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Journal of Gastrointestinal and Liver... Mar 2021While lipase content and appropriate acid protection of pancreatin preparations (PP) are well defined determinants of an effective therapy of exocrine pancreatic...
While lipase content and appropriate acid protection of pancreatin preparations (PP) are well defined determinants of an effective therapy of exocrine pancreatic insufficiency, the optimal sphere size of PP has remained a matter of discussion. We performed a systematic review to assess the optimal sphere size of enteric coated pancreatin products that may best guarantee coordinated delivery of PP and food to the duodenum. PubMed was searched for studies on gastric emptying of indigestible spheres in the digestive phase, using overlapping search algorithms; identified sources were searched for further leads, extending the investigation to Google Scholar. Of 739 screened publications, 26 were included in the final assessment. Contrary to current guideline recommendations, no scientific evidence was found to support a 2 mm diameter threshold for gastric emptying of indigestible particles. There is no documented advantage of ≤2 mm spheres regarding duodenal delivery and restoring maldigestion. The evolving picture is that of a gradation of sizes, over which gastric emptying becomes slower and more variable as particle size increases. Even 7 mm particles may be emptied from the stomach in conjunction with nutrient uptake. In conclusion sphere size of PP is not the essential parameter for selecting an effective PP fitting all patients. A variety of brands offer different lipase contents and sphere sizes that allow the physician to tailor treatment to the individual patient`s needs.
Topics: Duodenum; Exocrine Pancreatic Insufficiency; Gastric Emptying; Humans; Lipase; Pancreatin
PubMed: 33548122
DOI: 10.15403/jgld-2985 -
Environmental Health and Preventive... Jan 2021Previous studies have suggested that exposure to air pollution may increase stroke risk, but the results remain inconsistent. Evidence of more recent studies is highly... (Meta-Analysis)
Meta-Analysis
Association between exposure to ambient air pollution and hospital admission, incidence, and mortality of stroke: an updated systematic review and meta-analysis of more than 23 million participants.
BACKGROUND
Previous studies have suggested that exposure to air pollution may increase stroke risk, but the results remain inconsistent. Evidence of more recent studies is highly warranted, especially gas air pollutants.
METHODS
We searched PubMed, Embase, and Web of Science to identify studies till February 2020 and conducted a meta-analysis on the association between air pollution (PM, particulate matter with aerodynamic diameter less than 2.5 μm; PM, particulate matter with aerodynamic diameter less than 10 μm; NO, nitrogen dioxide; SO, sulfur dioxide; CO, carbon monoxide; O, ozone) and stroke (hospital admission, incidence, and mortality). Fixed- or random-effects model was used to calculate pooled odds ratios (OR)/hazard ratio (HR) and their 95% confidence intervals (CI) for a 10 μg/m increase in air pollutant concentration.
RESULTS
A total of 68 studies conducted from more than 23 million participants were included in our meta-analysis. Meta-analyses showed significant associations of all six air pollutants and stroke hospital admission (e.g., PM: OR = 1.008 (95% CI 1.005, 1.011); NO: OR = 1.023 (95% CI 1.015, 1.030), per 10 μg/m increases in air pollutant concentration). Exposure to PM, SO, and NO was associated with increased risks of stroke incidence (PM: HR = 1.048 (95% CI 1.020, 1.076); SO: HR = 1.002 (95% CI 1.000, 1.003); NO: HR = 1.002 (95% CI 1.000, 1.003), respectively). However, no significant differences were found in associations of PM, CO, O, and stroke incidence. Except for CO and O, we found that higher level of air pollution (PM, PM, SO, and NO) exposure was associated with higher stroke mortality (e.g., PM: OR = 1.006 (95% CI 1.003, 1.010), SO: OR = 1.006 (95% CI 1.005, 1.008).
CONCLUSIONS
Exposure to air pollution was positively associated with an increased risk of stroke hospital admission (PM, PM, SO, NO, CO, and O), incidence (PM, SO, and NO), and mortality (PM, PM, SO, and NO). Our study would provide a more comprehensive evidence of air pollution and stroke, especially SO and NO.
