A novel treatment strategy for preterm birth: Intra-vaginal progesterone-loaded fibrous patches

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for intra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth

Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug

Cost-effectiveness comparison between palpation- and ultrasound-guided thyroid fine-needle aspiration biopsies

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).</p> <p>Methods</p> <p>Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc^99mthyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.</p> <p>Results</p> <p>Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.</p> <p>Conclusion</p> <p>Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.</p> <p>Trial registration</p> <p>ClinicalTrials.gov, NCT00571090</p

Does the unification of health financing affect the distribution pattern of out‐of‐pocket health expenses in Turkey?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149529/1/ijsw12389_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149529/2/ijsw12389.pd

Macrovertebrate Paleontology and the Pliocene Habitat of Ardipithecus ramidus

International audienceA diverse assemblage of large mammals is spatially and stratigraphically associated with Ardipithecus ramidus at Aramis. The most common species are tragelaphine antelope and colobine monkeys. Analyses of their postcranial remains situate them in a closed habitat. Assessment of dental mesowear, microwear, and stable isotopes from these and a wider range of abundant associated larger mammals indicates that the local habitat at Aramis was predominantly woodland. The Ar. ramidus enamel isotope values indicate a minimal C4 vegetation component in its diet (plants using the C4 photosynthetic pathway), which is consistent with predominantly forest/woodland feeding. Although the Early Pliocene Afar included a range of environments, and the local environment at Aramis and its vicinity ranged from forests to wooded grasslands, the integration of available physical and biological evidence establishes Ar. ramidus as a denizen of the closed habitats along this continuum

Data Descriptor : A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins

Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.Peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030