Lycium barbarum polysaccharides induce Toll-like receptor 2- and 4-mediated phenotypic and functional maturation of murine dendritic cells via activation of NF-κB.
Dendritic cells (DCs) are potent antigen‑presenting cells that play pivotal roles in the initiation of primary immune responses. Lycium barbarum polysaccharides (LBPs) are known to have a variety of immunomodulatory functions. However, the cellular and molecular mechanisms underlying their therapeutic effects are poorly understood. In this study, we report that LBPs induce phenotypic and functional maturation of DCs. LBPs upregulated DC expression of I‑A/I‑E and CD11c, enhanced DC allostimulatory activity and induced IL‑12p40 production. Furthermore, the activity of LBPs on DCs was significantly reduced by treating the cells with anti‑TLR2 or anti‑TLR4 antibody prior to LBPs, indicating that both are possible receptors of LBPs. Maturation of DCs by LBPs was able to directly activate the nuclear transcription factor NF‑κB p65. The results revealed that LBP stimulation induces the phenotypic and functional maturation of DCs via TLR2- and/or TLR4-mediated NF‑κB signaling pathways.


TYPE TESTING OF LiF:Mg,Cu,P (TLD-100H) WHOLE-BODY DOSEMETERS FOR THE ASSESSMENT OF Hp(10) AND Hp(0.07).
In this work, the initial results of the type testing of the LiF:Mg,Cu,P (TLD-100H) whole-body personal dosemeters are presented. An assessment of reproducibility, linearity of the response, the residual signal as a function of the dose, energy and angular dependence of the response was performed. In general, the dosemeters show good reproducibility for different dose values and a linear behaviour for a range between 0.1 and 300 mSv. The detection limits obtained are lower than 50 μSv. The system presents a good energy and angular response for different radiation qualities.


Sympathetic modulation of cold-receptive neurones in the trigeminal system of the rat.
The effects of cervical sympathetic electrical stimulation on the activity of cold-receptive neurones in the trigeminal system of the rat have been studied. Sympathetic stimulation caused excitation and/or suppression of cold-receptive cells in the trigeminal nucleus caudalis. The responses were complex but within any one cell low-frequency stimulation (below 5 Hz) usually (81% of cells) caused excitation, while high-frequency stimulation (above 10 Hz) caused excitation and suppression. The temperature of the cutaneous receptive fields was 'clamped' with a thermode. Measurements of surface and intradermal temperatures suggested that the temperature fall caused by sympathetic stimulation was not sufficient to account for the increased firing rate observed. The suppression was blocked by a low dose of phentolamine; it was mimicked by carotid occlusion and may be a consequence of vasoconstriction. The excitation was resistant to beta-blockade; it was best mimicked by the alpha-agonist phenylephrine. Similar frequency-dependent excitations and suppressions, and responses to pharmacological agonists, were obtained in recordings from cold-receptive primary afferent neurones in the trigeminal ganglion. The excitation may be a complex secondary effect, or there may be a direct alpha-receptor-mediated excitation of cold-receptive primary afferent fibres by the sympathetic system.


A new model of bioterrorism risk assessment.
There has been an abundance of different bioterrorist attack scenarios and consequently an unclear biodefense strategy so far. We present a framework for bioterrorism risk assessment that we believe would be useful for policymakers and understandable without needing to be an expert in this field. We retrieved the Medline database via PubMed (from January 1987 to January 2009) and cross-referenced and reviewed the terms biological weapons, biological attacks, bioterror, bio(defense), bio(strategy) and epidemiologic models, and risk assessment. Additionally, we conducted an internet search with the same terms and strategy. We divided bioterrorist attacks into 3 categories: strategical (large-scale), operational (middle-scale), and tactical (small-scale). A bioterrorist attack is presented as a 4-component chain model, including perpetrators, agents, means of delivery, and targets. For any of these 4 components, we propose quantitative and qualitative risk assessment parameters. Here we present a simple scoring system within our model applied to the 2001 U.S. anthrax attacks.


Osmotic Pressure in Clinical Medicine with an Emphasis on Dialysis.
Since the beginning of life of the first multicellular organisms, the preservation of a physiologic milieu for every cell in the organism has been a critical requirement. A particular range of osmolality of the body fluids is essential for the maintenance of cell volume. In humans the stability of electrolyte concentrations and their resulting osmolality in the body fluids is the consequence of complex interactions between cell membrane functions, hormonal control, thirst, and controlled kidney excretion of fluid and solutes. Knowledge of these mechanisms, of the biochemical principles of osmolality, and of the relevant situations occurring in disease is of importance to every physician. This comprehensive review summarizes the major facts on osmolality, its relation to electrolytes and other solutes, and its relevance in physiology and in disease states with a focus on dialysis-related considerations.


Compressed Deep Learning to Classify Arrhythmia in an Embedded Wearable Device.
The importance of an embedded wearable device with automatic detection and alarming cannot be overstated, given that 15-30% of patients with atrial fibrillation are reported to be asymptomatic. These asymptomatic patients do not seek medical care, hence traditional diagnostic tools including Holter are not effective for the further prevention of associated stroke or heart failure. This is likely to be more so in the era of COVID-19, in which patients become more reluctant on hospitalization and checkups. However, little literature is available on this important topic. For this reason, this study developed efficient deep learning with model compression, which is designed to use ECG data and classify arrhythmia in an embedded wearable device. ECG-signal data came from Korea University Anam Hospital in Seoul, Korea, with 28,308 unique patients (15,412 normal and 12,896 arrhythmia). Resnets and Mobilenets with model compression (TensorFlow Lite) were applied and compared for the diagnosis of arrhythmia in an embedded wearable device. The weight size of the compressed model registered a remarkable decrease from 743 MB to 76 KB (1/10000), whereas its performance was almost the same as its original counterpart. Resnet and Mobilenet were similar in terms of accuracy, i.e., Resnet-50 Hz (97.3) vs. Mo-bilenet-50 Hz (97.2), Resnet-100 Hz (98.2) vs. Mobilenet-100 Hz (97.9). Here, 50 Hz/100 Hz denotes the down-sampling rate. However, Resnets took more flash memory and longer inference time than did Mobilenets. In conclusion, Mobilenet would be a more efficient model than Resnet to classify arrhythmia in an embedded wearable device.