Topics: Air Pollutants; Air Pollution; Environmental Exposure; Hospitalization; Humans; Incidence; Particle Size; Particulate Matter; Stroke
PubMed: 33499804
DOI: 10.1186/s12199-021-00937-1 -
JAMA Network Open Dec 2020Controversy remains regarding the transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
IMPORTANCE
Controversy remains regarding the transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
OBJECTIVE
To review current evidence on air contamination with SARS-CoV-2 in hospital settings and the factors associated with contamination, including viral load and particle size.
EVIDENCE REVIEW
The MEDLINE, Embase, and Web of Science databases were systematically queried for original English-language articles detailing SARS-CoV-2 air contamination in hospital settings between January 1 and October 27, 2020. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The positivity rate of SARS-CoV-2 viral RNA and culture were described and compared according to the setting, clinical context, air ventilation system, and distance from patients. The SARS-CoV-2 RNA concentrations in copies per meter cubed of air were pooled, and their distribution was described by hospital areas. Particle sizes and SARS-CoV-2 RNA concentrations in copies or median tissue culture infectious dose (TCID50) per meter cubed were analyzed after categorization as less than 1 μm, from 1 to 4 μm, and greater than 4 μm.
FINDINGS
Among 2284 records identified, 24 cross-sectional observational studies were included in the review. Overall, 82 of 471 air samples (17.4%) from close patient environments were positive for SARS-CoV-2 RNA, with a significantly higher positivity rate in intensive care unit settings (intensive care unit, 27 of 107 [25.2%] vs non-intensive care unit, 39 of 364 [10.7%]; P < .001). There was no difference according to the distance from patients (≤1 m, 3 of 118 [2.5%] vs >1-5 m, 13 of 236 [5.5%]; P = .22). The positivity rate was 5 of 21 air samples (23.8%) in toilets, 20 of 242 (8.3%) in clinical areas, 15 of 122 (12.3%) in staff areas, and 14 of 42 (33.3%) in public areas. A total of 81 viral cultures were performed across 5 studies, and 7 (8.6%) from 2 studies were positive, all from close patient environments. The median (interquartile range) SARS-CoV-2 RNA concentrations varied from 1.0 × 103 copies/m3 (0.4 × 103 to 3.1 × 103 copies/m3) in clinical areas to 9.7 × 103 copies/m3 (5.1 × 103 to 14.3 × 103 copies/m3) in the air of toilets or bathrooms. Protective equipment removal and patient rooms had high concentrations per titer of SARS-CoV-2 (varying from 0.9 × 103 to 40 × 103 copies/m3 and 3.8 × 103 to 7.2 × 103 TCID50/m3), with aerosol size distributions that showed peaks in the region of particle size less than 1 μm; staff offices had peaks in the region of particle size greater than 4 μm.
CONCLUSIONS AND RELEVANCE
In this systematic review, the air close to and distant from patients with coronavirus disease 2019 was frequently contaminated with SARS-CoV-2 RNA; however, few of these samples contained viable viruses. High viral loads found in toilets and bathrooms, staff areas, and public hallways suggest that these areas should be carefully considered.
Topics: Air Microbiology; COVID-19; Hospitals; Humans; Microbial Viability; Particle Size; RNA, Viral; SARS-CoV-2
PubMed: 33355679
DOI: 10.1001/jamanetworkopen.2020.33232 -
International Journal of Nanomedicine 2020With the increasing production and application of engineered amorphous silica nanoparticles (aSiNPs), people have more opportunities to be exposed to aSiNPs. However,...
