The effects of a protein-deficient diet associated with sunflower oil [adequate in 18:2(n-6), poor in 18:3(n-3)] or soybean oil [adequate in both 18:2(n-6) and 18:3(n-3)] on lipid serum and lipoprotein compositions were studied in growing rats. Four groups of rats were fed different diets: SFC (20% casein + 5% sunflower oil); SFd (2% casein + 5% sunflower oil); SC (20% casein + 5% soybean oil); Sd (2% casein + 5% soybean oil). After 28 d, both protein-deficient groups exhibited low concentrations of protein, phospholipid, triacylglycerol and total cholesterol in serum and VLDL. Compared with rats fed 20% casein diets, those fed low protein diets had lower 18:2(n-6) and 20:4(n-6) in phospholipids of serum, VLDL and HDL2-3, and the 20:4(n-6)/18:2(n-6) ratio was twofold higher in triacylglycerols of serum and VLDL. In the SFd-fed group, 22:5(n-6) was higher than in the SFC-fed group for both triacylglycerols and phospholipids in overall lipoprotein fractions studied. In addition, the 20:3(n-9)/20:4(n-6) ratio was 0.1 in HDL2-3 phospholipids of the SFd-fed group. Sunflower oil-fed rats compared with soybean oil-fed rats had greater monounsaturated fatty acids and lower total (n-3) fatty acids in both triacylglycerols and phospholipids of serum, VLDL and HDL2-3, as well as lower total (n-6) fatty acids in serum and VLDL triacylglycerols. Apolipoproteins (apo) of VLDL were drastically depressed in rats fed protein-deficient diets, whereas apo-AI of HDL2-3 showed a particular resistance. Likewise, sunflower oil-fed rats had enhanced apo-B48 of VLDL and apo-C, apo-AII and apo-AIV of HDL2-3. The present findings show that some effects of protein malnutrition were enhanced by alpha-linolenic acid deficiency, in particular reduced (n-6) and (n-3) fatty acid bioavailability.

The aim of this study was to examine empirical dietary patterns in UK adults and their association with sociodemographic characteristics, lifestyle factors, self-reported nutrient intake, nutrient biomarkers, and the Nutrient-based Diet Quality Score (NDQS) using National Diet and Nutrition Survey data 2008-2012 (n = 2083; mean age 49 years; 43.3% male). Four patterns explained 13.6% of the total variance: 'Snacks, fast food, fizzy drinks' (SFFFD), 'Fruit, vegetables, oily fish' (FVOF), 'Meat, potatoes, beer' (MPB), and 'Sugary foods, dairy' (SFD). 'SFFFD' was associated positively with: being male; smoking; body mass index (BMI); urinary sodium; intake of non-milk extrinsic sugars (NMES), fat and starch; and negatively with: age; plasma carotenoids; and NDQS. 'FVOF' was associated positively with: being non-white; age; income; socioeconomic classification (National Statistics Socio-economic Classifications; NSSEC); plasma carotenoids; intake of non-starch polysaccharides and polyunsaturated fatty acids. It was negatively associated with: being male, smoking, BMI, urinary sodium, intake of saturated fat; and NMES and NDQS. Whilst the patterns explained only 13.6% of the total variance, they were associated with self-reported nutrient intake, biomarkers of nutrient intake, sociodemographic and lifestyle variables, and the NDQS. These findings provide support for dietary patterns analyses as a means of exploring dietary intake in the UK population to inform public health nutrition policy and guidance.

OBJECTIVEL5-S1 stand-alone anterior lumbar interbody fusion (ALIF) is a reliable technique to treat symptomatic degenerative disc disease but remains controversial for treatment of isthmic spondylolisthesis. In the present study the authors aimed to identify risk factors of instrumentation failure and pseudarthrosis after stand-alone L5-S1 ALIF and to evaluate whether instrumentation failure influenced the rate of fusion.METHODSThe study included 64 patients (22 [34.4%] male and 42 [65.6%] female, mean age 46.4 years [range 21-65 years]) undergoing stand-alone L5-S1 ALIF using radiolucent anterior cages with Vertebridge plating fixation in each vertebral endplate. Clinical and radiographic data were reviewed, including age, sex, pelvic parameters, segmental sagittal angle (SSA), C7/sacro-femoral distance (SFD) ratio, C7 sagittal tilt, lumbar lordosis (LL), segmental LL, percentage of L5 slippage, L5-S1 disc angle, and posterior disc height ratio. Univariate and multivariate analyses were used to identify risk factors of instrumentation failure and pseudarthrosis.RESULTSAt a mean follow-up of 15.9 months (range 6.6-27.4 months), fusion had occurred in 57 patients (89.1%). Instrumentation failure was found in 12 patients (18.8%) and pseudarthrosis in 7 patients (10.9%). The following parameters influenced the occurrence of instrumentation failure: presence of isthmic spondylolisthesis (p < 0.001), spondylolisthesis grade (p < 0.001), use of an iliac crest bone autograft (p = 0.04), cage height (p = 0.03), pelvic incidence (PI) (p < 0.001), sacral slope (SS) (p < 0.001), SSA (p = 0.003), and LL (p < 0.001). Instrumentation failure was statistically linked to the occurrence of L5-S1 pseudarthrosis (p < 0.001). On multivariate analysis, no risk factors were found.CONCLUSIONSL5-S1 isthmic spondylolisthesis and high PI seem to be risk factors for instrumentation failure in case of stand-alone L5-S1 ALIF, findings that support the necessity of adding percutaneous posterior pedicle screw instrumentation in these cases.