Taxonomic re-evaluation of species in Talaromyces section Islandici, using a polyphasic approach.
The taxonomy of Talaromyces rugulosus, T. wortmannii and closely related species, classified in Talaromyces sect. Islandici, is reviewed in this paper. The species of Talaromyces sect. Islandici have restricted growth on MEA and CYA, generally have yellow mycelia and produce rugulosin and/or skyrin. They are important in biotechnology (e.g. T. rugulosus, T. wortmannii) and in medicine (e.g. T. piceus, T. radicus). The taxonomy of sect. Islandici was resolved using a combination of morphological, extrolite and phylogenetic data, using the Genealogical Concordance Phylogenetic Species Recognition (GCPSR) concept, with special focus on the T. rugulosus and T. wortmannii species complexes. In this paper, we synonymise T. variabilis, Penicillium concavorugulosum and T. sublevisporus with T. wortmannii, and introduce four new species as T. acaricola, T. crassus, T. infraolivaceus and T. subaurantiacus. Finally, we provide a synoptic table for the identification of the 19 species classified in the section.


Unintentional changes in the apparent stiffness of the multi-joint limb.
We explored the phenomenon of unintentional changes in the apparent stiffness of the human arm produced by transient changes in the external force. The subjects performed a positional task against a constant baseline force and were instructed not to react to changes in the force. A HapticMaster robot produced a smooth force increase (a perturbation) leading to a hand movement, followed by a dwell time. No visible hand drift was observed during the dwell time. After the robot force dropped to its initial baseline value, the hand moved toward the initial position but stopped short of it. Small perturbations were applied at different time intervals along different directions during the dwell time. Arm apparent stiffness distribution in a horizontal plane was approximated with an ellipse. The apparent stiffness magnitude along the main axis of the ellipse showed a non-monotonic increase with dwell time, while the apparent stiffness along the minor axis did not change significantly. We interpreted the early part of the changes in the apparent stiffness as due to peripheral muscle properties. The later part is interpreted as caused by a combination of two processes: a drift in the referent hand coordinate due to the hypothesized back-coupling between the referent and actual hand coordinates and an implicit instruction to keep the hand steady when no changes in robot-generated force took place. The data provide support for the idea of back-coupling between the referent and actual body configurations, which may be an important contributor to stability of motor actions.


Sickness absence and full return to work after cancer: 2-year follow-up of register data for different cancer sites.
Cancer survival has improved in recent years, but data on return to work (RTW) after cancer are sparsely published. Therefore, this study analysed RTW after cancer. Employees diagnosed with breast cancer, genital cancer, gastro-intestinal cancer, lung cancer, skin cancer, or blood malignancies were selected from an occupational health register. Sickness absence was followed for 2 years after diagnosis and full RTW at equal earnings as before sickness absence was assessed for each cancer site using Cox proportional hazards regression analysis stratifying for age and gender. 3701 (73%) of 5074 employees with cancer had full RTW after a median duration of 290 days. Employees with lung cancer had the longest duration of sickness absence and only 45% of them had full RTW 2 years after diagnosis compared with 88% of employees with genital cancer and 87% of employees with skin cancer. Age was associated with the time to full RTW among employees with genital cancer: women aged≥35 years had a longer time to full RTW compared with women <35 years and men aged≥55 years had a longer time to full RTW compared with men <35 years. Gender was associated with the time to full RTW among survivors of blood malignancies with women having a longer time to full RTW than men. Most employees had full RTW within 2 years after the diagnosis of cancer and the time to RTW was largely independent of age and gender.


[Study on genetic epidemiology on 815 patients with vitiligo in Zhejiang area].
Genetic factors are thought to be involved in the development of vitiligo. The aim of this study is to explore the possible genetic model of vitiligo by analyzing the genetic characteristics of 815 patients from Zhejiang province. Data for 815 patients with vitiligo together with their first- and second-degree relatives were obtained using a standardized questionnaire. All these information was requested to confirm the answers about family history in order to reduce the possibility of 'recall' bias. The 815 probands would include 411 (50.43%) males and 404 (49.57%) females with a varied age from 2 months to 71 years old. Since the information on general prevalence of vitiligo in this area was absent, a control group was set up to facilitate the calculations of heritability degree. 468 persons of the control group were from non-vitiligo population with a sex ratio of 241(male): 227(female) with varied age of 4 months to 80 years old. Both gender and age were comparable between the vitiligo and the control population. The inheritance pattern estimation, heritability calculation and complex segregation analysis were performed with Penrose method, Falconer regression method and SAGE-REGTL program. In 815 vitiligo probands, 128 had and 687 had not family histories, with a heritability rate of 15.7%. The vitiligo prevalence in proband's first degree relatives was 2.580%, higher than the prevalence of 0.618% in second degree relatives, and both of them were higher than general prevalence: 0.192%. By Penrose method, the rates on different catagories were as follows: sibling prevalence rates s = 0.080 18; population prevalence rate q = 0.001 92; s/q = 41.76. The ratio of s/q did not approach 1/2q (260.42) or 1/4q (130.21), but approached 1/square root of q(22.82), suggesting vitiligo was consistent with a mode of polygenic inheritance. Using Falconer's method, heritabilities of vitiligo in first-and second degree relatives of probands were 59.61% (95% confidence interval 65.37-53.84) and 55.20% (95% confidence interval 43.88-66.52), respectively. The weighted average of heritability in all relatives was 58.7% (95% confidence interval 53.56-63.83). The results of complex segregation analysis suggested that major gene model including the Mendelian dominant, recessive and additive hypotheses were not rejected (P > 0.05). Purely environmental model and no transmission model were rejected at a 0. 001 significance level. According to AIC, Mendelian dominant inheritance was the best-fitted hypothesis. Genetic factors played an important role in the occurrence of vitiligo, and the genetic model of vitiligo could serve as the polygenetic or multifactorial inheritance with major gene trait.