With the increasing production and application of engineered amorphous silica nanoparticles (aSiNPs), people have more opportunities to be exposed to aSiNPs. However, the knowledge of its adverse health effects and related mechanisms is still limited, compared with the well-studied crystalline micron-sized silica. Since small differences in the physical-chemical properties of nanoparticles could cause significant differences in the toxic effect, it is important to distinguish how these variations influence the outcoming toxicity. Notably, particle size, as one of the essential characterizations of aSiNPs, is relevant to its biological activities. Thus, the aim of this systematic review was to summarize the relationship between the particle size of aSiNPs and its adverse biological effects. In order to avoid the influence of complicated in vivo experimental conditions on the toxic outcome, only in vitro toxicity studies which reported on the cytotoxic effect of different sizes aSiNPs were included. After the systematic literature retrieval, selection, and quality assessment process, 76 eligible scientific papers were finally included in this review. There were 76% of the studies that concluded a size-dependent cytotoxicity of aSiNPs, in which smaller-sized aSiNPs possessed greater toxicity. However, this trend could be modified by certain influence factors, such as the synthetic method of aSiNPs, particle aggregation state in cell culture medium, toxicity endpoint detection method, and some other experimental conditions. The effects of these influence factors on the size-dependent cytotoxicity of aSiNPs were also discussed in detail in the present review.
Topics: Cell Line; Cell Survival; Humans; Nanoparticles; Particle Size; Silicon Dioxide; Toxicity Tests
PubMed: 33244229
DOI: 10.2147/IJN.S276105 -
PloS One 2020The aim of this study was to systematically collate and appraise the available evidence regarding the associations between small, dense low-density lipoprotein (sdLDL)... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aim of this study was to systematically collate and appraise the available evidence regarding the associations between small, dense low-density lipoprotein (sdLDL) and incident coronary heart disease (CHD), focusing on cholesterol concentration (sdLDL-C) and sdLDL particle characteristics (presence, density, and size).
BACKGROUND
Coronary heart disease (CHD) is the leading cause of death worldwide. Small, dense low-density lipoprotein (sdLDL) has been hypothesized to induce atherosclerosis and subsequent coronary heart disease (CHD). However, the etiological relevance of lipoprotein particle size (sdLDL) versus cholesterol content (sdLDL-C) remains unclear.
METHODS
PubMed, MEDLINE, Web of Science, and EMBASE were systematically searched for studies published before February 2020. CHD associations were based on quartile comparisons in eight studies of sdLDL-C and were based on binary categorization in fourteen studies of sdLDL particle size. Reported hazards ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) were standardized and pooled using a random-effects meta-analysis model.
RESULTS
Data were collated from 21 studies with a total of 30,628 subjects and 5,693 incident CHD events. The average age was 67 years, and 53% were men. Higher sdLDL and sdLDL-C levels were both significantly associated with higher risk of CHD. The pooled estimate for the high vs. low categorization of sdLDL was 1.36 (95% CI: 1.21, 1.52) and 1.07 (95% CI: 1.01, 1.12) for comparing the top quartiles versus the bottom of sdLDL-C. Several studies suggested a dose response relationship.
CONCLUSIONS
The findings show a positive association between sdLDL or sdLDL-C levels and CHD, which is supported by an increasing body of genetic evidence in favor of its causality as an etiological risk factor. Thus, the results support sdLDL and sdLDL-C as a risk marker, but further research is required to establish sdLDL or sdLDL-C as a potential therapeutic marker for incident CHD risk reduction.
Topics: Atherosclerosis; Biomarkers; Cholesterol, LDL; Coronary Disease; Humans; Lipoproteins; Particle Size; Risk Factors
PubMed: 33166340
DOI: 10.1371/journal.pone.0241993 -
Particle and Fibre Toxicology Nov 2020Fetal development is a crucial window of susceptibility in which exposure may lead to detrimental health outcomes at birth and later in life. The placenta serves as a...