Lung cancer, the deadliest solid tumor among all types of cancer, remains difficult to treat. This is a result of unavoidable exposure to carcinogens, poor diagnosis, the lack of targeted drug delivery platforms and limitations associated with delivery of drug to deep lung tissues. Development of a non-invasive, patient-convenient formula for the targeted delivery of chemotherapeutics to cancer in deep lung tissue is the aim of this study. The formulation consisted of inhalable polyvinylpyrrolidone (PVP)/maltodextrin (MD)-based microparticles (MPs) encapsulating chitosan (CS) nanoparticles (NPs) loaded with either drug only or drug and magnetic nanoparticles (MNPs). Drug release from CS NPs was enhanced with the aid of MNPs by a factor of 1.7 in response to external magnetic field. Preferential toxicity by CS NPs was shown towards tumor cells (A549) in comparison to cultured fibroblasts (L929). The prepared spray freeze dried (SFD) powders for CS NPs and CS MNPs were of the same size at ∼6μm. They had a fine particle fraction (FPF≤5.2μm) of 40-42% w/w and mass median aerodynamic diameter (MMAD) of 5-6μm as determined by the Next Generation Impactor (NGI). SFD-MPs of CS MNPs possess higher MMAD due to the high density associated with encapsulated MNPs. The developed formulation demonstrates several capabilities including tissue targeting, controlled drug release, and the possible imaging and diagnostic values (due to its MNPs content) and therefore represents an improved therapeutic platform for drug delivery to cancer in deep lung tissue.

OBJECTIVE

Effects of polyunsaturated fatty acids (PUFA) on carcinogenesis are discussed controversially. Thus, tumor growth seems to be influenced by type and composition of fat dietary; however, the pathomechanism is still unknown. Therefore, we investigated the impact of different PUFAs on liver metastasis and hepatic lipid peroxidation in a solid model of ductal pancreatic cancer in Syrian hamsters.

METHODS

90 male hamsters were randomized into 6 groups (n = 15). Accordingly groups 2, 4 and 6 received 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kg body weight weekly by subcutaneous injection for 12 weeks in order to induce ductal pancreatic cancer, while groups 1, 3 and 5 were treated with 0.5 ml 0.9% sodium chloride. All hamsters received a standard fat diet (SFD) rich in n-6 PUFA for 16 weeks (2.9% fat). Afterwards, groups 1 and 2 had free access to SFD, while groups 3 and 4 were given a diet enriched with n-3, n-6 and n-9 PUFA (SMOF) and groups 5 and 6 were fed a diet high in n-3 PUFA (FISH-OIL). After 32 weeks all hamsters were sacrificed in order to determine incidence of pancreatic carcinoma and liver metastasis. Furthermore hepatic activities of glutathionperoxidase (GSH-Px) and superoxiddismutase (SOD) as well as levels of lipidperoxidation were analyzed intra- and extrametastatically.

RESULTS

The incidence of liver metastasis was decreased in the FISH-OIL tumor group compared to the SFD and SMOF groups. However, GSH-Px activity was not influenced by different diets. Extrametastatic hepatic SOD activity did not differ between all groups, while intrametastatic hepatic SOD activity in the SFD-BOP group was increased. In the FISH-OIL-BOP and the SMOF-BOP group intrametastatic SOD activity was lower than in non-metastatic hepatic tissue. Furthermore levels of hepatic lipid peroxidation were decreased in the tumor groups treated with fish oil and SMOF compared to the SFD group. Comparing intra- and extrametastatic TBARS concentration there was no difference in the SFD-BOP and the SMOF-BOP groups, while in the FISH-OIL-BOP group intrametastatic TBARS concentration was increased.

