Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement

As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd2O3 nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r1 and r2 at 1.5 T and 21°C, for Gd2O3 nanoparticles in different cell samples were 3.6–5.3 s−1 mM−1 and 9.6–17.2 s−1 mM−1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd2O3 nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed

Simplified routines in prescribing physical activity can increase the amount of prescriptions by doctors, more than economic incentives only: an observational intervention study

<p>Abstract</p> <p>Background</p> <p>Physical inactivity is one well-known risk factor related to disease. Physical activity on prescription (PAP) has been shown in some studies to be a successful intervention for increasing physical activity among patients with a sedentary lifestyle. The method involves motivational counselling that can be time-consuming for the prescribing doctor and might be a reason why physical activity on prescription is not used more frequently. This study might show a way to make the method of prescribing physical activity more user-friendly. The purpose is to determine whether a change in procedures increases the use of physical activity on prescription, and thus the aim of this study is to describe the methodology used.</p> <p>Results</p> <p>The observational intervention study included an intervention group consisting of one Primary Health Care (PHC) clinic and a control group consisting of six PHC clinics serving 149,400 inhabitants in the County of Blekinge, Sweden.</p> <p>An economic incentive was introduced in both groups when prescribing physical activity on prescription. In the intervention group, a change was made to the process of prescribing physical activity, together with information and guidance to the personnel working at the clinics. Physical therapists were used in the process of carrying out the prescription, conducting the motivational interview and counselling the patient. This methodology was used to minimise the workload of the physician. The chi-2 test was used for studying differences between the two groups. PAP prescribed by doctors increased eightfold in the intervention group compared to the control group. The greatest increase of PAP was seen among physicians in the intervention group as compared to all other professionals in the control group. The economic incentive gave a significant but smaller increase of PAP by doctors.</p> <p>Conclusion</p> <p>By simplifying and developing PAP, this study has shown a concrete way to increase the implementation of physical activity on prescription in general practice, as opposed to what can be gained by an economic bonus system alone. This study indicates that a bonus system may not be enough to implement an evidence-based method.</p

Validating the Johns Hopkins ACG Case-Mix System of the elderly in Swedish primary health care

BACKGROUND: Individualbased measures for comorbidity are of increasing importance for planning and funding health care services. No measurement for individualbased healthcare costs exist in Sweden. The aim of this study was to validate the Johns Hopkins ACG Case-Mix System's predictive value of polypharmacy (regular use of 4 or more prescription medicines) used as a proxy for health care costs in an elderly population and to study if the prediction could be improved by adding variables from a population based study i.e. level of education, functional status indicators and health perception. METHODS: The Johns Hopkins ACG Case-Mix System was applied to primary health care diagnoses of 1402 participants (60–96 years) in a cross-sectional community based study in Karlskrona, Sweden (the Swedish National study on Ageing and Care) during a period of two years before they took part in the study. The predictive value of the Johns Hopkins ACG Case-Mix System was modeled against the regular use of 4 or more prescription medicines, also using age, sex, level of education, instrumental activity of daily living- and measures of health perception as covariates. RESULTS: In an exploratory biplot analysis the Johns Hopkins ACG Case-Mix System, was shown to explain a large part of the variance for regular use of 4 or more prescription medicines. The sensitivity of the prediction was 31.9%, whereas the specificity was 88.5%, when the Johns Hopkins ACG Case-Mix System was adjusted for age. By adding covariates to the model the sensitivity was increased to 46.3%, with a specificity of 90.1%. This increased the number of correctly classified by 5.6% and the area under the curve by 11.1%. CONCLUSION: The Johns Hopkins ACG Case-Mix System is an important factor in measuring comorbidity, however it does not reflect an individual's capability to function despite a disease burden, which has importance for prediction of comorbidity. In this study we have shown that information on such factors, which can be obtained from short questionnaires increases the probability to correctly predict an individual's use of resources, such as medications

Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study

BACKGROUND: Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom syndrome). Thus, genetic variants of BLM and proteins that form complexes with BLM, such as TOP3A and RMI1, might affect cancer risk as well. METHODS: In this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in RMI1, TOP3A, and BLM and their associations with cancer risk in acute myeloid leukemia/myelodysplatic syndromes (AML/MDS; N = 152), malignant melanoma (N = 170), and bladder cancer (N = 61). Two population-based control groups were used (N = 119 and N = 156). RESULTS: Based on consistency in effect estimates for the three cancer forms and similar allelic frequencies of the variant alleles in the control groups, two SNPs in TOP3A (rs1563634 and rs12945597) and two SNPs in BLM (rs401549 and rs2532105) were selected for analysis in breast cancer cases (N = 200) and a control group recruited from spouses of cancer patients (N = 131). The rs12945597 in TOP3A and rs2532105 in BLM showed increased risk for breast cancer. We then combined all cases (N = 584) and controls (N = 406) respectively and found significantly increased risk for variant carriers of rs1563634 A/G (AG carriers OR = 1.7 [95%CI 1.1-2.6], AA carriers OR = 1.8 [1.2-2.8]), rs12945597 G/A (GA carriers OR = 1.5 [1.1-1.9], AA carriers OR = 1.6 [1.0-2.5]), and rs2532105 C/T (CT+TT carriers OR = 1.8 [1.4-2.5]). Gene-gene interaction analysis suggested an additive effect of carrying more than one risk allele. For the variants of TOP3A, the risk increment was more pronounced for older carriers. CONCLUSION: These results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk

Значение пластики лоскутом на временной питающей ножке в замещении раневых дефектов