Fetal development is a crucial window of susceptibility in which exposure may lead to detrimental health outcomes at birth and later in life. The placenta serves as a gatekeeper between mother and fetus. Knowledge regarding the barrier capacity of the placenta for nanoparticles is limited, mostly due to technical obstacles and ethical issues. We systematically summarize and discuss the current evidence and define knowledge gaps concerning the maternal-fetal transport and fetoplacental accumulation of (ultra)fine particles and nanoparticles. We included 73 studies on placental translocation of particles, of which 21 in vitro/ex vivo studies, 50 animal studies, and 2 human studies on transplacental particle transfer. This systematic review shows that (i) (ultra)fine particles and engineered nanoparticles can bypass the placenta and reach fetal units as observed for all the applied models irrespective of the species origin (i.e., rodent, rabbit, or human) or the complexity (i.e., in vitro, ex vivo, or in vivo), (ii) particle size, particle material, dose, particle dissolution, gestational stage of the model, and surface composition influence maternal-fetal translocation, and (iii) no simple, standardized method for nanoparticle detection and/or quantification in biological matrices is available to date. Existing evidence, research gaps, and perspectives of maternal-fetal particle transfer are highlighted.
Topics: Animals; Female; Fetus; Humans; Maternal-Fetal Exchange; Nanoparticles; Particle Size; Particulate Matter; Placenta; Pregnancy; Rabbits
PubMed: 33138843
DOI: 10.1186/s12989-020-00386-8 -
Advanced Drug Delivery Reviews 2020The clinical success of polypeptides as polymeric drugs, covered by the umbrella term "polymer therapeutics," combined with related scientific and technological...
The clinical success of polypeptides as polymeric drugs, covered by the umbrella term "polymer therapeutics," combined with related scientific and technological breakthroughs, explain their exponential growth in the development of polypeptide-drug conjugates as therapeutic agents. A deeper understanding of the biology at relevant pathological sites and the critical biological barriers faced, combined with advances regarding controlled polymerization techniques, material bioresponsiveness, analytical methods, and scale up-manufacture processes, have fostered the development of these nature-mimicking entities. Now, engineered polypeptides have the potential to combat current challenges in the advanced drug delivery field. In this review, we will discuss examples of polypeptide-drug conjugates as single or combination therapies in both preclinical and clinical studies as therapeutics and molecular imaging tools. Importantly, we will critically discuss relevant examples to highlight those parameters relevant to their rational design, such as linking chemistry, the analytical strategies employed, and their physicochemical and biological characterization, that will foster their rapid clinical translation.
Topics: Animals; Chemistry Techniques, Analytical; Drug Delivery Systems; Drug Development; Drug Therapy, Combination; Humans; Hydrogen-Ion Concentration; Nanoparticles; Particle Size; Peptides; Technology, Pharmaceutical
PubMed: 33091502
DOI: 10.1016/j.addr.2020.10.007 -
Advanced Drug Delivery Reviews 2020Advances in medical science have led to diverse new therapeutic modalities, as well as enhanced understanding of the progression of various disease states. These...
Advances in medical science have led to diverse new therapeutic modalities, as well as enhanced understanding of the progression of various disease states. These findings facilitate the design and development of more customized and exquisite drug delivery systems that aim to improve therapeutic indices of drugs to treat a variety of conditions. Synthetic polymer-based drug carriers have often been the focus of such research. However, these structures suffer from challenges with heterogeneity of the starting material, limited chemical features, complex functionalization methods, and in some cases a lack of biocompatibility. Consequently, protein-based polymers have garnered much attention in recent years due to their monodisperse features, ease of production and functionalization, and biocompatibility. Genetic engineering techniques enable the advancement of protein-based drug delivery systems with finely tuned physicochemical properties, and thus an expanded level of customization unavailable with synthetic polymers. Of these genetically engineered proteins, elastin-like proteins (ELP), silk-like proteins (SLP), and silk-elastin-like proteins (SELP) provide a unique set of alternatives for designing drug delivery systems due to their inherent chemical and physical properties and ease of engineering afforded by recombinant DNA technologies. In this review we examine the advantages of genetically engineered drug delivery systems with emphasis on ELP and SLP constructions. Methods for fabrication and relevant biomedical applications will also be discussed.
Topics: Biocompatible Materials; Drug Delivery Systems; Elastin; Gene Transfer Techniques; Humans; Hydrogels; Nanoparticles; Particle Size; Protein Engineering; Recombinant Proteins; Silk
PubMed: 33080258
DOI: 10.1016/j.addr.2020.10.008 -
PloS One 2020Microplastics (MPs) are omnipresent in the environment, including the human food chain; a likely important contributor to human exposure is drinking water.