CONCLUSIONS

Conclusively, fish oil reduced the incidence of liver metastasis in experimental ductal pancreatic cancer. Maybe this effect is caused by an increase of intrametastatic hepatic lipid peroxidation.

Background & aims: While long-term obesity is a well-known risk factor for esophageal adenocarcinoma (ADC), recent weight loss represents a significant concern in esophageal cancer (EC), in relation with dysphagia and disease aggressiveness. These phenomenons may diversely impact the adipose tissue density, suggested in other cancer settings as an important prognostic biomarker. The analysis of body mass composition (BMC) parameters, including adipose tissue attenuation is studied here in a population of EC operated with curative intent.

Methods: BMC was retrospectively evaluated on Computed-Tomography (CT)-scan images from fluorodeoxyglucose (FDG)-positron-emitting (PET)/CT scans performed as a diagnostic procedure in a cohort of 145 EC patients operated with curative intent The mean subcutaneous (SFD) and visceral fat (VFD) density along with the index (area/height²) (SF index (SFI), VF index (VFI)) were assessed on two adjacent slides at the third lumbar vertebra level by two independent investigators. Overall survival (OS) was calculated from the date of the baseline FDG-PET/CT scan.

Results: Inter-observer correlations are excellent for all BMC parameters (r = 0.94-0.99). As expected, weight loss is associated with worse outcome. We show that low SFD (HR 0.5 (95% CI: 0.3-0.7), p < 0.001) and low VFD (HR 0.6 (95% CI: 0.4-0.9), p = 0.04) at diagnosis are associated with better OS. In contrast, body mass index (BMI) fails to show any relevance in predicting survival.

Conclusions: Adipose tissue density is an important prognostic factor in EC.

Keywords: Adipose tissue density; Body mass composition; CT-scan; Esophageal cancer.

Obesity has become a global health-threat for every age group. It is well known that young mice (10-12 weeks of age) fed a western-type diet (WD) become obese and develop higher cholesterol levels and liver steatosis whereas insulin sensitivity is reduced. Less is known, however, about the effect of a WD on advanced-age mice. Therefore, 10 week-old (young) and 22 month-old (advanced-age), male C57BL/6JRj mice were kept on either a WD or a control diet (SFD) for 15 weeks. In contrast to young mice, advanced-age mice on WD did not show a higher body weight or adipose tissue (AT)-masses, suggesting a protection against diet-induced obesity. Furthermore, plasma adiponectin and leptin levels were not affected upon WD-feeding. A WD, however, did induce more hepatic lipid accumulation as well as increased hepatic expression of the macrophage marker F4/80, in advanced-age mice. There were no significant differences in mRNA levels of uncoupling protein-1 or F4/80 in brown AT (BAT) or of several intestinal integrity markers in colon suggesting that the protection against obesity is not due to excessive BAT or to impaired intestinal absorption of fat. Thus, advanced-age mice, in contrast to their younger counterparts, appeared to be protected against diet-induced obesity.

The purpose of this study was to develop and pilot test an instrument, the Short Functional Dependence Scale (SFDS), to measure functional dependence in the older adult receiving cancer treatment. Patients from 2 oncology clinics affiliated with a teaching hospital participated in this descriptive, quantitative study. Participants consisted of older adults (N = 26; mean age 71, SD = 5; 54% female; 85% Caucasian) receiving chemotherapy intravenously for solid tumor cancer. Patients, nurses, oncologists, and social workers helped select instrument items and establish content validity. Measurements using the SFDS included baseline and follow-up visits. Data analysis included Cronbach alpha to determine internal consistency and repeated measures to evaluate SFDS scores and associated variables. Cronbach alpha ranged from 0.737 to 0.919 for the 12 items of the SFDS. Functional dependence increased with age, surgery, radiation therapy, and lower hemoglobin levels. Compared to participants with other types of cancer, participants with lung cancer were more dependent in basic activities of daily living, but participants with breast cancer had the highest degree of overall functional dependence. The SFDS has content validity and internal consistency. Pilot testing showed that the instrument performed well in differentiating the functional dependencies of patients receiving chemotherapy according to variables of interest.

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28 days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180 mg/dL (10.0 mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140 mg/dL (7.77 mmol/L) during follow-up. The recommended blood glucose target is 140-180 mg/dL (7.7-10 mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c) ≥ 8%) or severe/repeated hypoglycaemia.