РАНЫ И ТРАВМЫ /ХИРКОЖИ ТРАНСПЛАНТАЦИЯПЕРЕСАДКА КОЖИДЕРМАТОПЛАСТИКАЛОСКУТЫХИРУРГИЧЕСКИЕ ЛОСКУТЫХИРУРГИЧЕСКИЕ ОПЕРАЦИИ ВОССТАНОВИТЕЛЬНЫЕ /МЕТОДЫИТАЛЬЯНСКАЯ ПЛАСТИКАПЛАСТИКА ИТАЛЬЯНСКАЯРАНЕВЫЕ ПОКРЫТИЯЦель. Провести комплексный анализ возможностей, технических особенностей и недостатков методики пластики ран перемещенным из отдаленных областей сложносоставным кожным лоскутом на временной питающей ножке при закрытии раневых дефектов конечностей. Материал и методы. В исследование включено 14 пациентов с раневыми дефектами конечностей различного происхождения, которым на восстановительном этапе лечения применен метод пластики перемещенным из отдаленных областей сложносоставным кожным лоскутом на временной питающей ножке. Раневые дефекты имели различное происхождение (глубокие отморожения, хронический остеомиелит, нейротрофические нарушения), локализацию и площадь. Показанием к данному виду полнослойной пластики служила необходимость закрытия раны в функционально значимой зоне и невозможность применения других, более простых методов кожной пластики. Результаты. Положительный ближайший результат лечения получен во всех 14 случаях перемещения полнослойных кожных лоскутов из отдаленных частей тела. В 3 случаях в раннем послеоперационном периоде отмечено развитие осложнений (критический перегиб ножки лоскута, подлоскутная гематома, краевой некроз лоскута), не повлиявших существенно на ближайший результат операции. Отдаленные результаты лечения оценены у 8 пациентов в сроки от 1 до 22 лет после операции. Ключевым моментом, определяющим отдаленный результат лечения, стала комплаентность пациента в условиях денервации лоскута и закрытия ран в функционально значимых областях. В двух случаях у пациентов, не соблюдающих рекомендации, произошел некроз лоскута в зоне опорной поверхности стопы. В остальных наблюдениях получен стойкий положительный результат. Заключение. Пластика ран перемещенным из отдаленных областей сложносоставным кожным лоскутом является эффективным методом реконструкции в функционально значимых областях в условиях ограниченных пластических резервов окружающей кожи. Денервация таких лоскутов предъявляет дополнительные требования к пациентам в плане соблюдения рекомендаций. Успех операции в отдаленные сроки во многом определяется комплаентностью пациента.Objective. Comprehensive analysis of opportunities, technical features and disadvantages of wound plasty with distant pedicled flap closing wound defects of the limbs was performed. Methods. The study included 14 patients with limb wounds of different origin, who were treated using distant pedicled flaps grafting. Wounds were of different origin (deep frostbites, chronic osteomyelitis, neurotrophic disorders), diverse localization and perimeter. The indication for this type of full-layer plastics was the need to treat the wound in a functionally significant zone and the impossibility of using other, less complex methods of skin grafting. Results. A positive immediate result of treatment was obtained in all 14 cases of distant flaps grafting. The development of complications (critical bend of the pedicle of the flap, sub-flap hematoma, the flap’s edge necrosis) was registered in 3 cases in the early postoperative period, those complications did not significantly affect the immediate outcome of the operation. Long-term outcomes of treatment were evaluated in 8 patients in terms from 1 to 22 years after the operation. The key point determining the long-term treatment outcome was the patient’s compliance in the conditions of denervation of the flap and closure of wounds in functionally important areas. A flap necrosis in the plantar area occurred in two cases in patients, who did not follow the recommendations. In the remaining observations a stable positive result was obtained. Conclusions. The distant pedicled flaps grafting is an effective method of reconstruction in functionally important areas under the conditions of limited plastic reserves of the surrounding skin. Denervation of such flaps exposes additional requirements to patients in terms of compliance with recommendations. The success of the operation in the long term period is largely determined by the patient’s compliance

Arterial hypertension and diastolic blood pressure associate with aortic stenosis

OBJECTIVES: Due to age-related differences in aortic valve structure, it is likely that the pathophysiology of aortic stenosis (AS) and associated risk factors differ between age groups. Here we prospectively studied the influence of traditional cardiovascular risk factors on AS development requiring surgery among patients without concomitant coronary artery disease (CAD) and stratified for age. DESIGN: This study included 322 patients, who had prior to surgery for AS participated in population-based surveys, and 131 of them had no visible CAD upon preoperative coronary angiogram. For each case, we selected four referents matched for age, gender, and geographic area. To identify predictors for surgery, we used multivariable conditional logistic regression with a model including arterial hypertension (or measured blood pressure and antihypertensive medication), cholesterol levels, diabetes, body mass index (BMI), and smoking. RESULTS: In patients without CAD, future surgery for AS was associated with arterial hypertension and elevated levels of diastolic blood pressure in patients younger than 60 years at surgery (odds ratio [95% confidence interval]), (3.40 [1.45-7.93] and 1.60 [1.09-2.37], respectively), and with only impaired fasting glucose tolerance in patients 60 years or older at surgery (3.22 [1.19-8.76]). CONCLUSION: Arterial hypertension and elevated diastolic blood pressure are associated with a risk for AS requiring surgery in subjects below 60 years of age. Strict blood pressure control in this group is strongly advocated to avoid other cardiovascular diseases correlated to hypertension. If hypertension and elevated diastolic blood pressure are risk factors for developing AS requiring surgery need further investigations. Notably, elevated fasting glucose levels were related to AS requiring surgery in older adults without concomitant CAD