Design and development of poly-L/D-lactide copolymer and barium titanate nanoparticle 3D composite scaffolds using breath figure method for tissue engineering applications

In tissue engineering, the scaffold topography influences the adhesion, proliferation, and function of cells. Specifically, the interconnected porosity is crucial for cell migration and nutrient delivery in 3D scaffolds. The objective of this study was to develop a 3D porous composite scaffold for musculoskeletal tissue engineering applications by incorporating barium titanate nanoparticles (BTNPs) into a poly-L/D-lactide copolymer (PLDLA) scaffold using the breath figure method. The porous scaffold fabrication utilised 96/04 PLDLA, dioleoyl phosphatidylethanolamine (DOPE), and different types of BTNPs, including uncoated BTNPs, Al2O3-coated BTNPs, and SiO2-coated BTNPs. The BTNPs were incorporated into the polymer scaffold, which was subsequently analysed using field emission scanning electron microscopy (FE-SEM). The biocompatibility of each scaffold was tested using ovine bone marrow stromal stem cells. The cell morphology, viability, and proliferation were evaluated using FE-SEM, LIVE/DEAD staining, and Prestoblue assay. Porous 3D composite scaffolds were successfully produced, and it was observed that the incorporation of uncoated BTNPs increased the average pore size from 1.6 mu m (PLDLA) to 16.2 mu m (PLDLA/BTNP). The increased pore size in the PLDLA/BTNP scaffolds provided a suitable porosity for the cells to migrate inside the scaffold, while in the pure PLDLA scaffolds with their much smaller pore size, cells elongated on the surface. To conclude, the breath figure method was successfully used to develop a PLDLA/BTNP scaffold. The use of uncoated BTNPs resulted in a composite scaffold with an optimal pore size while maintaining the honeycomb-like structure. The composite scaffolds were biocompatible and yielded promising structures for future tissue engineering applications.Peer reviewe

Population pharmacokinetics of oxycodone in plasma and cerebrospinal fluid after epidural and intravenous administration

Objectives: To establish the first plasma and cerebrospinal fluid (CSF) oxycodone population pharmacokinetic (PopPK) model after epidural (EPI) and intravenous (IV) oxycodone administration.Methods: The study was conducted with 30 female subjects undergoing elective gynecological surgery with epidural analgesia. A parallel single dose of EPI oxycodone with IV placebo (EPI group; n = 18) or IV oxycodone with EPI placebo (IV group; n = 12) was administered. An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for CSF sampling at L3/4. Plasma and CSF for oxycodone analysis were frequently collected. A PopPK model was built using the NONMEM software package.Results: Plasma and CSF oxycodone concentrations were evaluated using separate central plasma and CSF compartments and separate peripheral plasma and CSF compartments. Epidural space served as a depot compartment with transfer to both the plasma and CSF central compartments. The population parameters for plasma clearance and apparent distribution volumes for central and peripheral compartments for plasma and CSF were 37.4 L/h, 90.2 L, 68.9 L, 0.035 L (fixed based on literature), and 0.039 L, respectively.Conclusion: A PopPK model was developed and found to precisely and accurately describe oxycodone time-concentration data in plasma and CSF.Pharmacolog

A New Method for Combined Hyperventilation and Hypoxia Training in a Tactical Fighter Simulator