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimalizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180mg/dL (10.0mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140mg/dL (7.77mmol/L) during follow-up. The recommended blood glucose target is 140-180mg/dL (7.7-10mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c)≥8%) or severe/repeated hypoglycaemia.

BACKGROUND

Fixation disparity is the condition in which the images of a binocularly fixated object are not imaged on exactly corresponding retinal points, but are still within Panum's fusional areas. Measurements of objective and subjective fixation disparity have indicated that subjective fixation disparity does not indicate the true eye position. However, the effect of the foveal fusional lock (FFL) on the relationship between objective and subjective fixation disparity is still not clear.

METHODS

This relationship was investigated in five subjects. The objective measurements were made using scleral search coils, and at the same time the Sheedy distance disparometer indicated the subjective fixation disparity. Measurements were obtained both with and without an FFL.

RESULTS

It was found that without an FFL there was a significant difference (p<0.05) between subjective and objective fixation disparity, whereas when an FFL was added, the difference was no longer significant. Additionally, the absolute sizes of both SFD and OFD were found to be significantly smaller with the FFL.

CONCLUSIONS

These results indicate that the presence of an FFL makes subjective fixation disparity a more accurate indicator of the objective eye position. An instrument with an FFL should therefore be used clinically. The difference between objective and subjective fixation disparity presumably indicates a change in correspondence.

Background Flow-diverter stents have been successfully used in the treatment of complex aneurysms with limited therapeutic alternatives. We report our experience using the Silk flow diverter (SFD; Balt Extrusion, Montmorency, France) for the treatment of complex aneurysms in four Argentine centers. Methods We conducted a retrospective review of 246 consecutive patients who were treated with the SFD at four Argentine centers between January 2009 and January 2017. The patient and aneurysm characteristics, as well as the details of the procedure, were analyzed. The angiographic and clinical findings were recorded during and immediately after the procedure and at 12-month follow-up. Results Angiography follow-up at 12 months was possible in 235 patients (95.5%) with 282 aneurysms. A total of 265 aneurysms (93.9%) presented with complete occlusion of the aneurysmal sac (class 1) and 17 aneurysms (6.1%) presented with partial occlusion (class 2). The 12-month clinical follow-up showed 11 patients with major events (seven, scale 2; five, scale 3; and two, scale 4). The morbidity and mortality rates were 4.2% (11/289) and 2.1% (5/289), respectively. Conclusions The treatment of aneurysms with the SFD was associated with a low rate of complications and a high percentage of aneurysmal occlusion. These findings suggest that SFD is an effective and safe alternative in the endovascular treatment of complex aneurysms.

Based on the concept of somatization, psychological distress can be experienced as symptoms of physical illness. This suggests a close-fitting intra-individual association between bodily complaints and mood in patients with somatoform disorder (SFD). The contemporaneous day-to-day complaints-mood association was investigated in patients with severe chronic SFD using an ecological momentary assessment (EMA) design. Eleven patients, who had recently received specialized tertiary care treatment for severe chronic SFD, kept an online electronic diary for four consecutive weeks. They were prompted at intervals throughout the day to complete questions on their momentary primary symptoms (pain and fatigue), and mood state (negative and positive). For each measure, day-mean aggregated values were computed and analyzed using linear multilevel (mixed model) regression analysis. Fixed factor results showed that symptoms were associated with both negative mood state (β = 0.47) and positive mood state (β = -0.59). Random results, however, indicated large inter-individual differences, with correlations varying between 0.17 and 0.99 for negative affect, and between -0.88 and 0.14 for positive affect. A substantial day-to-day contemporaneous association between symptoms and affect across subjects, as well as large inter-individual differences in this association, were demonstrated in patients with severe chronic SFD. EMA-data showing the relationship between both negative and (inverse) positive mood and complaints has potential clinical relevance: providing SFD patients with feedback consisting of their personal day-to-day concurrency graph may promote their understanding of their own complaints in a broader context than the somatic area.

