Molecular and histological studies of bladder wound healing in a rodent model

The field of regenerative medicine encounters different challenges. The success of tissue‐engineered implants is dependent on proper wound healing. Today, the process of normal urinary bladder wound healing is poorly characterized. We aspired to explore and elucidate the natural response to injury in an in vivo model in order to further optimize tissue regeneration in future studies. In this study, we aimed to characterize histological and molecular changes during normal healing in a rat model by performing a standardized incisional wound followed by surgical closure. We used a rodent model (n = 40) to follow the healing process in the urinary bladder for 28 days. Surgical exposure of the bladder without incision (n = 40) was performed in controls. Histological characterization and western blot analyses of proteins was carried out using specific staining and markers for inflammation, proliferation, angiogenesis, and tissue maturation. For the molecular characterization of gene expression total RNA was collected for RT²‐PCR in wound healing pathway arrays. Analysis of histology revealed distinct, but overlapping, phases of healing with a local inflammatory response (days 1‐8) simultaneous with a rapid formation of granulation tissue and proliferation (days 2‐8). We also identified significant changes in gene expression related to inflammation, proliferation, and extracellular matrix formation. Healing of an incisional wound in a rodent urinary bladder demonstrated that all the classical phases of wound healing: hemostasis, inflammation, proliferation followed by tissue maturation were present. Our data suggest that the bladder and the skin share similar molecular signaling during wound healing, although we noted differences in the duration of each phase compared to previous studies in rat skin. Further studies will address whether our findings can be extrapolated to the human bladder.     

Liquid phase assisted grain growth in Cu2ZnSnS4 nanoparticle thin films by alkali element incorporation

The effect of adding LiCl, NaCl, and KCl to Cu₂ZnSnS₄ (CZTS) nanoparticle thin-film samples annealed in a nitrogen and sulfur atmosphere is reported. We demonstrate that the organic ligand-free nanoparticles previously developed can be used to produce an absorber layer of high quality. The films were Zn-rich and Cu-poor, and no secondary phases except ZnS could be detected within the detection limit of the characterization tools used. Potassium was the most effective alkali metal to enhance grain growth, and resulted in films with a high photoluminescence signal and an optical band gap of 1.43 eV. The alkali metals were introduced in the form of chloride salts, and a significant amount of Cl was detected in the final films, but could be removed in a quick water rinse.

We present a route where organic ligand-free, KCl-functionalized Cu₂ZnSnS₄ nanoparticles grow into large, dense grains during annealing in nitrogen/sulfur atmosphere.

Thin-film photovoltaic materials with an absorber layer consisting of either CuInGaSe₂ (CIGS) or CdTe exhibit high power conversion efficiencies of 22.6% and 22.1%, respectively, and are already available on the solar panel market.¹ However, due to the relatively poor abundance of In, Ga, and partly Te, as well as the toxicity of Cd, it is important to look for substituting compounds, and here Cu₂ZnSnS₄ (CZTS) is a promising alternative. CZTS has reached a record efficiency of 9.5%,¹ and it has a high absorption coefficient of >10⁴ cm⁻¹ and a direct band gap of 1.45–1.51 eV, which furthermore also makes it an interesting material for a tandem solar cell with silicon.²For solution-processed CZTS, the current record efficiency for a nanoparticle solar cell is 4.8%,³ while devices made from molecular/precursor inks approach 6%.⁴ For the molecular precursor route, the synthesis step is circumvented, which should favor this method. It is, however, still important to develop the nanoparticle approach, as it allows a higher concentration of CZTS in the ink, and therefore facilitates different deposition techniques. As it is yet unknown which method will work best for future upscaling it is important to have different technologies.One challenge for the nanoparticle approach is to obtain uniform grain growth during the annealing step.³ CZTS nanoparticles are typically synthesized with long hydrocarbons as ligands/surfactants, e.g. oleylamine (OLA). After annealing thin films consisting of these particles, the formation of large grains on the surface can be observed, while a fine-grain layer is formed at the bottom interface.^3,5,6 This fine-grained material contains carbon, and its effect on the solar cell is not known. Even with ligands consisting of shorter hydrocarbon chains,⁶ the annealed CZTS nanoparticle film will remain porous. Therefore, it seems that solid state material diffusion which promotes grain growth is very slow under the specific annealing conditions.Grain growth in the form of sintering is desired as it can result in a dense film. In sintering particles are merged at a temperature below the melting point, and it occurs to minimize the surface area and thus the surface energy of a colloidal system.^7,8 The rate of sintering can be increased by hot pressing, impurity doping to enhance grain boundary diffusion, or incorporating an element that becomes a liquid phase at elevated temperature, i.e. liquid phase reactive sintering.^7,8For solution-processed CZTS, both hot-pressing⁹ and including a dopant have been attempted with promising film morphologies. Typically, the alkali metals Na and K are used, but promising results have also been achieved for Li and Sb. The incorporation of these elements has been done through a selection of different processes. For precursor CZTS films, the dopants can be incorporated directly in the ink, which has resulted in some of the highest efficiencies to date when using Sb(OAc)₃ and NaCl.⁴ A common way to include these elements in nanoparticle films is by soaking the film in a sodium salt solution,⁵ or depositing a thin NaF layer on top of the absorber before annealing, which adds an extra vacuum-deposition step;³ for both methods, the beneficial effects of the incorporated elements is typically restricted to the close proximity of the surface, and limited by its diffusion within the film.¹⁰ To obtain a more uniform distribution of incorporated dopants, the surface of the nanoparticles can be functionalized with e.g. SbCl₃,¹¹ or CF₃COONa.¹⁰We have previously reported a one-step synthesis of organic ligand-free nanoparticles, which minimizes the amount of organic material in the film, allows for using solvents like water and ethanol, and furthermore makes it possible to directly dissolve controllable amounts of various chloride salts in the ink.^12,13 In this paper we investigate the effect of LiCl, NaCl, and KCl on the structural evolution and opto-electronic properties of these thin films.     

