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International Journal of Hygiene and... Apr 2019Phthalic acid esters are widely used to improve the plasticity of PVC in medical devices (MD). The most famous plasticizer is DEHP, whose use in medical devices has been...
BACKGROUND
Phthalic acid esters are widely used to improve the plasticity of PVC in medical devices (MD). The most famous plasticizer is DEHP, whose use in medical devices has been contested by the European authorities since 2008. Several alternative plasticizers are being considered to replace DEHP, such as DEHT, TOTM, DINP or DINCH, but they are also released from the PVC throughout their life cycle and are metabolized in the same way as DEHP.
OBJECTIVES
Our study focuses on the in vitro cytotoxicity of two alternative plasticizers (DINCH and DINP) contained in certain medical devices. They are likely to migrate and be transformed in vivo into the primary and secondary metabolites by a metabolism similar to that of DEHP. This preliminary study is the first to assess the in vitro cytotoxicity of oxidized metabolites of DINCH and DINP based on the EN ISO 10-993-5 standards documents.
METHODS
We have studied the complete multi-step organic synthesis of secondary metabolites of DINP and DINCH and have performed cytotoxicity tests on L929 murine cells according to the EN ISO 10993-5 standard design for the biocompatibility of a MD. The tested concentrations of obtained metabolites (0.01, 0.05 and 0.1 mg/mL) covered the range likely to be found for DEHP (total metabolism) in biological fluids coming into direct contact with the MD. The concentrations tested in our study were chosen based on a complete transformation of the plasticizers released after direct contact between a MD and the patient's blood.
RESULTS
Only 7-oxo-MMeOCH is cytotoxic at the highest concentration (0.1 mg/mL) after 7 days of exposure, just like 5-oxo-MEHP for the same concentration. By contrast, 7-OH-MMeOP, 7-cx-MMeOP, 7-oxo-MMeOP, 7-OH-MMeOCH and 7-cx-MMeOCH were not found to be cytotoxic.
CONCLUSION
The known concentrations of these secondary metabolites in urinary samples are in the μg/L range, i.e. about 100-1000 times lower than the concentrations tested in this study. Cytotoxicity is known to be dose-dependent but it is not always the case for endocrine perturbations and the secondary metabolites could induce endocrine perturbations at very low doses.
Topics: Animals; Cell Line; Cell Survival; Cyclohexanecarboxylic Acids; Dicarboxylic Acids; Diethylhexyl Phthalate; Equipment and Supplies; Mice; Phthalic Acids; Plasticizers
PubMed: 30898526
DOI: 10.1016/j.ijheh.2019.03.005 -
BMC Surgery Dec 2018Based on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70-80%) or complicated (20-30%) disease. Recent studies have shown...
BACKGROUND
Based on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70-80%) or complicated (20-30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis.
METHODS
APPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients. Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin.
DISCUSSION
To our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis.
TRIAL REGISTRATION
Clinicaltrials.gov , NCT03236961, retrospectively registered on the 2nd of August 2017.
Topics: Humans; Acute Disease; Administration, Intravenous; Anti-Bacterial Agents; Appendicitis; Cost-Benefit Analysis; Finland; Length of Stay; Quality of Life; Tomography, X-Ray Computed; Multicenter Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 30558607
DOI: 10.1186/s12893-018-0451-y -
IUCrJ Nov 2018This paper reports on the polymorphism of 2-propyl-1-benzimidazole (2PrBzIm) induced by temperature change. Upon heating, an irreversible reconstructive-type phase...
This paper reports on the polymorphism of 2-propyl-1-benzimidazole (2PrBzIm) induced by temperature change. Upon heating, an irreversible reconstructive-type phase transition at = 384 K from the ordered form (222) to a new polymorph, form (), was observed. The structural transformation between forms and involves significant changes in the crystal packing, as well as a key conformational variation around the propyl chain of the molecule. After the first irreversible phase transition, the form undergoes two further (reversible) phase transitions upon cooling at 361 K ( ) and 181 K ( ). All three phases (forms , and ) have almost identical crystal packing and, given the reversibility of the conversions as a function of temperature, they are referred to as form temperature phases. They differ, however, with respect to conformational variations around the propyl chain of 2PrBzIm. Energy calculations of the gas-phase conformational energy landscape of this compound about its flexible bonds allowed us to classify the observed conformational variations of all forms into changes and adjustments of conformers. This reveals that forms and are related by conformational change, and that two of the form phases (HT and RT) are related by conformational adjustment, whilst the other two (RT and LT) are related by conformational change. We introduce the term 'conformational phases' for different crystal phases with almost identical packing but showing changes in conformation.
PubMed: 30443355
DOI: 10.1107/S2052252518011685 -
International Journal of Molecular... Jul 2018Human adipose-derived stromal cells (hASCs) are widely known for their immunomodulatory and anti-inflammatory properties. This study proposes a method to protect cells...