[Genetic polymorphism of fifteen short tandem repeat loci in Chinese Drungs].
To study the short tandem repeat (STR) polymorphism in Chinese Drungs (Tulungs). The genetic distributions of fifteen STR loci were investigated with the use of coamplification, genescan and genotype from 67 Drungs. There were 144 STR alleles in Drung nationality, with their frequencies ranging from 0.0077 to 0.7846, heterozygosity(H) 0.3723-0.8639, discrimination power(DP) 0.5567-0.9548, probability of paternity exclusion(EPP) 0.2738-0.8358, polymorphism information content (PIC) 0.3461-0.8456 the accumulative DP 0.99999998 and EPP 0.99999894. The results of this study on the STR polymorphism in Chinese Drungs could be used as a basis for the genetic structure of Chinese ethnic groups and also be of significant application in anthropology and forensic science.


The Weekend Warrior: Common Foot and Ankle Injuries in Recreational Athletes.
Weekend warriors are recreational athletes who compress their physical activity into 1-2 weekly exercise sessions. The characteristic combination of general deconditioning and excessive activity can predispose these individuals to a multitude of foot and ankle injuries. The purpose of this review is to highlight the etiology and management of common foot and ankle injuries in recreational athletes.


[Treatment of constipation in pregnant women. A multicenter study in a gynecological practice].
Constipation is a common problem during pregnancy. It is essential to relieve the condition without putting the developing child at risk or further stressing the mother. The fact that lactulose is not absorbed in the small intestine is of great significance when treating constipation during pregnancy, as it presents no threat to the foetus. Lactulose also does not appear in breast milk so that the treatment can also be continued during nursing. The present study was an open base-line controlled study to show the efficacy, safety and acceptability of dry lactulose (Duphalac Dry) in pregnant women suffering from chronic or occasional constipation. It was a multi-center study in 12 gynecological practices. 62 women aged between 19 and 40 years were treated during 4 weeks with lactulose. 34% had chronic constipation and the remaining 66% constipation due to the pregnancy. The main criteria for efficacy were frequency of defecation and consistency of stools. There was overall judgement of the efficacy by patients and doctors. Safety was assessed by the number of reported side-effects and compared to the reported concomitant symptoms before treatment. Here also, the patients and their doctors gave a global impression. In addition, patients rated the product flavor and administration methods. The frequency of defecation was significantly increased after 1 week (4.0 vs. 2.5 [median per week], p < 0.001) and normalized after 2 weeks (6 stools per week). Also, the consistency of the stools was normalized during the treatment. The global assessment of efficacy by the treating physicians was good or very good in 84% of the cases and by the patients in 81%.(ABSTRACT TRUNCATED AT 250 WORDS)


Enhanced seed carotenoid levels and branching in transgenic Brassica napus expressing the Arabidopsis miR156b gene.
The Arabidopsis AtmiR156b gene was expressed in Brassica napus under the control of the cauliflower mosaic virus (CaMV) 35S promoter and the seed-specific napin promoter. Seed carotenoid levels, branching habit, seed yield, and seed weight were examined in the transgenic B. napus. Our results demonstrated that constitutive expression of AtmiR156b in B. napus resulted in enhanced levels of seed lutein and beta-carotene and a 2-fold increase in the number of flowering shoots, whereas AtmiR156b driven by the napin promoter did not affect these traits. This suggested that enhancement of seed quality and shoot branching are both related to AtmiR156b expression patterns. Seed yield and seed weight varied significantly within the transgenic lines. However, one line was found to have enhanced seed carotenoid levels but unchanged seed weight or yield. These data suggest that AtmiR156b gene expression could be applied in plant breeding initiatives for enhancing carotenoid production in canola and other crop species.


Association between Cervical Lymph Node Metastasis and the Incidence of Radiation-Induced Hypothyroidism in Nasopharyngeal Carcinoma.
It is controversial and unclear how N-stage would increase the risk of incidence of hypothyroidism (HT) for patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Our study aimed to explore the correlation between cervical lymph node metastasis and the incidence of HT in NPC. A total of 206 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences, and their clinical information were retrospectively collected. A series of univariate logistic regression models were performed to explore the association of clinical and lymph node indices with the development of HT. Significant features in univariate analysis were then used to construct three prediction models, for HT prediction using multivariate logistic regression based on Bayesian information criterion. Prediction performance of those models was measured by area under the receiver operating characteristic curve (AUC) using 10-fold cross-validation. A total of 111 patients developed HT, and the incidence of HT in N 2-3 and N 0-1 patients was 58.82% and 44.29%, respectively. Compared to Model 1 (consisted of pretreatment TSH concentration, thyroid volume, and N-stage) whose AUCs were 0.801 and 0.766 in training and validation sets, with N-stage be replaced by shortest distance from thyroid, Model 2 achieved more stable AUCs of 0.824 and 0.801. While with numbers of positive lymph nodes in Level IIb additionally added, Model 3 improved its AUCs to 0.841 and 0.813. The shortest distance between the lymph nodes and thyroid gland and the number of lymph nodes in IIb are better predictors of radiation-induced HT than the N-stage.


Experimental mesangial proliferative glomerulonephritis (the anti-Thy-1.1 model).
The anti-Thy-1.1 model is a rat model of mesangial proliferative glomerulonephritis characterized by initial mesangiolysis followed by mesangial cell proliferation and accumulation of mesangial matrix with subsequent resolution and the return to almost normal histology. In this review we discuss the pathogenesis of the initial injury, the mechanisms governing mesangial cell proliferation and matrix expansion, and some of the processes involved in the resolution of glomerular injury. Understanding these processes of mesangial cell injury and recovery may provide insights into the pathogenesis of human mesangial cell diseases such as IgA nephropathy.


Cisplatin- and dietary ascorbic acid-mediated changes in the mitochondria of Dalton's lymphoma-bearing mice.
Cisplatin treatment caused a significant increase in the life span of ascites Dalton's lymphoma (DL) Tumor-bearing (TB) mice. However, as compared to cisplatin (CP) alone, combination treatment with ascorbic acid plus CP resulted in better therapeutic efficacy against murine DL. Cisplatin treatment of TB mice resulted in the appearance of thickened and irregular arrangement of mitochondrial cristae in the liver, kidney and DL tumor cells. Combination treatment of the hosts with ascorbic acid and CP lessened deformities in the mitochondria of liver and kidney, while in tumor cells, this increased the formation of vacuoles and disruption in mitochondrial cristae. Cisplatin treatment decreased the succinate dehydrogenase (SDH) activity in the mitochondria of kidney and DL cells and combination treatment caused further decrease in SDH activity in kidney and DL cells during 24-48 h of treatment. After CP treatment, the protein content in the mitochondria of these tissues decreased, and during combination treatment, it showed significant improvement. Mitochondrial lipid peroxidation (LPO) increased in these tissues after CP treatment. However, combination treatment significantly decreased mitochondrial LPO in liver and kidney but increased in DL cells. This increase in mitochondrial LPO in DL cells and decrease in liver and kidney could play an important role in the antitumor activity of combination treatment and at the same time reduce CP-induced toxicity in the host. However, further study may be desirable to explore some aspects of the mechanism(s) involved in these changes in mitochondria.


