The Incidence of Infection Complicating Snakebites in Tropical Australia: Implications for Clinical Management and Antimicrobial Prophylaxis

Objective. To define the incidence of infection following snakebite in tropical Australia and the resulting implications for the routine prescription of prophylactic antibiotics. Methods. A retrospective study of all individuals presenting to Cairns Hospital, a tertiary referral hospital in tropical Australia, after a snakebite between December 2013 and October 2020. Results. There were 732 hospitalisations, 720 (98.4%) patients presented within 8 hours of the snakebite, and 29/732 (4.0%) were envenomated. Envenomated patients were more likely to receive empirical antibiotics than nonenvenomated patients (8/29 (27.6%) versus 14/703 (2.0%), p < 0.001 ), although this was frequently as a bundle of care for critically ill individuals. Superficial skin infection was diagnosed by clinicians in 6/732 (0.8%) patients during their hospitalisation; infection was diagnosed more commonly in envenomated than in nonenvenomated patients (3/29 (10.3%) versus 3/703 (0.4%), p = 0.001 ). All 3 envenomated individuals diagnosed with infection were believed to have taipan (genus Oxyuranus) bites. Five (83%) of the six patients diagnosed with infection had received empirical antibiotics at presentation; only 1/710 (0.1%) patients who received no antibiotics developed a (superficial) infection. Conclusion. Infection is a very uncommon complication of snakebite in tropical Australia. Individuals bitten by snakes in tropical Australia should not routinely receive antibiotic prophylaxis

Comparison of the effect of two human milk fortifiers on clinical outcomes in premature infants

The use of human milk fortifiers (HMF) helps to meet the high nutritional requirements of the human milk-fed premature infant. Previously available powdered products have not met the protein requirements of the preterm infant population and many neonatologists add powder protein modulars to help meet protein needs. The use of powdered products is discouraged in neonatal intensive care units (NICU) due to concern for invasive infection. The use of a commercially available acidified liquid product with higher protein content was implemented to address these two concerns. During the course of this implementation, poor growth and clinically significant acidosis of infants on Acidified Liquid HMF (ALHMF) was observed. The purpose of this study was to quantify those observations by comparing infant outcomes between groups receiving the ALHMF vs. infants receiving powdered HMF (PHMF). A retrospective chart review compared outcomes of human milk-fed premature infants(n=23) and the PHMF (n=46). Infant growth, enteral feeding tolerance and provision, and incidence of necrotizing enterocolitis (NEC), metabolic acidosis, and diaper dermatitis were compared between the two groups. No infants were excluded from this study based on acuity. Use of ALHMF resulted in a higher incidence of metabolic acidosis (p=0.002). Growth while on HMF as measured in both g/kg/day (10.59 vs. 15.37,

Proteomic analysis of the \u3cem\u3eS. cerevisiae\u3c/em\u3e response to the anticancer ruthenium complex KP1019

Like platinum-based chemotherapeutics, the anticancer ruthenium complex indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(iii)], or KP1019, damages DNA, induces apoptosis, and causes tumor regression in animal models. Unlike platinum-based drugs, KP1019 showed no dose-limiting toxicity in a phase I clinical trial. Despite these advances, the mechanism(s) and target(s) of KP1019 remain unclear. For example, the drug may damage DNA directly or by causing oxidative stress. Likewise, KP1019 binds cytosolic proteins, suggesting DNA is not the sole target. Here we use the budding yeast Saccharomyces cerevisiae as a model in a proteomic study of the cellular response to KP1019. Mapping protein level changes onto metabolic pathways revealed patterns consistent with elevated synthesis and/or cycling of the antioxidant glutathione, suggesting KP1019 induces oxidative stress. This result was supported by increased fluorescence of the redox-sensitive dye DCFH-DA and increased KP1019 sensitivity of yeast lacking Yap1, a master regulator of the oxidative stress response. In addition to oxidative and DNA stress, bioinformatic analysis revealed drug-dependent increases in proteins involved ribosome biogenesis, translation, and protein (re)folding. Consistent with proteotoxic effects, KP1019 increased expression of a heat-shock element (HSE) lacZ reporter. KP1019 pre-treatment also sensitized yeast to oxaliplatin, paralleling prior research showing that cancer cell lines with elevated levels of translation machinery are hypersensitive to oxaliplatin. Combined, these data suggest that one of KP1019’s many targets may be protein metabolism, which opens up intriguing possibilities for combination therapy

Parenting while living with advanced cancer: A qualitative study

Patients with advanced cancer who have dependent children are an important population with a life-limiting illness and high levels of psychological distress. Few studies have addressed the experience of being a parent with advanced cancer and their potential palliative needs

The Arg59Trp variant in ANGPTL8 (betatrophin) is associated with total and HDL-cholesterol in American Indians and Mexican Americans and differentially affects cleavage of ANGPTL3

We previously identified a locus linked to total cholesterol (TC) concentration in Pima Indians on chromosome 19p. To characterize this locus, we genotyped \u3e2000 SNPs in 1838 Pimas and assessed association with log(TC). We observed evidence for association with log(TC) with rs2278426 (3.5% decrease/copy of the T allele; P=5.045×10(-6)) in the ANGPTL8 (angiopoietin-like 8) gene. We replicated this association in 2413 participants of the San Antonio Mexican American Family Study (SAMAFS: 2.0% decrease per copy of the T allele; P=0.005842). In a meta-analysis of the combined data, we found the strongest estimated effect with rs2278426 (P=2.563×10(-7)). The variant T allele at rs2278426 predicts an Arg59Trp substitution and has previously been associated with LDL-C and HDL-C. In Pimas and SAMAFS participants, the T allele of rs2278426 was associated with reduced HDL-C levels (P=0.000741 and 0.00002, respectively), and the combined estimated effect for the two cohorts was -3.8% (P=8.526×10(-8)). ANGPTL8 transcript and protein levels increased in response to both glucose and insulin. The variant allele was associated with increased levels of cleaved ANGPTL3. We conclude that individuals with the variant allele may have lower TC and HDL-C levels due to increased activation of ANGPTL3 by ANGPTL8

The X-ray spectra and spectral variability of intermediate type Seyfert galaxies: ASCA observations of NGC 4388 and ESO 103-G35

The X-ray spectra of two intermediate type Seyfert galaxies are investigated using ASCA observations separated by more than a year. Both NGC 4388 and ESO 103-G35 exhibit strong, narrow Fe K alpha line emission and absorption by cold neutral gas with a column density ~ 10^23 cm^-2, characteristic of the X-ray spectra of type 2 Seyfert galaxies. The power law continuum flux has changed by a factor of 2 over a time-scale of ~ 2 years for both objects, declining in the case of NGC 4388 and rising in ESO 103-G35. No variation was observed in the equivalent width of the Fe K alpha line in the spectra of NGC 4388, implying that the line flux declined with the continuum. We find that the strength of the line cannot be accounted for by fluorescence in line-of-sight material with the measured column density unless a `leaky-absorber' model of the type favored for IRAS 04575-7537 is employed. The equivalent width of the Fe K alpha emission line is seen to decrease between the observations of ESO 103-G35 while the continuum flux increased. The 1996 observation of ESO 103-G35 can also be fitted with an absorption edge at 7.4 $\pm$ 0.2 keV due to partially ionized iron, and when an ionized absorber model is fitted to the data it is found that the equivalent column of neutral hydrogen rises to 3.5 x 10^23 cm^-2. The Fe K alpha line flux can be accounted by fluorescence in this material alone and this model is also a good representation of the 1988 and 1991 Ginga observations. There is then no requirement for a reflection component in the ASCA spectra of ESO 103-G35 or NGC 4388.Comment: 45 pages, 5 tables, 11 figures. Accepted for publication in the Astrophysical Journa

Family planning, antenatal and delivery care: cross-sectional survey evidence on levels of coverage and inequalities by public and private sector in 57 low- and middle-income countries.

OBJECTIVE: The objective of this study was to assess the role of the private sector in low- and middle-income countries (LMICs). We used Demographic and Health Surveys for 57 countries (2000-2013) to evaluate the private sector's share in providing three reproductive and maternal/newborn health services (family planning, antenatal and delivery care), in total and by socio-economic position. METHODS: We used data from 865 547 women aged 15-49, representing a total of 3 billion people. We defined 'met and unmet need for services' and 'use of appropriate service types' clearly and developed explicit classifications of source and sector of provision. RESULTS: Across the four regions (sub-Saharan Africa, Middle East/Europe, Asia and Latin America), unmet need ranged from 28% to 61% for family planning, 8% to 22% for ANC and 21% to 51% for delivery care. The private-sector share among users of family planning services was 37-39% across regions (overall mean: 37%; median across countries: 41%). The private-sector market share among users of ANC was 13-61% across regions (overall mean: 44%; median across countries: 15%). The private-sector share among appropriate deliveries was 9-56% across regions (overall mean: 40%; median across countries: 14%). For all three healthcare services, women in the richest wealth quintile used private services more than the poorest. Wealth gaps in met need for services were smallest for family planning and largest for delivery care. CONCLUSIONS: The private sector serves substantial numbers of women in LMICs, particularly the richest. To achieve universal health coverage, including adequate quality care, it is imperative to understand this sector, starting with improved data collection on healthcare provision

Hydrogenation of Organic Matter as a Terminal Electron Sink Sustains High CO2:CH4 Production Ratios During Anaerobic Decomposition

Once inorganic electron acceptors are depleted, organic matter in anoxic environments decomposes by hydrolysis, fermentation, and methanogenesis, requiring syntrophic interactions between microorganisms to achieve energetic favorability. In this classic anaerobic food chain, methanogenesis represents the terminal electron accepting (TEA) process, ultimately producing equimolar CO2 and CH4 for each molecule of organic matter degraded. However, CO2:CH4 production in Sphagnum-derived, mineral-poor, cellulosic peat often substantially exceeds this 1:1 ratio, even in the absence of measureable inorganic TEAs. Since the oxidation state of C in both cellulose-derived organic matter and acetate is 0, and CO2 has an oxidation state of +4, if CH4 (oxidation state -4) is not produced in equal ratio, then some other compound(s) must balance CO2 production by receiving 4 electrons. Here we present evidence for ubiquitous hydrogenation of diverse unsaturated compounds that appear to serve as organic TEAs in peat, thereby providing the necessary electron balance to sustain CO2:CH4 \u3e1. While organic electron acceptors have previously been proposed to drive microbial respiration of organic matter through the reversible reduction of quinone moieties, the hydrogenation mechanism that we propose, by contrast, reduces C-C double bonds in organic matter thereby serving as 1) a terminal electron sink, 2) a mechanism for degrading complex unsaturated organic molecules, 3) a potential mechanism to regenerate electron-accepting quinones, and, in some cases, 4) a means to alleviate the toxicity of unsaturated aromatic acids. This mechanism for CO2 generation without concomitant CH4 production has the potential to regulate the global warming potential of peatlands by elevating CO2:CH4 production ratios

Defining Advance Care Planning for Adults: A Consensus Definition From a Multidisciplinary Delphi Panel

Despite increasing interest in advance care planning (ACP) and prior ACP descriptions, a consensus definition does not yet exist to guide clinical, research, and policy initiatives