Human adipose-derived stromal cells (hASCs) are widely known for their immunomodulatory and anti-inflammatory properties. This study proposes a method to protect cells during and after their injection by encapsulation in a hydrogel using a droplet millifluidics technique. A biocompatible, self-hardening biomaterial composed of silanized-hydroxypropylmethylcellulose (Si-HPMC) hydrogel was used and dispersed in an oil continuous phase. Spherical particles with a mean diameter of 200 μm could be obtained in a reproducible manner. The viability of the encapsulated hASCs in the Si-HPMC particles was 70% after 14 days in vitro, confirming that the Si-HPMC particles supported the diffusion of nutrients, vitamins, and glucose essential for survival of the encapsulated hASCs. The combination of droplet millifluidics and biomaterials is therefore a very promising method for the development of new cellular microenvironments, with the potential for applications in biomedical engineering.
Topics: Biocompatible Materials; Cell Differentiation; Cells, Cultured; Humans; Hydrogels; Hypromellose Derivatives; Mesenchymal Stem Cells
PubMed: 29970871
DOI: 10.3390/ijms19071952 -
PLoS Neglected Tropical Diseases Apr 2018The human treponematoses comprise venereal syphilis and the three non-venereal or endemic treponematoses yaws, bejel, and pinta. Serological assays remain the most...
INTRODUCTION
The human treponematoses comprise venereal syphilis and the three non-venereal or endemic treponematoses yaws, bejel, and pinta. Serological assays remain the most common diagnostic method for all treponemal infections. Point-of-care tests (POCTs) for syphilis and yaws allow testing without further development of infrastructure in populations where routine laboratory facilities are not available. Alongside the test's performance characteristics assessed through diagnostic evaluation, it is important to consider broader issues when rolling out a POCT. Experience with malaria POCT roll-out in sub-Saharan Africa has demonstrated that both healthcare worker and patient beliefs may play a major role in shaping the real-world use of POCTs. We conducted a qualitative study evaluating healthcare worker and patient perceptions of using a syphilis/yaws POCT in clinics in the East Malaita region of Malaita province in the Solomon Islands. Prior to the study serology was only routinely available at the local district hospital.
METHODS
The POCT was deployed in the outpatient and ante-natal departments of a district hospital and four rural health clinics served by the hospital. Each site was provided with training and an SOP on the performance, interpretation and recording of results. Treatment for those testing positive was provided, in line with Solomon Islands Ministry of Health and Medical Services' guidelines for syphilis and yaws respectively. Alongside the implementation of the POCT we facilitated semi-structured interviews with both nurses and patients to explore individuals' experiences and beliefs in relation to use of the POCT.
RESULTS AND DISCUSSION
Four main themes emerged in the interviews: 1) training and ease of performing the test; 2) time taken and ability to fit the test into a clinical workflow; 3) perceived reliability and trustworthiness of the test; and 4) level of the health care system the test was most usefully deployed. Many healthcare workers related their experience with the POCT to their experience using similar tests for malaria. Although the test was considered to take a relatively long time to perform the benefits of improved access to testing were considered positive by most healthcare workers. Qualitative data is needed to help inform better training packages to support the implementation of POCT in low-resource settings.
Topics: Health Personnel; Humans; Interviews as Topic; Melanesia; Point-of-Care Testing; Poverty; Qualitative Research; Reproducibility of Results; Syphilis; Yaws
PubMed: 29672524
DOI: 10.1371/journal.pntd.0006360 -
Revista Brasileira de Parasitologia... 2018The helminthological examination of nine individuals of Aetobatus cf. narinari (spotted eagle ray; raya pinta; arraia pintada) revealed the presence of an undescribed...
The helminthological examination of nine individuals of Aetobatus cf. narinari (spotted eagle ray; raya pinta; arraia pintada) revealed the presence of an undescribed species of cestode of the genus Acanthobothrium. The stingrays were collected from four locations in México: Laguna Términos, south of Isla del Carmen and the marine waters north of Isla del Carmen and Champotón, in the State of Campeche, and Isla Holbox, State of Quintana Roo. The new species, nominated Acanthobothrium marquesi, is a category 3 species (i.e, the strobila is long, has more than 50 proglottids, the numerous testicles greater than 80, and has asymmetrically-lobed ovaries); at the present, the only category 3 species that has been reported in the Western Atlantic Ocean is Acanthobothrium tortum. Acanthobothrium marquesi n. sp. can be distinguished from A. tortum by length (26.1 cm vs. 10.6 cm), greater number of proglottids (1,549 vs. 656), a larger scolex (707 µm long by 872 µm wide vs. 699 µm long by 665 µm wide), larger bothridia (626 µm long by 274 µm wide vs. 563 µm long by 238 µm wide). This is the first report of a species of Acanthobothrium from the Mexican coast of the Gulf México.