Fast determination of the tetracyclines in milk samples by the aptamer biosensor.
A novel aptamer biosensor for fast tetracyclines determination was established and illustrated in this paper. The tetracyclines aptamer as a specific affinity molecule was immobilized on the surface of the glassy carbon (GC) electrodes. It can specifically bind tetracyclines quickly in milk and other samples without sample treatment. Subsequently, the electrochemical signals are produced and measured accurately. The linear relationship between the currents and the tetracyclines concentration is 0.1-100 ng ml(-1). The sensitivity limit of the device is 1 ng ml(-1). The detection time is 5 min.


Breast cancer resistance protein (BCRP/MXR/ABCG2) in adult acute lymphoblastic leukaemia: frequent expression and possible correlation with shorter disease-free survival.
Drugs used in treatment of adult acute lymphoblastic leukaemia (ALL) are substrates for breast cancer resistance protein (BCRP, MXR, ABCG2), which may thus play a role in resistance in this disease. Pretreatment blasts from 30 adult ALL patients were studied for BCRP mRNA by quantitative reverse transcription polymerase chain reaction analysis, BCRP protein by immunophenotyping with three antibodies and BCRP function by fumitremorgin C modulation of intracellular mitoxantrone retention, measured by flow cytometry. BCRP mRNA in all cases encoded wild type protein (BCRP(R482)), which mediates mitoxantrone and methotrexate resistance, but only low-level anthracycline resistance. The BXP-21, BXP-34 and anti-ABCG2 antibodies stained blasts in 13, 11 and 14 cases (43%, 37% and 47%); BXP-21 correlated well with BXP-34 and anti-ABCG2, but BXP-34 and anti-ABCG2 did not correlate, and antibody staining did not correlate with mRNA levels. BCRP function was seen in 21 cases (70%), but correlated poorly with antibody staining. An exploratory statistical analysis indicated that BXP-21 staining was predictive of shorter disease-free survival (DFS) (P = 0.0374) in this small patient population. Poor correlations between mRNA, protein and function indicate the complex biology of BCRP in adult ALL, and the possible correlation of BCRP expression with DFS should be studied in larger series.


Delivery of full predicted energy from nutrition and the effect on mortality in critically ill adults: A systematic review and meta-analysis of randomised controlled trials.
The amount of energy required to improve clinical outcomes in critically ill adults is unknown. The aim of this systematic review and meta-analysis was to evaluate the impact of near target energy delivery to critically ill adults on mortality and other clinically relevant outcomes. Following PRISMA guidelines, MEDLINE, EMBASE, CINHAL and the Cochrane Library were searched for randomised controlled trials evaluating nutrition interventions in adult critical care populations. Included studies compared delivery of ≥80% of predicted energy requirements (near target) from enteral and/or parenteral nutrition to <80% (standard care) and reported mortality. The quality of individual studies was assessed using the Cochrane 'Risk of Bias' tool, and the overall body of evidence using the GRADE approach. Fixed or random effect meta-analyses were used pending the presence of heterogeneity (I2 > 50%) when 3 or more studies reported the same outcome. Outcomes are presented as risk ratio (RR), 95% confidence interval (CI). Ten trials with 3155 participants were included. Mortality was unaffected by the intervention (RR 1.02, 95% CI 0.81, 1.27, p = 0.89, I2 = 25%). Evaluation of studies of higher quality and low risk of bias did not alter the mortality inference (3 trials, 352 participants, RR 0.83, 95% CI 0.49, 1.40, p = 0.19, I2 = 39%). The quality of evidence across outcomes was very low. The delivery of near target energy when compared to standard care in adult critically ill patients was not associated with an effect on mortality. Because the quality of the evidence across outcomes was very low there is considerable uncertainty surrounding this estimate. This has implications for clinical utility of the evidence within the included reviews.


Knockdown RBM15 Inhibits Colorectal Cancer Cell Proliferation and Metastasis Via N6-Methyladenosine (m6A) Modification of MyD88 mRNA.
Colorectal cancer (CRC) is one of the most common cancers worldwide. In this study, we explored the role of RNA binding motif protein 15 (RBM15)-mediated MyD88 mRNA N6-methyladenosine (m6A) in CRC development. Cell proliferation, apoptosis, and invasion were detected by EdU, Annexin V-FITC/PI staining, and Transwell assays, respectively. RBM15 and MyD88 expression was detected by RT-qPCR and Western blot. RNA-seq, RIP-seq, and MeRIP-seq were used for RBM15 downstream target gene prediction and expression detection. In this research, we confirmed that RBM15 was highly expressed in CRC tissues and was negatively correlated with overall and disease-free survival rate. Silencing RBM15 significantly inhibited the proliferative and invasive abilities and promoted cell apoptosis in the CRC cell lines (SW480 and HCT116). Moreover, tumor growth and CRC liver metastasis were inhibited by silencing RBM15 in vivo. m6A methylation level was decreased in RBM15-silenced SW480 and HCT116 cells. MyD88 was the target mRNA of RBM15-mediated m6A methylation in CRC. MyD88 was lowly expressed in CRC and negatively correlated with RBM15 expression. Taken together, RBM15 silencing inhibited the CRC growth and metastasis in vitro and in vivo. RBM15 mediated m6A methylation modification of MyD88 mRNA in CRC cells.