Physiological episodes are an issue in military aviation. Some non-pressure-related in-flight symptoms are proved to be due to hyperventilation rather than hypoxia. The aim of this study was to validate a new training method provoking hyperventilation during normobaric hypoxia (NH) training in an F/A-18 Hornet simulator. METHODS: In a double-blind setting, 26 fighter pilots from the Finnish Air Force performed 2 setups in a WTSAT simulator in randomized order with full flight gear. Without the pilot's knowledge, 6% O2 in nitrogen or 6% O2 + 4% CO2 in nitrogen was turned on. Ventilation (VE) was measured before, during, and after hypoxia. SpO2 and ECG were monitored and symptoms documented. The subjects performed a tactical identification flight until they recognized symptoms of hypoxia. Thereafter, they performed hypoxia emergency procedures with 100% O2 and returned to the base with a GPS malfunction and executed an instrument landing system (ILS) approach with the waterline HUD mode evaluated by the flight instructor on a scale of 1 to 5. RESULTS: Ventilation increased during normobaric hypoxia (NH) from 12 L · min−1 to 19 L · min−1 at SpO2 75% with 6% O2, and from 12 L · min−1 to 26 L · min−1 at SpO2 77% with 6% O2 + 4% CO2. ILS flight performance was similar 10 min after combined hyperventilation and hypoxia (3.1 with 6% O2 + 4% CO2 and 3.2 with 6% O2). No adverse effects were reported during the 24-h follow-up. DISCUSSION: Hyperventilation-provoking normobaric hypoxia training is a new and well-tolerated method to meet NATO Standardization Agreement hypoxia training requirements

Cancer Risk Near a Polluted River in Finland

The River Kymijoki in southern Finland is heavily polluted with polychlorinated dibenzo-p-dioxins and dibenzofurans and may pose a health threat to local residents, especially farmers. In this study we investigated cancer risk in people living near the river (< 20.0 km) in 1980. We used a geographic information system, which stores registry data, in 500 m × 500 m grid squares, from the Population Register Centre, Statistics Finland, and Finnish Cancer Registry. From 1981 to 2000, cancer incidence in all people (N = 188,884) and in farmers (n = 11,132) residing in the study area was at the level expected based on national rates. Relative risks for total cancer and 27 cancer subtypes were calculated by distance of individuals to the river in 1980 (reference: 5.0–19.9 km, 1.0–4.9 km, < 1.0 km), adjusting for sex, age, time period, socioeconomic status, and distance of individuals to the sea. The respective relative risks for total cancer were 1.00, 1.09 [95% confidence interval (CI), 1.04–1.13], and 1.04 (95% CI, 0.99–1.09) among all residents, and 1.00, 0.99 (95% CI, 0.85–1.15), and 1.13 (95% CI, 0.97–1.32) among farmers. A statistically significant increase was observed for basal cell carcinoma of the skin (not included in total cancers) in all residents < 5.0 km. Several other common cancers, including cancers of the breast, uterine cervix, gallbladder, and nervous system, showed slightly elevated risk estimates at < 5.0 km from the river. Despite the limitations of exposure assessment, we cannot exclude the possibility that residence near the river may have contributed to a small increase in cancer risk, especially among farmers

Cerebrospinal Fluid Diagnostics of Alzheimer’s Disease in Patients with Idiopathic Normal Pressure Hydrocephalus

Background: Alzheimer’s disease (AD) is the most common cause of dementia worldwide and a frequent comorbidity in idiopathic normal pressure hydrocephalus (iNPH). The presence of AD pathology is associated with worse outcomes after a shunt procedure in iNPH. Preoperative diagnosis of AD is challenging in patients with iNPH, which involves reduced concentrations of the cerebrospinal fluid (CSF) AD biomarkers.// Objective: Our aim was to estimate the effect size of iNPH as a factor in CSF levels of AD biomarkers and to test if correction could be used to improve diagnostic value.// Methods: Our cohort included 222 iNPH patients with data in the Kuopio NPH registry and brain biopsy and CSF samples available. We divided the patients into groups according to AD pathology per brain biopsy. For control cohorts, we had CSF samples from cognitively healthy individuals (n = 33) and patients with diagnosed AD and no iNPH (n = 39).// *-31pt// Results: Levels of all investigated biomarkers differed significantly between groups, with the exception of t-Tau levels between healthy individuals and iNPH patients with AD pathology. Applying a correction factor for each biomarker (0.842*Aβ₁ ₋ ₄₂, 0.779*t-Tau, and 0.610*P-Tau₁₈₁) for the effect of iNPH yielded a sensitivity of 2.4% and specificity of 100%. The ratio of P-Tau₁₈₁ to Aβ₁ ₋ ₄₂ was moderately effective in aiding recognition of AD pathology in iNPH patients (sensitivity 0.79, specificity 0.76, area under the curve 0.824). Conclusion: Correcting for iNPH as a factor failed to improve diagnostic effectiveness, but the P-Tau₁₈₁ /Aβ₁ ₋ ₄₂ ratio showed some utility in the diagnosis of AD in iNPH patients