Topics: Animals; Cestoda; Cestode Infections; Fish Diseases; Mexico; Microscopy, Electron, Scanning; Skates, Fish
PubMed: 29538487
DOI: 10.1590/S1984-29612018009 -
PloS One 2018Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading,...
Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading, migration, proliferation, and differentiation to needed cell types. However, dynamic gene transcription in the early events after mucosal injury has not been studied in AEC. We examined gene expression using microarrays following mechanical injury (MI) in primary human AEC grown in submersion culture to generate basal cells and in the air-liquid interface to generate differentiated AEC (dAEC) that include goblet and ciliated cells. A select group of ~150 genes was in differential expression (DE) within 2-24 hr after MI, and enrichment analysis of these genes showed over-representation of functional categories related to inflammatory cytokines and chemokines. Network-based gene prioritization and network reconstruction using the PINTA heat kernel diffusion algorithm demonstrated highly connected networks that were richer in differentiated AEC compared to basal cells. Similar experiments done in basal AEC collected from asthmatic donor lungs demonstrated substantial changes in DE genes and functional categories related to inflammation compared to basal AEC from normal donors. In dAEC, similar but more modest differences were observed. We demonstrate that the AEC transcription signature after MI identifies genes and pathways that are important to the initiation and perpetuation of airway mucosal inflammation. Gene expression occurs quickly after injury and is more profound in differentiated AEC, and is altered in AEC from asthmatic airways. Our data suggest that the early response to injury is substantially different in asthmatic airways, particularly in basal airway epithelial cells.
Topics: Asthma; Bronchi; Chemokines; Epithelial Cells; Gene Expression Profiling; Humans; Mechanical Phenomena; Signal Transduction; Time Factors; Trachea
PubMed: 29534074
DOI: 10.1371/journal.pone.0193334 -
Nature Communications Jan 2018The originally published version of this Article contained an error in Equation 30, which was inadvertently introduced during the production process. This has now been...
The originally published version of this Article contained an error in Equation 30, which was inadvertently introduced during the production process. This has now been corrected in the PDF and HTML versions of the Article.
PubMed: 29386503
DOI: 10.1038/s41467-018-03023-3 -
Breast Cancer (Dove Medical Press) 2017Pleomorphic invasive lobular carcinoma (P-ILC) is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the...
BACKGROUND
Pleomorphic invasive lobular carcinoma (P-ILC) is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic.
MATERIALS AND METHODS
We reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC) and 574 cases of high-grade invasive ductal carcinoma (HG-IDC). We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment.
RESULTS
P-ILC is diagnosed at the same age and tumor diameter as those of the other two histologic types. It is associated more frequently with multiple lymph node metastases and high proliferative index, and HER2/neu is amplified in 10% of cases. In spite of sharing some histologic characteristics with C-ILC (same growth pattern, loss of E-cadherin expression, same genetic pathway), its clinical and pathologic features define an autonomous entity. Its surgical treatment is similar to those of C-ILC and HG-IDC.
CONCLUSION
This is the first review comparing these three pathologic entities. Our findings may be useful in understanding this variety of invasive lobular carcinoma, and further studies are certainly needed in this field.
PubMed: 29263698
DOI: 10.2147/BCTT.S145570 -
Stem Cells International 2017While therapeutically interesting, the injection of MSCs suffers major limitations including cell death upon injection and a massive leakage outside the injection site....
While therapeutically interesting, the injection of MSCs suffers major limitations including cell death upon injection and a massive leakage outside the injection site. We proposed to entrap MSCs within spherical particles derived from alginate, as a control, or from silanized hydroxypropyl methylcellulose (Si-HPMC). We developed water in an oil dispersion method to produce small Si-HPMC particles with an average size of about 68 m. We evidenced a faster diffusion of fluorescein isothiocyanate-dextran in Si-HPMC particles than in alginate ones. Human adipose-derived MSCs (hASC) were encapsulated either in alginate or in Si-HPMC, and the cellularized particles were cultured for up to 1 month. Both alginate and Si-HPMC particles supported cell survival, and the average number of encapsulated hASC per alginate and Si-HPMC particle (7102 and 5100, resp.) did not significantly change. The stimulation of encapsulated hASC with proinflammatory cytokines resulted in the production of IDO, PGE, and HGF whose concentration was always higher when cells were encapsulated in Si-HPMC particles than in alginate ones. We have demonstrated that Si-HPMC and alginate particles support hASC viability and the maintenance of their ability to secrete therapeutic factors.
PubMed: 29158741
DOI: 10.1155/2017/9303598