Acroplate--a modern solution for the treatment of acromioclavicular joint dislocation.
Two main ways to fix the reduction were imposed in surgical treatment of the acromioclavicular joint dislocations: fixation with trans acromioclavicular pin (Phemister method) and fixation with plate and screws type acroplate. The purpose of the present paper work is to compare immediate and later postoperative results between the two types of surgical interventions. During 2005-2007, 37 surgical reductions and fixation of acromioclavicular joint dislocations were performed in the Orthopedic-Traumatology Clinic of SUUB. In 17 cases a fixation with screws and plates type acroplate has been performed and in 20 cases with pins using the Phemister method. Sex ratio: 31 men and 8 women. Patients were aged between 17 and 56 years old. Follow up at 6 weeks, 3, 6, 12 and 18 post-operatory months. Osteosintesis material removing was done postoperatively, at 4 weeks in case of acroplate's and at 6 weeks in case of the pins. All patients treated of fixation with plate and screws acroplate type had a favorable evolution/development, starting with the shoulder joint mobilization at 24 hours postoperatively, with a complete recovery 4 weeks after the operation, at the same time with the ablation, and without immediate other late complications. As far as the patients treated by using the Phemister method are concerned, they were applied an immobilization, postoperatively. Desault bandage or the scarf for a period between 1 and 3 weeks, beginning with the shoulder joint mobilization later on and a full recovery after a minimum of 6 weeks. However, 3 of the cases showed a migration of one or both pins. Following the study, a more rapid recovery resulted, complete, and without complications of mobility in the shoulder joint, when using plate type acroplate vs pin.


Pressure-Driven Reversible Switching between n- and p-Type Conduction in Chalcopyrite CuFeS2.
Temperature-dependent switching between p- and n-type conduction is a newly observed phenomenon in very few Ag-based semiconductors, which may promote fascinating applications in modern electronics. Pressure, as an efficient external stimulus that has driven collective phenomena such as spin-crossover and Mott transition, is also expected to initialize a conduction-type switching in transition metal-based semiconductors. Herein, we report the observation of a pressure-driven dramatic switching between p- and n-type conduction in chalcopyrite CuFeS2 associated with a structural phase transition. Under compression around 8 GPa, CuFeS2 undergoes a phase transition with symmetry breakdown from space group I-42 d to space group I-4 accompanying with a remarkable volume shrinkage of the FeS4 tetrahedra. A high-to-low spin-crossover of Fe2+ ( S = 2 to S = 0) is manifested along with this phase transition. Instead of pressure-driven metallization, a surprising semiconductor-to-semiconductor transition is observed associated with the structural and electronic transformations. Significantly, both photocurrent and Hall coefficient measurements confirm that CuFeS2 undergoes a reversible pressure-driven p- n conduction type switching accompanying with the structural phase transition. The absence of cationic charge transfer between copper and iron during the phase transition is confirmed by both X-ray absorption near-edge spectra (Cu/Fe, K-edge) and total-fluorescence-yield X-ray absorption spectra (Fe, K-edge) results, and the valence distribution maintains Cu2+Fe2+S2 in the high-pressure phase. The observation of an abrupt pressure-driven p- n conduction type switching in a transition metal-based semiconductor paves the way to novel pressure-responsive switching devices.


[CT-guided biopsy of small lung nodules: usefulness of frozen-section pathologic diagnosis].
To improve the diagnostic accuracy of computed tomography (CT)-guided biopsy of small lung nodules. The usefulness of fine-needle core biopsy combined with immediate frozen-section diagnosis by pathologists was prospectively studied. Forty-six biopsies of small lung nodules (less than 3 cm in greatest diameter) were performed under CT guidance in 46 patients with 31 malignant and 15 benign processes. Initial biopsy was always attempted with a 20 or 21G histological needle; tissue samples were sent to the pathology department immediately after biopsy for pathologic diagnosis of the frozen sections. In 41 of 46 lesions (89.1%), sufficient material was obtained for diagnosis, permitting a correct final diagnosis. For malignancy, the sensitivity was 100%, whereas 81.8% of the benign lesions were diagnosed as specifically benign. Pneumothorax occurred in 41.3%. Histological diagnosis using frozen sections is a useful adjunct for CT-guided biopsy of the chest.


Hydrogen-deuterium exchange in bovine serum albumin protein monitored by Fourier transform infrared spectroscopy, part II: kinetic studies.
The set of infrared spectra recorded at different levels of hydrogen-deuterium (H/D) exchange as a function of time were processed using spectral decomposition. The most precise information about H/D exchange of the NH groups of the protein backbone was retrieved by observing the intensity change of the nearest C=O stretching vibration. The H/D exchange at the protein backbone begins with NH groups bonded to C=O with a characteristic frequency of 1683 cm(-1). These amide groups were initially free and are the first to accept H-bonds from water during the hydration process. The NH groups, which are connected to C=O groups with a characteristic band at 1657 cm(-1), exchange at a slower rate. For both populations the pairs of comparable exchange rates were calculated with rate constants of 10(-3) min(-1), 0.014 min(-1), 0.0046 min(-1), and 0.09 min(-1). The appearance of two different exchange rates for each population is a consequence of the distinct exposure of particular molecular groups to the solvent. Two additional bands sensitive to exchange are attributed to NH bending modes in the side chains and are located at 1610 cm(-1) and 1585 cm(-1). These NH groups undergo H/D exchange at the beginning of the exchange with exchange rates of 0.019 min(-1) and 0.17 min(-1), respectively. The calculated exchange rate for hydrating water molecules is 0.037 min(-1). The distribution of water's exchange rate is extremely broad and covers almost the entire interval of the time-dependent experiment. From the efficiency of the exchange (96%) it is evident that some parts of the protein are completely forbidden to water molecules.