Intracapsular tonsillectomy in the treatment of recurrent and chronic tonsillitis in adults : a protocol of a prospective, single-blinded, randomised study with a 5-year follow-up (the FINITE trial)

Introduction The standard surgical treatment for recurrent or chronic tonsillitis is extracapsular tonsillectomy. Recent studies show that intracapsular tonsillectomy has the potential to reduce the postoperative morbidity of patients undergoing tonsil surgery. The Finnish Intracapsular Tonsillectomy (FINITE) trial aims to provide level I evidence to support the hypothesis that the recovery time from tonsil surgery can be reduced with intracapsular tonsillectomy. Additionally, from this trial, major benefits in quality of life, reduction of postoperative complications, treatment costs and throat symptoms might be gained. Methods and analysis The FINITE trial is a prospective, randomised, controlled, patient-blinded, three-arm clinical trial. It is designed to compare three different surgical methods being extracapsular monopolar tonsillectomy versus intracapsular microdebrider tonsillectomy versus intracapsular coblation tonsillectomy in the treatment of adult patients (16-65 years) suffering from recurrent or chronic tonsillitis. The study started in September 2019, and patients will be enrolled until a maximum of 200 patients are randomised. Currently, we are in the middle of the study with 125 patients enrolled as of 28 February 2022 and data collection is scheduled to be completed totally by December 2027. The primary endpoint of the study will be the recovery time from surgery. Secondary endpoints will be the postoperative pain scores and the use of analgesics during the first 3 weeks of recovery, postoperative haemorrhage, quality of life, tonsillar remnants, need for revision surgery, throat symptoms, treatment costs and sick leave. A follow-up by a questionnaire at 1-21 days and at 1, 6, 24 and 60 months will be conducted with a follow-up visit at the 6-month time point. Ethics and dissemination Ethical approval was obtained from the Medical Ethics Committee of the Hospital District of Southwest Finland (reference number 29/1801/2019). Results will be made publicly available in peer-reviewed scientific journals.Peer reviewe

Kuopio birth cohort - design of a Finnish joint research effort for identification of environmental and lifestyle risk factors for the wellbeing of the mother and the newborn child

Background: A Finnish joint research effort Kuopio Birth Cohort (KuBiCo) seeks to evaluate the effects of genetics, epigenetics and different risk factors (medication, nutrition, lifestyle factors and environmental aspects) during pregnancy on the somatic and psychological health status of the mother and the child. Methods: KuBiCo will ultimately include information on 10,000 mother-child pairs who have given their informed consent to participate in this cohort. Identification of foetal health risk factors that can potentially later manifest as disease requires a repository of relevant biological samples and a flexible open up-to-date data handling system to register, store and analyse biological, clinical and questionnaire-based data. KuBiCo includes coded questionnaire-based maternal background data gathered before, during and after the pregnancy and bio-banking of maternal and foetal samples that will be stored in deep freezers. Data from the questionnaires and biological samples will be collected into one electronic database. KuBiCo consists of several work packages which are complementary to each other: Maternal, foetal and placental metabolism and omits; Paediatrics; Mental wellbeing; Prenatal period and delivery; Analgesics and anaesthetics during peripartum period; Environmental effects; Nutrition; and Research ethics. Discussion: This report describes the set-up of the KuBiCo and descriptive analysis from 3532 parturients on response frequencies and feedback to KuBiCo questionnaires gathered from June 2012 to April 2016. Additionally, we describe basic demographic data of the participants (n = 1172). Based on the comparison of demographic data between official national statistics and our descriptive analysis, KuBiCo represents a cross-section of Finnish pregnant women.Peer reviewe

