Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain ...infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3 and 4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. 41 participants were randomised to placebo, 39 to aspirin 81 mg/day, and 40 to aspirin 1000 mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120 (76.7%) and baseline brain imaging revealed ≥1 infarct in 40/114 (35.1%) participants. The primary safety outcome occurred in 5/36 (13.9%) given placebo, and in 8/35 (22.9%) and 8/40 (20.0%) given 81 mg and 1000 mg aspirin, respectively (p=0.59). The primary efficacy outcome occurred in 11/38 (28.9%) given placebo, 8/36 (22.2%) given aspirin 81 mg, and 6/38 (15.8%) given 1000 mg aspirin (p=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (P
= 0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32 (34.4%) events in placebo vs. 4/27 (14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000 mg; p=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A
and upregulation of pro-resolving CSF protectins. The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial.
Talaromyces marneffei
is a dimorphic fungus that causes substantial disease in Asia, especially among persons infected with the human immunodeficiency virus. In this randomized, controlled trial, ...initial therapy with amphotericin B was found to be superior to itraconazole.
The dimorphic fungus
Talaromyces
(previously
Penicillium
)
marneffei
causes a life-threatening mycosis in immunocompromised persons living in or traveling to Southeast Asia, China, and India.
1
Talaromycosis (previously penicilliosis) is a major cause of human immunodeficiency virus (HIV)–related death; its prevalence is surpassed only by the prevalence of tuberculosis and cryptococcosis,
2
and it leads to 4 to 15% of HIV-related hospital admissions in regions in which the disease is endemic.
3
–
7
Talaromycosis is increasingly diagnosed among patients who are not infected with HIV but who have other immunodeficiency conditions
8
and is reported to be the second most common cause of all . . .
Goat and sheep milks have long been used to produce a range of dairy products due to their nutritional value and health benefits. Information about the microstructure and rheology of goat and sheep ...yoghurts, however, is scarce. In this study, the microstructure, texture and rheological properties of cow, goat and sheep yoghurts were investigated and compared. The results show that a longer fermentation and gelation time was required for goat yoghurt with a lower storage modulus compared to cow and sheep yoghurts. Cooling resulted in an increase in the storage modulus at different magnitudes for cow, goat and sheep yoghurts. Goat yoghurt had a smaller particle size and a softer gel, which is linked with a more porous microstructure. The results obtained here demonstrate the effect of different milk types on the properties of yoghurts and provide a better understanding into the link between the microstructure and physical properties of the product.
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•Cow, goat and sheep milks exhibited different physicochemical properties.•Goat yoghurt required a longer fermentation and gelation time.•Goat yoghurt had the most porous microstructure which is linked with the softest gel.•Sheep yoghurt had the most dense protein network and highest gel firmness.•The storage modulus increased at a smaller degree for goat yoghurt when cooling.
Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the ...parasite responds to-or is selected by-this environment remains unclear. From previous studies, the parasites that cause severe malaria appear to increase expression of a restricted but poorly defined subset of the PfEMP1 variant, surface antigens. PfEMP1s are major targets of protective immunity. Here, we used RNA sequencing (RNAseq) to analyse gene expression in 44 parasite isolates that caused severe and uncomplicated malaria in Papuan patients. The transcriptomes of 19 parasite isolates associated with severe malaria indicated that these parasites had decreased glycolysis without activation of compensatory pathways; altered chromatin structure and probably transcriptional regulation through decreased histone methylation; reduced surface expression of PfEMP1; and down-regulated expression of multiple chaperone proteins. Our RNAseq also identified novel associations between disease severity and PfEMP1 transcripts, domains, and smaller sequence segments and also confirmed all previously reported associations between expressed PfEMP1 sequences and severe disease. These findings will inform efforts to identify vaccine targets for severe malaria and also indicate how parasites adapt to-or are selected by-the host environment in severe malaria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
From an EtOAc-soluble extract of the roots of Taxus wallichiana, six new (1–6) and 11 known lignans were isolated. The structures of the new compounds were elucidated based on interpretation of ...spectroscopic data. (+)-7′-epi-Tsugacetal (1) is a rare aryltetralin-type lignan having a cis-orientation of H-7′ and H-8′. Compounds 3–6 were identified as the first naturally occurring tetrahydrofuranoid lignans having a cis-orientation of H-7 and H-8. All tested compounds were found to possess α-glucosidase inhibitory activity, with formosanol (9) showing the most potent effect with an IC50 value of 35.3 μM.
•Peptides from in vitro digestion of cow, goat and sheep products were different.•β-CN and β-Lg were digested faster in yogurt samples.•Yoghurts produced a greater amount of bioactive peptides than ...milks.•The majority of bioactive peptides had antihypertensive activity.