Down-regulation of IL-8 by high-dose vitamin D is specific to hyperinflammatory macrophages and involves mechanisms beyond up-regulation of DUSP1.
There is current interest in vitamin D as a potential anti-inflammatory treatment for chronic inflammatory lung disease, including cystic fibrosis (CF). Vitamin D transcriptionally up-regulates the anti-inflammatory gene DUSP1, which partly controls production of the inflammatory chemokine IL-8. IL-8 is overabundant in CF airways, potentially due to hyperinflammatory responses of CF macrophages. We tested the ability of vitamin D metabolites to down-regulate IL-8 production in CF macrophages. CF and healthy monocyte-derived macrophages (MDM) were treated with two vitamin D metabolites, 25-hydroxyvitamin D3 (25OHD3 ) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), or paricalcitol, synthetic analogue of 1,25(OH)2 D3 . 25OHD3 was tested at doses of 25-150 nM, whereas 1,25(OH)2 D3 and paricalcitol at doses of up to 100 nM. IL-8 was stimulated by bacterial virulence factors. As potential anti-inflammatory mechanism of vitamin D metabolites, we assessed up-regulation of DUSP1. MDM from patients with CF and some healthy donors showed excessive production of stimulated IL-8, highlighting their hyperinflammatory phenotype. Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory MDM, and only when used at high doses (>100 nM for 25OHD3 , or >1 nM for 1,25(OH)2 D3 and paricalcitol). The magnitude of IL-8 down-regulation by vitamin D metabolites or paricalcitol was moderate (∼30% vs. >70% by low-dose dexamethasone). Transcriptional up-regulation of DUSP1 by vitamin D metabolites was seen in all tested MDM, regardless of IL-8 down-regulation. Vitamin D metabolites and their analogues moderately down-regulate IL-8 in hyperinflammatory macrophages, including those from CF. This down-regulation appears to go through DUSP1-independent mechanisms.


Shock mesenteric lymph-induced rat polymorphonuclear neutrophil activation and endothelial cell injury is mediated by aqueous factors.
After trauma and hemorrhagic shock (T/HS), mesenteric lymph (ML) activates polymorphonuclear neutrophils (PMNs), injures endothelial cells (ECs), and predisposes to lung injury. The involved mediators, however, are unknown. We studied the ability of aqueous (AQ) and lipid (LIP) extracts of rat T/HS ML to activate PMNs and injure ECs. ML was collected from male rats undergoing trauma (laparotomy) plus hemorrhagic shock (30 mm Hg, 90 minutes) or sham shock. AQ and LIP ML fractions were separated using the Bligh-Dyer technique. Human umbilical vein endothelial cells were incubated 18 hours in 5% LIP or AQ lymph fractions and viability was assessed using the MTT assay. Rat PMNs incubated 5 minutes with 3% LIP or AQ fractions were assessed for respiratory burst (RB) and cytosolic calcium ([Ca(2+)](i)) using dihydrorhodamine 123 and fura-2AM. Human PMN responses to AQ and LIP T/HS lymph were studied similarly. EC incubated in AQ showed 19 +/- 4% viability as compared with 65 +/- 11% in LIP (p < 0.001). Whole lymph affected ECs comparably to AQ T/HS lymph. Rat PMN basal [Ca(2+)](i) increased after exposure to AQ but not LIP T/HS lymph extracts. AQ T/HS lymph primed [Ca(2+)](i) responses to macrophage inflammatory protein-2 and platelet-activating factor; neither LIP T/HS nor any trauma and sham shock lymph fraction caused PMN priming. Rat PMN RB was elevated after AQ T/HS lymph incubation when compared with buffer (610 +/- 122 U/s vs. 225 +/- 38 U/s, p = 0.01). Rat PMN incubation in LIP T/HS lymph caused minimal activation (289 +/- 28 U/s, p = NS). Conversely, human PMN showed [Ca(2+)](i) and RB priming by rat T/HS LIP and not AQ extracts. T/HS mesenteric lymph contains multiple biologically active mediators. Both AQ and LIP extracts of T/HS lymph are toxic to human umbilical vein endothelial cells, with AQ more active than LIP. Only AQ T/HS lymph activates rat PMNs, although LIP rat lymph extract activates human PMNs. These findings demonstrate the complex nature of gut lymph-derived biologic factors as well as species-specific differences on PMN and EC physiology. Therapies directed at any one specific molecule or mediator are therefore unlikely to be successful.


Targeting the checkpoint kinase Chk1 in cancer therapy.
A paramount objective of the eukaryotic cell division cycle is to overcome numerous internal and external insults to faithfully duplicate the genetic information once per every cycle. This is carried out by elaborate networks of genome surveillance signaling pathways, termed replication checkpoints. Central to replication checkpoints are two protein kinases, the upstream kinase ATR, and its downstream target kinase, Chk1. When the DNA replication process is interrupted, the ATR-Chk1 pathway transmits signals to delay cell cycle progression, and to maintain fork viability so that DNA duplication can resume after the initial damage is corrected. Previous studies showed that replicative stress not only activated Chk1, but also triggered the ubiquitin-dependent destruction of Chk1 in cultured human cells. In a recent study, we identified the F-box protein, Fbx6, as the mediator that regulates Chk1 ubiquitination and degradation in both normally cycling cells and during replication stress. We further showed that expression levels of Chk1 and Fbx6 exhibited an overall inverse correlation in both cultured cancer cell lines and in breast tumor tissues, and that defects in Chk1 degradation, for instance, due to reduced expression of Fbx6, rendered tumor cells resistant to anticancer treatment. Here we highlight those findings and their implications in the replication checkpoint and cellular sensitivity to cancer therapies.


Imaging of language-related brain regions in detoxified alcoholics.
Neuroimaging studies showed clear evidence of alcoholism-related damage to the frontal lobes and cerebellum. Although these regions have been involved in language processing, language skills are relatively spared in alcoholics. Here, we aimed at identifying neural substrates associated with the preserved mechanisms of language processing in alcoholics. We hypothesized that alcoholics would show a different pattern of neural activity compared with the controls. Alcoholic and nonalcoholic subjects performed an auditory language task while receiving a functional magnetic resonance imaging (fMRI) scan in a 1.5 T magnet. This task has been previously shown to solicit the comprehension processing in healthy controls, with reliable fMRI response in the left frontal and temporal/parietal lobes. Behavioral results showed comparable performance (error rates, response time) between the alcoholics and the matched controls. However, analysis of the functional data revealed that the alcoholics exhibited greater fMRI response in the left middle frontal gyrus (pars triangularis), the right superior frontal gyrus, and the cerebellar vermis relative to the controls. These findings suggest that frontocerebellar neural activity, supporting the comprehension processing of the auditory language task, may require compensatory mechanisms in alcoholics in order to maintain the same level of performance as the controls.