Risk factors for poor tuberculosis treatment outcome in Finland: a cohort study

<p>Abstract</p> <p>Background</p> <p>We investigated the patient- and treatment-system dependent factors affecting treatment outcome in a two-year cohort of all treated culture-verified pulmonary tuberculosis (TB) cases to establish a basis for improving outcomes.</p> <p>Methods</p> <p>Medical records of all cases in 1995 – 1996 were abstracted to assess outcome of treatment. Outcome was divided into three groups: favourable, death and other unfavourable. Predictors of unfavourable outcome were assessed in univariate and multivariate analysis.</p> <p>Results</p> <p>Among 629 cases a favourable outcome was achieved in 441 (70.1%), 17.2% (108) died and other unfavourable outcome took place in 12.7% (80). Significant independent risk factors for death were male sex, high age, non-HIV -related immunosuppression and any other than a pulmonary specialty being responsible for stopping treatment. History of previous tuberculosis was inversely associated with the risk of death. For other unfavourable treatment outcomes, significant risk factors were pause(s) in treatment, treatment with INH+RIF+EMB/SM, and internal medicine specialty being responsible at the end of the treatment.</p> <p>Conclusion</p> <p>We observed a significant association with unfavourable outcome for the specialty responsible for treatment being other than pulmonary, but not for the volume of cases, which has implications for system arrangements. Poor outcomes associated with immunosuppression and advanced age, with frequent comorbidity, stress a low threshold of suspicion, availability of rapid diagnostics, and early empiric treatment as probable approaches in attempting to improve treatment outcomes in countries with very low incidence of TB.</p

Intracapsular tonsillectomy in the treatment of recurrent and chronic tonsillitis in adults: a protocol of a prospective, single-blinded, randomised study with a 5-year follow-up (the FINITE trial)

INTRODUCTIONThe standard surgical treatment for recurrent or chronic tonsillitis is extracapsular tonsillectomy. Recent studies show that intracapsular tonsillectomy has the potential to reduce the postoperative morbidity of patients undergoing tonsil surgery. The Finnish Intracapsular Tonsillectomy (FINITE) trial aims to provide level I evidence to support the hypothesis that the recovery time from tonsil surgery can be reduced with intracapsular tonsillectomy. Additionally, from this trial, major benefits in quality of life, reduction of postoperative complications, treatment costs and throat symptoms might be gained.METHODS AND ANALYSISThe FINITE trial is a prospective, randomised, controlled, patient-blinded, three-arm clinical trial. It is designed to compare three different surgical methods being extracapsular monopolar tonsillectomy versus intracapsular microdebrider tonsillectomy versus intracapsular coblation tonsillectomy in the treatment of adult patients (16-65 years) suffering from recurrent or chronic tonsillitis. The study started in September 2019, and patients will be enrolled until a maximum of 200 patients are randomised. Currently, we are in the middle of the study with 125 patients enrolled as of 28 February 2022 and data collection is scheduled to be completed totally by December 2027. The primary endpoint of the study will be the recovery time from surgery. Secondary endpoints will be the postoperative pain scores and the use of analgesics during the first 3 weeks of recovery, postoperative haemorrhage, quality of life, tonsillar remnants, need for revision surgery, throat symptoms, treatment costs and sick leave. A follow-up by a questionnaire at 1-21 days and at 1, 6, 24 and 60 months will be conducted with a follow-up visit at the 6-month time point.ETHICS AND DISSEMINATIONEthical approval was obtained from the Medical Ethics Committee of the Hospital District of Southwest Finland (reference number 29/1801/2019). Results will be made publicly available in peer-reviewed scientific journals.</p