The Opportunity Costs of Informal Elder-Care in the United States: New Estimates from the American Time Use Survey

ObjectivesTo provide nationally representative estimates of the opportunity costs of informal elder-care in the United States.ConclusionsInformal caregiving remains a significant phenomenon in the United States with a high opportunity cost, although it remains more economical (in the aggregate) than skilled paid care.     

Treatment of infantile hemangiomas before and after the introduction of propranolol: a retrospective study

Background

Propranolol was introduced as systemic pharmacotherapy for problematic hemangiomas in 2008 and is now considered superior to corticosteroid. Other available treatment modalities include surgery and laser therapy. In November 2008, the first patient was treated with propranolol at The Center for Vascular Anomalies, Aarhus University Hospital. The aim of this study was to compare the treatment modalities applied before and after the actual date.

Methods

The present study was a retrospective study of patients treated for hemangioma between 1995 and 2012 at the University Hospital of Aarhus, Denmark. Outcome measures of interest included age at referral, the extent of evaluation by different specialties, and the treatments administered.

Results

One hundred twenty-one patients were included in the study. The patients were divided into two groups, patients treated before (study period 1) and after (study period 2) November 2008, respectively. In study period 2, patients were referred earlier for evaluation (0.82 versus 1.91 years, p?=?0.011). Fewer patients were seen by plastic surgeons in study period 2 (63.9 versus 98.8 %, p?<?0.001), with more patients being referred for systemic treatment (12.9 versus 86.1 %, p?<?0.001). No difference in the number of patients evaluated by dermatologists was detected (p?=?0.417). In study period 2, fewer patients were treated with surgery (38.9 versus 92.2, p?<?0.001) and laser therapy (13.9 versus 42.4, p?=?0.003). After November 2008, more patients have been treated with systemic pharmacotherapy (4.7 versus 80.6 %, p?<?0.001).

Conclusion

The introduction of propranolol has resulted in a decline in surgery and laser therapy at our institution. More patients are being referred for systemic pharmacotherapy due to the treatment protocol of propranolol. Level of Evidence: Level IV, therapeutic study.     

High incidence of Campylobacter concisus in gastroenteritis in North Jutland,Denmark: a population-based study