An Evaluation of Different Types of Peptone as Partial Substitutes for Animal-derived Serum in Vero Cell Culture.
Vero cells are one of the most frequently used cell types in virology. They can be used not only as a vehicle for the replication of viruses, but also as a model for investigating viral infectivity, cytopathology and vaccine production. There is increasing awareness of the need to limit the use of animal-derived components in cell culture media for a number of reasons, which include reducing the risk of contamination and decreasing costs related to the downstream processing of commercial products obtained via cell culture. The current study evaluates the use of protein hydrolysates (PHLs), also known as peptones, as partial substitutes for fetal bovine serum (FBS) in Vero cell culture. Eleven plant-based, two yeast-based, and three casein-based peptones were assessed, with different batches evaluated in the study. We tested the effects of three concentration ratios of FBS and peptone on Vero cell proliferation, four days after the initial cell seeding. Some of the tested peptones, when in combination with a minimal 1% level of FBS, supported cell proliferation rates equivalent to those achieved with 10% FBS. Collectively, our findings showed that plant-based peptones could represent promising options for the successful formulation of serum-reduced cell culture media for vaccine production. This is especially relevant in the context of the current COVID-19 pandemic, in view of the urgent need for SARS-CoV-2 virus production for certain types of vaccine. The current study contributes to the Three Rs principle of reduction, as well as addressing animal ethics concerns associated with FBS, by repurposing PHLs for use in cell culture.


Ryanodine receptors are expressed in epidermal keratinocytes and associated with keratinocyte differentiation and epidermal permeability barrier homeostasis.
Ryanodine receptors (RyRs) have an important role as calcium channels in the regulation of intracellular calcium levels in the nervous system and muscle. In the present study, we investigated the expression of RyR in human epidermis. Immunohistochemical studies and reverse transcription-PCR indicated the expression of RyR type 1, 2, and 3 proteins in epidermal keratinocytes. The expression level of each RyR subtype was higher in differentiating keratinocytes than in proliferative cells. We also demonstrated the functional expression of RyR by calcium imaging. In cultured human keratinocytes, application of the RyR agonist 4-chloro-m-cresol (CMC) induced elevation of the intracellular calcium concentration, and co-application of the RyR antagonist 1,1'-diheptyl-4,4'-bipyridinium dibromide (DHBP) blocked the elevation. Application of CMC accelerated keratinocyte differentiation in vitro. On the other hand, topical application of CMC after tape-stripping of hairless mouse skin delayed barrier recovery, whereas application of an RyR antagonist, dantrolene or DHBP, accelerated the barrier recovery. These results suggest that RyR expressed in epidermal keratinocytes is associated with both differentiation of keratinocytes and epidermal barrier homeostasis.


Sprint running: from fundamental mechanics to practice-a review.
In this review, we examine the literature in light of the mechanical principles that govern linear accelerated running. While the scientific literature concerning sprint mechanics is comprehensive, these principles of fundamental mechanics present some pitfalls which can (and does) lead to misinterpretations of findings. Various models of sprint mechanics, most of which build on the spring-mass paradigm, are discussed with reference to both the insight they provide and their limitations. Although much research confirms that sprinters to some extent behave like a spring-mass system with regard to gross kinematics (step length, step rate, ground contact time, and lower limb deformation), the laws of motion, supported by empirical evidence, show that applying the spring-mass model for accelerated running has flaws. It is essential to appreciate that models are pre-set interpretations of reality; finding that a model describes the motor behaviour well is not proof of the mechanism behind the model. Recent efforts to relate sprinting mechanics to metabolic demands are promising, but have the same limitation of being model based. Furthermore, a large proportion of recent literature focuses on the interaction between total and horizontal (end-goal) force. We argue that this approach has limitations concerning fundamental sprinting mechanics. Moreover, power analysis based on isolated end-goal force is flawed. In closing, some prominent practical concepts and didactics in sprint running are discussed in light of the mechanical principles presented. Ultimately, whereas the basic principles of sprinting are relatively simple, the way an athlete manages the mechanical constraints and opportunities is far more complex.


The voltage-dependent non-selective cation channel sensitive to the L-type calcium channel blocker efonidipine regulates Ca2+ influx in brain vascular smooth muscle cells.
The present study investigated the ion channel responsible Ca2+ influx in cultured smooth muscle cells from bovine brain arteries by monitoring Ba2+ currents. Voltage pulses at a range between -100 and +100 mV from a holding potential of 0 mV induced currents and the current/voltage (I/V) relations were linear with a reversal potential of +/- 0 mV. The currents were increased by elevating extracellular Ba2+ concentrations, suggesting that the voltage-sensitive non-selective cation channel, which favors Ca2+ influx, is expressed in brain vascular smooth muscle cells. In contrast, when voltage pulses at a range between -50 to +50 mV from a holding potential of -80 mV were applied to carotid smooth muscle cells, inward currents were evoked by depolarization to > or = -10 mV and the I/V relations were bell-shaped, typical for the L-type calcium channels. The dihydropyridine derivatives, efonidipine and nicardipine, inhibited the L-type Ca2+ channel-operated currents in carotid smooth muscles, and further efonidipine had an inhibitory effect also on non-selective cation currents in brain vascular smooth muscle cells. These results suggest that the voltage-dependent non-selective cation channel expressed in brain vascular smooth muscle cells is sensitive to a kind of the dihydropyridine derivatives and regulates Ca2+ influx.


Hetero-Type Benzannulation Leading to Substituted Benzothio-Phenes.
TiCl4 (or SnCl4)-promoted hetero-type benzannulation reactions using various (2,2-dichlorocyclopropyl)(thiophen-2-yl)methanols proceeded smoothly to produce uniquely substituted 4-chlorobenzothiophenes (five examples). The present approach involves the first distinctive thiophene formation from thiophene cores, in contrast to traditional methods of thiophene formation from benzene cores. The stereocongested (less reactive) Cl position in the obtained 4-chlorobenzothiophenes functioned successfully as the partners of three cross-coupling reactions: (i) a Suzuki-Miyaura cross-couplings using Pd(OAc)2/SPhos/K3PO4 catalysis (seven examples; 63-91%), (ii) a hydroxylation using KOH/Pd(dba)2/tBu-XPhos catalysis (85%), and (iii) a borylation using a B2(pin)2/Pd(dba)2/XPhos/NaOAc catalysis-provided 4-(pin)B-benzothiophene (58%).


