingestion and required NAC therapy. Significant hepatotoxicity was defined by alanine transaminase > 1,000 U/L or the international normalized ratio > 1.3 after a standardized intravenous administration of 300 mg/kg NAC.Results:  There were 362 patients, including 178 (49.2%) who coingested ethanol acutely. The prevalence of hepatotoxicity was 5.1% (95% CI = 2.6% to 9.5%) in those who ingested ethanol, compared to 15.2% (95% CI = 10.7% to 21.2%) in those who did not (p = 0.0027 by chi‐square proportional test). Acute ethanol intake conferred a lower risk of hepatotoxicity in patients who had acetaminophen concentrations above or below the “200‐line” and was independent of the interval between ingestion and assessment.Conclusions:  Acute ethanol intake is associated with a lower risk of hepatotoxicity after acetaminophen overdose. This apparent protective effect cannot be explained solely by lower exposure to acetaminophen in this group, nor differences in the interval between ingestion and initiation of treatment. Further work is required to establish mechanisms by which ethanol might confer protection against hepatotoxicity, so as to identify novel strategies for reducing risk after acute acetaminophen ingestion.