Hypertension (HT) is an extreme increment in blood pressure that can prompt a stroke, kidney disease, and heart attack. HT does not show any symptoms at the early stage, but can lead to various cardiovascular diseases. Hence, it is essential to identify it at the beginning stages. It is tedious to analyze electrocardiogram (ECG) signals visually due to their low amplitude and small bandwidth. Hence, to avoid possible human errors in the diagnosis of HT patients, an automated ECG-based system is developed. This paper proposes the computerized segregation of low-risk hypertension (LRHT) and high-risk hypertension (HRHT) using ECG signals with an optimal orthogonal wavelet filter bank (OWFB) system. The HRHT class is comprised of patients with myocardial infarction, stroke, and syncope ECG signals. The ECG-data are acquired from physionet's smart health for accessing risk via ECG event (SHAREE) database, which contains recordings of a total 139 subjects. First, ECG signals are segmented into epochs of 5 min. The segmented epochs are then decomposed into six wavelet sub-bands (WSBs) using OWFB. We extract the signal fractional dimension (SFD) and log-energy (LOGE) features from all six WSBs. Using Student's t-test ranking, we choose the high ranked WSBs of LOGE and SFD features. We develop a novel hypertension diagnosis index (HDI) using two features (SFD and LOGE) to discriminate LRHT and HRHT classes using a single numeric value. The performance of our developed system is found to be encouraging, and we believe that it can be employed in intensive care units to monitor the abrupt rise in blood pressure while screening the ECG signals, provided this is tested with an extensive independent database.

BACKGROUND

In order to reconceptualize somatoform disorders (SFDs), the psychological characteristics of SFD patients are increasingly investigated. The cognitive style of magical thinking (MT) has not been studied so far in patients with SFDs.

METHODS

In a cross-sectional study, 201 allergy workup patients were interviewed using the Structured Clinical Interview for DSM-IV; they answered a set of self-report questionnaires including the Schizotypal Personality Questionnaire subscale for MT and the Patient Health Questionnaire (PHQ). The expression of MT was explored in 61 patients with SFDs compared to 140 patients without SFDs.

RESULTS

Patients with SFDs reached higher scores of MT, also when controlled for gender, depression, and anxiety. In particular, they stated more frequently that they were believers in telepathy (64 vs. 44%) and clairvoyance (43 vs. 16%). MT correlated only weakly with somatization/somatic symptom severity, depression, and anxiety.

CONCLUSIONS

Among allergy workup patients with SFDs we found considerable MT. This indicates that SFD patients may tend to mistake correlation for causality in a more general way, and not just in an illness-related context. The relation to indicators of illness severity (somatic symptom severity/somatization, depression, and anxiety) was relatively weak. Possible implications for research, diagnostics, and therapy are discussed.

BACKGROUND

The mechanisms underlying spontaneous atrial fibrillation (AF) associated with atrial ischemia/infarction are incompletely elucidated. Here, we investigate the mechanisms underlying spontaneous AF in an ovine model of left atrial myocardial infarction (LAMI).

RESULTS

LAMI was created by ligating the atrial branch of the left anterior descending coronary artery. ECG loop recorders were implanted to monitor AF episodes. In 7 sheep, dantrolene-a ryanodine receptor blocker-was administered in vivo during the 8-day observation period (LAMI-D, 2.5 mg/kg, IV, BID). LAMI animals experienced numerous spontaneous AF episodes during the 8-day monitoring period that were suppressed by dantrolene (LAMI, 26.1±5.1; sham, 4.3±1.1; LAMI-D, 2.8±0.8; mean±SEM episodes per sheep, P<0.01). Optical mapping showed spontaneous focal discharges (SFDs) originating from the ischemic/normal-zone border. SFDs were calcium driven, rate dependent, and enhanced by isoproterenol (0.03 µmol/L, from 210±87 to 3816±1450, SFDs per sheep) but suppressed by dantrolene (to 55.8±32.8, SFDs per sheep, mean±SEM). SFDs initiated AF-maintaining reentrant rotors anchored by marked conduction delays at the ischemic/normal-zone border. NOS1 (NO synthase-1) protein expression decreased in ischemic zone myocytes, whereas NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) oxidase and xanthine oxidase enzyme activities and reactive oxygen species (DCF [6-carboxy-2',7'-dichlorodihydrofluorescein diacetate]-fluorescence) increased. CaM (calmodulin) aberrantly increased [3H]ryanodine binding to cardiac RyR2 (ryanodine receptors) in the ischemic zone. Dantrolene restored the physiological binding of CaM to RyR2.

CONCLUSIONS

Atrial ischemia causes spontaneous AF episodes in sheep, caused by SFDs that initiate reentry. Nitroso-redox imbalance in the ischemic zone is associated with intense reactive oxygen species production and altered RyR2 responses to CaM. Dantrolene administration normalizes the CaM response, prevents LAMI-related SFDs, and AF initiation. These findings provide novel insights into the mechanisms underlying ischemia-related atrial arrhythmias.