The incidence of non-thermophilic Campylobacter species was assessed in an unselected population-based study in a mixed urban and rural community in North Jutland, Denmark. In a 2-year study period, 11 314 faecal samples from 8302 patients with gastroenteritis were cultured with supplement of the filter method. We recovered a high incidence of Campylobacter concisus (annual incidence 35/100 000 inhabitants), almost as high as the common Campylobacter jejuni/coli. In contrast, there was a very low incidence of other non-thermophilic Campylobacter species, such as Campylobacter upsaliensis. Campylobacter concisus was, unlike C. jejuni/coli, found more frequently among small children (<1 year) and the elderly (≥65 years). Around 10% of the patients with C. consisus had co-infections dominated by Clostridium difficile and Salmonella enterica, whereas co-infections occurred in about 5% of C. jejuni/coli patients. We observed a seasonal variation in C. jejuni/coli with a peak incidence in late summer months and autumn, whereas there was an almost constant monthly prevalence of C. concisus. Among patients participating in a questionnaire sub-study, there was a higher degree of close contacts with animals, especially dogs, as well as a higher travel exposure among C. jejuni/coli patients compared with C. concisus patients. We did not culture any C. concisus in stool samples from a small cohort of healthy individuals. Future studies have to focus on the clinical follow-up and the long-term risk of inflammatory bowel diseases in C. concisus-positive patients. We conclude that there is a high incidence of C. concisus in Denmark.     

Evidence-Based Digital Tools for Weight Loss Maintenance: The NoHoW Project

BackgroundEffective interventions and commercial programmes for weight loss (WL) are widely available, but most people regain weight. Few effective WL maintenance (WLM) solutions exist. The most promising evidence-based behaviour change techniques for WLM are self-monitoring, goal setting, action planning and control, building self-efficacy, and techniques that promote autonomous motivation (e.g., provide choice). Stress management and emotion regulation techniques show potential for prevention of relapse and weight regain. Digital technologies (including networked-wireless tracking technologies, online tools and smartphone apps, multimedia resources, and internet-based support) offer attractive tools for teaching and supporting long-term behaviour change techniques. However, many digital offerings for weight management tend not to include evidence-based content and the evidence base is still limited.The ProjectFirst, the project examined why, when, and how many European citizens make WL and WLM attempts and how successful they are. Second, the project employed the most up-to-date behavioural science research to develop a digital toolkit for WLM based on 2 key conditions, i.e., self-management (self-regulation and motivation) of behaviour and self-management of emotional responses for WLM. Then, the NoHoW trial tested the efficacy of this digital toolkit in adults who achieved clinically significant (≥5%) WL in the previous 12 months (initial BMI ≥25). The primary outcome was change in weight (kg) at 12 months from baseline. Secondary outcomes included biological, psychological, and behavioural moderators and mediators of long-term energy balance (EB) behaviours, and user experience, acceptability, and cost-effectiveness.ImpactThe project will directly feed results from studies on European consumer behaviour, design and evaluation of digital toolkits self-management of EB behaviours into development of new products and services for WLM and digital health. The project has developed a framework and digital architecture for interventions in the context of EB tracking and will generate results that will help inform the next generation of personalised interventions for effective self-management of weight and health.     

Exercise intervention and health checks for middle-aged men with elevated cardiovascular risk: A randomized controlled trial

Objective. To study the effects of a health check by a nurse alone or combined with an exercise intervention in middle-aged men at increased cardiovascular risk. Design. A randomized controlled trial. Setting and intervention. Primary care in Kirkkonummi municipality with 36 000 inhabitants. A health check by a nurse alone or combined with an exercise intervention to controls with no intervention was compared. Subjects. A total of 168 men aged 35 to 45 years with at least two cardiovascular risk factors and physical activity (PA) frequency < 3 times a week. Main outcome measures. Metabolic syndrome (MetS) as defined by International Diabetes Federation/American Heart Association and self-reported PA frequency. Results. Overall, focusing on health increased physical activity frequency in middle-aged men. After one year, 19% had increased PA to ≥ 3 times a week (95% CI 12–26). All study groups increased PA to ≥ 3 times: 26% of men in the exercise intervention group, 15% of men in the health check group, and 16% of controls. The differences between the groups were not statistically significant. The intervention did not have any meaningful impact on MetS or other cardiovascular outcomes at one-year follow up. Conclusions. Physical activity increased in all study groups of middle-aged men in this health-promotion trial. The interventions had no effect on metabolic syndrome or other cardiovascular outcomes in the participants. The trial increased awareness and collaboration in physical activity promotion among municipal health care and exercise services.Key Words: Cardiovascular risk, exercise intervention, Finland, general practice, health check, metabolic syndromeIt is known that promotion of physical activity in primary care to sedentary adults leads to a small to medium improvement in self-reported physical activity at 12 months.

• A 19% increase was observed at one year in overall self-reported physical activity in middle-aged men who participated in a health-promotion trial.
• The change in physical activity did not have an effect on the health outcomes at one-year follow-up.
• The trial had community effects: groups of men continued exercising together and the trial increased collaboration between health and exercise services in the municipality.