Simulating Pathogen Transport within a Naturally Ventilated Hospital Ward

Understanding how airborne pathogens are transported through hospital wards is essential for determining the infection risk to patients and healthcare workers. This study utilizes Computational Fluid Dynamics (CFD) simulations to explore pathogen transport within a six-bed Nightingale hospital ward. Grid independence of a ward model was addressed using the Grid Convergence Index (GCI) from solutions obtained using three fully-structured grids. Pathogens were simulated using source terms in conjunction with a scalar transport equation and a RANS turbulence model. Errors were found to be less than 4% in the prediction of air velocities but an average of 13% was seen in the scalar field. A parametric study into the pathogen release point illustrated that its distribution is strongly influenced by the local velocity field and the degree of mixing present

An Effective Surrogate Tracer Technique for S. aureus Bioaerosols in a Mechanically Ventilated Hospital Room Replica Using Dilute Aqueous Lithium Chloride

Finding a non-pathogenic surrogate aerosol that represents the deposition of typical bioaerosols in healthcare settings is beneficial from the perspective of hospital facility testing, general infection control and outbreak analysis. This study considers aerosolization of dilute aqueous lithium chloride (LiCl) and sodium chloride (NaCl) solutions as surrogate tracers capable of representing Staphylococcus aureus bioaerosol deposition on surfaces in mechanically ventilated rooms. Tests were conducted in a biological test chamber set up as a replica hospital single patient room. Petri dishes on surfaces were used to collect the Li, Na and S. aureus aerosols separately after release. Biological samples were analyzed using cultivation techniques on solid media, and flame atomic absorption spectroscopy was used to measure Li and Na atom concentrations. Spatial deposition distribution of Li tracer correlated well with S. aureus aerosols (96% of pairs within a 95% confidence interval). In the patient hospital room replica, results show that the most contaminated areas were on surfaces 2 m away from the source. This indicates that the room’s airflow patterns play a significant role in bioaerosol transport. NaCl proved not to be sensitive to spatial deposition patterns. LiCl as a surrogate tracer for bioaerosol deposition was most reliable as it was robust to outliers, sensitive to spatial heterogeneity and found to require less replicates than the S. aureus counterpart to be in good spatial agreement with biological results

New records of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae) in the Central East Region of Sao Paulo State, Brazil

Cutaneous (LTA) and Visceral (LVA) American Leishmaniasis incidences are increasing in human and canine hosts, especially LVA, which is expanding its range through Sao Paulo State. Distribution and ecology knowledge of different sand fly species is essential for leishmaniasis epidemiology vigilance. The communication of new findings of its vectors is mandatory for risk determination for transmission of these illnesses. On this study sand flies were trapped in bushed areas, in different localities at rural areas of Ipeuna, Itirapina and Analandia counties, between August and September 2007. A total of 248 specimens of nine different species were sampled in Ipeuna, six and seven specimens of two different species were trapped in Itirapina and Analandia, respectively. The most abundant species in Ipeuna was Pintomyia pessoai (37.5%), followed by Pintomyia fischeri (33.06%) and Migonemyia migonei (16.53%), all three species are considered vectors of LTA in Sao Paulo State. Lutzomyia longipalpis was found in Ipeuna and Analandia for the first time and its presence confirmed in Itirapina, indicating a risk of LVA essablishment in the area and the need for further local studies on its ecology, especially regarding its occupation of the anthropic environment.181626

International burden of cancer deaths and years of life lost from cancer attributable to four major risk factors: a population-based study in Brazil, Russia, India, China, South Africa, the United Kingdom, and United States

Background: We provide a comprehensive view of the impact of alcohol consumption, tobacco smoking, excess body weight, and human papillomavirus (HPV) infection on cancer mortality and years of life lost (YLLs) in Brazil, Russia, India, China, South Africa, the United Kingdom (UK), and United States (US). Methods: We collected population attributable fractions of the four risk factors from global population-based studies and applied these to estimates of cancer deaths in 2020 to obtain potentially preventable cancer deaths and their 95% confidence intervals (CIs). Using life tables, we calculated the number and age-standardised rates of YLLs (ASYR). Findings: In Brazil, Russia, India, China, South Africa, the UK, and the US in 2020, an estimated 5.9 million (3.3 million–8.6 million) YLLs from cancer were attributable to alcohol consumption, 20.8 million (17.0 million–24.6 million) YLLs to tobacco smoking, 3.1 million (2.4 million–3.8 million) YLLs to excess body weight, and 4.0 million (3.9 million–4.2 million) YLLs to HPV infection. The ASYR from cancer due to alcohol consumption was highest in China (351.4 YLLs per 100,000 population [95% CI 194.5–519.2]) and lowest in the US (113.5 [69.6–157.1]) and India (115.4 [49.7–172.7). For tobacco smoking, China (1159.9 [950.6–1361.8]) had the highest ASYR followed by Russia (996.8 [831.0–1154.5). For excess body weight, Russia and the US had the highest ASYRs (385.1 [280.6–481.2] and 369.4 [299.6–433.6], respectively). The highest ASYR due to HPV infection was in South Africa (457.1 [453.3–462.6]). ASYRs for alcohol consumption and tobacco smoking were higher among men than women, whereas women had higher ASYRs for excess body weight and HPV infection. Interpretation: Our findings demonstrate the importance of cancer control efforts to reduce the burden of cancer death and YLLs due to modifiable cancer risk factors and promote the use of YLLs to summarise disease burden. Funding: Cancer Research UK