For the first time, we aimed to estimate the burden of serious fungal infections or diseases (SFD) and highlight national epidemiological features in Serbia. Data on population and underlining conditions were extracted from the Statistical Office of the Republic of Serbia, World Bank, the Institute of Public Health of Serbia, the World Health Organization, National reference laboratory for medical mycology, the national registries of Serbian professional societies, and relevant publications. The population structure/inhabitants in 2016 (not including the autonomous region Kosovo & Metohija) was 7,058,322; with 6,041,743 adults (85.6%). The populations at risk (total cases per year) were: HIV infected 2441; acute myeloid leukemia 212; stem cell transplantation 151; solid organ transplants 59; chronic obstructive pulmonary disease 250,302; adult asthmatics 311,806; adult cystic fibrosis 65; pulmonary tuberculosis 898; lung cancer 7260; intensive care unit admissions 19,821; and renal support 520. Annual fungal disease cases estimated are: candidemia 518; invasive aspergillosis 619; Candida peritonitis 187; Pneumocystis jirovecii pneumonia 62; cryptococcosis 5; mucormycosis or fusariosis 23; severe asthma with fungal sensitization 10,393; allergic bronchopulmonary aspergillosis 9094; chronic pulmonary aspergillosis 448, recurrent Candida vaginitis 135,303; oral candidiasis 208,489; esophageal candidiasis 173, fungal keratitis 70; tinea capitis 300; and onychomycosis 342,721. We expect that 156,825 people suffer from serious SFD each year (2221/100,000), and 409 dies annually. Additionally, the prevalence of superficial infections exceeds 1,008,995 cases (14,295/100,000). The first Rhinosporidium outbreak in Europe was associated with Serbian Silver Lake. The plant pathogen Fusarium seems to be emerging in Serbian pediatric haematooncology settings. Candida auris and endemic mycoses have not been observed to date. These general estimates provide a primer for further efforts to study fungal epidemiology in Serbia.

OBJECTIVE

To evaluate the correlation between osteoporotic vertebral compression fractures and spinal sagittal imbalance, in order to provide a reference for clinical treatment.

METHODS

From September 2013 to March 2015, 60 elderly patients with old osteoporotic vertebral compression factures (observation group) and 60 healthy elderly people (control group) were studied. Whole-spine anteroposterior and lateral view X‑ray photographs were taken from all participants, the number and location of fractured vertebrae were recorded, and sagittal parameters in both groups were compared. The observation group was divided into three subgroups according to the number of fractured vertebrae. The C7/sacrofemoral distance (SFD) ratio in the three subgroups was compared, and the correlation between the number of fractured vertebrae and the C7/SFD ratio was analyzed.

RESULTS

The thoracic kyphotic angle in patients in the observation group was higher than in the control group (P < 0.05), the lumbar lordotic angle in patients in the observation group was lower than in the control group (P < 0.05), the absolute value of the T1 spinopelvic inclination angle in patients in the observation group was lower than in the control group (P < 0.05), and the C7/SFD ratio of patients in the observation group was higher than in the control group (P < 0.05). C7/SFD ratios of the subgroups differed from each other, and the number of fractured vertebrae and C7/SFD ratio were positively correlated.

CONCLUSIONS

Osteoporotic vertebral compression fractures can change local spinal sagittal alignment, multiple vertebral compression fractures can cause spinal sagittal imbalance, and the number of fractured vertebrae and the degree of forward movement of the spine were positively correlated.

In spray freeze-drying (SFD), the solution is typically dispersed into a gaseous cold environment producing frozen microparticles that are subsequently dried via sublimation. This technology can potentially manufacture bulk lyophilized drugs at higher rates compared with conventional freeze-drying in trays and vials because small frozen particles provide larger surface area available for sublimation. Although drying in SFD still has to meet the material collapse temperature requirements, the final characteristics of the respective products are mainly controlled by the spray-freezing dynamics. In this context, the main goal of this work is to present a single droplet spray-freezing model and validate it with previously published simulations and experimental data. For the investigated conditions, the droplet temperature evolutions predicted by the model agree with experiments within an error of ±10%. The proposed engineering-level modeling framework is intended to assist future development of efficient SFD processes and support scale up from laboratory to commercial scale equipment.

