Systemic granulomatous necrotizing vasculitis in a MPO-ANCA-positive patient.
We present a case of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis that demonstrated a systemic granulomatous lesion at autopsy. The patient initially showed anorexia, general malaise and anemia. Colon fiber was examined to detect the bleeding site, which revealed ischemic mucosal damage associated with venous fibrin thrombus. Because a high titer of MPO-ANCA was found, ANCA-associated vasculitis was suspected and the patient was started on steroid pulse therapy. However, anemia, renal failure and respiratory failure worsened and the patient died of sudden cardiac failure 2 days after the start of the therapy. An autopsy revealed systemic arteritis in multiple organs including the kidneys, liver, spleen, gastrointestinal system and genital organs that indicated fibrinoid necrosis accompanied by granulomatous reaction with multinucleated giant cells; the granulomatous reaction further extended along the splenic capsule. Glomerulonephritis and diffuse pulmonary damage, which are common in MPO-ANCA-associated vasculitis, were almost absent but parapleural fibrosis was present. The direct cause of death was presumed to be hemorrhagic shock due to rupture of an aneurysm in the gastric subserosa. As far as we know, this is the first case of a systemic granulomatous reaction in MPO-ANCA-positive vasculitis, although the cause of the granulomatous lesion is unknown.


Formaldehyde as Tethering Organocatalyst: Highly Diastereoselective Hydroaminations of Allylic Amines.
Catalysts possessing sufficient activity to achieve intermolecular alkene hydroaminations under mild conditions are rare, and this likely accounts for the scarcity of asymmetric variants of this reaction. Herein, highly diastereoselective hydroaminations of allylic amines utilizing hydroxylamines as reagents and formaldehyde as catalyst are reported. This catalyst induces temporary intramolecularity, which results in high rate accelerations, and high diastereocontrol with either chiral allylic amines or chiral hydroxylamines. The reaction scope includes internal alkenes. Overall this work provides a new, stereocontrolled route to form complex vicinal diamines.


Leveraging Charge-Transfer Interactions in Through-Space-Coupled Pentacene Dendritic Oligomer for Singlet Exciton Fission.
Singlet exciton fission in organic chromophores has received much attention during the past decade. Inspired by numerous spectroscopic studies in the solid state, there have been vigorous efforts to study singlet exciton fission dynamics in covalently bonded oligomers, which aims to investigate underlying mechanisms of this intriguing process in simplified model systems. In terms of through-space orbital interactions, however, most of covalently bonded pentacene oligomers studied so far fall into weakly interacting systems since they manifest chain-like structures based on various (non)conjugated linkers. Therefore, it remains as a compelling question to answer how through-space interactions in the solid state intervene this photophysical process since it is hypersensitive to displacements and orientations between neighboring chromophores. Herein, as one of experimental studies to answer this question, we introduced a tight-packing dendritic structure whose mesityl-pentacene constituents are coupled via moderate through-space orbital interactions. Based on the comparison with a suitably controlled dendritic structure, which is in a weak coupling regime, important mechanistic viewpoints are tackled such as configurational mixings between singlet, charge-transfer, and triplet pair states and the role of chromophore multiplication. We underscore that our through-space-coupled dendritic oligomer in a quasi-intermediate coupling regime provides a hint on the interplay of multiconfigurational excited-states, which might have drawn complexity in singlet exciton fission kinetics throughout numerous solid-state morphologies.


Impact of the National Health Insurance Coverage Policy on the Utilisation and Accessibility of Innovative Anti-cancer Medicines in China: An Interrupted Time-Series Study.
Objective: The study aimed to evaluate the impact of the National Health Insurance Coverage (NHIC) policy on the utilisation and accessibility of innovative anti-cancer medicines in Nanjing, China. Methods: We used the adjusted World Health Organisation and Health Action International methodology to calculate the price and availability of 15 innovative anti-cancer medicines included in the National Health Insurance drug list in 20 tertiary hospitals and six secondary hospitals in Nanjing before and after NHIC policy implementation. Interrupted time-series regression was used to analyse the changes in the utilisation of the study medicines. Results: The price reduction rates of innovative anti-cancer medicines ranged between 34 and 65%. The mean availability rate was 27.44% before policy implementation and increased to 47.33% after policy implementation. The utilisation of anti-cancer medicines suddenly increased with a slope of 33.19-2,628.39 when the policy was implemented. Moreover, the usage rate of bevacizumab, bortezomib, and apatinib significantly increased (p < 0.001, p = 0.009, and p < 0.001, respectively) after policy implementation. With regard to price reduction and medical insurance reimbursement, the medicines became more affordable after policy implementation (0.06-1.90 times the per capita annual disposable income for urban patients and 0.13-4.46 times the per capita annual disposable income for rural patients). Conclusion: The NHIC policy, which was released by the central government, effectively improved the utilisation and affordability of innovative anti-cancer medicines. However, the availability of innovative anti-cancer medicines in hospitals remained low and the utilisation of innovative anti-cancer medicines was affected by some factors, including the incidence of cancer, limitation of indications within the insurance program, and the rational use of innovative anti-cancer medicines. It is necessary to improve relevant supporting policies to promote the affordability of patients. The government should speed up the process of price negotiation to include more innovative anti-cancer medicines in the medical insurance coverage, consider including both medical examinations and adjuvant chemotherapy in the medical insurance, and increase investment in health care.


Type-2 diabetes: a cocktail of genetic discovery.
Diabetes is one of the most challenging health problems of the 21st century with an alarming increase in the prevalence of type-2 diabetes mellitus (T2DM) and associated conditions such as hypertension, dyslipidemias and obesity. T2DM is a complex genetic disease comprised of many metabolic disorders with a common phenotype of glucose intolerance. Patients with T2DM would have inherited a variety of different genetic factors that together with environmental factors combine as the primary cause. This complicates the genetic study of the disease and means that different methodological approaches are needed if we hope to identify susceptibility genes and genetic variants. The biochemical and physiological processes that underpin T2DM are still unclear although most certainly involve impairment in insulin secretion and insulin action. In this review, we will discuss the most exciting advances in understanding the genetics of T2DM by looking at recent discoveries employing human association studies and candidate genes arising from animal models.


Post-treatment change in serum estrone predicts mammographic percent density changes in women who received combination estrogen and progestin in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
Postmenopausal estrogen and progestin therapy (EPT) increases mammographic percent density and breast cancer risk substantially more than does estrogen therapy alone. We determined whether increases in serum estrone as a function of treatment predict increases in mammographic percent density. We measured mammographic percent density and serum estrone levels in participants in the Postmenopausal Estrogen/Progestin Interventions Trial who were randomly assigned to receive conjugated equine estrogens (CEE) 0.625 mg/d; CEE and medroxyprogesterone acetate (MPA) 10 mg on days 1 to 12 per 28-day cycle; CEE and MPA 2.5 mg/d; or CEE and micronized progesterone (MP) 200 mg on days 1 to 12 per 28-day cycle. We used linear regression to determine whether serum estrone changes predicted mammographic percent density changes from baseline to 1 year. Mammographic percent density increased with increasing change in estrone level in the EPT groups, but not in the CEE group. Combined, the mammographic percent density in the three EPT groups demonstrated an absolute increase of 2.95% per 100 pg/mL increase in serum estrone level (P =.0003). The absolute increases were 4.09% (P =.0018) in the CEE + MPA continuous group, 2.79% (P =.0292) in the CEE + MPA cyclical group, and 1.40% (P =.36) in the CEE + MP group, but the differences among the EPT groups were not statistically significant. Greater increase in serum estrone level as a function of treatment is a significant predictor of increase in mammographic percent density in women randomly assigned to the combination of estrogen and progestin.


Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.
Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.


Adverse effects of increased dietary folate. Relation to measures to reduce the incidence of neural tube defects.
Folate given in the periconceptional period reduced the numbers of births with neural tube defects (NTD) by 75%. Extension of these observations to all those at risk requires an increase in dietary folate, which can only be achieved by fortification of food. This will result in increased folate consumption by the whole population. Folate in excess of 1 mg daily can have adverse effects in patients with untreated cobalamin deficiency, usually undiagnosed pernicious anaemia (PA). In such patients, the anaemia is ameliorated with a return of normoblastic haemopoiesis, but in about half the patients neuropathy progresses or will develop for the first time. If continued long enough, such neuropathy is not reversed by subsequent cobalamin therapy. The lowest dose of folate that proved effective in preventing NTDs was 0.36 mg daily. This amount, added to a diet that already supplies about 0.2 mg folate, will give an average folate intake of 0.56 mg daily. To avoid exceeding this amount of folate significantly, folate should no longer be added to multivitamin preparations or the amount added should be considerably curtailed. Close surveillance should be set up to determine whether adverse effects are produced as a result of folate fortification of food. This surveillance should identify patients developing cobalamin neuropathy in the absence of anaemia and usually with a normoblastic marrow, a situation that is rare at the present time.


Immobilization of radionuclides and heavy metals through anaerobic bio-oxidation of Fe(II).
Adsorption of heavy metals and radionuclides (HMR) onto iron and manganese oxides has long been recognized as an important reaction for the immobilization of these compounds. However, in environments containing elevated concentrations of these HMR the adsorptive capacity of the iron and manganese oxides may well be exceeded, and the HMR can migrate as soluble compounds in aqueous systems. Here we demonstrate the potential of a bioremediative strategy for HMR stabilization in reducing environments based on the recently described anaerobic nitrate-dependent Fe(II) oxidation by Dechlorosoma species. Bio-oxidation of 10 mM Fe(II) and precipitation of Fe(III) oxides by these organisms resulted in rapid adsorption and removal of 55 microM uranium and 81 microM cobalt from solution. The adsorptive capacity of the biogenic Fe(III) oxides was lower than that of abiotically produced Fe(III) oxides (100 microM for both metals), which may have been a result of steric hindrance by the microbial cells on the iron oxide surfaces. The binding capacity of the biogenic oxides for different heavy metals was indirectly correlated to the atomic radius of the bound element. X-ray absorption spectroscopy indicated that the uranium was bound to the biogenically produced Fe(III) oxides as U(VI) and that the U(VI) formed bidentate and tridentate inner-sphere complexes with the Fe(III) oxide surfaces. Dechlorosoma suillum oxidation was specific for Fe(II), and the organism did not enzymatically oxidize U(IV) or Co(II). Small amounts (less than 2.5 microM) of Cr(III) were reoxidized by D. suillum; however, this appeared to be inversely dependent on the initial concentration of the Cr(III). The results of this study demonstrate the potential of this novel approach for stabilization and immobilization of HMR in the environment.


[Renal artery embolization in the treatment of middle-aged and elderly patients with kidney cancer].
Renal artery embolization (RAE) was carried out in 24 renal carcinoma patients aged 60-81. Nineteen of them underwent nephrectomy. Six lethal outcomes were due to RAE complications, of which renal failure and/or purulent inflammation were most frequent (37.5% and 29.2%, respectively). Post-nephrectomy patients as compared to those with prior RAE developed postoperative complications, acute renal failure or aggravation of chronic renal failure 1.4, 1.9, 2.5 times less frequently, respectively. The lethality among them was also less (1.4 times). A 5-year survival for those operated after RAE reached 61.7%, without RAE 30.6%. Despite better results of operative treatment following RAE, it is recommended only for correction of macrohematuria in failure of conservative hemostatic therapy because of high risk of life threatening complications in senile patients. It may be also used in contraindications to surgery or in need of preoperative preparation in the presence of associated diseases.


Bio-Based Covered Stents: The Potential of Biologically Derived Membranes.
The use of bio-based materials (i.e., biologically derived materials that have either a biological origin, including engineered tissues, or a bio-inspired chemical composition) offers the potential to obtain covered stents (CS) with superior performance with respect to the currently available ones, which employ synthetic materials. This will advance and expand the clinical applicability of CS not only in the cardiovascular field but also for the treatment of other target areas such as segments of the respiratory, gastrointestinal, biliary, and urinary tracts.


Sex-related differences of bone properties of pelvic limb and bone metabolism indices in 14-month-old ostriches (Struthio camelus).
1. Sex-related differences of long pelvic limb bones and serum bone metabolism indices were evaluated in 14-month-old female (N = 7) and male (N = 7) ostriches of similar body weights. 2. Densitometric parameters of femur, tibia and tarsometatarsus were determined using quantitative computed tomography (volumetric bone mineral density, calcium hydroxyapatite density and mean volumetric bone mineral density) and dual energy X-ray absorptiometry (bone mineral density and bone mineral content) methods. Geometrical parameters such as cortical bone area, cross-sectional area, second moment of inertia, mean relative wall thickness and cortical index were determined in the midshaft of bones. Mechanical properties of bones (maximum elastic strength and ultimate strength) were evaluated using three-point bending test. Serum concentrations of free amino acids, osteocalcin, N-terminal propeptide of type I procollagen, C-terminal telopeptides of type II collagen and total antioxidative capacity were also determined. 3. Bone weight and relative bone weight of all bones were significantly higher in males than in females. Significantly lower values of trabecular bone mineral density and calcium hydroxyapatite density were found in the trabecular bone of tibia in males. The highest number of the sex-related differences was observed in the tarsometatarsus where bone length, bone mineral content, cortical bone area, cross-sectional area and ultimate strength were higher in males. Serum concentrations of taurine, hydroxyproline, valine and isoleucine were significantly higher in males. 4. Higher loading of the tarsometatarsus in comparison to femur and tibia may be an important factor interacting with sex hormones in regulation of bone formation and mineralisation processes. Sex-related differences of bone properties were associated with increased serum concentration of selected amino acids in males.


Lung cancer in Northern India in relation to age, sex and smoking habits.
Primary lung cancer in Northern India was analysed in relation to age, sex and smoking history in 480 histologically diagnosed cases. The M:F ratio rose progressively up to the 51-60 years age group and was about the same thereafter. The M:F ratio was very high in smokers and was almost identical for all cell types (greater than 20:1). In non-smokers, the M:F ratio differed with the cell type. The smoker:non-smoker ratio differed significantly in the age groups below and above 40. In those up to 40 years of age, the predominant cell type was small cell carcinoma and the cell type had no significant association with smoking habit. Above 40 years of age, the squamous cell type was most common in smokers and adenocarcinoma in non-smokers.


Agonist and antagonist effects of tobacco-related nitrosamines on human α4β2 nicotinic acetylcholine receptors.
Regulation of the "neuronal" nicotinic acetylcholine receptors (nAChRs) is implicated in both tobacco addiction and smoking-dependent tumor promotion. Some of these effects are caused by the tobacco-derived N-nitrosamines, which are carcinogenic compounds that avidly bind to nAChRs. However, the functional effects of these drugs on specific nAChR subtypes are largely unknown. By using patch-clamp methods, we tested 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) on human α4β2 nAChRs. These latter are widely distributed in the mammalian brain and are also frequently expressed outside the nervous system. NNK behaved as a partial agonist, with an apparent EC50 of 16.7 μM. At 100 μM, it activated 16% of the maximal current activated by nicotine. When NNK was co-applied with nicotine, it potentiated the currents elicited by nicotine concentrations ≤ 100 nM. At higher concentrations of nicotine, NNK always inhibited the α4β2 nAChR. In contrast, NNN was a pure inhibitor of this nAChR subtype, with IC50 of approximately 1 nM in the presence of 10 μM nicotine. The effects of both NNK and NNN were mainly competitive and largely independent of Vm. The different actions of NNN and NNK must be taken into account when interpreting their biological effects in vitro and in vivo.


Systematic differences in effect estimates between observational studies and randomized control trials in meta-analyses in nephrology.
The limited availability of randomized controlled trials (RCTs) in nephrology undermines causal inferences in meta-analyses. Systematic reviews of observational studies have grown more common under such circumstances. We conducted systematic reviews of all comparative observational studies in nephrology from 2006 to 2016 to assess the trends in the past decade. We then focused on the meta-analyses combining observational studies and RCTs to evaluate the systematic differences in effect estimates between study designs using two statistical methods: by estimating the ratio of odds ratios (ROR) of the pooled OR obtained from observational studies versus those from RCTs and by examining the discrepancies in their statistical significance. The number of systematic reviews of observational studies in nephrology had grown by 11.7-fold in the past decade. Among 56 records combining observational studies and RCTs, ROR suggested that the estimates between study designs agreed well (ROR 1.05, 95% confidence interval 0.90-1.23). However, almost half of the reviews led to discrepant interpretations in terms of statistical significance. In conclusion, the findings based on ROR might encourage researchers to justify the inclusion of observational studies in meta-analyses. However, caution is needed, as the interpretations based on statistical significance were less concordant than those based on ROR.


Incidence of Guillain-Barré syndrome during a nationwide oral poliovirus vaccine campaign.
Concomitant with a nationwide oral poliovirus vaccine (OPV) campaign in Finland in 1985, an unexpected rise in the number of patients hospitalized with the Guillain-Barré syndrome (GBS) occurred. An analysis based on hospital records covering a population of 1.17 million and 6 years revealed a significantly increased incidence of GBS coinciding with the OPV campaign. We carefully examined 10 cases with onset of GBS within 10 weeks after immunization. Only 4 patients could recall recent symptomatic infection, and we found no specific agent in these cases. Our study suggests that live-attenuated polioviruses may, like other infectious viruses, sometimes trigger the GBS.


Type specific and genotype cross reactive B epitopes of the L1 protein of HPV16 defined by a panel of monoclonal antibodies.
Mouse monoclonal antibodies (mAbs) were raised against the major capsid protein, L1, of human papillomavirus type 16 (HPV16), produced in Escherichia coli with the expression plasmid pTrcL1. Epitope specificity could be assigned to 11 of these 12 antibodies using a series of linear peptides and fusion proteins from HPV16. One mAb (MC53) recognized a novel linear epitope that appears to be unique to the HPV16 genotype. A further 11 mAbs were characterized as recognizing novel and previously defined linear and conformational epitopes shared among more than one HPV genotype. The apparently genotype specific mAb could be useful for the development of diagnostic tests for vegetative virus infection in clinical specimens.


Exact Results for Quenched Bond Randomness at Criticality.
We introduce an exact replica method for the study of critical systems with quenched bond randomness in two dimensions. For the q-state Potts model, we show that a line of renormalization group fixed points interpolates from weak to strong randomness as q-2 grows from small to large values. This theory exhibits a q-independent sector, and allows at the same time for a correlation length exponent which keeps the Ising value and continuously varying magnetization exponent and effective central charge. These findings appear to solve long-standing numerical and theoretical puzzles, and to illustrate the peculiarities which may characterize the conformal field theories of random fixed points.


Matrine inhibits the activity of translation factor eIF4E through dephosphorylation of 4E-BP1 in gastric MKN45 cells.
Matrine, from Sophora flavescens, could remarkably inhibit tumor growth and induce apoptosis in various cancer cells in vitro. eIF4E and its inhibitor 4E-BP1 play key roles in regulating mRNA translation and cell proliferation. However, it remained elusive whether matrine inhibited cancer cells growth through attenuating the activity of 4E-BP1. In this study, we analyzed the effects of matrine on 4E-BP1 and eIF4E in gastric cancer MKN45 cells. Immunoblots showed that matrine inhibited the activity of eIF4E through dephosphorylation of 4E-BP1 in a dose- and time-dependent manner. We found that matrine inactivated Erk1/2, an upstream regulator of 4E-BP1 and eIF4E, and remarkably reduced the phosphorylation level of 4E-BP1 and eIF4E, whereas 4E-BP1 was little influenced by JNK, p38 or Akt/mTOR. Inactivation of PP2A obviously decreased the phosphorylation of 4E-BP1 in matrine-treated cells. These findings suggested that matrine inhibits the activity of eIF4E by dephosphorylating 4E-BP1, which partly counts for the growth inhibition in gastric MKN45 cells.


High-sensitivity GafChromic film dosimetry for 125I seed.
The dose response of high-sensitivity GafChromic film to photons from 125I seeds for doses up to 200 Gy was established. The optical densities were measured using two types of densitometers: (a) a Macbeth spot densitometer with broadband light spectrum, and (b) an LKB He-Ne laser scanning microdensitometer with red light of wavelength 632.8 nm. The net optical density was found to be a power function of dose with exponents of 0.858 and 0.997, for the Macbeth and LKB densitometers, respectively. Film sensitivity with the LKB densitometer was about double of that with the Macbeth densitometer. The dose measurements were performed using the high-sensitivity GafChromic films for 125I model 6702 seed in solid water phantom. Each film was positioned parallel to the seed's long axis and centered at the seed's transverse axis. Films were exposed at various distances, ranging from contact to 3 cm from the seed center. The radiation dose delivered to the film center varied from 7 to 50 Gy, depending on the distance. The optical density at the film center was measured using both types of densitometers. Dose conversion was achieved with the established dose response curves for the respective densitometers. The dose values, along the seed's transverse axis obtained using both densitometers, were compared with each other, and also compared with published thermoluminescent dosimeter (TLD) data and Monte Carlo results. General agreement was found. It was concluded that the high-sensitivity GafChromic film measurement is a feasible method for 125I seed dosimetry in solid water phantom.(ABSTRACT TRUNCATED AT 250 WORDS)


[Simultaneous Analysis of 18 Glucocorticoids in Surface Water].
A method of ultra-performance liquid chomatography tandam mass spectrometry(UPLC-MS/MS) combined with solid-phase extraction (SPE) has been developed for simultaneous analysis of 18 glucocorticoids in surface water. The analytes were first enriched and purified through a HLB cartridge, and eluted with acetonitrile/ethyl acetate (1:1, V/V), then detected by UPLC-MS/MS. The detection used gradient elution process with methanol and 0. 1% formic acid/water (V/V) as the mobile phase to achieve baseline separations of these 18 analytes. The linear range was 1. 0-1 000 µg.L-1. The method detection limits (MDLs) were 0. 10-1. 0 ng.L-1 except for cortisone acetate and cortisol acetate(10 ng.L-1) with overall mean recoveries of 65% - 108% in surface water. Application of this method for 5 surface waters from Beijing area showed that 8 glucocorticoids were detected with the concentration range of 0. 20-476 ng.L-1. Triamcinolone, triamcinolone acetonide, cortisol acetate and clobetasol propionate were detected for the first time in surface water samples, suggesting that this method is efficient for real sample analysis.


Adeno-associated virus RNA transcription in vivo.
We have studied RNA transcripts of the defective parvovirus, adeno-associated virus (AAV) present in poly(A)rich and poly-(A)free fractions of nuclear and cytoplasmic RNA prepared from cells infected together with a helper adenovirus. Cytoplasmic poly-(A)rich RNA contains three overlapping spliced AAV RNAs having sizes of 3.9 X 10(3), 3.3 X 10(3) and 2.3 X 10(3) bases respectively. The nuclear precursors of these RNAs appear to be the coterminal unspliced poly(A)-rich RNAs containing 4.2 X 10(3), 3.6 X 10(3) and 2.6 X 10(3) bases respectively. These unspliced RNAs were also found in the cytoplasm. The nuclear poly(A)-free RNA contained a heterogenous population of AAV RNAs that were generally smaller than 2.3 X 10(3) bases. In addition, the Hirt pellet fraction of the nuclear RNA contained two discrete AAV poly(A)-free RNAs having sizes of 2.5 X 10(3) and 2.8 X 10(3) bases. The 4.2 X 10(3) and 3.6 X 10(3)-base unspliced RNAs are more abundant than the coterminal 3.9 X 10(3) and 3.3 X 10(3)-base spliced RNAs whereas the 2.3 X 10(3)-base spliced RNA is much more abundant than the 2.6 X 10(3)-base unspliced RNA. Thus, the cytoplasmic abundance of the AAV spliced RNAs appears to be controlled in part by the post-transcriptional events of splicing or message stability. We also analysed the effects of AAV defective-interfering genomes upon AAV transcription. These studies showed that when synthesis of standard AAV genomes was inhibited more than 10-fold by defective-interfering genomes there was no significant effect on the types or amounts of AAV RNA transcripts which accumulated. These observations indicate that interference by defective-interfering genomes occurs mostly at the level of DNA replication rather than transcription.


p66shc siRNA-Encapsulated PLGA Nanoparticles Ameliorate Neuropathic Pain Following Spinal Nerve Ligation.
p66shc, a member of the shc adaptor protein family, has been shown to participate in regulation of mitochondrial homeostasis, apoptosis, and autophagosome formation. The present study was performed to investigate whether p66shc siRNA-encapsulated poly(d,l-lactic-co-glycolic acid) nanoparticles (p66shc siRNA-PLGA NPs) can attenuate spinal nerve ligation (SNL)-induced neuropathic pain in rats. The SNL-induced pain behavior was decreased in the p66shc siRNA-PLGA NP-treated group compared with the scrambled siRNA-PLGA NP-treated group. In the L5 spinal cord of the p66shc siRNA-PLGA NP-treated group, expression levels of phosphorylated p66shc, cleaved caspase-3, p62, and PINK1, as well as microglial activation, were also decreased. In addition, p66shc knockdown using p66shc siRNA reduced the expression levels of cleaved caspase-3, p62, and PINK1, as well as proinflammatory mediators in the H2O2-treated HT22 neuronal cells. These results suggest that downregulation of p66shc expression in the spinal cord using p66shc siRNA-PLGA NPs could reduce the SNL-induced neuropathic pain by attenuating the SNL-induced aberrant autophagic, mitophagic, and neuroinflammatory processes in rats.


Prediction of SAMPL2 aqueous solvation free energies and tautomeric ratios using the SM8, SM8AD, and SMD solvation models.
We applied the solvation models SM8, SM8AD, and SMD in combination with the Minnesota M06-2X density functional to predict vacuum-water transfer free energies (Task 1) and tautomeric ratios in aqueous solution (Task 2) for the SAMPL2 test set. The bulk-electrostatic contribution to the free energy of solvation is treated as follows: SM8 employs the generalized Born model with the Coulomb field approximation, SM8AD employs the generalized Born approximation with asymmetric descreening, and SMD solves the nonhomogeneous Poisson equation. The non-bulk-electrostatic contribution arising from short-range interactions between the solute and solvent molecules in the first solvation shell is treated as a sum of terms that are products of geometry-dependent atomic surface tensions and solvent-accessible surface areas of the individual atoms of the solute. On average, three models tested in the present work perform similarly. In particular, we achieved mean unsigned errors of 1.3 (SM8), 2.0 (SM8AD), and 2.6 kcal/mol (SMD) for the aqueous free energies of 30 out of 31 compounds with known reference data involved in Task 1 and mean unsigned errors of 2.7 (SM8), 1.8 (SM8AD), and 2.4 kcal/mol (SMD) in the free energy differences (tautomeric ratios) for 21 tautomeric pairs in aqueous solution involved in Task 2.


The amplitude of fibrillatory waves on leads aVF and V1 predicting the recurrence of persistent atrial fibrillation patients who underwent catheter ablation.
To evaluate whether the amplitude of fibrillatory wave (F wave) on electrocardiography could predict the recurrence in persistent atrial fibrillation (AF) patients who underwent catheter ablation. All consecutive persistent AF patients who underwent catheter ablation at Peking Union Medical College Hospital between November 2006 and February 2012, were enrolled. The amplitude of F wave was measured on three orthogonal leads (leads I, V1 and aVF) on the Prucka CardioLab recording system. The primary end point was the recurrence after catheter ablation. A total of 54 persistent AF patients were enrolled. Fifty patients (age: 58 ± 11years, 72% male) constituted the study population after excluding four patients lost of follow-up. The duration of AF was 9 ± 7 (2-18) months. Twenty-four patients (48%) recurred during the follow-up of 25 ± 19 months, constituted recurrence group. The remaining 26 patients constituted control group. The F-wave amplitude in recurrence group was significantly lower than control group (lead aVF, 0.085 ± 0.018 vs. 0.111 ± 0.036mV, P = 0.002; lead V1 , 0.116 ± 0.031 vs. 0.148 ± 0.047mV, P = 0.008). The amplitudes of leads aVF (P = 0.023) and V1 (P = 0.031) were the independent predictors of AF recurrence. The sensitivity and specificity of F-wave amplitude of lead aVF < 0.093mV or V1 < 0.123mV to predict the recurrence were 75% and 73%, 68% and 64%, respectively. The low amplitudes of F wave in leads aVF and V1 could predict the recurrence of patients with persistent AF who underwent catheter ablation.


Ethanol production from sweet sorghum bagasse through process optimization using response surface methodology.
In this study, comparative evaluation of acid- and alkali pretreatment of sweet sorghum bagasse (SSB) was carried out for sugar production after enzymatic hydrolysis. Results indicated that enzymatic hydrolysis of alkali-pretreated SSB resulted in higher production of glucose, xylose and arabinose, compared to the other alkali concentrations and also acid-pretreated biomass. Response Surface Methodology (RSM) was, therefore, used to optimize parameters, such as alkali concentration, temperature and time of pretreatment prior to enzymatic hydrolysis to maximize the production of sugars. The independent variables used during RSM included alkali concentration (1.5-4%), pretreatment temperature (125-140 °C) and pretreatment time (10-30 min) were investigated. Process optimization resulted in glucose and xylose concentration of 57.24 and 10.14 g/L, respectively. Subsequently, second stage optimization was conducted using RSM for optimizing parameters for enzymatic hydrolysis, which included substrate concentration (10-15%), incubation time (24-60 h), incubation temperature (40-60 °C) and Celluclast concentration (10-20 IU/g-dwt). Substrate concentration 15%, (w/v) temperature of 60 °C, Celluclast concentration of 20 IU/g-dwt and incubation time of 58 h led to a glucose concentration of 68.58 g/l. Finally, simultaneous saccharification fermentation (SSF) as well as separated hydrolysis and fermentation (SHF) was evaluated using Pichia kudriavzevii HOP-1 for production of ethanol. Significant difference in ethanol concentration was not found using either SSF or SHF; however, ethanol productivity was higher in case of SSF, compared to SHF. This study has established a platform for conducting scale-up studies using the optimized process parameters.


Risk factors for thrombosis in an african population.
Little is known about the biological, epidemiological, and clinical risk factors for thrombosis and venous thromboembolism (VTE) among Black Africans. We undertook a study of the prevalence of VTE risk factors for thrombosis in a Senegalese population. A three-year cross-sectional and case-control study involving 105 cases and 200 controls was conducted in various hospitals in Dakar (Senegal). Our results demonstrate that oral contraception, immobilization by casts, surgery, and blood group were significantly associated with VTE occurrence. Additionally, 16 cases and 2 controls had protein S (PS) values of less than 48.4% (M-2SD), exhibiting a highly significant difference (P < 1 × 10(-4)). The number of cases with a low protein C (PC) level was significantly higher than the respective number of controls. Using logistic regression methods, we established a correlation between significantly associated variables and deep venous thrombosis (DVT) occurrence. Age, obesity, sickle cell disease, and PC deficiency were not significantly associated with thrombosis. In contrast, gender, PS deficiency, varicose veins, surgery, non-O blood type, and the presence of antiphospholipid antibodies were significantly and independently associated with DVT. These findings are extremely useful for clinical management of patients suffering from DVT and can help to reduce the high recurrence rate observed in our study.


Reconstructing the Hopfield network as an inverse Ising problem.
We test four fast mean-field-type algorithms on Hopfield networks as an inverse Ising problem. The equilibrium behavior of Hopfield networks is simulated through Glauber dynamics. In the low-temperature regime, the simulated annealing technique is adopted. Although performances of these network reconstruction algorithms on the simulated network of spiking neurons are extensively studied recently, the analysis of Hopfield networks is lacking so far. For the Hopfield network, we found that, in the retrieval phase favored when the network wants to memory one of stored patterns, all the reconstruction algorithms fail to extract interactions within a desired accuracy, and the same failure occurs in the spin-glass phase where spurious minima show up, while in the paramagnetic phase, albeit unfavored during the retrieval dynamics, the algorithms work well to reconstruct the network itself. This implies that, as an inverse problem, the paramagnetic phase is conversely useful for reconstructing the network while the retrieval phase loses all the information about interactions in the network except for the case where only one pattern is stored. The performances of algorithms are studied with respect to the system size, memory load, and temperature; sample-to-sample fluctuations are also considered.


Low Power Multi-Hop Networking Analysis in Intelligent Environments.
Intelligent systems are driven by the latest technological advances in many different areas such as sensing, embedded systems, wireless communications or context recognition. This paper focuses on some of those areas. Concretely, the paper deals with wireless communications issues in embedded systems. More precisely, the paper combines the multi-hop networking with Bluetooth technology and a quality of service (QoS) metric, the latency. Bluetooth is a radio license-free worldwide communication standard that makes low power multi-hop wireless networking available. It establishes piconets (point-to-point and point-to-multipoint links) and scatternets (multi-hop networks). As a result, many Bluetooth nodes can be interconnected to set up ambient intelligent networks. Then, this paper presents the results of the investigation on multi-hop latency with park and sniff Bluetooth low power modes conducted over the hardware test bench previously implemented. In addition, the empirical models to estimate the latency of multi-hop communications over Bluetooth Asynchronous Connectionless Links (ACL) in park and sniff mode are given. The designers of devices and networks for intelligent systems will benefit from the estimation of the latency in Bluetooth multi-hop communications that the models provide.


Effectiveness and safety of sublingual misoprostol in medical treatment of the 1st trimester miscarriage: experience of off-label use in Korea.
This study was conducted to determine the effectiveness and safety of medical treatment with sublingual misoprostol (MS) in the 1st trimester miscarriage under the approval by Health Insurance Review and Assessment Service (HIRA) for off-label usage by the single medical center in Korea. A retrospective cohort study was performed in one institution between April 2013 and June 2016. Ninety-one patients diagnosed with miscarriage before 14 weeks of gestation and wanted to try medical treatment were included. A detailed ultrasound scan was performed to confirm the diagnosis. Patients took 600 microgram (mcg) of MS sublingually at initial dose, and repeated the same dose 4-6 hours apart. Successful medical abortion was defined as spontaneous expulsion of gestational products (including gestational sac, embryo, fetus, and placenta). If gestational products were not expelled, surgical evacuation was performed at least 24 hours later from the initial dose. Information about side effects was obtained by medical records. About two-thirds of patients had a successful outcome. The median interval time from pill to expulsion was 18 hours in the successful medical treatment group. There was no serious systemic side effect or massive vaginal bleeding. Presence or absence of vaginal spotting before diagnosis of miscarriage, uterine leiomyomas, subchorionic hematoma, or distorted shape of gestational sac on ultrasound scan were not statistically different between the two groups. Medical treatment with sublingual MS can be a proper option for the 1st trimester miscarriage, especially for the patient who want to avoid surgical procedure. We can reduce the unnecessary sedation or surgical intervention in the patients with the 1st trimester miscarriage.


Impact of antiretroviral therapy on decreasing hospitalization rates of HIV-infected patients in 2001.
Effective antiretroviral therapy initially resulted in large decreases in hospitalization rates of HIV-infected patients. The goal of this study was to determine whether these gains were being maintained in 2001. A cross-sectional study of hospital admission characteristics during four time periods was performed. All patients receiving care at the HIV clinics of New York Presbyterian Hospital-Cornell Medical Center (NYPH) in New York City were included. In 1995, 883 outpatients were receiving care for HIV infection at NYPH; this increased to 1990 outpatients by 2001. Demographic and laboratory information was obtained for these outpatients, and diagnoses were recorded for all patients requiring hospitalization on at NYPH during the time periods January 1 through June 30, in 1995, 1997, 1999, and 2001. The incidence of hospital admission declined in all four time periods: 1995 (95 per 100 patient-years [pt-yr]), 1997 (48 per 100 pt-yr), 1999 (38 per 100 pt-yr, p < 0.05), and 2001 (25 per 100 pt-yr). The incidence of bacterial pneumonia and opportunistic infections (OIs) decreased in all four time periods. The median hospitalization were CD4(+) cell count for outpatients increased from 231 (1995) to 364 (2001). Important predictors of hospitalization were CD4(+) < 200, and IVDU as an HIV risk factor. Since 1995 and the introduction of highly active antiretroviral therapy, continuing increases in CD4(+) cell counts of outpatients has been reflected in persistent declines in hospitalization rates. Large decreases in OIs and pneumonia have been minimally offset by stable rates of hospital admissions for diagnoses such as hepatitis, cirrhosis, and cellulitis.


What intervention is best practice for vestibular schwannomas? A systematic review of controlled studies.
Largely, watchful waiting is the initial policy for patients with small-sized or medium-sized vestibular schwannoma, because of slow growth and relatively minor complaints, that do not improve by an intervention. If intervention (microsurgery, radiosurgery or fractionated radiotherapy) becomes necessary, the choice of intervention appears to be driven by the patient's or clinician's preference rather than by evidence based. This study addresses the existing evidence based on controlled studies of these interventions. A systematic Boolean search was performed focused on controlled intervention studies. The quality of the retrieved studies was assessed based on the Sign-50 criteria on cohort studies. Pubmed/Medline, Embase, Cochrane Central Register of Controlled Trials and reference lists. Six eligibility criteria included a controlled intervention study on a newly diagnosed solitary, vestibular schwannoma reporting on clinical outcomes. Two prospective and four retrospective observational, controlled studies published before November 2011 were selected. Two reviewers independently assessed the methodological quality of the studies and extracted the outcome data using predefined formats. Neither randomised studies, nor controlled studies on fractionated radiotherapy were retrieved. Six studies compared radiosurgery and microsurgery in a controlled way. All but one were confined to solitary tumours less than 30 mm in diameter and had no earlier interventions. Four studies qualified for trustworthy conclusions. Among all four, radiosurgery showed the best outcomes: there were no direct mortality, no surgical or anaesthesiological complications, but better facial nerve outcome, better preservation of useful hearing and better quality of life. The available evidence indicates radiosurgery to be the best practice for solitary vestibular schwannomas up to 30 mm in cisternal diameter.


Prenatal diagnosis of disease.
We are still in the early days as far as antenatal diagnosis of fetal disease and abnormality are concerned. All of the techniques show a high degree of accuracy if used in the correct circumstances but, apart from the use of maternal blood to assess the Rhesus status and screen for neural tube defects and amniocentesis to search for age-dependent mongolism, present techniques are too cumbersome, inaccurate and dangerous to be offered as routine antenatal tests. The rapid development in ultrasound equipment and expertise and the recent advances in fetal blood sampling and biochemistry suggest that there will be continued and rapid expansion within the field.


Physiological variables, psychosocial factors and age at menarche among Punjabi girls.
The term menarche signifying the onset of menstruation is merely one manifestation of puberty. The age at menarche has been getting earlier all over the world with varying rates. An average decline of about 4 months per decade has been reported from the United States and in Western Europe over the period 1830-1960, while that in Eastern Europe since the late nineteenth century. There have been reports that there is a fairly good correlation between the age of menarche of mothers' and their daughters'. The objective of this study was to find out the present age at menarche among Punjabi girls and correlate it with relevant variables. The age at menarche in the present study has been found to be significantly less as compared to data from the same region (Punjab, India). The decline in the mean age at menarche between the mothers and the daughters was statistically highly significant. There was a positive correlation between menarche and weight, height, triceps skinfold thickness, body mass index and maternal age at menarche. No significant correlation was obtained between menarche and income class and a negative correlation was obtained between menarche and birth order.


Inhibition of the vacuolar H(+)-pump with bafilomycin A1 does not induce acrosome reaction or activate proacrosin in mouse spermatozoa.
Acrosomal protease activation is regarded as an important event triggered by acrosomal reaction and leading to sperm passage through zona pellucida. Mammalian acrosome has an internal acid pH that probably helps to maintain inactive proenzymes that otherwise could be precociously activated and prevent normal fertilization. In this work, we have studied the effect of bafilomycin A1, a potent and specific inhibitor of vacuolar H(+)-pump (V-ATPase), on acrosome reaction and proacrosin activation. We used the pH-sensitive probe Lysotracker Green DND-26 to monitor qualitatively intra-acrosomal pH in cauda epididymal mouse spermatozoa. Our results showed that loss of Lysotracker label induced by bafilomycin A1 (acrosome alkalinization) did not induce acrosome reaction or proacrosin activation. We also developed a new technique for imaging the acrosome, and for evaluating the acrosome reaction, in live mouse spermatozoa using Lysotracker DND-26. These results showed that the V-ATPase is a key regulator of mammalian acrosome pH, and that acrosome alkalinization is not the only prerequisite to activate proacrosin under in vivo conditions. Our results suggest that acrosome alkalinization and acrosome reaction are two processes that could be independently regulated during mammalian sperm capacitation.


A Training Data Set Cleaning Method by Classification Ability Ranking for the k -Nearest Neighbor Classifier.
The k -nearest neighbor (KNN) rule is a successful technique in pattern classification due to its simplicity and effectiveness. As a supervised classifier, KNN classification performance usually suffers from low-quality samples in the training data set. Thus, training data set cleaning (TDC) methods are needed for enhancing the classification accuracy by cleaning out noisy, or even wrong, samples in the original training data set. In this paper, we propose a classification ability ranking (CAR)-based TDC method to improve the performance of a KNN classifier, namely CAR-based TDC method. The proposed classification ability function ranks a training sample in terms of its contribution to correctly classify other training samples as a KNN through the leave-one-out (LV1) strategy in the cleaning stage. The training sample that likely misclassifies the other samples during the KNN classifications according to the LV1 strategy is considered to have lower classification ability and will be cleaned out from the original training data set. Extensive experiments, based on ten real-world data sets, show that the proposed CAR-based TDC method can significantly reduce the classification error rates of KNN-based classifiers, while reducing computational complexity thanks to a smaller cleaned training data set.


Targetting ferroptosis for blood cell-related diseases.
Ferroptosis is an iron-dependent cell death pathway and participates in various diseases. Current evidence suggests that ferroptosis can obviously affect the function of blood cells. This paper aims to elaborate the role of ferroptosis in blood cells and related diseases. First, abnormal ferroptosis damages the developing red blood cells by breaking systemic iron homeostasis, leading to erythropoiesis suppression and anaemia. Ferroptosis mediates neutrophils recruitment and neutrophil extracellular trap formation (NETosis). In T-cells, ferroptosis induces a novel point of synergy between immunotherapy and radiotherapy. Additionally, ferroptosis may mediate B cells differentiation, antibody responses and lymphoma. Nevertheless, increased ferroptosis can ameliorate acute myeloid leukaemia and T-cell leukaemia/lymphoma by inducing iron-dependent cancer cells death. Besides, ferroptosis activates platelets by increasing P-selectin, thus causing thromboembolism. Ferroptosis mediates virus infection and parasite infection by driving T-cell death and preventing T-cell immunity. Interestingly, ferroptosis is also considered as a critical player in COVID-19 infections, while targetting ferroptosis may also improve thromboembolism and prognosis in patients with COVID-19 infection. Overall, the crucial role of ferroptosis in blood cells will show a new therapeutic potential in blood cell-related diseases.HighlightsFerroptosis shows a new therapeutic potential for blood cell-related diseases.Ferroptosis damages erythropoiesis and thus induces anaemia.Ferroptosis induces platelet activation and leads to thromboembolism.Ferroptosis regulates T-cell and B-cell immunity, which participant in infectious diseases.Inversely, ferroptosis ameliorates acute myeloid leukaemia and T-cell leukaemia.


[Comparison of Seven Intubation Devices in Difficult Airway Model].
The efficacy in tracheal intubation may differ between different video-optical devices, in particular in patients with difficult airways. The purpose of this study was to evaluate the efficacy of video-laryngoscopes and fiberoptic bronchoscope (FOB) in tracheal intubation on a mannequin with several difficult airways, including limited mouth opening, cervical spine rigidity and tongue edema. Residents performed tracheal intubation on a mannequin using Macintosh laryngoscope (Mac), rigid indirect-optical intubation devices and FOB. The laryngeal view, the success rate of tracheal intubation, and the time to intubate trachea were recorded. With limited mouth opening and cervical spine rigidity, video-optical intubation devices showed a significantly higher success rate of tracheal intubation than the Mac or FOB. In contrast, with tongue edema, the success rate of tracheal intubation was lower when Mac-type videolaryngoscopes were used. Videolaryngoscopes can generally be useful in patients with all difficult airways, but may be difficult in some circumstances (such as tongue edema). The FOB provided good laryngeal view in all cases, but the success rate of tracheal intubation was low and the time to intubate trachea was long.


Radixin expression in microglia after cortical stroke lesion.
Stroke induces extensive tissue remodeling, resulting in the activation of several cell types in the brain as well as recruitment of blood-borne leucocytes. Radixin is part of a cytoskeleton linker protein family with the ability to connect transmembrane proteins to the actin cytoskeleton, promoting cell functions involving a dynamic cytoskeleton such as morphological changes, cell division and migration which are common events of different cell types after stroke. In the healthy adult brain radixin is expressed in Olig2(+) cells throughout the brain and in neural progenitor cells in the subventricular zone. In the current study, we detected a 2.5 fold increase in the number of radixin positive cells in the peri-infarct cortex two weeks after the induction of cortical stroke by photothrombosis. Similarly, the number of Olig2(+) cells increased in the peri-infarct area after stroke; however, the number of radixin(+)/Olig2(+) cells was unchanged. Neural progenitor cells maintained radixin expression on their route to the infarct. More surprising however, was the expression of radixin in activated microglia in the peri-infarct cortex. Seventy percent of Iba1(+) cells expressed radixin after stroke, a population which was not present in the control brain. Furthermore, activation of radixin was predominantly detected in the peri-infarct region of oligodendrocyte progenitors and microglia. The specific location of radixin(+) cells in the peri-infarct region and in microglia suggests a role for radixin in microglial activation after stroke.


C1-C2 intraarticular distraction with anterior cervical cages for basilar invagination realignment: Operative technique nuances and review of literature.
Neurosurgical management of basilar invagination (BI) has traditionally been aimed at direct cervicomedullary decompression through transoral dens resection or suboccipital decompression with supplemental instrumented fixation. Dr. Goel introduced chronic atlantoaxial dislocation (AAD) as the etiology in most cases of BI and described a technique for distracting the C1-C2 joint with interfacet spacers to achieve reduction and anatomic realignment. We present our modification to Goel's surgical technique, in which we utilize anterior cervical discectomy (ACD) cages as C1-C2 interfacet implants. A young adult male presented to our institution with BI, cervicomedullary compression, occipitalization of C1, and Chiari 1 malformation. There was AAD of C1 over the C2 lateral masses. This reduced some with preoperative traction. He underwent successful C1-C2 interfacet joint reduction and arthrodesis with anterior cervical discectomy (ACD) cages and concomittant occiput to C2 instrumented fusion. BI can be effectively treated through reduction of AAD and by utilizing ACD cages as interfacet spacers.


IgG4-related pleural effusion with high adenosine deaminase levels: A case report and literature review.
Levels of pleural fluid adenosine deaminase (ADA), a useful marker for the diagnosis of tuberculous pleurisy, are elevated in some reports of immunoglobulin G4 (IgG4)-related pleural effusion. We describe a patient with IgG4-related pleural effusion who exhibited a high concentration of ADA. Furthermore, we reviewed the literature to compare patients with IgG4-related pleural effusion and tuberculous pleurisy. A 75-year-old male patient had dyspnea for 1 month with a left pleural effusion that was exudative, lymphocyte dominant. The pleural fluid test results revealed a total protein (TP) concentration of 6.60 g/dl, a lactate dehydrogenase (LDH) level of 383 IU/dl, and an ADA concentration of 54.5 U/L. An interferon gamma release assay showed a negative result. Histological analysis of the thoracoscopic pleural biopsy revealed lymphoplasmacytic infiltration, with 80 IgG4-positive plasma cells/high-power field, and an IgG4/IgG ratio of approximately 40% to 50%. Other diseases were ruled out based on symptoms, negative autoimmune antigen results, and histopathologic findings. Thus, he was diagnosed with IgG4-related pleural effusion. He received 15 mg of prednisolone as therapy. His pleural effusion and symptoms improved gradually within several months, and prednisolone was tapered to 6 mg daily. It is important to distinguish between IgG4-related pleural effusion and tuberculous pleurisy. Therefore, we compared 22 patients with IgG4-related pleural effusion from PubMed and the Japan Medical Abstracts Society to 40 patients with tuberculous pleurisy at Fukujuji Hospital from January 2017 to May 2019. According to thoracentesis findings, 14 of 18 patients with IgG4-related pleural effusion had high ADA more than 40 U/L. The pleural effusion of patients with IgG4-related pleural effusion showed higher TP levels (P < .001) and lower LDH (P < .001) and ADA levels (P = .002) than those with tuberculous pleurisy. Moreover, the pleural fluid ADA/TP ratio was a good predictor for differentiating IgG4-related pleural effusion and tuberculous pleurisy (area under the receiver operating characteristic curve of 0.909; 95% confidence level: 0.824-0.994).


An evaluation of exercise pen use by circus tigers (Pathera tigris tigris).
This study quantified the behavior of 11 tigers during periodic access to an exercise pen throughout the day and night. The study determined the amount of time spent in the pen and the percentage of time spent performing stereotypic pacing, normal locomotor behavior, and lying down while in the pen. Average access to the exercise pen was 10 hr 49 min overnight and 5 hr 30 min during the day. At night, the tigers spent 29.1% of their time in the exercise pen, during which they paced 19.6% and performed normal locomotor behavior for 23.1% of that time. By day, they spent 40.4% of their time in the exercise pen, during which they paced 10.0% and performed normal locomotor behavior 35.7% of that time. The tigers spent the rest of the time in the pen lying down. Overall, tigers will utilize an exercise pen, spending a greater percentage of time in the pen during the day than at night and also performing less stereotyped pacing than at night.


A study of the risk factor profile of cardiovascular diseases in rural Punjabi male patients.
One hundred rural Punjabi males (40-60 years old) admitted to Hero DMC Heart Institute, Ludhiana with first cardiac attack were studied to identify major determinants of cardiovascular diseases (CVD) among this group. The results revealed that 20% and 56% of the subjects were smokers and alcohol takers, respectively. Smoking had a significant (p< or =0.01) correlation with serum LDL-C, triglycerides and systolic blood pressure. 84% had sedentary life style. 36% and 7% of the subjects were overweight and obese. The body mass index was positively and significantly (p< or =0.01) correlated with serum triglycerides. 32% and 20% of the subjects had systolic and diastolic blood pressure above normal. 22% were diagnosed for hyperglycemia. 6% suffered from hypercholesterolemia and 28% had borderline high values of serum cholesterol. 22% and 6% had high triglyceride and LDL-C levels, respectively. The study concluded that the etiology of CVD is multifactorial and no single factor is an absolute cause among the rural Punjabi male patients. Therefore, desirable modification in diet and life style can significantly reduce the risk of CVD among rural males of Punjab.


Advanced carrier systems in cosmetics and cosmeceuticals: a review.
Carrier systems refer to carrier vesicles such as liposomes, nano/microparticles, emulsions, etc., that are coupled with active agents and applied to products to achieve the promoted effects of the active ingredients. This article reviews the recent research on carrier systems, focusing on cosmetic and cosmeceutical applications; the pros and cons of each carrier system and products on the market utilizing the technologies are discussed.


Disturbed eating attitudes and behaviors in South Korean boys and girls: a school-based cross-sectional study.
This study was designed to assess the prevalence and correlates of disturbed eating attitudes and behaviors in South Korean students. In a cross-sectional survey, 2,226 fourth and seventh grade students filled out questionnaires on eating attitudes and behaviors (Eating Attitude Test -26, EAT-26), coping strategies, fear of being overweight, behavioral problems, anxiety, depression, and self-esteem. Disturbed eating attitudes and behaviors were found in 7 percent of students. In the multivariate analyses, disturbed eating attitudes and behaviors were associated with the passive coping strategies, fear of being overweight, total behavioral difficulties, fourth grade, and high socioeconomic status (SES). Differences in the associations were found between boys and girls. There were significant associations between elevated EAT-26 scores and passive coping strategies, desired underweight body mass index (BMI), and low SES in boys; and between elevated EAT-26 scores and passive coping strategies, fear of being overweight, behavioral problems, being in the fourth grade, and high and low SES in girls. In South Korean children, disturbed eating attitudes and behaviors were associated with various psychological and sociocultural factors; some gender-related differences are also evident.


Granular cell tumour (a case report).
The granular cell tumour (GCT) is a relatively uncommon neoplasm that shows a predilection for the oral cavity, especially the tongue. The tumour usually presents as a slow-growing, non-ulcerated nodular mass. It is most common in young and middle-aged adults and is twice as common in women as in men. Some studies have shown it to be relatively more common in coloured people. Multiple granular cell tumours occasionally may occur. Treatment consists of local surgical excision; recurrence is uncommon. This case report presents a case of GCT in a 32 years old woman's tongue and its treatment.


Metahybrid density functional theory and correlated ab initio studies on microhydrated adenine-thymine base pairs.
Monohydrated and dihydrated adenine-thymine base pairs are characterized using metahybrid density functional theory and correlated ab initio approaches. The motivation of this work is twofold. First, the high-level geometries and interaction energies computed for different complexes serve as a reference for the testing of recently developed density functional theory (DFT) with respect to its ability to correctly describe the balance between the electrostatic and the dispersion contributions that bind these complexes. Second, these studies of nucleic acid base pairs are important for finding binding sites of water molecules around bases and for a better understanding of the influence of the solvent on the stability of the structure of DNA duplexes.


Effect of calories-only vs physical activity calorie expenditure labeling on lunch calories purchased in worksite cafeterias.
Calorie labeling on restaurant menus is a public health strategy to guide consumer ordering behaviors, but effects on calories purchased have been minimal. Displaying labels communicating the physical activity required to burn calories may be a more effective approach, but real-world comparisons are needed. In a quasi-experimental study, we examined the effect of physical activity calorie expenditure (PACE) food labels compared to calorie-only labels on point-of-decision food purchasing in three worksite cafeterias in North Carolina. After a year of quarterly baseline data collection, one cafeteria prominently displayed PACE labels, and two cafeterias prominently displayed calorie-only labels. Calories from foods purchased in the cafeteria during lunch were assessed over 2 weeks every 3 months for 2 years by photographs of meals. We compared differences in purchased calorie estimates before and after the labeling intervention was introduced using longitudinal generalized linear mixed model regressions that included a random intercept for each participant. In unadjusted models comparing average meal calories after vs before labeling, participants exposed to PACE labels purchased 40.4 fewer calories (P = 0.002), and participants exposed to calorie-only labels purchased 38.2 fewer calories (P = 0.0002). The small difference of 2 fewer calories purchased among participants exposed to PACE labeling vs calorie-only labeling was not significant (P = 0.90). Models adjusting for age, sex, race, occupation, numeracy level, and health literacy level did not change estimates appreciably. In this workplace cafeteria setting, PACE labeling was no more effective than calorie-only labeling in reducing lunchtime calories purchased.


[Depression and suicide prevention].
Suicide is a major public health problem and the number of suicide victims has exceeded 30,000 a year since 1998 in Japan. The rates of depression are extremely high in suicide victims. Social and environmental factors, such as the slow recovery of Japanese economy, could have a strong effect on depression and suicide, especially in middle-aged men. To reduce the number of suicide victims, we need to use both population-based and high-risk approaches, targeting individuals with high psychological and socioeconomic risks of suicide, especially depressed patients. On the other hand, the role of antidepressants in suicide prevention is a major question given the high prevalence of both depression and depression-related suicidality. Because treatment and prevention of suicide are complex and encompass many factors, success will need multi-sector collaboration.


Frequency-Modulated Continuous Wave Radar Respiratory Pattern Detection Technology Based on Multifeature.
Respiratory diseases including apnea are often accompanied by abnormal respiratory depth, frequency, and rhythm. If different abnormal respiratory patterns can be detected and recorded, with their depth, frequency, and rhythm analyzed, the detection and diagnosis of respiratory diseases can be achieved. High-frequency millimeter-wave radar (76-81 GHz) has low environmental impact, high accuracy, and small volume, which is more suitable for respiratory signal detection and recognition compared with other contact equipment. In this paper, the experimental platform of frequency-modulated continuous wave (FMCW) radar was built at first, realizing the noncontact measurement of vital signs. Secondly, the energy intensity and threshold of respiration signal during each period were calculated by using the rectangular window, and the accurate judgment of apnea was realized via numerical comparison. Thirdly, the features of respiratory and heart rate signals, the number of peaks and valleys, the difference between peaks and valleys, the average and the standard deviation of normalized short-term energy, and the average and the standard deviation and the minimum of instantaneous frequency, were extracted and analyzed. Finally, support vector machine (SVM) and K-nearest neighbor (KNN) were used to classify the extracted features, and the accuracy was 98.25% and 88.75%, respectively. The classification and recognition of respiratory patterns have been successfully realized.


The marmoset: An emerging model to unravel the evolution and development of the primate neocortex.
Throughout evolution, the neocortex has undergone a dramatic expansion providing the substrate for increasingly complex cognitive abilities, culminating with humans. The enlargement of the neocortex did not affect its' basic organization, which is remarkably conserved from rodents to primates. The mouse has thus proven an advantageous model to decipher the molecular and cellular mechanisms supporting neocortical development. However, it is of limited benefit when studying the mechanisms leading to the inclusion of higher order association areas, which form the largest fraction of the primate neocortex. In the quest for a suitable nonhuman primate model to study the developmental mechanism of neocortical patterning and expansion, researchers focussed on the Old World macaque, routinely employed in functional and behavioral studies. However, the species has many limitations making studies difficult and/or impractical. Therefore, in the past couple of decades, the New World common marmoset (Callithrix jacchus) has drawn much attention and become an accepted model. The marmoset has the advantage of a smooth neocortical sheet, enabling the direct correspondence between developing cortices and the comprehensive map established for the adult, with a significant amount of cortical maturation occurring during the postnatal period. This review presents the contributions of recent marmoset studies to our understanding of the mechanisms regulating corticogenesis in a complex species, the molecular control of neocortical patterning and the sequential maturation of visual cortical areas while commenting on the future of the species in the field. Furthermore, while these new findings are relevant to developmental biology, in order to understand how new cortical areas have emerged to expand cognitive abilities, they also represent a foundation for the better understanding of developmental cognitive disorders. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 263-272, 2017.


Terahertz disk resonator on a substrateless dielectric waveguide platform.
Resonant cavities are fundamental to and versatile for terahertz integrated systems. So far, integrated resonant cavities have been implemented in relatively lossy terahertz platforms. In this Letter, we propose a series of integrated disk resonators built into a low-loss substrateless silicon waveguide platform, where the resonances and associated quality factor (Q-factor) can be controlled via an effective medium. The measurement results demonstrate that the Q-factor can reach up to 9146 at 274.4 GHz due to the low dissipation of the platform. Additionally, these resonators show strong tunability of the resonance under moderate optical power. These terahertz integrated disk resonators can be employed in sensing and communications.


Two new eriophyoid mites from Iran in the subfamilies Phyllocoptinae and Eriophyinae (Acari: Trombidiformes: Eriophyidae).
Two new species of eriophyoid mites from Fars province, Iran, are described and illustrated, namely: Tetra aparinea n. sp. causing distortion of Galium aparine L. (Rubiaceae) and representing the first record of the genus Tetra on plants of the family Rubiaceae; and Acaralox shiraziensis n. sp. from Tragopogon graminifolius DC. (Asteraceae), causing no visible damage except for slight wilting.


Antiviral drug development for the treatment of human immunodeficiency virus infections. An overview.
During 1987, a new era in the approach to treatment of severe human immunodeficiency virus (HIV)-I infections was entered. The increased availability of zidovudine and its licensure in many countries have resulted in its widespread use. With these developments have come a multitude of new questions. How long will clinical benefit be sustained? Will zidovudine be useful in asymptomatic HIV carriers and in other HIV-related conditions? How can the diversion of zidovudine to unproven indications be averted so that properly controlled clinical trials are conducted? Can better treatment regimens be developed to enhance the therapeutic/toxic ratio of zidovudine? What are the proper roles of governments in assuring patient access to zidovudine? How should newer anti-HIV drugs be compared with zidovudine? Will combinations of zidovudine and other active agents be useful? To address many of these issues in the United States, the Federal Government has established an AIDS Clinical Trials Group (ACTG) program. Over 3,000 patients have been enrolled in AIDS Clinical Trials Group trials, which span the spectrum from asymptomatic to advanced HIV-I infections. In addition, drug development and screening programs have been established to evaluate new compounds and regimens. Although control of AIDS will be a long and arduous journey, an important beginning has been made.


Generalized fundamental measure theory for atomistic modeling of macromolecular crowding.
Macromolecular crowding inside cells affects the thermodynamic and kinetic properties of proteins. The scaled particle theory (SPT) has played an important role toward establishing a qualitative picture for the effects of crowding. However, SPT-based modeling lacks molecular details. Molecular dynamics simulations overcome this limitation, but at great computational cost. Here, we present a theoretical method for modeling crowding at the atomic level. The method makes it possible to achieve exhaustive conformational sampling in modeling crowding effects and to tackle challenges posed by large protein oligomers and by complex mixtures of crowders.


[Nail changes and loss of hair: cardinal signs of mercury poisoning from hair bleaches (author's transl)].
In the German Federal Republic it has recently become known that generalised disorders of chronic mercury poisoning (loss of weight, stomatitis, hearing and sensory loss, emotional disturbances) have accompanied the cardinal signs of nail discolouration and loss of hair. The mercury content of nails in such patients was extremely high (1720 mg/l). The urinary level of mercury after dimercaprol injection was 1.97 mg/l, about 400 times above the upper limit of normal (0.005 mg/l). The poisoning was apparently caused by the use of mercury-containing bleaches (about 5% and 6% Hg) which do not require prescription and are marketed without any statement about composition or possible side-effects. The cases are a warning against uncontrolled use of external application of mercury-containing preparations.


Acarbose With Comparable Glucose-Lowering but Superior Weight-Loss Efficacy to Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Background: Acarbose and dipeptidyl peptidase-4 inhibitors (DPP-4is) have several similarities regarding their efficacy. Assessing the hypoglycemic and weight-loss effects, as well as the tolerability between them at their optimal dosages, could provide a better management of adult type 2 diabetics. Methods: We performed a systematic review and network meta-analysis (NMA) on randomized controlled trials that were identified from the databases of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Conference Proceedings Citation Index, ClinicalTrials.gov, China National Knowledge Infrastructure, Wan Fang, and SinoMed. The trials with 300 mg/day of acarbose or the recommended doses of DPP-4is were the most optimal for our NMA. The mean differences (MD) and relative risk (RR) derived from eligible studies were used. Results: Among the 15,411 obtained potential studies, 13 pair-wise trials and 48 monotherapy studies were included in the meta-analysis and NMA, respectively. DPP-4is had a greater glucose-lowering effect, but a weaker weight-loss effect than acarbose in pair-wise meta-analysis (p < 0.05). However, NMA with 11,877 participants showed that, at their optimal doses, acarbose and DPP-4is had similar glucose-lowering effects on the 2-h postprandial glucose (MD 0.96 mmol/L, 95% credible interval -0.56 to 2.54), HbA1c (0.05%, -0.25 to 0.33), fasting plasma glucose reductions (-0.27 mmol/L, -0.76 to 0.24), and HbA1c < 7.0% target goal achievement (RR 1.33, 0.51 to 3.64). Acarbose was superior to DPP-4is regarding weight loss (MD -1.23 kg, -2.08 to -0.33). Acarbose had more withdrawal, gastrointestinal, and overall adverse events than DPP-4is (p < 0.05), but the differences disappeared after longer treatment (p > 0.05). Conclusions: Acarbose and DPP-4is have similar glucose-lowering effects, but the weight-loss effects of acarbose are superior. Therefore, in the use of the most optimal dosages, overweight/obese type 2 diabetics might benefit more from a treatment with acarbose than DPP-4is.


The Effect of Pudilan Anti-Inflammatory Oral Liquid on the Treatment of Mild Recurrent Aphthous Ulcers.
Recurrent aphthous ulcers are the most common recurrent oral mucosal lesions characterized by recurrence and pain. The aim of this research is to evaluate the short-term curative effect of the traditional Chinese medicine "Pudilan anti-inflammatory oral liquid" on mild recurrent aphthous ulcers. A total of 234 patients were divided into a treatment group and a control group. Both groups used vitamin B2 as the basis of treatment. The treatment group took a Pudilan anti-inflammatory oral solution for 8 days while the control group was given a liquid placebo. The ulcer size, pseudomembrane, peripheral congestion, and pain scores of the treatment group were lower than before treatment. The curative effect on the Pudilan group was statistically significant compared with the control group. The final therapeutic effect on the treatment group was better than that on the control group. The healing time of mild recurrent aphthous ulcers can be shortened by Pudilan anti-inflammatory oral liquid, and pain is relieved without adverse reactions. Pudilan provides a new reference drug for the treatment of mild recurrent oral ulcers.


Exploring attitudes toward older workers among Australian employers: an empirical study.
Research suggests that negative stereotyping is at the heart of age discrimination in not hiring older workers. As the aging of the population creates pressures to maintain older adults in the work force, it is important to gain knowledge of such stereotyping. A random sample of 128 hiring decision-makers across Australian industries responded to a questionnaire that was specifically developed to assess attitudes toward older workers. Results showed systematic negative stereotyping: Respondents indicated that they were unlikely to hire older workers. The likelihood of hiring significantly correlated with employers' attitudes. Specific attributes for which older workers were seen as inferior compared to younger workers included trainability, adaptability, creativity, and interest in new technology. The findings could inform policymakers and be utilized to develop interventions aimed to reduce hiring discrimination.


The use of long-acting opioids in chronic pain management.
The consensus statement from the American Pain Society and American Academy of Pain Medicine states that the undertreatment of pain is unjustified [6]. It has been suggested that opioid therapy can be used effectively to treat noncancer pain in a subset of patients [26], and this is becoming more acceptable [3]. Providing sustained analgesia is an important aspect of therapy, and medications should be administered on an around-the-clock basis, because regular administration of doses maintains a constant level of drug in the body and helps prevent recurrence of pain. Ideal treatment for persistent pain is a long-acting opioid administered around the clock to prevent baseline pain, with the use of short-acting opioids as supplemental agents for breakthrough pain. Controlled-release formulations can lessen the inconvenience associated with around-the-clock administration of short-acting opioids. Sustained analgesia also can be achieved with transdermal fentanyl, which combines a strong opioid with a 72-hour release profile and the benefits of a parenteral route, avoiding first-pass metabolism. Controlled-release formulations of morphine and oxycodone are available in the United States, and hydromorphone preparations are being reviewed for approval. Clinical experience with these formulations and transdermal fentanyl indicates that these agents are equally effective in controlling pain. Studies have demonstrated improved quality of life with the transdermal route and with controlled-release morphine and oxycodone. Because of patch reapplication every 72 hours, the transdermal route also enhances compliance. Use of an opioid without the need for oral or intravenous administration and the opportunity to improve compliance are among the advantages of the transdermal route in clinical practice. The nurse has an important role in the management of patients receiving long-acting opioids for chronic noncancer pain, Facilitation of the conversion from short-acting to long-acting opioids may be the initial step. Individualization of therapy to determine which route and product best suits the patient's needs and lifestyle can be accomplished through a comprehensive nursing assessment. Titration of dose along with institution of a short-acting opioid for break-through pain may require frequent interventions that a nurse familiar with the patient can provide. Prevention and management of opioid-related adverse events are essential for effective opioid therapy. Providing patient and family education regarding administration, monitoring, and management of opioid therapy is an important nursing role. Lastly, documentation of pain level, functional status, and opioid-related adverse events is required for each contact with the patient, to make this information available to all who assist in the management of the patient's pain. Chronic noncancer pain is an experience that affects all aspects of a patient's life. Effective pain management with long-acting opioids may help the patient to focus on the positive aspects of life, decreasing the focus on pain.


Vitamin D3 Promotes Structural and Functional Recovery After Vincristine-Induced Peripheral Neuropathy in Rats: An Experimental Study.
Background Vincristine-induced peripheral neuropathy (VIPN) is a distal axonopathy characterized by the loss of distal myelinated axons. This study aimed to assess the potential neuroregenerative roles of vitamin D3 using functional and electron microscopic analyses in a rat model of VIPN. Methodology A total of 40 female Wistar rats were randomly divided into four main groups: Group 1 (control, n = 10), Group 2 (vincristine, n = 10), Group 3 (vincristine + vitamin D3, n = 10), and Group 4 (vincristine + vehicle, n = 10). Vincristine was administered intraperitoneally at a dose of 0.15 mg/kg, for two weeks, to induce peripheral neuropathy. Following successful induction, vitamin D3 (500 IU/kg/day) and vehicle treatments were applied weekly over four weeks. Structural (electron microscopic analysis) and functional analysis (von Frey test, pinch test, and electrophysiological analysis) were performed to assess functional recovery after peripheral nerve impairment. Results Withdrawal responses to mechanical allodynia and pinch tests were significantly higher in the vitamin D3-treated group (P < 0.05). The electrophysiological analysis also supported these results. Electron microscopic evaluation revealed that the remyelinated nerve fibers in the vitamin D3-treated group (Group 3) had thick myelin sheaths and normal axonal morphology. Conclusions Our study demonstrated that vitamin D3 could promote functional and structural recovery in a rat model of VIPN. Further studies should be conducted to elucidate the underlying mechanisms by which vitamin D3 exerts its regenerative effects in VIPN, using alternative administration protocols.


Specific immune responses induced by multi-epitope DNA derived from Mycobacterium tuberculosis DosR antigens.
One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model. LC3-fused multi-epitope DNA construct induced strong specific Th1 immune responses with high increase in IFN-γ+ CD4+ and IL-2+ CD4+ T cell populations (both with p < 0.0001) and IFN-γ+ IL-2+ CD4+ T cell population (p < 0.0001) compared with empty vector, BCG, and multi-epitope DNA construct groups. The LC3-fused construct induced IFN-γ+ CD8+ T cell population (p < 0.0001) compared with empty vector and BCG groups but could not induce the T cell population compared with construct without LC3. Importantly, LC3-fused DNA construct did not induce epitope-specific IL-4 and IL-10 from CD4+ and CD8+ T cell populations. The results indicated that LC3-fused multi-epitope DNA construct has a potential to be investigated for future development of a new TB vaccine.


Effect of chronic angiotensin converting enzyme inhibition on spatial memory and anxiety-like behaviours in rats.
Angiotensin converting enzyme inhibitors (ACEis) are widely used anti-hypertensive agents that are also reported to have positive effects on mood and cognition. The present study examined the influence of the ACEi, perindopril, on cognitive performance and anxiety measures in rats. Two groups of rats were treated orally for one week with the ACEi, perindopril, at doses of 0.1 and 1.0mg/kg/day. Learning was assessed by the reference memory task in the water maze, comparing treated to control rats. Over five training days both perindopril-treated groups learnt the location of the submerged platform in the water maze task significantly faster than control rats. A 60s probe trial on day 6 showed that the 1.0mg/kg/day group spent significantly longer time in the training quadrant than control rats. This improved performance in the swim maze task was not due to the effect of perindopril on motor activity or the anxiety levels of the rats as perindopril-treated and control animals behaved similarly in activity boxes and on the elevated+maze. These results confirm the anecdotal human studies that ACEis have a positive influence on cognition and provide possibilities for ACEis to be developed into therapies for memory loss.


Assessment of the opportunities for increasing the availability of EU data on consumer product-related injuries.
The availability of data on consumer products-related accidents and injuries is of interest to a wide range of stakeholders, such as consumer product safety and injury prevention policymakers, market surveillance authorities, consumer organisations, standardisation organisations, manufacturers and the public. While the amount of information available and potentially of use for product safety is considerable in some European Union (EU) countries, its usability at EU level is difficult due to high fragmentation of the data sources, the diversity of data collection methods and increasing data protection concerns. To satisfy the policy need for more timely information on consumer product-related incidents, apart from injury data that have been historically collected by the public health sector, a number of 'alternative' data sources were assessed as potential sources of interest. This study explores the opportunities for enhancing the availability of data of consumer product-related injuries, arising from selected existing and 'alternative' data sources, widely present in Europe, such as firefighters' and poison centres' records, mortality statistics, consumer complaints, insurance companies' registers, manufacturers' incident registers and online news sources. These data sources, coupled with the use of IT technologies, such as interlinking by remote data access, could fill in the existing information gap. Strengths and weaknesses of selected data sources, with a view to support a common data platform, are evaluated and presented. Conducting the study relied on the literature review, extensive use of the surveys, interviews, workshops with experts and online data-mining pilot study.


Associations between causal attributions for obesity and long-term weight loss.
Obesity is a complex disease caused by a wide array of behavioral, biological, and environmental factors. However, obesity is often attributed to oversimplified and stigmatizing causal factors such as laziness, lack of willpower, and failure to take personal responsibility for one's health. Understanding of the causal factors that contribute to obesity among people with obesity may affect their weight management efforts. The current study explored associations between causal attributions for obesity and long-term weight loss, as well as examined potential changes in attributions with weight reduction. The 16-item Causal Attributions for Obesity scale (rated 1-7) was administered to 178 patients seeking behavioral/pharmacological weight-loss treatment. Causal attributions and weight were assessed at baseline, after 14 weeks of a low-calorie diet, and again at weeks 24 and 52 of a subsequent randomized trial (i.e., 66 weeks total). Logistic and linear regression examined effects of baseline causal attribution ratings on weight loss. Higher baseline ratings of personal responsibility attributions predicted 38% reduced odds of achieving ≥10% weight loss at week 52 (p = 0.02). Causal attribution ratings did not change over time or correlate continuously with weight change. Thus, attributing obesity to a failure of personal responsibility may impair long-term weight management efforts for individuals seeking ≥10% weight loss. Targeted techniques are needed to reduce patients' stigmatizing beliefs about the causes of obesity.


Objective evaluation of reconstruction methods for quantitative SPECT imaging in the absence of ground truth.
Quantitative single-photon emission computed tomography (SPECT) imaging is emerging as an important tool in clinical studies and biomedical research. There is thus a need for optimization and evaluation of systems and algorithms that are being developed for quantitative SPECT imaging. An appropriate objective method to evaluate these systems is by comparing their performance in the end task that is required in quantitative SPECT imaging, such as estimating the mean activity concentration in a volume of interest (VOI) in a patient image. This objective evaluation can be performed if the true value of the estimated parameter is known, i.e. we have a gold standard. However, very rarely is this gold standard known in human studies. Thus, no-gold-standard techniques to optimize and evaluate systems and algorithms in the absence of gold standard are required. In this work, we developed a no-gold-standard technique to objectively evaluate reconstruction methods used in quantitative SPECT when the parameter to be estimated is the mean activity concentration in a VOI. We studied the performance of the technique with realistic simulated image data generated from an object database consisting of five phantom anatomies with all possible combinations of five sets of organ uptakes, where each anatomy consisted of eight different organ VOIs. Results indicate that the method provided accurate ranking of the reconstruction methods. We also demonstrated the application of consistency checks to test the no-gold-standard output.


Hepatitis C virus envelope protein dynamics and the link to hypervariable region 1.
Conformational dynamics of viral envelope proteins seem to be involved in mediating evasion from neutralizing antibodies (NAbs) by mechanisms that limit exposure of conserved protein motifs. For hepatitis C virus (HCV), molecular studies have only recently begun to unveil how such dynamics of the envelope protein heterodimer, E1/E2, are linked to viral entry and NAb evasion. Here, we review data suggesting that E1/E2 exists in an equilibrium between theoretical 'open' (NAb-sensitive) and 'closed' (NAb-resistant) conformational states. We describe how this equilibrium is influenced by viral sequence polymorphisms and that it is critically dependent on the N-terminal region of E2, termed hypervariable region 1 (HVR1). Finally, we discuss how it appears that the virus binding site for the HCV entry co-receptor CD81 is less available in 'closed' E1/E2 states and that NAb-resistant viruses require a more intricate entry pathway involving also the entry co-receptor, SR-BI.


β-Adrenergic-stimulated macrophages: Comprehensive localization in the M1-M2 spectrum.
β-Adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1-M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one pre-defined category of the M1-M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1-M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1-M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1-M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages.


The quartic piecewise-linear criterion for the multiaxial yield behavior of human trabecular bone.
Prior multiaxial strength studies on trabecular bone have either not addressed large variations in bone volume fraction and microarchitecture, or have not addressed the full range of multiaxial stress states. Addressing these limitations, we utilized micro-computed tomography (lCT) based nonlinear finite element analysis to investigate the complete 3D multiaxial failure behavior of ten specimens (5mm cube) of human trabecular bone, taken from three anatomic sites and spanning a wide range of bone volume fraction (0.09–0.36),mechanical anisotropy (range of E3/E1¼3.0–12.0), and microarchitecture. We found that most of the observed variation in multiaxial strength behavior could be accounted for by normalizing the multiaxial strength by specimen-specific values of uniaxial strength (tension,compression in the longitudinal and transverse directions). Scatter between specimens was reduced further when the normalized multiaxial strength was described in strain space.The resulting multiaxial failure envelope in this normalized-strain space had a rectangular boxlike shape for normal–normal loading and either a rhomboidal box like shape or a triangular shape for normal-shear loading, depending on the loading direction. The finite element data were well described by a single quartic yield criterion in the 6D normalized strain space combined with a piecewise linear yield criterion in two planes for normalshear loading (mean error SD: 4.660.8% for the finite element data versus the criterion).This multiaxial yield criterion in normalized-strain space can be used to describe the complete 3D multiaxial failure behavior of human trabecular bone across a wide range of bone volume fraction, mechanical anisotropy, and microarchitecture.