Fermentation of milk is commonly used throughout the world to produce a variety of foods with different health benefits. We hypothesised that due to differences in physicochemical properties and protein sequences among milk from different species and their fermented yogurt samples, their protein digestion and resulting peptide profiles would differ. Cow, goat and sheep milk and yogurt were compared at designated timepoints throughout in vitro gastric and intestinal digestion for differences in peptide profiles and peptide bioactivities. The results showed that most proteins in all milk and yogurt samples were digested within the early phase of gastric digestion. β-Lg and β-CN were digested faster in yogurt than milk, which was most evident for sheep products. Regardless of species, in vitro gastric and intestinal digestion released a higher concentration of specific peptides, particularly anti-hypertensives, from yogurt compared with their milk counterparts.
Development and validation of large animal models of Pseudomonas aeruginosa ventilator-associated pneumonia are needed for testing new drug candidates in a manner that mimics how they will be used ...clinically. We developed a new model in which rabbits were ventilated with low tidal volume and challenged with P. aeruginosa to recapitulate hallmark clinical features of acute respiratory distress syndrome (ARDS): acute lung injury and inflammation, progressive decrease in arterial oxygen partial pressure to fractional inspired oxygen PaO
:FiO
, leukopenia, neutropenia, thrombocytopenia, hyperlactatemia, severe hypotension, bacterial dissemination from lung to other organs, multiorgan dysfunction, and ultimately death. We evaluated the predictive power of this rabbit model for antibiotic efficacy testing by determining whether a humanized dosing regimen of meropenem, a potent antipseudomonal β-lactam antibiotic, when administered with or without intensive care unit (ICU)-supportive care (fluid challenge and norepinephrine), could halt or reverse natural disease progression. Our humanized meropenem dosing regimen produced a plasma concentration-time profile in the rabbit model similar to those reported in patients with ventilator-associated bacterial pneumonia. In this rabbit model, treatment with humanized meropenem and ICU-supportive care achieved the highest level of survival, halted the worsening of ARDS biomarkers, and reversed lethal hypotension, although treatment with humanized meropenem alone also conferred some protection compared to treatment with placebo (saline) alone or placebo plus ICU-supportive care. In conclusion, this rabbit model could help predict whether an antibiotic will be efficacious for the treatment of human ventilator-associated pneumonia.
A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans ...in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 and subsequent avian outbreaks in 2001 and 2002. These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The effect of environmental pollution on the safety of vegetable crops is a serious global public health issue. This study was conducted to assess heavy metal concentrations in soil, irrigation ...water, and 21 local vegetable species collected from four sites near mining activities and one control site in Northern Vietnam. Soils from vegetable fields in the mining areas were contaminated with cadmium (Cd), lead (Pb), and arsenic (As), while irrigation water was contaminated with Pb. Average concentrations of Pb and As in fresh vegetable samples collected at the four mining sites exceeded maximum levels (MLs) set by international food standards for Pb (70.6 % of vegetable samples) and As (44.1 % of vegetable samples), while average Cd concentrations in vegetables at all sites were below the MLs of 0.2. The average total target hazard quotient (TTHQ) across all vegetable species sampled was higher than the safety threshold of 1.0, indicating a health risk. Based on the weight of evidence, we find that cultivation of vegetables in the studied mining sites is an important risk contributor for local residents’ health.
Carbapenemase-producing Enterobacteriaceae (CPE) are well known to cause many serious infections resulting in increasing mortality rate, treatment cost, and prolonged hospitalization. Among the ...widely recognized types of carbapenemases, New Delhi β-lactamase (NDM) and Klebsiella pneumoniae carbapenemase (KPC) are the most important enzymes. However, in Vietnam, there are only scattered reports of CPE due to the lack of simple and affordable methods that are suitable to laboratory conditions. This study aims to survey the characteristics of carbapenem-resistant E. coli and K. pneumoniae (CR-E/K) at two hospitals in Southern Vietnam and perform some simple methods to detect the two enzymes. A total of 100 CR-E/K strains were collected from clinical isolates of Gia Dinh People’s Hospital and Dong Nai General Hospital, Vietnam, from November 2017 to May 2018. The patient-related information was also included in the analysis. We conducted real-time polymerase chain reaction (PCR), Modified Hodge Test (MHT), and combined disk test (CDT) on all isolates. Carbapenemase-encoding genes were detected in 47 isolates (36 NDM, 10 KPC, and one isolate harboring both genes). The E. coli strain carrying simultaneously these two genes was the first case reported here. Most of isolates were collected from patients in ICU, Infectious Disease Department, and Department of Urologic Surgery. Urine and sputum were two common specimens. The true positive rate (sensitivity, TPR) and specificity (SPC) of the imipenem–EDTA (ethylen diamine tetra acetic acid) for NDM detection and the imipenem–PBA (phenylboronic acid) for KPC detection on E. coli were 93.8%, 97.1% and 66.7%, 95.7%, respectively. Meanwhile, the imipenem–EDTA for NDM detection and the imipenem–PBA for KPC detection among K. pneumonia achieved 90.5%, 100% and 100%, 92.9% TPR and SPC, respectively. However, MHT showed low sensitivity and specificity. Our findings showed that CP-E/K were detected with high prevalence in the two hospitals. We suggest that CDT can be used as a low-priced and accurate method of detection.
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