We aimed to prepare spray-freeze-dried powder of IgG considering physicochemical stability and aerodynamic aspects. Spray-freeze drying (SFD) exposes proteins to various stresses which should be compensated by suitable stabilizers. The competence of cyclodextrins (CDs), namely beta-cyclodextrin (βCD) and hydroxypropyl βCD (HPβCD), at very low concentrations, was investigated in the presence of separate mannitol- and trehalose-based formulations. Spray-freeze-dried preparations were quantified in terms of monomer recovery and conformation by size exclusion chromatography (SEC-HPLC) and Fourier transform infrared (FTIR) spectroscopy, respectively. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) were employed to identify the thermal characteristics of powders. Particle morphology was visualized by scanning electron microscopy (SEM). Aerodynamic behavior of powders was checked through an Anderson cascade impactor (ACI). Although all formulations protected antibody from aggregation during the SFD process (aggregation < 1%), mannitol-containing ones failed upon the storage (19.54% in the worst case). Trehalose-HPβCD incomparably preserved the formulation with fine particle fraction (FPF) of 51.29%. Crystallization of mannitol resulted in IgG destabilization upon storage. Although employed concentration of CDs is too low (less than 50:1 molar ratio to protein), they successfully served as stabilizing agents in SFD with perfect improvement in aerosol functionality. Graphical Abstract ᅟ.

Alzheimer's disease (AD) is the most common neurodegenerative disease, affecting the elderly at a high incidence. AD is of unknown etiology and currently, no cure is available. Present medication is restricted to treating symptoms; thus, a need exists for the development of effective remedies. Medicinal plants constitute a large pool, from which active compounds of great pharmaceutical potential can be derived. Various Salvia spp. are considered as neuroprotective, and here, the ability of Salvia fruticosa (SF) to protect against toxic effects induced in an AD cell model was partly assessed. Two of AD's characteristic hallmarks are the presence of elevated oxidative stress levels and the cytotoxic aggregation of amyloid beta (Aβ) peptides. Thus, we obtained SF extracts in three different solvents of increasing polarity, consecutively, to evaluate (a) their antioxidant capacity with the employment of the free radical scavenging assay (DPPH^•), of the ferric reducing ability of plasma assay (FRAP), and of the cellular reactive oxygen species assay (DCFDA) and (b) their neuroprotective properties against Aβ _25-35-induced cell death with the use of an MTT assay. All three SF extracts showed a considerable antioxidant capacity, with the methanol (SFM) extract being the strongest. The results of the total phenolic and flavonoid contents (TPC and TFC) of the extracts and of the FRAP and the DCFDA assays showed a similar pattern. In addition, and most importantly, the dichloromethane (SFD) and the petroleum ether (SFP) extracts had an effect on Aβ toxicity, exhibiting a significant neuroprotective potential. To our knowledge, this is the first report of SF extracts demonstrating neuroprotective potential against Aβ toxicity. In combination with their antioxidant capacity, SF extracts may be beneficial in combating AD and other neurodegenerative diseases.

Obesity is a chronic disease with rising worldwide prevalence and largely associated with several other comorbidities, such as cancer, non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome. Hepatic steatosis, a hallmark of NAFLD, is strongly correlated with obesity and has been correlated with changes in the gut microbiota, which can promote its development through the production of short-chain fatty acids (SCFAs) that regulate insulin resistance, bile acid, choline metabolism, and inflammation. Recent studies have suggested a controversial role for the inflammasome/caspase-1 in the development of obesity and non-alcoholic steatohepatitis (NASH). Here, we evaluated the role of inflammasome NLRP3 and caspases 1/11 in the establishment of obesity and hepatic steatosis in diet-induced obese mice, correlating them with the global lipid profile of the liver and gut microbiota diversity. After feeding wild-type, caspases 1/11, and NLRP3 knockout mice with a standard fat diet (SFD) or a high-fat diet (HFD), we found that the caspases 1/11 knockout mice, but not NLRP3 knockout mice, were more susceptible to HFD-induced obesity, and developed enhanced hepatic steatosis even under SFD conditions. Lipidomics analysis of the liver, assessed by MALDI-MS analysis, revealed that the HFD triggered a significant change in global lipid profile in the liver of WT mice compared to those fed an SFD, and this profile was modified by the lack of caspases 1/11 and NLRP3. The absence of caspases 1/11 was also correlated with an increased presence of triacylglycerol in the liver. Gut microbial diversity analysis, using 16S rRNA gene sequencing, showed that there was also an increase of Proteobacteria and a higher Firmicutes/Bacteroidetes ratio in the gut of caspases 1/11 knockout mice fed an HFD. Overall, mice without caspases 1/11 harbored gut bacterial phyla involved with weight gain, obesity, and hepatic steatosis. Taken together, our data suggest an important role for caspases 1/11 in the lipid composition of the liver and in the modulation of the gut microbial community composition. Our results further suggest that HFD-induced obesity and the absence of caspases 1/11 may regulate both lipid metabolism and gut microbial diversity, and therefore may be associated with NAFLD and obesity.

OBJECTIVE

To evaluate the feasibility of using compressed sensing (CS) to accelerate 3D-T1ρ mapping of cartilage and to reduce total scan times without degrading the estimation of T1ρ relaxation times.

METHODS

Fully sampled 3D-T1ρ datasets were retrospectively undersampled by factors 2-10. CS reconstruction using 12 different sparsifying transforms were compared, including finite differences, temporal and spatial wavelets, learned transforms using principal component analysis (PCA) and K-means singular value decomposition (K-SVD), explicit exponential models, low rank and low rank plus sparse models. Spatial filtering prior to T1ρ parameter estimation was also tested. Synthetic phantom (n = 6) and in vivo human knee cartilage datasets (n = 7) were included.

RESULTS

Most CS methods performed satisfactorily for an acceleration factor (AF) of 2, with relative T1ρ error lower than 4.5%. Some sparsifying transforms, such as spatiotemporal finite difference (STFD), exponential dictionaries (EXP) and low rank combined with spatial finite difference (L+S SFD) significantly improved this performance, reaching average relative T1ρ error below 6.5% on T1ρ relaxation times with AF up to 10, when spatial filtering was used before T1ρ fitting, at the expense of smoothing the T1ρ maps. The STFD achieved 5.1% error at AF = 10 with spatial filtering prior to T1ρ fitting.

CONCLUSIONS

Accelerating 3D-T1ρ mapping of cartilage with CS is feasible up to AF of 10 when using STFD, EXP or L+S SFD regularizers. These three best CS methods performed satisfactorily on synthetic phantom and in vivo knee cartilage for AFs up to 10, with T1ρ error of 6.5%.

OBJECTIVE

To evaluate the cost-utility of the treatment with a long acting beta-agonist (LABA) and inhaled corticosteroid (ICS) combination inhaler [salmeterol xinafoate (SAL)/fluticasone propionate (FP) combination inhaler (SFC) (Advair(®))] to continuing on current ICS dose (no ICS dose change) or increased ICS dose [fluticasone propionate (FP)] in patients with uncontrolled asthma in Canada.

METHODS

A cost-utility analysis was conducted from a Canadian public healthcare perspective with a one year time horizon. In the no FP dose change scenarios, remaining on daily low (FP 100 ug BID) or medium (FP 200-250 ug BID) or high dose (FP 500 ug BID) was considered. In the increased FP dose scenarios, doubling the FP dose from low to medium dose and from medium to high dose regimens were considered. A decision model was developed with two health states: "symptom free" or "with symptoms". Clinical efficacy was based on a meta-analysis of relevant randomized controlled trials. Over the one year time horizon the percentage with symptom free days (SFD) was used as the measure of differential treatment scenario effectiveness. Drug costs and non-drug costs were incorporated into the analysis. Utilities, derived from EQ5D scores and health services resource use based on patient diaries for 'symptom free' and 'with symptoms' were based on regression analyses of individual patient data from the Gaining Optimal Asthma controL (GOAL) trial. Costs were assessed by assigning unit cost for each health services resource use for each patient. The incremental cost-utility ratios (ICUR) for SFC vs no FP dose change or increased FP dose were estimated using descriptive statistics. Uncertainty was assessed by deterministic and probabilistic sensitivity analysis (PSA).

RESULTS

Over one year, SFC resulted in an incremental cost per patient of $544-$655 compared to no FP dose change and $47-$380 per year compared to increased FP dose. SFC results in incremental QALYs per patient of 0.0100-0.0149 compared to no FP dose change and 0.0136-0.0152 compared to increased FP dose. The one year ICURs were $43,000 to $54,400 per QALY gained for SFC compared to no FP dose change and $25,000 to $3500 per QALY gained compared to increased FP dose scenarios. The probability of SFC being cost-effective at $50,000 per QALY gained was greater than 75% compared to increased FP dose scenarios and compared to no dose change for patients on low or medium dose FP. The results were robust to changes in assumptions within the model.

CONCLUSIONS

In Canadian patients with inadequately controlled asthma on FP, it is cost-effective to use SFC for patients 12 years and over compared to doubling their FP dose. It is also cost-effective to use SFC for patients on low or medium dose FP compared to remaining on the current FP dose in patients with uncontrolled asthma.