BACKGROUND
Microplastics (MPs) are omnipresent in the environment, including the human food chain; a likely important contributor to human exposure is drinking water.
OBJECTIVE
To undertake a systematic review of MP contamination of drinking water and estimate quantitative exposures.
METHODS
The protocol for the systematic review employed has been published in PROSPERO (PROSPERO 2019, Registration number: CRD42019145290). MEDLINE, EMBASE and Web of Science were searched from launch to the 3rd of June 2020, selecting studies that used procedural blank samples and a validated method for particle composition analysis. Studies were reviewed within a narrative analysis. A bespoke risk of bias (RoB) assessment tool was used.
RESULTS
12 studies were included in the review: six of tap water (TW) and six of bottled water (BW). Meta-analysis was not appropriate due to high statistical heterogeneity (I2>95%). Seven studies were rated low RoB and all confirmed MP contamination of drinking water. The most common polymers identified in samples were polyethylene terephthalate (PET) and polypropylene (PP), Methodological variability was observed throughout the experimental protocols. For example, the minimum size of particles extracted and analysed, which varied from 1 to 100 μm, was seen to be critical in the data reported. The maximum reported MP contamination was 628 MPs/L for TW and 4889 MPs/L for BW, detected in European samples. Based on typical consumption data, this may be extrapolated to a maximum yearly human adult uptake of 458,000 MPs for TW and 3,569,000 MPs for BW.
CONCLUSIONS
This is the first systematic review that appraises the quality of existing evidence on MP contamination of drinking water and estimates human exposures. The precautionary principle should be adopted to address concerns on possible human health effects from consumption of MPs. Future research should aim to standardise experimental protocols to aid comparison and elevate quality.
Topics: Drinking Water; Environmental Monitoring; Food Chain; Microplastics; Polyethylene Terephthalates; Polypropylenes; Public Health; Water Pollutants, Chemical
PubMed: 32735575
DOI: 10.1371/journal.pone.0236838 -
Hypertension (Dallas, Tex. : 1979) Jul 2020Air pollution is a major contributor to cardiovascular morbidity and mortality. Fine particulate matter <2.5 µm in diameter may be a modifiable risk factor for... (Meta-Analysis)
Meta-Analysis
Air pollution is a major contributor to cardiovascular morbidity and mortality. Fine particulate matter <2.5 µm in diameter may be a modifiable risk factor for hypertension. The benefits of in-home air filtration on systolic blood pressure (BP) and diastolic BP are unclear. To examine the effects of in-home personal air cleaner use on fine particulate exposure and BP, we queried PubMed, Web of Science, Cochrane Central Register, Inspec, and EBSCO GreenFILE databases for relevant clinical trials. Included studies were limited to nonsmoking participants in smoke-free homes with active or sham filtration on indoor fine particulate concentrations and changes in systolic and diastolic BP. Of 330 articles identified, 10 trials enrolling 604 participants who met inclusion criteria were considered. Over a median 13.5 days, there was a significant reduction of mean systolic BP by ≈4 mm Hg (-3.94 mm Hg [95% CI, -7.00 to -0.89]; =0.01) but a nonsignificant difference in mean diastolic BP (-0.95 mm Hg [95% CI, -2.81 to 0.91]; =0.32). Subgroup analyses indicated no heterogeneity of effect by age, level of particulate exposure, or study duration. Given the variation in study design, additional study is warranted to confirm and better quantify the observed benefits in systolic BP found with personal air cleaner use.
Topics: Adult; Age Factors; Aged; Air Filters; Air Pollution, Indoor; Blood Pressure; Clinical Trials as Topic; Environmental Exposure; Filtration; Humans; Hypertension; Middle Aged; Non-Smokers; Particle Size; Particulate Matter; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32475316
DOI: 10.1161/HYPERTENSIONAHA.119.14456