Heterozygous <em>COL17A1 </em>variants are a frequent cause of amelogenesis imperfecta

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.Background: Collagen XVII is most typically associated with human disease when biallelic COL17A1 variants (&gt;230) cause junctional epidermolysis bullosa (JEB), a rare, genetically heterogeneous, mucocutaneous blistering disease with amelogenesis imperfecta (AI), a developmental enamel defect. Despite recognition that heterozygous carriers in JEB families can have AI, and that heterozygous COL17A1 variants also cause dominant corneal epithelial recurrent erosion dystrophy (ERED), the importance of heterozygous COL17A1 variants causing dominant non-syndromic AI is not widely recognised. Methods: Probands from an AI cohort were screened by single molecule molecular inversion probes or targeted hybridisation capture (both a custom panel and whole exome sequencing) for COL17A1 variants. Patient phenotypes were assessed by clinical examination and analyses of affected teeth. Results: Nineteen unrelated probands with isolated AI (no co-segregating features) had 17 heterozygous, potentially pathogenic COL17A1 variants, including missense, premature termination codons, frameshift and splice site variants in both the endo-domains and the ecto-domains of the protein. The AI phenotype was consistent with enamel of near normal thickness and variable focal hypoplasia with surface irregularities including pitting. Conclusion: These results indicate that COL17A1 variants are a frequent cause of dominantly inherited non-syndromic AI. Comparison of variants implicated in AI and JEB identifies similarities in type and distribution, with five identified in both conditions, one of which may also cause ERED. Increased availability of genetic testing means that more individuals will receive reports of heterozygous COL17A1 variants. We propose that patients with isolated AI or ERED, due to COL17A1 variants, should be considered as potential carriers for JEB and counselled accordingly, reflecting the importance of multidisciplinary care

Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data.

BACKGROUND: A previous aggregate data meta-analysis of randomised controlled trials showed that vitamin D supplementation reduces the rate of asthma exacerbations requiring treatment with systemic corticosteroids. Whether this effect is restricted to patients with low baseline vitamin D status is unknown. METHODS: For this systematic review and one-step and two-step meta-analysis of individual participant data, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for double-blind, placebo-controlled, randomised controlled trials of vitamin D3 or vitamin D2 supplementation in people with asthma that reported incidence of asthma exacerbation, published between database inception and Oct 26, 2016. We analysed individual participant data requested from the principal investigator for each eligible trial, adjusting for age and sex, and clustering by study. The primary outcome was the incidence of asthma exacerbation requiring treatment with systemic corticosteroids. Mixed-effects regression models were used to obtain the pooled intervention effect with a 95% CI. Subgroup analyses were done to determine whether effects of vitamin D on risk of asthma exacerbation varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, age, ethnic or racial origin, body-mass index, vitamin D dosing regimen, use of inhaled corticosteroids, or end-study 25(OH)D levels; post-hoc subgroup analyses were done according to sex and study duration. This study was registered with PROSPERO, number CRD42014013953. FINDINGS: Our search identified 483 unique studies, eight of which were eligible randomised controlled trials (total 1078 participants). We sought individual participant data for each and obtained it for seven studies (955 participants). Vitamin D supplementation reduced the rate of asthma exacerbation requiring treatment with systemic corticosteroids among all participants (adjusted incidence rate ratio [aIRR] 0·74, 95% CI 0·56-0·97; p=0·03; 955 participants in seven studies; high-quality evidence). There were no significant differences between vitamin D and placebo in the proportion of participants with at least one exacerbation or time to first exacerbation. Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0·33, 0·11-0·98; p=0·046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0·77, 0·58-1·03; p=0·08; 764 participants in six studies; moderate-quality evidence; pinteraction=0·25). p values for interaction for all other subgroup analyses were also higher than 0·05; therefore, we did not show that the effects of this intervention are stronger in any one subgroup than in another. Six studies were assessed as being at low risk of bias, and one was assessed as being at unclear risk of bias. The two-step meta-analysis did not reveal evidence of heterogeneity of effect (I2=0·0, p=0·56). INTERPRETATION: Vitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall. We did not find definitive evidence that effects of this intervention differed across subgroups of patients. FUNDING: Health Technology Assessment Program, National Institute for Health Research (reference number 13/03/25).Health Technology Assessment Program, National Institute for Health Research (reference number 13/03/25)

Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi