A shrinkage estimator for subgroup analysis without the exchangeability assumption.
Shrinkage estimators for exploratory subgroup analyses are intuitively appealing and can greatly improve estimation over standard analysis approaches; however, adoption of these estimators has been limited by reliance on the exchangeability assumption. This paper describes a new shrinkage estimator that does not rely on this assumption. Rather than assuming that treatment effect sizes within subgroups are randomly distributed around an overall mean, this new estimator assumes that the difference between the effect sizes in any given pair of subgroups is randomly distributed around zero. The estimator is illustrated using data from a clinical trial in which the treatment effect size in one region was substantially different from the sizes in other regions. Simulation results show that the estimator has properties that are comparable to or superior to a standard shrinkage estimator when exchangeability is assumed, while allowing the flexibility to handle situations where exchangeability cannot be assumed.


Pregnancy outcome in patients with adult onset Still's disease.
Pregnancy outcome of patients with adult onset Still's disease (AOSD) has not been addressed. We report the maternal and fetal morbidity of 5 pregnancies from 3 Chinese patients with AOSD and review another 17 pregnancies from 14 patients reported in the English literature. Nine patients had their first manifestation in the 5th to 6th gestational month. Disease relapse in patients with known AOSDoccurred most commonly in the post-partum period. Most did not respond satisfactorily to nonsteroidal antiinflammatory agents alone, but responded to administration of corticosteroids, especially in high doses.


Is the -174 C/G polymorphism of the IL6 gene associated with elite power performance? A replication study with two different Caucasian cohorts.
A functional -174 C/G polymorphism in the interleukin-6 gene (IL6) is a candidate to explain individual variations in exercise-related phenotypes. To replicate recent findings showing an association between the G allele and GG genotype of elite power sports performance in European (Spanish) Caucasian males, we compared allelic and genotypic frequencies of the IL6 -174 C/G polymorphism among elite endurance athletes (n = 74) and power athletes (n = 81) and non-athletic control subjects (n = 205) of both sexes from Israel. All subjects were Israeli Caucasians (with an equivalent ratio of non-Ashkenazi and Ashkenazi descent in each group; 2:1). We found no differences in the genotype or allele frequencies among groups (all P > 0.3). We further compared the genotype and allele frequencies between national- (n = 109) and international-level Israeli athletes (n = 46) in the endurance and power group, and found no significant genotype or allele differences after adjusting for multiple comparisons. We repeated all the analyses after pooling the Israeli and Spanish control subjects, endurance and power elite athletes, and found no genotypic and allelic differences among groups. The results did not change when the analyses were repeated including only the best Israeli athletes (i.e. the international-level group) together with the group of elite Spanish athletes (P > 0.2). In conclusion, the results of the present study did not show an association between the G allele of the IL6 -174 G/C polymorphism and power sports performance in the Israeli (Caucasian) population. Our findings support the need to replicate association results between genetic polymorphisms and athletic status in populations of different ethnic backgrounds with the largest possible population samples.


Characterization of the Tn916 conjugative transposon in a food-borne strain of Lactobacillus paracasei.
Food-borne antibiotic-resistant lactic acid bacteria have received growing attention in the past few years. We have recently identified tetracycline-resistant Lactobacillus paracasei in samples of milk and natural whey starter cultures employed in the manufacturing process of a typical Italian fermented dairy product, Mozzarella di Bufala Campana. In the present study, we have characterized at the molecular level the genetic context of tetracycline resistance determinants in these natural strains, which we have identified as tet(M). This gene was present in 21 independent isolates, whose fingerprinting profiles were distributed into eight different repetitive extragenic palindromic groups by cluster analysis. We provide evidence that the gene is associated with the broad-host, conjugative transposon Tn916, which had never before been described to occur in L. paracasei. PCR analysis of four independent isolates by use of specifically designed primer pairs detected the presence of a circular intermediate form of the transposon, carrying a coupling sequence (GGCAAA) located between the two termini of Tn916. This novel coupling sequence conferred low conjugation frequency in mating experiments with the recipient strain JH2-2 of Enterococcus faecalis.


Enhanced Performance of Perovskite Single-Crystal Photodiodes by Epitaxial Hole Blocking Layer.
Introducing hole/electron transporting and blocking layers is considered to enhance the performance of electronic devices based on organic-inorganic hybrid halide perovskite single crystals (PSCs). In many photodiodes, the hole/electron transporting or blocking materials are spin-coated or thermal-evaporated on PSC to fabricate heterojunctions. However, the heterojunction interfaces due to lattice mismatch between hole/electron, transporting or blocking materials and perovskites easily form traps and cracks, which cause noise and leakage current. Besides, these low-mobility transporting layers increase the difficulty of transporting carriers generated by photons to the electrode; hence, they also increase the response time for photo detection. In the present study, MAPbCl3-MAPbBr2.5Cl0.5 heterojunction interfaces were realized by liquid-phase epitaxy, in which MAPbBr2.5Cl0.5 PSC acts as an active layer and MAPbCl3 PSC acts as a hole blocking layer (HBL). Our PIN photodiodes with epitaxial MAPbCl3 PSC as HBL show better performance in dark current, light responsivity, stability, and response time than the photodiodes with spin-coated organic PCBM as HBL. These results suggest that the heterojunction interface formed between two bulk PSCs with different halide compositions by epitaxy growth is very useful for effectively blocking the injected charges under high external electric field, which could improve the collection of photo-generated carriers and hereby enhance the detection performance of the photodiode. Furthermore, the PIN photodiodes made of PSC with epitaxial HBL show the sensitivities of 7.08 mC Gyair -1 cm-2, 4.04 mC Gyair -1 cm-2, and 2.38 mC Gyair -1 cm-2 for 40-keV, 60-keV, and 80-keV X-ray, respectively.


Human root and cord potentials evoked by Achilles tendon tap.
Lumbosacral root potentials and sacral spinal cord segmental responses were recorded epidurally in 24 normal adult subjects by tapping the Achilles Tendon with the electronic hammer (mechanical). The averaged responses were also recorded from the same epidural levels after the electrical stimulation of the Posterior Tibial nerve at the popliteal fossa (electrical). While the dorsal and reflexively evoked ventral root responses were easily obtained by the electrical stimulation; by the mechanical stimulation only a late and small ventral root response with two negative deflections could be evoked at the L4-5 or L5-S1 I.V. (intervertebral) epidural levels. The ventral root responses elicited by mechanical stimulation appeared 4.0 msec later than those elicited by the electrical stimulation. This time interval was exactly the same when the latencies of the Soleus reflexes to both stimuli were compared that for the Achilles tendon reflex being 4.0 msec delayed. When the sums of their afferent and the efferent conduction times (to and from Th12-L1 I.V. levels) were extracted from the total conduction times of the Soleus H and Achilles tendon reflex obtained by the EMG recordings, the sacral cord conduction delay was found 1.8 msec for the H-Reflex and 4.1 msec for the Achilles tendon reflex. It was suggested that the twice longer time delay along the sacral cord to Achilles tendon tap might be due to the oligosynaptic linkage of the Achilles tendon reflex or it may result from highly dispersed afferent volley producing a slowly rising wave or excitation that takes longer to reach threshold for the soleus motoneurone discharges.


Sex ratio in the Iranian urban and rural areas.
Factors affecting the sex ratio are examined using data for 1,169,489 births occurring in rural and urban districts of Tehran, Iran, between 1971 and 1979. Attention is given to geographic, socioeconomic, psychological, and nutritional factors. It is found that "male births occurred more in Winter and Spring in the urban and rural areas, respectively. Female births occurred more in Fall in both urban and rural areas. Mean sex ratio was 108.20 in rural and 105.44 in urban areas." Reasons for the differentials between urban and rural areas are suggested.


Relationship between the concentration of volatile sulphur compound and periodontal disease severity in Nigerian young adults.
The aim of this study was to determine the relationship between the concentration of volatile sulphur compounds (VSC) in mouth air and the severity of periodontal diseases in young adults. A total of 400 subjects were studied. Estimation of periodontal disease severity was done using the basic periodontal examination (BPE) and the baseline measurement of the concentration of VSC in the mouth air of the subjects was done objectively using the Halimeter(®). The mean concentration of VSC for the group with BPE code 0 was 91.0 ± 5.9 parts per billion (ppb), 156.4 ± 9.4 ppb for BPE code 1, 275.2 ± 38.5 ppb for BPE code 2, 353.5 ± 72.3 ppb for BPE code 3, and 587.0 ± 2.1 ppb for BPE code 4 (P = 0.001). Majority (79.0%) of the subjects with BPE code 0 had concentration of VSC <181 ppb. Sixty-two (54.9%) with BPE code 1 had concentration of VSC <181 ppb, 34% with BPE code 2 had concentration of VSC <181 ppb and 42.9% with BPE code 3 had concentration of VSC <181 ppb. Only 6.5% of the subjects with BPE code 0 had VSC concentration >250 ppb, whereas all (100%) of those with BPE code 4 had VSC concentration >250 ppb (P = 0.001). It was concluded that a relationship exists between the periodontal pocket depth and the concentration of VCS in mouth air of young adults.


Noise and selectivity of velocity-selective multi-electrode nerve cuffs.
Using a multi-electrode nerve-signal recording cuff and a method of signal processing described previously, activity in axons with different propagation velocities can be distinguished, and the relative amplitude of the small-fibre signals increased. This paper is, largely, an analysis of the selectivity and noise of this system though impedance measurements from an actual cuff are included. The signal processor includes narrow band-pass filters. It is shown that the selectivity and noise both increase with the centre frequencies of these filters. A convenient approach is to make the filter frequencies inversely related to the artificial time delays so that the filter 'Q's are approximately constant and the noise densities are equal for all velocity filters. Numerical calculations, using formulae for this system and for the conventional tripole, based on a fixed cuff size and tissue resistivity, find the number of action potentials per second that must pass through the cuff so that the signal power equals the noise power. For slow fibres (20 m/s), the rate is 14 times lower for the multi-electrode cuff than the tripole, a significant advantage for recording from these fibres.


Elemental analysis and clinical implications of calcification deposits associated with silicone breast implants.
Calcification of the fibrous capsule surrounding silicone breast implants is a well-recognized occurrence that increases with time following implantation. These mineralized deposits potentially confound mammographic breast cancer surveillance already made difficult by the obscuring effects of silicone breast implants. The authors performed elemental analysis of silicone breast implant-associated calcifications to define better their chemical composition as related to mammographic and clinical significance. Electron probe microanalysis and infrared spectroscopy revealed all of the calcification deposits to be calcium complexed with tribasic phosphate. No evidence of calcium oxalate, calcium carbonate, silicone, or talc was observed. Caution must be employed in interpreting mammograms in women with silicone breast implants as well as those who have had their silicone breast implants removed. High-density mammographic calcifications indicative of calcium phosphate associated with a silicone breast implant may represent an accepted consequence of implantation or nearby carcinoma. We recommend baseline mammography on women who have had their silicone breast implants removed to prevent unnecessary fine-needle aspiration or tissue biopsy of retained breast capsule calcifications during subsequent routine surveillance for carcinoma.


Degradation of the Organochlorinated Herbicide Diuron by Rainforest Basidiomycetes.
The main organochlorinated compounds used on agricultural crops are often recalcitrant, affecting nontarget organisms and contaminating rivers or groundwater. Diuron (N-(3,4-dichlorophenyl)-N',N'-dimethylurea) is a chlorinated herbicide widely used in sugarcane plantations. Here, we evaluated the ability of 13 basidiomycete strains of growing in a contaminated culture medium and degrading the xenobiotic. Dissipation rates in culture medium with initial 25 mg/L of diuron ranged from 7.3 to 96.8%, being Pluteus cubensis SXS 320 the most efficient strain, leaving no detectable residues after diuron metabolism. Pycnoporus sanguineus MCA 16 removed 56% of diuron after 40 days of cultivation, producing three metabolites more polar than parental herbicide, two of them identified as being DCPU and DCPMU. Despite of the strong inductive effect of diuron upon laccase synthesis and secretion, the application of crude enzymatic extracts of P. sanguineus did not catalyzed the breakdown of the herbicide in vitro, indicating that diuron biodegradation was not related to this oxidative enzyme.


Life expectancy with chronic kidney disease: an educational review.
Can renal prognosis and life expectancy be accurately predicted? Increasingly, the answer is yes. The natural history of different forms of renal disease is becoming clearer; the degree of reduction in glomerular filtration rate (GFR) and the magnitude of proteinuria are strong predictors of renal outcome. Actuarial data on life expectancy from the start of renal replacement therapy are available from renal registries such as the U.S. Renal Data System (USRDS), and the UK Renal Registry. Recently, similar data have become available for patients with chronic kidney disease. Data collected from a large population-based registry in Alberta, Canada and stratified for different levels of estimated GFR (eGFR) have shown that the reduction in life expectancy with kidney failure is not a uremic event associated with starting dialysis but a continuous process that is evident from an eGFR of ≤60 ml/min. Nevertheless, despite the poor prognosis of the last stages of renal failure, progress in the treatment and management of these patients and, in particular, of their cardiovascular risk factors continues to improve long-term outcome.


Tongxinluo attenuates oxygen-glucose-serum deprivation/restoration-induced endothelial barrier breakdown via peroxisome proliferator activated receptor-α/angiopoietin-like 4 pathway in high glucose-incubated human cardiac microvascular endothelial cells.
Traditional Chinese medicine Tongxinluo (TXL) has been widely used to treat coronary artery disease in China, since it could reduce myocardial infarct size and ischemia/reperfusion injury in both non-diabetic and diabetic conditions. It has been shown that TXL could regulate peroxisome proliferator activated receptor-α (PPAR-α), a positive modulator of angiopoietin-like 4 (Angptl4), in diabetic rats. Endothelial junction substructure components, such as VE-cadherin, are involved in the protection of reperfusion injury. Thus, we hypothesized cell-intrinsic and endothelial-specific Angptl4 mediated the protection of TXL on endothelial barrier under high glucose condition against ischemia/reperfusion-injury via PPAR-α pathway. Incubated with high glucose medium, the human cardiac microvascular endothelial cells (HCMECs) were then exposed to oxygen-glucose-serum deprivation (2 hours) and restoration (2 hours) stimulation, with or without TXL, insulin, or rhAngptl4 pretreatment. TXL, insulin, and rhAngptl4 had similar protective effects on the endothelial barrier. TXL treatment reversed the endothelial barrier breakdown in HCMECs significantly as identified by decreasing endothelial permeability, upregulating the expression of JAM-A, VE-cadherin, and integrin-α5 and increasing the membrane location of VE-cadherin and integrin-α5, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with small interfering RNA (siRNA) interference and PPAR-α inhibitor MK886 partially abrogated these beneficial effects of TXL. Western blotting also revealed that similar with insulin, TXL upregulated the expression of Angptl4 in HCMECs, which could be inhibited by Angptl4 siRNA or MK886 exposure. TXL treatment increased PPAR-α activity, which could be diminished by MK886 but not by Angptl4 siRNA. These data suggest cell-intrinsic and endothelial-specific Angptl4 mediates the protection of TXL against endothelial barrier breakdown during oxygen-glucose-serum deprivation and restoration under high glucose condition partly via the PPAR-α/Angptl4 pathway.


Time dependence of the expression of ICAM-1 (CD 54) in human skin wounds.
To characterize the vitality and age of skin wounds by means of the ICAM-1 pattern, 157 intravital human skin wounds (time since injury ranging from 5 min to 730 days) were immunohistochemically investigated. ICAM-1 was detected in paraffin sections after autoclaving and using the ABC technique in 86% of the wounds investigated. The correlation between ICAM-1 expression and the degree of wound inflammation is weak. Strong positive staining was observed 1.5 h at the earliest and 3.5 days at the latest after the time of injury. ICAM-1 also appeared at low concentrations in samples of uninjured skin (n = 65), on keratinocytes and the endothelial cells of blood vessels. Moderate to strong ICAM-1 expression is a valuable indication of the vitality of the wound. However, at present the detection of ICAM-1 alone is not sufficient to fix the wound age with the accuracy which is required for forensics applications.


[Significance of CA19-9 values in the feces of patients with colorectal carcinoma].
We measured CA19-9 value in feces of 119 cases with malignant disease, 78 cases with benign diseases and 36 healthy volunteers, and studied its usefulness for the diagnosis of digestive tract cancer. Mean value of CA19-9 in feces of healthy volunteer was 276.4 +/- 643.3 U/ml (mean +/- 2S.D.) and cut off value was defined as 1000 U/ml. The positive ratio of CA19-9 in feces of patients with malignant diseases as 44.5%. On the other hand, the mean of the false positive ratio was only 1.4% in benign diseases. Regarding to its breakdown, CA19-9 in feces revealed the highest positive ratio as 68% in colonic cancer. In colonic cancer, CA19-9 in feces showed a high positive ratio of 83% at advanced stage. Histologically, the positive ratios of CA19-9 in feces were higher, such as in more than 80% of the reaching degree of depth ss, a1, more than 82% of the disease due to higher parasites of lymph vessel ly1 and more than 95% of the metastasis of lymph node n1. Moreover, all CA19-9 in feces were positive in positive cases of CEA in serum.


An Accurate and Lightweight Method for Human Body Image Super-Resolution.
In this paper, we propose a new method to super-resolve low resolution human body images by learning efficient multi-scale features and exploiting useful human body prior. Specifically, we propose a lightweight multi-scale block (LMSB) as basic module of a coherent framework, which contains an image reconstruction branch and a prior estimation branch. In the image reconstruction branch, the LMSB aggregates features of multiple receptive fields so as to gather rich context information for low-to-high resolution mapping. In the prior estimation branch, we adopt the human parsing maps and nonsubsampled shearlet transform (NSST) sub-bands to represent the human body prior, which is expected to enhance the details of reconstructed human body images. When evaluated on the newly collected HumanSR dataset, our method outperforms state-of-the-art image super-resolution methods with ∼ 8× fewer parameters; moreover, our method significantly improves the performance of human image analysis tasks (e.g. human parsing and pose estimation) for low-resolution inputs.


Light-Induced Oxidase Activity of DNAzyme-Modified Quantum Dots.
Here, we report the synthesis of a quantum dot (QD)-DNA covalent conjugate to be used as an H2O2-free DNAzyme system with oxidase activity. Amino-coupling conjugation was carried out between amino-modified oligonucleotides (CatG4-NH2) and carboxylated quantum dots (CdTe@COOH QDs). The obtained products were characterized by spectroscopic methods (UV-Vis, fluorescence, circular dichroizm (CD), and IR) and the transmission electron microscopy (TEM) technique. A QD-DNA system with a low polydispersity and high stability in aqueous solutions was successfully obtained. The catalytic activity of the QD-DNA conjugate was examined with Amplex Red and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate)) indicators using reactive oxygen species (ROS) generated by visible light irradiation. The synthesized QD-DNAzyme exhibited enhanced catalytic activity compared with the reference system (a mixture of QDs and DNAzyme). This proved the assumption that the covalent attachment of DNAzyme to the surface of QD resulted in a beneficial effect on its catalytic activity. The results proved that the QD-DNAzyme system can be used for generation of the signal by light irradiation. The light-induced oxidase activity of the conjugate was demonstrated, proving that the QD-DNAzyme system can be useful for the development of new cellular bioassays, e.g., for the determination of oxygen radical scavengers.


Targeted Molecular Therapies in Allergy and Rhinology.
Biologic agents, monoclonal antibodies that target highly-specific molecular pathways of inflammation, are becoming integrated into care pathways for multiple disorders that are relevant in otolaryngology and allergy. These conditions share common inflammatory mechanisms of so-called Type 2 inflammation with dysregulation of immunoglobulin E production and eosinophil and mast cell degranulation leading to tissue damage. Biologic agents are now available for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, eosinophilic granulomatosis with polyangiitis (EGPA), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). This paper summarizes the diagnosis and management of these conditions and critically reviews the clinical trial data that has led to regulatory approval of biologic agents for these conditions.


Relationship between Net CO(2) Assimilation and Dry Weight Accumulation in Field-Grown Tobacco.
To assess the variability of net photosynthetic CO(2) exchange per unit leaf area and to construct budgets for stands of field-grown tobacco (Nicotiana tabacum, Connecticut Broadleaf), a number of short-time measurements were made on all available leaf positions on two varieties using a hand-held transparent chamber for conducting gas exchange measurements on leaves. Measurements of net CO(2) exchange were carried out on 18 separate days during a 35-day period, beginning 22 days after the seedlings were transplanted to the field. Gas exchange assays on leaves were conducted under ambient conditions of temperature and light intensity at all times of day. Solar radiation was monitored throughout the period, and losses of respiratory CO(2) from stems, roots, and leaves (in the dark) were estimated. A simple model was proposed to relate daily total CO(2) input to irradiance and total leaf area. The total leaf area was assumed to be a function of day number. Dark respiratory losses accounted for 41% to 47% of total CO(2) assimilation. Analysis of variance indicated that the two varieties were not significantly different in whole plant rate of CO(2) fixation per unit of leaf area. CO(2) input was closely associated with leaf area within each variety. Throughout the experiment, the difference between the two varieties in total leaf area per plant was the largest single factor in determining net CO(2) inputs. The cumulative dry weight increase for each variety was similar to the prediction of net dry matter input obtained by gas exchange measurements, thus confirming the close relationship between total plant net CO(2) assimilation and dry weight yield.


Conservation of core complex subunits shaped the structure and function of photosystem I in the secondary endosymbiont alga Nannochloropsis gaditana.
Photosystem I (PSI) is a pigment protein complex catalyzing the light-driven electron transport from plastocyanin to ferredoxin in oxygenic photosynthetic organisms. Several PSI subunits are highly conserved in cyanobacteria, algae and plants, whereas others are distributed differentially in the various organisms. Here we characterized the structural and functional properties of PSI purified from the heterokont alga Nannochloropsis gaditana, showing that it is organized as a supercomplex including a core complex and an outer antenna, as in plants and other eukaryotic algae. Differently from all known organisms, the N. gaditana PSI supercomplex contains five peripheral antenna proteins, identified by proteome analysis as type-R light-harvesting complexes (LHCr4-8). Two antenna subunits are bound in a conserved position, as in PSI in plants, whereas three additional antennae are associated with the core on the other side. This peculiar antenna association correlates with the presence of PsaF/J and the absence of PsaH, G and K in the N. gaditana genome and proteome. Excitation energy transfer in the supercomplex is highly efficient, leading to a very high trapping efficiency as observed in all other PSI eukaryotes, showing that although the supramolecular organization of PSI changed during evolution, fundamental functional properties such as trapping efficiency were maintained.


Cesarean scar pregnancy - a retrospective analysis of cases in the years 2012-2021.
With the increasing number of caesarean sections, the number of cesarean scar pregnancies (CSP) is also increasing. This is a relatively new entity of an ectopic pregnancy, which is risky mainly because of its possible association with placenta accreta spectrum. CSP is thought to represent about 6% of the total number of ectopic pregnancies in all women who have a history of at least one caesarean section. The estimated incidence of CSP is about 1/1,688 of all pregnancies and about 1/2,000 of all caesarean sections. Retrospective analysis of individual cases of cesarean scar pregnancies managed in our health care facility in the years 2012-2021. In total, we managed 16 cases of pregnancy in the caesarean scar in 15 women. In one woman, we recorded CSP twice. The mean age of the women was 36.6 years (27-41). The mean number of caesarean sections was 1.6 (1-3) and gestational week was 7 (4-10). The average time since the caesarean section was 3.6 years (2-11). The management was methotrexate administration once, hysteroscopic resection once and 11times primarily vacuum aspiration only, when in two cases we had to attach laparoscopic uterine artery ligation due to postoperative bleeding. We performed primary ligature of uterine arteries twice before performing vacuum aspiration. In pregnancies above 10 weeks of gestation, we observed more bleeding complications requiring surgical management. Bleeding complications were also related to the presence of fetal cardiac action. Early correct dia-gnosis is essential in the management of CSP. Pregnancies up to the 10th week of gestation are managed by simple vacuum aspirations under ultrasound guidance. If the pregnancy is over the 10th week of gestation and especially with cardiac activity, we add laparoscopic uterine artery ligation before vacuum aspiration. All patients are subsequently advised to undergo laparoscopic resuturing of the lower uterine segment.


Not everyone with ductal carcinoma in situ of the breast treated with breast preservation needs post-excisional radiation therapy.
While the results of NSABP protocol B-17 and EORTC protocol 10853 prove that radiation therapy decreases the overall rate of local recurrence in patients with DCIS, there are clearly subgroups of patients who do not benefit from radiation therapy or whose benefit is so small that the addition of radiation therapy to their treatment regimen is simply not worthwhile. Identifying these subgroups is of paramount importance. Factors like tumour size, margin width, nuclear grade, and the presence or absence of comedonecrosis can be used to define favorable subgroups that do not require post-excisional radiation therapy. The most recent results of NSABP protocol B-17 and EORTC protocol 10853 confirm that, regardless of treatment, there is no difference in the single most important end-point: survival. If there is no difference in breast cancer mortality, it is clearly worthwhile to try to define the subgroups of patients who can be spared the time, costs, and side-effects of a treatment that they do not need.


Non-secretory multiple myeloma in a patient with chronic kidney disease.
Multiple myeloma (MM) ) is a malignant plasma cell disorder from the group of monoclonal gammopathies. One of the most frequent diagnostic findings is the M-spike in serum protein electrophoresis (SPEP), which is notably absent in a rare non-secretory subtype of this disease. A case report describes a 55-year old woman with a history of chronic kidney disease (CKD) in stage 3, proteinuria, asthma and Graves' disease. She presented for a diagnosis of proteinuria (of 2,2 g/24 h). Her SPEP was normal, and she underwent a kidney biopsy, which showed mild glomerulal abnormalities. She returned to the clinic after 5 years with progression of CKD (between hospitalizations creatinine rose from 1,27 mg/dl to 2,8) and proteinuria (2,7 g/24 h). She had normocytic anemia, normocalcemia and normal ESR. The SPEP showed no suspicious findings, but suspecting multiple myeloma, immunofixation was performed. It showed excessive levels of kappa FLC in serum and urine. A bone marrow biopsy showed plasmocytes characteristic for MM in both number and phenotype. No osteolytic lesions were shown in diagnostic imaging, and beta-2-microglobulin was elevated to 6,5 μg. Thus, the patient was diagnosed with ISS stage 3 multiple myeloma and referred to a hematology clinic for treatment. The diagnosis of atypical cases of multiple myeloma may pose a difficulty to clinicians. Knowledge of diagnostic tests is required to introduce proper treatment.


Microvascular Free Flaps in Oral and Maxillofacial Reconstruction following Cancer Ablation.
Microsurgical free flaps have become the first choice for reconstruction of oral and maxillofacial (OMF) defects after tumor resection. Till recently the pectoralis major myocutaneous flap (PMMC) was considered to be the benchmark for OMF reconstruction. This philosophy is changing fast with rapid advancement in reconstructive microsurgery. Years of innovation in reconstructive microsurgery has given us a reasonably good number of excellent flaps. Tremendous work has been put into producing some exceptionally brilliant research articles, sometimes contradicting each other. This has led to the need for clarity in some areas in this field. This article reviews the most common microvascular free flaps (MFF) namely, radial forearm free flap (RFFF), anterolateral thigh flap (ALT) and free fibula flap (FFF) that are commonly used in OMF reconstruction. Since they can cater to almost all sizeable defects we come across after ablative surgery in the OMF region, they can aptly be titled as the workhorses of OMF reconstruction with regard to free flaps. Key words: Free tissue flaps, oral surgical procedures, microsurgery.


[Distribution of glycoconjugates in gerbil hippocampal neurons--histochemical study with lectins].
Paraffin-embedded sections of gerbil hippocampus were made and stained by use of lectins with different sugar specificities: Concanavalin A (Con A), wheat germ agglutinin (WGA), Ricinus communis agglutinin (RCA), Phaseolus vulgaris agglutinin (PHA-E), peanut agglutinin (PNA), soybean agglutinin (SBA), and Vicia villosa agglutinin (VVA) to investigate the distribution of glycoconjugates in this brain region. Nuclear membranes of all the neurons in the hippocampus were positively stained with Con A and PHA-E, whereas WGA revealed definite staining of cell membranes. Endothelial cells of blood vessels were intensely positive to RCA, suggesting its usefulness as a marker of endothelial cells. With SBA and VVA, a few neurons in Ammon's horn were positively stained, while no positive cells were observed in the dentate gyrus. CA2 and the medial part of the CA1 were also positive bilaterally with SBA and VVA. Some neurons in Ammon's horn and dentate gyrus were selectively stained on the surface of their cell bodies with PNA. The present results show that lectins used distinguish different subpopulations of hippocampal neurons, indicating a new possible classification of hippocampal neurons based on their differences in glycoconjugates.


Kinetic analysis of tissue distribution of doxorubicin incorporated in liposomes in rats (II).
The objective of this study is to perform kinetic modelling of the tissue distribution of doxorubicin encapsulated into liposomes (L-DXR), especially to the heart and liver. The release process of doxorubicin (DXR) from liposomes in blood was quantified by a release clearance. This parameter defines a release rate of DXR based on the concentration of L-DXR in blood and was estimated from kinetic modelling of DXR distribution to the heart after L-DXR administration. The distribution of free DXR to the heart was modelled separately. The experimental data for this modelling were reported previously (Harashima et al., Biopharm. Drug. Disposit., 13, 155-170 (1992)). This analysis provided a free DXR concentration profile as well as a release clearance of DXR after L-DXR administration. There was a remarkable difference in the free DXR concentration in blood between free and liposomal administration. The area under the DXR curve in the heart was reduced by approximately one third from that for the first two hours after DXR administration by liposomal encapsulation, which could be the reason for reduced cardiac toxicity. In our previous report, the distribution of L-DXR to the liver was shown to be explained by a sequentially linked two-compartment model with efflux process. The validity of this efflux model was examined in this study by a repeated dose study. The apparent uptake clearance decreased with time and showed a second peak after the repeated dose, which justified the efflux model. These kinetic analyses give quantitative understanding of the effect of liposomal encapsulation on the tissue distribution of DXR.


Lack of Strategic Funding and Long-Term Job Security Threaten to Have Profound Effects on Cardiovascular Researcher Retention in Australia.
Cardiovascular disease is the leading cause of death in Australia. Investment in research solutions has been demonstrated to yield health and a 9.8-fold return economic benefit. The sector, however, is severely challenged with success rates of traditional peer-reviewed funding in decline. Here, we aimed to understand the perceived challenges faced by the cardiovascular workforce in Australia prior to the COVID-19 pandemic. We used an online survey distributed across Australian cardiovascular societies/councils, universities and research institutes over a period of 6 months during 2019, with 548 completed responses. Inclusion criteria included being an Australian resident or an Australian citizen who lived overseas, and a current or past student or employee in the field of cardiovascular research. The mean age of respondents was 42±13 years, 47% were male, 85% had a full-time position, and 40% were a group leader or laboratory head. Twenty-three per cent (23%) had permanent employment, and 82% of full-time workers regularly worked >40 hours/week. Sixty-eight per cent (68%) said they had previously considered leaving the cardiovascular research sector. If their position could not be funded in the next few years, a staggering 91% of respondents would leave the sector. Compared to PhD- and age-matched men, women were less likely to be a laboratory head and to feel they had a long-term career path as a cardiovascular researcher, while more women were unsure about future employment and had considered leaving the sector (all p<0.05). Greater job security (76%) and government and philanthropic investment in cardiovascular research (72%) were highlighted by responders as the main changes to current practices that would encourage them to stay. Strategic solutions, such as diversification of career pathways and funding sources, and moving from a competitive to a collaborative culture, need to be a priority to decrease reliance on government funding and allow cardiovascular researchers to thrive.


Replicative transposition contributes to the evolution and dissemination of KPC-2-producing plasmid in Enterobacterales.
ABSTRACTKlebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales are prevalent worldwide and pose an alarming threat to public health. The incidence and transmission of blaKPC-2 gene via horizontal gene transfer (e.g. transposition) have been well documented. However, the dynamics of transposon structure bearing blaKPC-2 and their exact effects on the evolution and dissemination of blaKPC-2 gene are not well characterized. Here, we collected all 161 carbapenem-resistant Enterobacterales (CRE) isolates during the early stage of CRE pandemic. We observed that the prevalence of KPC-2-producing Enterobacterales was mediated by multiple species and sequence types (STs), and that blaKPC-2 gene was located on three diverse variants of Tn1721 in multi-drug resistance (MDR) region of plasmid. Notably, the outbreak of KPC-2-producing plasmid is correlated with the dynamics of transposon structure. Furthermore, we experimentally demonstrated that replicative transposition of Tn1721 and IS26 promotes horizontal transfer of blaKPC-2 and the evolution of KPC-2-producing plasmid. The Tn1721 variants appearing concurrently with the peak of an epidemic (A2- and B-type) showed higher transposition frequencies and a certain superior ability to propagation. Overall, our work suggests replicative transposition contributes to the evolution and transmission of KPC-2-producing plasmid and highlights its important role in the inter- and intra-species dissemination of blaKPC-2 gene in Enterobacterales.


Engineering for the 21st century: synthetic biology.
For years, scientists have hoped that biology would find its engineering counterpart--a series of principles that could be used as reliably as chemical engineering is for chemistry. Thanks to major advances in synthetic biology, those hopes may soon be realized.


Color Doppler flow imaging.
The performance requirements and operational parameters of a color Doppler system are outlined. The ability of an operator to recognize normal and abnormal variations in physiologic flow and artifacts caused by noise and aliasing is emphasized. The use of color Doppler flow imaging is described for the vessels of the neck and extremities, upper abdomen and abdominal transplants, obstetrics and gynecology, dialysis fistulas, and testicular and penile flow imaging.


Systematic Review of the Socioeconomic Consequences in Patients With Multiple Sclerosis With Different Levels of Disability and Cognitive Function.
Multiple sclerosis (MS) is a challenging and disabling condition, predominantly affecting individuals in early adulthood. MS affects the physical, cognitive, and mental health of persons suffering from the disease as well as having a great impact on their financial status and quality of life. However, there is a lack of systematic approach toward assessing the socioeconomic consequences of MS. Our objective was to systematically review analytical observational studies investigating the socioeconomic consequences in persons with MS with different levels of physical disability and cognitive function. We conducted a systematic review on socioeconomic consequences of MS with a focus on employment-, income-, work ability-, and relationship-related outcomes in persons with MS with special focus on disability and cognition. Additionally, the educational characteristics were examined. From 4,957 studies identified, 214 were assessed for eligibility and a total of 19 studies were included in this qualitative assessment; 21 different outcomes were identified. All identified studies reported higher unemployment, higher early retirement, and higher risk of unemployment in relation to higher physical disability. Also, cognitive function was found to be a predictor of employment (unemployment). The studies pointed out significant correlations between greater disability and lower earnings and higher income from benefits. A study found the same correlation in relation to cognitive function. The studies reported higher work disability in relation to higher physical disability and lower cognitive function. In conclusion, this systematic review summarizes the pronounced differences in various socioeconomic outcomes between patients with MS with regards to their physical disability and cognitive function. In addition, we identified a lack of studies with longitudinal design in this field that can provide more robust estimates with covariate adjustments, such as disease modifying treatments.


Rapid proliferation of repetitive palindromic elements in mtDNA of the endemic Baikalian sponge Lubomirskia baicalensis.
Animal mitochondrial DNA (mtDNA) is a remarkably compact molecule largely because of the scarcity of noncoding "selfish" DNA. Recently, however, we found that mitochondrial genomes of several phylogenetically diverse species of demosponges contain small repetitive palindromic sequences, interspersed within intergenic regions and fused in protein and ribosomal RNA genes. Here, I report and analyze the proliferation of such elements in the mitochondrial genome of the endemic sponge of Lake Baikal Lubomirskia baicalensis. Because Baikal sponges are closely related to the circumglobally distributed freshwater sponge Ephydatia muelleri with which they shared a common ancestor approximately 3-10 Ma, both the rate of single nucleotide substitutions and the rate of palindromic repeat insertions can be calculated in this system. I found the rate of nucleotide substitutions in mtDNA of freshwater sponges to be extremely low (0.5-1.6 x 10(-9) per site per year), more similar to that in plants than bilaterian animals. By contrast, the per/nucleotide rate of insertions of repetitive elements is at least four times higher. This rapid rate of proliferation combined with the broad phylogenetic distribution of hairpin elements can make them a defining force in the evolution of mitochondrial genomes of demosponges.


In vitro proliferation and cloning of CD3- CD16+ cells from human thymocyte precursors.
Purified CD3-4- thymocytes were obtained by depletion of CD3+ and CD4+ cells from fresh thymocyte suspensions. 5-15% of these cells were found to express CD16 antigen, while other natural killer (NK) cell markers were virtually absent. Double fluorescence analysis revealed that 20-40% of thymic CD16+ cells coexpressed CD1, while approximately half were cyCD3+. When cultured in the presence of peripheral blood lymphocytes and H9 leukemia cell line as a source of irradiated feeder cells and interleukin 2 (IL-2), CD3-4- thymocytes underwent extensive proliferation. In addition, after 1-2 wk of culture, 30-50% of these cells were found to express CD16 surface antigen. Cloning under limiting dilution conditions of either CD3-4- or CD3-4-16- thymocytes in the presence of irradiated H9 cells resulted in large proportions (approximately 50%) of CD16+ clones. On the basis of the expression of surface CD16 and/or cyCD3 antigen, clones could be grouped in the following subsets: CD16+ cyCD3+; CD16+ cyCD3-; CD16- cyCD3+; and CD16- cyCD3-. All clones expressed CD56 surface antigen, displayed a strong cytolytic activity against NK sensitive (K562) and NK-resistant (M14) target cells, and produced IFN-gamma and tumor necrosis factor, but not IL-2. Similar to peripheral NK cells, thymic CD16+ cells expressed transcripts for CD16 and for CD3 epsilon (Biassoni, R., S. Ferrini, I. Prigione, A. Moretta, and E.O. Long, 1988. J. Immunol. 140:1685.) and zeta chains (Anderson, P., M. Caligiuri, J. Ritz, and S.F. Schlossman. 1989. Nature [Lond.]. 341:159). Therefore, it appears that cells that are phenotypically and functionally similar to CD3- CD16+ NK cells may arise from immature thymocytes.


Encouraging good antimicrobial prescribing practice: a review of antibiotic prescribing policies used in the South East Region of England.
Good prescribing practice has an important part to play in the fight against antimicrobial resistance. Whilst it was perceived that most hospitals and Health Authorities possessed an antibiotic policy, a review of antibiotic policies was conducted to gain an understanding of the extent, quality and usefulness of these policies. Letters were sent to pharmacists in hospitals and health authorities in across the South East region of the National Health Service Executive (NHSE) requesting antibiotic policies. data were extracted from the policies to assess four areas; antibiotic specific, condition specific, patient specific issues and underpinning evidence. Of a possible 41 hospital trusts and 14 health authorities, 33 trusts and 9 health authorities (HAs) provided policies. Both trust and HA policies had a median publication date of 1998 (trust range 1993-99, HA 1994-99). Eleven policies were undated. The majority of policies had no supporting references for the statements made. All policies provided some details on specific antibiotics. Gentamicin and ciprofloxacin were the preferred aminoglycoside and quinolone respectively with cephalosporins being represented by cefuroxime or cefotaxime in trusts and cephradine or cephalexin in HAs. 26 trusts provided advice on surgical prophylaxis, 17 had meningococcal prophylaxis policies and 11 covered methicillin resistant Staphylococcus aureus (MRSA). There was little information for certain groups such as neonates or children, the pregnant or the elderly. There was considerable variation in content and quality across policies, a clear lack of an evidence base and a need to revise policies in line with current recommendations.


Bacillus Calmette-Guerin vaccine-mediated neuroprotection is associated with regulatory T-cell induction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.
We previously showed that, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD), vaccination with bacillus Calmette-Guerin (BCG) prior to MPTP exposure limited the loss of striatal dopamine (DA) and dopamine transporter (DAT) and prevented the activation of nigral microglia. Here, we conducted BCG dose studies and investigated the mechanisms underlying BCG vaccination's neuroprotective effects in this model. We found that a dose of 1 × 10(6) cfu BCG led to higher levels of striatal DA and DAT ligand binding (28% and 42%, respectively) in BCG-vaccinated vs. unvaccinated MPTP-treated mice, but without a significant increase in substantia nigra tyrosine hydroxylase-staining neurons. Previous studies showed that BCG can induce regulatory T cells (Tregs) and that Tregs are neuroprotective in models of neurodegenerative diseases. However, MPTP is lymphotoxic, so it was unclear whether Tregs were maintained after MPTP treatment and whether a relationship existed between Tregs and the preservation of striatal DA system integrity. We found that, 21 days post-MPTP treatment, Treg levels in mice that had received BCG prior to MPTP were threefold greater than those in MPTP-only-treated mice and elevated above those in saline-only-treated mice, suggesting that the persistent BCG infection continually promoted Treg responses. Notably, the magnitude of the Treg response correlated positively with both striatal DA levels and DAT ligand binding. Therefore, BCG vaccine-mediated neuroprotection is associated with Treg levels in this mouse model. Our results suggest that BCG-induced Tregs could provide a new adjunctive therapeutic approach to ameliorating pathology associated with PD and other neurodegenerative diseases.


HSV-1 neuroinvasiveness.
Neuroinvasiveness, the capacity of virus to enter and progress through the nervous system, may be accomplished by hematogenous or neural routes. We have been interested in defining HSV-1 genes specifically concerned with the neural pathway. In one system (involving HSV strain Ang), we have found that a single amino acid change in glycoprotein D, a viral membrane protein, confers invasiveness upon a noninvasive agent. Preliminary studies of another noninvasive agent, KOS, suggests that at least 2 genes are related to the phenotype. Experiments which establish specificity for the noninvasive phenotype and a discussion of the potential mechanisms involved in the glycoprotein D localization are also discussed.


Bacterial microbiota associated with flower pollen is influenced by pollination type, and shows a high degree of diversity and species-specificity.
Diverse microorganisms colonise the different plant-microhabitats, such as rhizosphere and phyllosphere, and play key roles for the host. However, bacteria associated with pollen are poorly investigated, despite its ecological, commercial and medical relevance. Due to structure and nutritive composition, pollen provides a unique microhabitat. Here the bacterial abundance, community structure, diversity and colonization pattern of birch, rye, rapes and autumn crocus pollens were examined, by using cultivation, high-throughput sequencing and microscopy. Cultivated bacteria belonged to Proteobacteria, Actinobacteria and Firmicutes, with remarkable differences at species level between pollen species. High-throughput sequencing of 16S rRNA gene amplicon libraries showed Proteobacteria as the dominant phylum in all pollen species, followed by Actinobacteria, Acidobacteria and Firmicutes. Both plant species and pollination type significant influenced structure and diversity of the pollen microbiota. The insect-pollinated species possessed a more similar microbiota in comparison to the wind-pollinated ones, suggesting a levelling effect by insect vectors. Scanning electron microscopy as well as fluorescent in situ hybridisation coupled with confocal laser scanning microscopy (FISH-CLSM) indicated the tectum surface as the preferred niche of bacterial colonisation. This work is the most comprehensive study of pollen microbiology, and strongly increases our knowledge on one of the less investigated plant-microhabitats.


Overexpression of the insulin-like growth factor-1 receptor and autocrine stimulation in human cervical cancer cells.
We characterized mechanisms of growth control involving insulin-like growth factor-1 (IGF-1), IGF-2, and IGF-1 receptor (IGF-1R) by investigating their expression in human cervical cancer cell lines, primary cervical tumor cell cultures, and normal ectocervical epithelial cells maintained in short-term culture. By reverse transcription followed by PCR, IGF-1 mRNA was not detected in any of the cell lines, whereas IGF-2 mRNA transcripts were detected in all of them. Using the RNase protection assay, low levels of IGF-2 mRNA were also detected in all of the cervical cancer cell lines, primary cervical tumor cell cultures, and normal ectocervical cultures tested, but no IGF-1 transcripts were detected. Scatchard analysis revealed 3- and 5-fold increases in IGF-1R expression by the primary cervical cancer cell cultures and cervical cancer cell lines, respectively, compared with the normal ectocervical cells. In proliferation assays, epidermal growth factor (EGF) consistently enhanced cervical cancer cell growth, but an antisense oligonucleotide to IGF-2 uniformly inhibited the EGF-induced mitogenic effect. These studies suggest that autocrine production of IGF-2 and overexpression of the IGF-1R are important components controlling the proliferation of cervical carcinoma cells, and that autocrine IGF-2 production in cervical cancer cells may participate in the mitogenic signaling of EGF.


An unusual case of fungal ball on implantable cardioverter defibrillator wire and literature review.
Cardiac Implantable Electronic Device (CIED) includes pacemakers and implantable cardioverter defibrillators (ICD). The device infection is classified into pocket and systemic infection. We present a case of candida fungemia secondary to dissemination from the fungal ball found on an ICD. Patient was successfully managed with IV fluconazole, ICD explantation and reimplantation. The purpose of this report is to highlight rare complications of ICD implantation and guide its clinical course and management.


Exploring the "fold-in" strategy toward the construction of a highly-strained triazasumanene skeleton.
The synthesis of tribenzotriazasumanene was attempted on the basis of the "fold-in" synthesis of cyclic pyrrole trimer 5 and its analogues under oxidative and reductive conditions. While unexpectedly triply-fused product 6 was obtained in the oxidation of 5 with FeCl3 and AgOTf, the reductive coupling of hexabromo-tri-N-methylpyrrole trimer 9 furnished partially fused product 10. These results indicate the potential of the "fold-in" strategy that gave complementary outcomes depending on the reaction conditions.


Ethics of Scholarly Collaboration.
Scholarly collaboration with others involves endeavors filled with known-unknown expectations and ambiguity in the development of projects, presentations, and publications. This article begins an exploration of potential ethics involved in situations of collaboration among scholars as potential conflicts of interest unfold. The straight-thinking ethos surrounding collaboration is highlighted from a humanbecoming leading-following model.


UPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactions.
Protein-protein interactions have been widely used to study gene expression pathways and may be considered as a new approach to drug discovery. Here I report the development of a universal protein array (UPA) system that provides a sensitive, quantitative, multi-purpose, effective and easy technology to determine not only specific protein-protein interactions, but also specific interactions of proteins with DNA, RNA, ligands and other small chemicals. (i) Since purified proteins are used, the results can be easily interpreted. (ii) UPA can be used multiple times for different targets, making it economically affordable for most laboratories, hospitals and biotechnology companies. (iii) Unlike DNA chips or DNA microarrays, no additional instrumentation is required. (iv) Since the UPA uses active proteins (without denaturation and renaturation), it is more sensitive compared with most existing methods. (v) Because the UPA can analyze hundreds (even thousands on a protein microarray) of proteins in a single experiment, it is a very effective method to screen proteins as drug targets in cancer and other human diseases.


[Surgery of parapharyngeal space neoplasms].
To study the diagnosis, treatment and the choice of operative entrance for parapharyngeal space neoplasm. In a retrospective study the data of 34 patients between 1993 and 2002 were analyzed with regard to presenting signs and symptoms, histological diagnosis, imaging technique and surgical approach. 88.2% of the tumors were benign. Sixteen tumors originated from salivary glands. Neurogenic tumors were found in 14 patients. Thirty-four patients were treated surgically: the trans-cervical approach was used in 26 cases, trans-oral in 5 cases, the combined transoral-cervical approach in 2 cases, and trans-infratemporal fossa in 1 case. Thirty-two tumors were removed completely. The complications after operation were Horner syndrome (3 cases), vocal cord paralysis (5 cases) and facial nerve palsy (3 cases). One patient had both vocal cord paralysis and hypoglossal nerve paralysis. With the follow-up time of 13 months to 10.5 years, 30 patients had been cured, one patient turned to better, 3 cases had recurrence local tumour (pleomorphic adenoma). The majority of tumors can be excised safely and completely using the trans-cervical approach. Intra-oral excisions should be indicated only for small tumors that tend to pharynx with clear border.


Machine Learning-Based Estimation of Ground Reaction Forces and Knee Joint Kinetics from Inertial Sensors While Performing a Vertical Drop Jump.
Nowadays, the use of wearable inertial-based systems together with machine learning methods opens new pathways to assess athletes' performance. In this paper, we developed a neural network-based approach for the estimation of the Ground Reaction Forces (GRFs) and the three-dimensional knee joint moments during the first landing phase of the Vertical Drop Jump. Data were simultaneously recorded from three commercial inertial units and an optoelectronic system during the execution of 112 jumps performed by 11 healthy participants. Data were processed and sorted to obtain a time-matched dataset, and a non-linear autoregressive with external input neural network was implemented in Matlab. The network was trained through a train-test split technique, and performance was evaluated in terms of Root Mean Square Error (RMSE). The network was able to estimate the time course of GRFs and joint moments with a mean RMSE of 0.02 N/kg and 0.04 N·m/kg, respectively. Despite the comparatively restricted data set and slight boundary errors, the results supported the use of the developed method to estimate joint kinetics, opening a new perspective for the development of an in-field analysis method.


Cell type-dependent cytokine expression after canine distemper virus infection.
Canine cells of different histogenesis were infected with the Onderstepoort strain of distemper virus (CDV) to study the effect of viral infection on cytokine production. Included were primary brain cells, dermal fibroblasts, and two cell lines, DH 82 cells (macrophage-like) and epithelial Madin-Darby canine kidney (MDCK) cells. All cultures produced infective virus. MDCK cells had the lowest percentage of CDV-antigen positive cells, and infection did not cause a significant increase of cell death. After infection, mRNA steady state levels of interleukin (IL)-1, IL-6, IL-8, IL-12, tumor necrosis factor-alpha (TNF), and transforming growth factor-beta (TGF) were analyzed using RT-PCR. IL-6 and TNF protein were assessed immunohistochemically. In general, CDV infection resulted in induction of pro-inflammatory cytokines. In primary brain and DH 82 cells, IL-1, IL-6, and TNF were induced, and IL-1 and TNF but not IL-6 were upregulated in dermal fibroblasts. In contrast, in MDCK cells IL-1 and TNF expression was similar in infected and noninfected cells, whereas IL-6 was not produced in either condition. In addition, cytokine induction correlated to the degree of level of CDV production, and therefore cytopathic effects are presumed to be due to a direct virus-mediated or cytokine-mediated process. These findings suggest that pro-inflammatory cytokines, namely IL-1, IL-6, and TNF, which might play an important role in CDV pathogenesis, are induced in a cell-specific manner.


Association of Barley Root Elongation with ABA-Dependent Transport of Cytokinins from Roots and Shoots under Supra-Optimal Concentrations of Nitrates and Phosphates.
Changes in root elongation are important for the acquisition of mineral nutrients by plants. Plant hormones, cytokinins, and abscisic acid (ABA) and their interaction are important for the control of root elongation under changes in the availability of ions. However, their role in growth responses to supra-optimal concentrations of nitrates and phosphates has not been sufficiently studied and was addressed in the present research. Effects of supra-optimal concentrations of these ions on root elongation and distribution of cytokinins between roots and shoots were studied in ABA-deficient barley mutant Az34 and its parental variety, Steptoe. Cytokinin concentration in the cells of the growing root tips was analyzed with the help of an immunohistochemical technique. Increased concentrations of nitrates and phosphates led to the accumulation of ABA and cytokinins in the root tips, accompanied by a decline in shoot cytokinin content and inhibition of root elongation in Steptoe. Neither of the effects were detected in Az34, suggesting the importance of the ability of plants to accumulate ABA for the control of these responses. Since cytokinins are known to inhibit root elongation, the effect of supra-optimal concentration of nitrates and phosphates on root growth is likely to be due to the accumulation of cytokinins brought about by ABA-induced inhibition of cytokinin transport from roots to shoots.


Reliable fabrication of sub-10 nm silicon nanowires by optical lithography.
The reliable and controllable fabrication of silicon nanowires is achieved, using mature CMOS technology processes. This will enable a low-cost route to integrating novel nanostructures with CMOS logic. The challenge of process repeatability has been overcome by careful study of material properties for processes such as etching and oxidation. By controlling anisotropic wet etching conditions, selection of nitride mask layer properties and sidewall oxidation, a robust process was achieved to realize silicon nanowires with sub 10 nm features. Surface roughness of nanowires was improved by a suitable oxidation step. The influence of process conditions on the shape of the nanowire was studied using TCAD simulation.


Impact of storage conditions and premix type on fat-soluble vitamin stability.
Feed ingredients and additives could be a potential medium for foreign animal disease entry into the United States. The feed industry has taken active steps to reduce the risk of pathogen entry through ingredients. Medium chain fatty acid (MCFA) and heat pulse treatment could be an opportunity to prevent pathogen contamination. The objective of experiment 1 was to determine the impact of 0, 30, 60, or 90 d storage time on fat-soluble vitamin stability when vitamin premix (VP) and vitamin trace mineral premix (VTM) were blended with 1% inclusion of MCFA (1:1:1 blend of C6:C8:C10) or mineral oil (MO) with different environmental conditions. Samples stored at room temperature (RT) (~22 °C) or in an environmentally controlled chamber set at 40 °C and 75% humidity, high-temperature high humidity (HTHH). The sample bags were pulled out at days 0, 30, 60 and 90 for RT condition and HTHH condition. The objective of experiment 2 was to determine the effect of heat pulse treatment and MCFA addition on fat-soluble vitamin stability with two premix types. A sample from each treatment was heated at 60 °C and 20% humidity. For experiment 1, the following effects were significant for vitamin A: premix type × storage condition (P = 0.031) and storage time × storage condition (P = 0.002) interactions; for vitamin D3: main effect of storage condition (P < 0.001) and storage time (P = 0.002); and for vitamin E: storage time × storage condition interaction (P < 0.001). For experiment 2, oil type did not affect the stability of fat-soluble vitamins (P > 0.732) except for vitamin A (P = 0.030). There were no differences for fat-soluble vitamin stability between VP and VTM (P > 0.074) except for vitamin E (P = 0.016). Therefore, the fat-soluble vitamins were stable when mixed with both vitamin and VTM and stored at 22 °C with 28.4% relative humidity (RH). When premixes were stored at 39.5 °C with 78.8%RH, the vitamin A and D3 were stable up to 30 d while the vitamin E was stable up to 60 d. In addition, MCFA did not influence fat-soluble vitamin degradation during storage up to 90 d and in the heat pulse process. The vitamin stability was decreased by 5% to 10% after the premixes was heated at 60 °C for approximately nine and a half hours. If both chemical treatment (MCFA) and heat pulse treatment have similar efficiency at neutralizing or reducing the target pathogen, the process of chemical treatment could become a more practical practice.


Transcriptional plasticity of schizotrophic Sclerotinia sclerotiorum responds to symptomatic rapeseed and endophytic wheat hosts.
The broad host range of fungi with differential fungal responses leads to either a pathogenic or an endophytic lifestyle in various host plants. Yet, the molecular basis of schizotrophic fungal responses to different plant hosts remains unexplored. Here, we observed a general increase in the gene expression of S. sclerotiorum associated with pathogenicity in symptomatic rapeseed, including small protein secretion, appressorial formation, and oxalic acid toxin production. Conversely, in wheat, many carbohydrate metabolism and transport-associated genes were induced, indicating a general increase in processes associated with carbohydrate acquisition. Appressorium is required for S. sclerotiorum during colonization in symptomatic hosts but not in endophytic wheat. These findings provide new clues for understanding schizotrophic fungi, fungal evolution, and the emergence pathways of new plant diseases.


Scoping the common antecedents of job stress and job satisfaction for nurses (2000-2013) using the job demands-resources model of stress.
To identify core antecedents of job stress and job satisfaction, and to explore the potential of stress interventions to improve job satisfaction. Decreased job satisfaction for nurses is strongly associated with increased job stress. Stress management strategies might have the potential to improve job satisfaction. Comparative scoping review of studies (2000-2013) and location of their outcomes within the 'job demands-job resources' (JD-R) model of stress to identify commonalities and trends. Many, but not all, antecedents of both phenomena appeared consistently suggesting they are common mediators. Others were more variable but the appearance of 'emotional demands' as a common antecedent in later studies suggests an evolving influence of the changing work environment. The occurrence of 'shift work' as a common issue in later studies points to further implications for nurses' psychosocial well-being. Job satisfaction problems in nursing might be co-responsive to stress management intervention. Improving the buffering effectiveness of increased resilience and of prominent perceived job resource issues are urgently required. Participatory, psychosocial methods have the potential to raise job resources but will require high-level collaboration by stakeholders, and participative leadership and facilitation by managers to enable better decision-latitude, support for action planning and responsive changes.


Plasticity of circle of Willis: a longitudinal observation of flow patterns in the circle of Willis one week after stenting for severe internal carotid artery stenosis.
The purpose of the present study was to assess whether the direction of flow via the circle of Willis (CoW) changed after stenting for severe internal carotid artery (ICA) stenosis. 65 patients (38 men, mean age 63.2 +/- 8.4 years, range 44-82) with a symptomatic ICA occlusion were investigated. Magnetic resonance angiography was performed prior to and 1 week after carotid artery stenting (CAS). The pattern in the CoW was assessed. One third of the subjects (35.38%) had a significantly altered flow pattern in the CoW after unilateral CAS, including blocked ipsilateral A1 segment collateral (n = 4), blocked contralateral A1 segment collateral (n = 5), blocked ipsilateral posterior communicating artery (PCoA) segment collateral (n = 4), blocked ipsilateral A1 segment and P1 segment collateral (n = 1), opening of ipsilateral A1 segment collateral (n = 5), opening of ipsilateral PCoA segment collateral (n = 3) and opening of ipsilateral P1 segment collateral (n = 1). CoW segmental hypoplasia is not a static feature. Willisian collateralization with recruitment of the CoW segment (A1, P1 and PCoA) may be blocked after CAS. CAS also leads to the opening of new willisian collateralization, either for relief of reperfusion pressure or for other hypoperfused areas.


Protective and risk factors for acute respiratory infections in hospitalized urban Malaysian children: a case control study.
We performed a case control study to examine protective and risk factors for acute respiratory infections (ARI) in hospitalized children in Kuala Lumpur. Consecutive children between the ages of one month and five years hospitalized for pneumonia (n = 143), acute bronchiolitis (n = 92), acute laryngotracheobronchitis (n = 32) and empyema (n = 4) were included as cases and were compared with 322 children hospitalized during the same 24 hour period for non-respiratory causes. Potential risk and protective factors were initially analysed by univariate analysis. Logistic regression analysis confirmed that several home environmental factors were significantly associated with ARI. The presence of a coughing sibling (OR = 3.76, 95%CI 2.09, 6.77), a household with more than five members (OR = 1.52, 95%CI 1.03, 2.19) and sleeping with three other persons (OR = 1.45, 95%CI 1.00, 2.08) were independent risk factors. Significant host factors were history of allergy (OR = 2.50, 95%CI 1.74, 3.61) and ethnicity (Malay race) (OR = 2.07 95%CI, 1.27, 3.37). Breast feeding for at least one month was confirmed as an independent protective factor (OR = 0.58, 95%CI 0.38, 0.86). However, the study was not able to demonstrate that domestic air pollution had an adverse effect. This study provides further evidence that home environmental factors, particularly those associated with crowding, may predispose to ARI and that breast feeding is an important protective factor.


A single nucleotide polymorphism assay sheds light on the extent and distribution of genetic diversity, population structure and functional basis of key traits in cultivated north American cannabis.
The taxonomic classification of Cannabis genus has been delineated through three main types: sativa (tall and less branched plant with long and narrow leaves), indica (short and highly branched plant with broader leaves) and ruderalis (heirloom type with short stature, less branching and small thick leaves). While still under discussion, particularly whether the genus is polytypic or monotypic, this broad classification reflects putative geographical origins of each group and putative chemotype and pharmacologic effect. Here we describe a thorough investigation of cannabis accessions using a set of 23 highly informative and polymorphic SNP (Single Nucleotide Polymorphism) markers associated with important traits such as cannabinoid and terpenoid expression as well as fibre and resin production. The assay offers insight into cannabis population structure, phylogenetic relationship, population genetics and correlation to secondary metabolite concentrations. We demonstrate the utility of the assay for rapid, repeatable and cost-efficient genotyping of commercial and industrial cannabis accessions for use in product traceability, breeding programs, regulatory compliance and consumer education. We identified 5 clusters in the sample set, including industrial hemp (K5) and resin hemp, which likely underwent a bottleneck to stabilize cannabidiolic acid (CBDA) accumulation (K2, Type II & III). Tetrahydrocannabinolic acid (THCA) resin (Type I) makes up the other three clusters with terpinolene (K4 - colloquial "sativa" or "Narrow Leaflet Drug" (NLD), myrcene/pinene (K1) and myrcene/limonene/linalool (K3 - colloquial "indica", "Broad Leaflet Drug" (BLD), which also putatively harbour an active version of the cannabichrometic acid Synthase gene (CBCAS). The final chemical compositions of cannabis products have key traits related to their genetic identities. Our analyses in the context of the NCBI Cannabis sativa Annotation Release 100 allows for hypothesis testing with regards to secondary metabolite production. Genetic markers related to secondary metabolite production will be important in many sectors of the cannabis marketplace. For example, markers related to THC production will be important for adaptable and compliant large-scale seed production under the new US Domestic Hemp Production Program.


Akt Phosphorylates Wnt Coactivator and Chromatin Effector Pygo2 at Serine 48 to Antagonize Its Ubiquitin/Proteasome-mediated Degradation.
Pygopus 2 (Pygo2/PYGO2) is an evolutionarily conserved coactivator and chromatin effector in the Wnt/β-catenin signaling pathway that regulates cell growth and differentiation in various normal and malignant tissues. Although PYGO2 is highly overexpressed in a number of human cancers, the molecular mechanism underlying its deregulation is largely unknown. Here we report that Pygo2 protein is degraded through the ubiquitin/proteasome pathway and is posttranslationally stabilized through phosphorylation by activated phosphatidylinositol 3-kinase/Akt signaling. Specifically, Pygo2 is stabilized upon inhibition of the proteasome, and its intracellular level is regulated by Cullin 4 (Cul4) and DNA damage-binding protein 1 (DDB1), components of the Cul4-DDB1 E3 ubiquitin ligase complex. Furthermore, Pygo2 is phosphorylated at multiple residues, and Akt-mediated phosphorylation at serine 48 leads to its decreased ubiquitylation and increased stability. Finally, we provide evidence that Akt and its upstream growth factors act in parallel with Wnt to stabilize Pygo2. Taken together, our findings highlight chromatin regulator Pygo2 as a common node downstream of oncogenic Wnt and Akt signaling pathways and underscore posttranslational modification, particularly phosphorylation and ubiquitylation, as a significant mode of regulation of Pygo2 protein expression.


Planar chiral azobenzenophanes as chiroptic switches for photon mode reversible reflection color control in induced chiral nematic liquid crystals.
In this report, for the first time, a planar chiral photoresponsive compound has been employed in commercially available nematic liquid crystals to achieve phototunable reflection colors. We designed an azobenzenophane compound having conformational restriction on the free rotation of naphthalene moiety to impose an element of planar chirality and the corresponding enantiomers were resolved by HPLC on chiral column. We have determined the absolute configuration by comparison of density functional theory (DFT) calculations of its electronic circular dichroism (ECD) spectrum and specific rotation [alpha] D to experimental ECD and [alpha] D data. Enantiomers exhibit photochemically reversible isomerization in solution without undergoing thermal or photoinduced racemization. As chiroptic switches in different host nematic liquid crystals, they exhibit good solubility, moderately high helical twisting power, as well as a large change in helical twisting power due to photoisomerization. A unique feature of these chiral photochromic compounds is that no other auxiliary chiral agents is required to achieve a fast photon mode reversible full-range color control in induced cholesterics, that is, both the hypsochromic and bathochromic shift can be obtained from a single LC formulation by reversible photoisomerization of the single chiral compound.


Kinetic characterization of substrate-binding sites of thermostable tRNA methyltransferase (TrmB).
TrmB is a eubacterial tRNA methyltransferase which catalyzes the formation of N7-methylguanosine at position 46 (m7G46) in tRNA consuming S-adenosyl-L-methionine (AdoMet) as the methyl group donor during the reaction. Previously, we purified TrmB from Aquifex aeolicus, a hyper-thermophilic eubacterium, and clarified the recognition sites in tRNA. Furthermore, we reported that an additional C-terminal region of A. aeolicus TrmB is required for protein stability at high temperatures. In the current study, we devised a new purification method to remove contaminating RNA completely. The purified enzyme is mainly in a monomeric form. We prepared 17 mutant A. aeolicus TrmB proteins and performed kinetic studies. Our analyses reveal that Glu47, Tyr95, Arg108, Thr165 and Tyr167 residues are important for AdoMet binding and that Asp74, Asp97, and Thr132 are important for the methyltransfer reaction. Furthermore, substitution of Asp133 by alanine caused complete loss of enzymatic activity. Based on the results of our current studies and previous bioinformatic, biochemical and structural studies by others, a reaction mechanism for TrmB is proposed.


Assessment of the impact of changes related to the system transformation on the evolution of the process of mortality in Poland.
"The article presents an attempt to make a quantitative evaluation of the impact of the environment on the rate of mortality, focusing on the group of stress-bearing factors that, according to some hypotheses, make up the set of potential, indirect determinants in the process of mortality. According to these opinions, the environment can be a source of different forms of stress. One stressor can be the social and economic status of individuals, being the function of the economic development of the region, another the instability of the social situation in the region. Both types of stress sources seem to be particularly adequate in the evaluation of the impact of this type of factor on the process of mortality in Poland in the period of system transformation."


Associations between range of motion, strength, tear size, patient-reported outcomes, and glenohumeral kinematics in individuals with symptomatic isolated supraspinatus tears.
Clinical failure associated with nonoperative treatment of rotator cuff tears may be due to inadequate characterization of the individual's functional impairments. Clinically, restricted passive range of motion (ROM) (restrictions imply capsular tightness), limitations in muscle strength, and larger rotator cuff tears are hypothesized to be related to altered glenohumeral kinematics. Understanding these relationships, as well as the relationship between glenohumeral kinematics and patient-reported outcomes (PROs) prior to exercise therapy, may help characterize functional impairments in individuals with rotator cuff tears. The objectives of the study were to describe the baseline presentation of individuals with an isolated supraspinatus tear, including passive ROM, rotator cuff muscle strength, tear size, PROs, and glenohumeral kinematics, and to determine associations among these variables. One hundred one individuals with symptomatic isolated supraspinatus tears were recruited for the study and underwent assessments of passive glenohumeral ROM, isometric muscle strength, and ultrasonography to assess anterior-posterior tear size. Glenohumeral kinematics during scapular-plane abduction were measured using biplane radiography. Furthermore, PROs including the American Shoulder and Elbow Surgeons (ASES) score and the Western Ontario Rotator Cuff Index (WORC) score were collected. Individuals presented with decreased ROM, external rotation weakness compared with the uninvolved side, and pain and disability as measured by the ASES and WORC scores. These findings were not associated with glenohumeral kinematics, with the exception of a weak positive association between glenohumeral contact path lengths and WORC scores (ρ = 0.25, P = .03). Tear size was 11.7 ± 5.7 mm, and maximum anterior translation, superior translation, and contact path length were 3.0% ± 3.8% of glenoid width, 3.5% ± 3.8% of glenoid height, and 38.2% ± 20.7% of glenoid size, respectively. Individuals with a symptomatic isolated supraspinatus tear presented with decreased ROM, external rotation weakness, and pain and disability as measured by the ASES and WORC scores. However, no abnormal kinematics associated with these limitations were observed. Thus, given that the tear is isolated to the supraspinatus tendon and no capsular restrictions are present, normal function of the glenohumeral joint may be possible during scapular-plane abduction.


Novel mutations of SLC26A4 in Chinese patients with nonsyndromic hearing loss.
This study demonstrated high prevalence of GJB2, SLC26A4, and mtDNA A1555G mutations in Chinese patients with nonsyndromic hearing loss and discovered eight novel mutations in SLC26A4. Most of these novel mutations were predicted pathogenic variants. Nonsyndromic hearing loss is the most common neurosensory deafness where the majority of patients have highly diversified genetic defects. This study aimed to define the genetic profile of deafness in a Chinese population with potential to discover novel mutations. A total of 227 segregating deaf students and 200 individuals with normal hearing were enrolled. With the Sanger sequencing chemistry, direct sequencing was performed on entire coding regions of GJB2, GJB3, SLC26A4, and mtDNA m.C1494T and m.A1555G. Direct sequencing analysis revealed that 53 (23.35%) of 227 patients carried at least 1 mutant allele in GJB2, 40 (17.62%) patients in SLC26A4, 5 (2.20%) patients in mtDNA A1555G, and 1 (0.44%) patient in mtDNA C1494T mutations. Four patients carried three unclassified mutations in GJB3 genes. Overall 38 mutant variants were detected in this cohort of patients, including 8 novel mutations in SLC26A4. The eight novel variants were six missense substitutions (p.V163L, p.G222S, p.A456D, p.N457I, p.C466Y, p.F667L), one nonsense mutation (p.W472X), and one frameshift (p.Asn612Ilefs×23).


The past, present and future of RNA respiratory viruses: influenza and coronaviruses.
Influenza virus and coronaviruses continue to cause pandemics across the globe. We now have a greater understanding of their functions. Unfortunately, the number of drugs in our armory to defend us against them is inadequate. This may require us to think about what mechanisms to address. Here, we review the biological properties of these viruses, their genetic evolution and antiviral therapies that can be used or have been attempted. We will describe several classes of drugs such as serine protease inhibitors, heparin, heparan sulfate receptor inhibitors, chelating agents, immunomodulators and many others. We also briefly describe some of the drug repurposing efforts that have taken place in an effort to rapidly identify molecules to treat patients with COVID-19. While we put a heavy emphasis on the past and present efforts, we also provide some thoughts about what we need to do to prepare for respiratory viral threats in the future.


Synthesis and properties of chiral N,N-maleoyl derivatives and Diels-Alder reactions with cyclopentadiene.
Maleyl amino acid derivatives were prepared from maleic anhydride and cyclized by reaction with ZnCl2 and hexamethyldisilazane yielding maleoyl derivatives. These derivatives were used as dienophiles in cycloadditions with cyclopentadiene. The isolated norbornene derivatives resulted from an endo addition, and might be interpreted as analogues of thalidomide. For comparing the properties of compounds prepared by this route, some reference compounds were synthesized from endo-bicyclo[2.2.1]hept-2-ene-5,6-dicarboxylic anhydride and amino acid derivatives. All compounds were characterized by spectroscopic methods, their stereochemistry is discussed, and results were compared with results from calculations.


Antiviral activity of glycoprotein GP-1 isolated from Streptomyces kanasensis ZX01.
Plant virus diseases have seriously damaged global food security. However, current antiviral agents are not efficient enough for the requirement of agriculture production. So, developing new efficient and nontoxic antiviral agents is imperative. GP-1, from Streptomyces kanasensis ZX01, is a new antiviral glycoprotein, of which the antiviral activity and the mode of action against Tobacco mosaic virus (TMV) were investigated in this study. The results showed that GP-1 could fracture TMV particles, and the infection and accumulation of TMV in host plants were inhibited. Moreover, GP-1 could induce systematic resistance against TMV in the host, according to the results of activities of defensive enzymes increasing, MDA decreasing and overexpression of pathogenesis-related proteins. Furthermore, GP-1 could promote growth of the host plant. In conclusion, GP-1 showed the ability to be developed as an efficient antiviral agent and a fertilizer for agriculture.


What Is the Comparative Ability of 18F-FDG PET/CT, 99mTc-MDP Skeletal Scintigraphy, and Whole-body MRI as a Staging Investigation to Detect Skeletal Metastases in Patients with Osteosarcoma and Ewing Sarcoma?
Skeletal metastases of bone sarcomas are indicators of poor prognosis. Various imaging modalities are available for their identification, which include bone scan, positron emission tomography/CT scan, MRI, and bone marrow aspiration/biopsy. However, there is considerable ambiguity regarding the best imaging modality to detect skeletal metastases. To date, we are not sure which of these investigations is best for screening of skeletal metastasis. Which staging investigation-18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT), whole-body MRI, or 99mTc-MDP skeletal scintigraphy-is best in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in detecting skeletal metastases in patients with osteosarcoma and those with Ewing sarcoma? A prospective diagnostic study was performed among 54 of a total 66 consecutive osteosarcoma and Ewing sarcoma patients who presented between March 2018 and June 2019. The institutional review board approved the use of all three imaging modalities on each patient recruited for the study. Informed consent was obtained after thoroughly explaining the study to the patient or the patient's parent/guardian. The patients were aged between 4 and 37 years, and their diagnoses were proven by histopathology. All patients underwent 99mTc-MDP skeletal scintigraphy, 18F-FDG PET/CT, and whole-body MRI for the initial staging of skeletal metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were determined and compared with each other. Multidisciplinary team meetings were held to reach a consensus about the total number of metastases present in each patient, and this was considered the gold standard. The sensitivity, specificity, PPV, and NPV of each imaging modality, along with their 95% confidence intervals, were generated by the software Stata SE v 15.1. Six of 24 patients in the osteosarcoma group had skeletal metastases, as did 8 of 30 patients in the Ewing sarcoma group. The median (range) follow-up for the study was 17 months (12 to 27 months). Although seven patients died before completing the minimum follow-up, no patients who survived were lost to follow-up. With the number of patients available, we found no differences in terms of sensitivity, specificity, PPV, and NPV among the three staging investigations in patients with osteosarcoma and in patients with Ewing sarcoma. Sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 67% (4 of 6 [95% CI 22% to 96%]) and specificities were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 78% (14 of 18 [95% CI 52% to 94%]), respectively, in patients with osteosarcoma. In patients with Ewing sarcoma, sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 88% (7 of 8 [95% CI 47% to 100%]), 88% (7 of 8 [95% CI 47% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and specificities were 100% (22 of 22 [95% CI 85% to 100%]), 95% (21 of 22 [95% CI 77% to 100%]), and 95% (21 of 22 [95% CI 77% to 100%]), respectively. Further, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and the NPVs were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 88% (14 of 16 [95% CI 62% to 98%]), respectively, in patients with osteosarcoma. Similarly, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (7 of 7 [95% CI 59% to 100%]), 88% (7 of 8 [95% CI 50% to 98%]), and 80% (4 of 5 [95% CI 28% to 100%]), and the NPVs were 96% (22 of 23 [95% CI 78% to 100%]), 95% (21 of 22 [95% CI 77% to 99%]), and 84% (21 of 25 [95% CI 64% to 96%]), respectively, in patients with Ewing sarcoma. The confidence intervals around these values overlapped with each other, thus indicating no difference between them. Based on these results, we could not demonstrate a difference in the sensitivity, specificity, PPV, and NPV between 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy for detecting skeletal metastases in patients with osteosarcoma and Ewing sarcoma. For proper prognostication, a thorough metastatic workup is essential, which should include a highly sensitive investigation tool to detect skeletal metastases. However, our study findings suggest that there is no difference between these three imaging tools. Since this is a small group of patients in whom it is difficult to make broad recommendations, these findings may be confirmed by larger studies in the future. Level II, diagnostic study.


Swelling properties of graphite oxides and graphene oxide multilayered materials.
Graphite oxide (GtO) and graphene oxide (GO) multilayered laminates are hydrophilic materials easily intercalated by water and other polar solvents. By definition, an increase in the volume of a material connected to the uptake of a liquid or vapour is named swelling. Swelling is a property which defines graphite oxides and graphene oxides. Less oxidized materials not capable of swelling should be named oxidized graphene. The infinite swelling of graphite oxide yields graphene oxide in aqueous dispersions. Graphene oxide sheets dispersed in a polar solvent can be re-assembled into multilayered structures and named depending on applications as films, papers or membranes. The multilayered GO materials exhibit swelling properties which are mostly similar to those of graphite oxides but not identical and in some cases surprisingly different. Swelling is a key property of GO materials in all applications which involve the sorption of water/solvents from vapours, immersion of GO into liquid water/solvents and solution based chemical reactions. These applications include sensors, sorption/removal of pollutants from waste waters, separation of liquid and gas mixtures, nanofiltration, water desalination, water-permeable protective coatings, etc. Swelling defines the distance between graphene oxide sheets in solution-immersed GO materials and the possibility for penetration of ions and molecules inside of interlayers. A high sorption capacity of GO towards many molecules and cations is defined by swelling which makes the very high surface area of GO accessible. GtO and GO swelling is a surprisingly complex phenomenon which is manifested in a variety of different ways. Swelling is strongly different for materials produced using the most common Brodie and Hummers oxidation procedures; it depends on the degree of oxidation, ad temperature and pressure conditions. The value of the GO interlayer distance is especially important in membrane applications. Diffusion of solvent molecules and ions is defined by the size of "permeation channels" provided by the swelled GO structure. According to extensive studies performed over the last decade the exact value of the inter-layer distance in swelled GO depends on the nature of solvent, temperature and pressure conditions, and the pH and concentration of solutions and exhibits pronounced aging effects. This review provides insight into the fundamental swelling properties of multilayered GO and demonstrates links to advanced applications of these materials.


Immiscible inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation.
Poly(glycine-alanine) (polyGA) is one of the polydipeptides expressed in Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 1 caused by C9ORF72 mutations and accumulates as inclusion bodies in the brain of patients. Superficially these inclusions are similar to those formed by polyglutamine (polyQ)-expanded Huntingtin exon 1 (Httex1) in Huntington's disease. Both have been reported to form an amyloid-like structure suggesting they might aggregate via similar mechanisms and therefore recruit the same repertoire of endogenous proteins. When co-expressed in the same cell, polyGA101 and Httex1(Q97) inclusions adopted immiscible phases suggesting different endogenous proteins would be enriched. Proteomic analyses identified 822 proteins in the inclusions. Only 7 were specific to polyGA and 4 specific to Httex1(Q97). Quantitation demonstrated distinct enrichment patterns for the proteins not specific to each inclusion type (up to ~8-fold normalized to total mass). The proteasome, microtubules, TriC chaperones, and translational machinery were enriched in polyGA aggregates, whereas Dnaj chaperones, nuclear envelope and RNA splicing proteins were enriched in Httex1(Q97) aggregates. Both structures revealed a collection of folding and degradation machinery including proteins in the Httex1(Q97) aggregates that are risk factors for other neurodegenerative diseases involving protein aggregation when mutated, which suggests a convergence point in the pathomechanisms of these diseases.


Poly-Lactide/Exfoliated C30B Interactions and Influence on Thermo-Mechanical Properties Due to Artificial Weathering.
Thermal stability as well as enhanced mechanical properties of poly-lactide (PLA) can increase PLA applications for short-use products. The conjunction of adequate molecular weight (MW) as well as satisfactory thermo-mechanical properties, together, can lead to the achievement of suitable properties. However, PLA is susceptible to thermal degradation and thus an undesired decay of MW and a decrease of its mechanical properties during processing. To avoid this PLA degradation, nanofiller is incorporated as reinforcement to increase its thermo-mechanical properties. There are many papers focusing on filler effects on the thermal stability and mechanical properties of PLA/nanocomposites; however, these investigations lack an explanation of polymer/filler interactions. We propose interactions between PLA and Cloisite30B (C30B) as nanofiller. We also study the effects on the thermal and mechanical properties due to molecular weight decay after exposure to artificial weathering. PLA blank and nanocomposites were subjected to three time treatments (0, 176, and 360 h) of exposure to artificial weathering in order to achieve comparable materials with different MW. MW was acquired by means of Gel Permeation Chromatography (GPC). Thermo-mechanical properties were investigated through Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), Dynamic Mechanical Thermal Analysis (DMTA) and Fourier Transform Infrared Spectroscopy (FTIR).


Lipid metabolism emerges as a promising target for malignant glioma therapy.
Malignant gliomas are one of the most treatment-refractory cancers. Development of resistance to chemo- and radio-therapies contributes to these tumors' aggressive phenotypes. Elevated lipid levels in gliomas have been reported for the last 50 years. However, the molecular mechanisms of how tumor tissues obtain lipids and utilize them are not well understood. Recently, the oncogenic signaling EGFR/PI3K/Akt pathway has been shown to enhance lipid synthesis and uptake by upregulating SREBP-1, a master transcriptional factor, to control lipid metabolism. This article discusses the analytical chemistry results of lipid components in glioma tissues from different research groups. The molecular mechanisms that link oncogenes with lipid programming, and identification of the key molecular targets and development of effective drugs to inhibit lipid metabolism in malignant gliomas will be discussed.