Dissociation of protamine-DNA complexes by Xenopus nucleoplasmin and minichromosome assembly in vitro.
Nucleoplasmin, an acidic thermostable protein abundant in the nucleus of Xenopus laevis oocytes, has been found to dissociate complexes of pUC19 DNA and protein phi 1, an intermediate protamine present in ripe sperm from the mollusc Mytilus edulis. Cruder preparations of nucleoplasmin, such as the amphibian oocyte S150 extract and its thermostable fraction, also dissociate the heterologous DNA-phi 1 complexes and, in addition, promote the assembly of plasmid DNA into a minichromosome displaying regular nucleosomal periodicity, as revealed by micrococcal nuclease digestion. In contrast, purified nucleoplasmin complemented with rat hepatocyte core histone octamers in the presence of DNA topoisomerase I, although capable of inducing nucleoprotein formation onto the complexed DNA, fails to position nucleosomes at the native spacings seen in chromatin in vivo. These data favour the existence of a general mechanism to bring about, in a concerted manner, removal of sperm-specific nuclear proteins and reconstitution of somatic chromatin following fertilization.


Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania.
Although humans have cospeciated with their gut-resident microbes, it is difficult to infer features of our ancestral microbiome. Here, we examine the microbiome profile of 350 stool samples collected longitudinally for more than a year from the Hadza hunter-gatherers of Tanzania. The data reveal annual cyclic reconfiguration of the microbiome, in which some taxa become undetectable only to reappear in a subsequent season. Comparison of the Hadza data set with data collected from 18 populations in 16 countries with varying lifestyles reveals that gut community membership corresponds to modernization: Notably, the taxa within the Hadza that are the most seasonally volatile similarly differentiate industrialized and traditional populations. These data indicate that some dynamic lineages of microbes have decreased in prevalence and abundance in modernized populations.


Occupational Exposure to Bisphenol A (BPA): A Reality That Still Needs to Be Unveiled.
Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, is one of the most utilized industrial chemicals worldwide, with the ability to interfere with/or mimic estrogenic hormones with associated biological responses. Environmental human exposure to this endocrine disruptor, mostly through oral intake, is considered a generalized phenomenon, particularly in developed countries. However, in the context of occupational exposure, non-dietary exposure sources (e.g., air and contact) cannot be underestimated. Here, we performed a review of the literature on BPA occupational exposure and associated health effects. Relevantly, the authors only identified 19 studies from 2009 to 2017 that demonstrate that occupationally exposed individuals have significantly higher detected BPA levels than environmentally exposed populations and that the detection rate of serum BPA increases in relation to the time of exposure. However, only 12 studies performed in China have correlated potential health effects with detected BPA levels, and shown that BPA-exposed male workers are at greater risk of male sexual dysfunction across all domains of sexual function; also, endocrine disruption, alterations to epigenetic marks (DNA methylation) and epidemiological evidence have shown significant effects on the offspring of parents exposed to BPA during pregnancy. This overview raises awareness of the dramatic and consistent increase in the production and exposure of BPA and creates urgency to assess the actual exposure of workers to this xenoestrogen and to evaluate potential associated adverse health effects.


Differences in visual fixation duration according to the position of graphic health warning labels: An eye-tracking approach.
The Framework Convention on Tobacco Control (FCTC) recommends that graphic health warning labels (GHWLs) be positioned at the top of the principal area of cigarette packs, rather than at the bottom, to increase visibility. However, during the legislative process of introducing GHWLs in South Korea, the position of GHWLs has become a contested issue. The pro-tobacco industry group argued that the warnings should be placed at the bottom of cigarette packs because evidence for the effectiveness of the upper position was insufficient. Therefore, this study investigated whether the position of the GHWL affects eye movement. Participants (30 daily smokers and 24 non-smokers) were shown six cigarette packs in random order with different position combinations (top, middle, bottom) and image concepts (skin aging, toxic constituents). Participants' eye movements were recorded using eye-tracking equipment to measure visual fixation duration in milliseconds (ms). Participants visually fixated longer on the health warning area than on the tobacco branding area (p<0.05). Mean fixation duration on the health warning area was significantly longer at the top or middle positions compared to the bottom, by 28% (mean difference=340 ms, p=0.006) and by 30% (mean difference=368 ms, p=0.002), respectively. By contrast, mean fixation duration on the branding area was longer with the warning at the bottom compared to top or middle positions by 25% and 33%, with mean differences of 157 ms (p=0.100) and 212 ms (p=0.026), respectively. No significant difference in fixation time was observed between the top and middle positions (p>0.05). The duration of visual fixation on GHWLs was longer when they were displayed at the top and middle, rather than at the bottom. Therefore, GHWLs should be positioned from the top to the middle of the tobacco package.


Immigration to the Federal Republic of Germany as a demographic and social problem.
"Addressing the question of immigration to Western Europe and especially to Germany from east and southeast Europe and from developing countries of the South, this article considers whether such immigration can compensate for reductions in population in developed countries. It is argued that the demographic deficits of an aging population can only be corrected to a limited extent through immigration. Any solution, in order to be effective, must include a simultaneous increase in the birthrates of Germany and other European Community countries. With particular regard to future social development in Germany and the EC, it would be advisable for governments to effect measures that will provide both for controlled admissions of immigrants from outside the EC and an increase in local reproductive capabilities."


Atypical squamous cells: improvement in cytohistological correlation by the 2001 Bethesda System.
To evaluate the advantages of the 2001 Bethesda System over the 1991 Bethesda System in the management of atypical squamous cells. The cytology files of the 8,748 patients were reviewed for diagnosis of atypical squamous cells of undetermined significance (ASCUS) at Zeynep Kamil Hospital. Seventy-two of the 259 smear specimens with the diagnosis of ASCUS were reviewed and reclassified according to Bethesda 2001. Of the 8,748 specimens, 259 (2.96%) were diagnosed as ASCUS. In re-evaluation of the 72 specimens according to the 2001 Bethesda system, the number of cervical smears with a diagnosis of atypical squamous cells (ASC) decreased to 21 in number. Of the 21 cervical smears with an ASC category, eight patients (38.1%) had high-grade intraepithelial squamous lesions (HSIL) and six (28.6%) had low-grade intraepithelial squamous lesions (LSIL) in histopathological specimens. The detection rates of squamous abnormalities (chi2 = 24.79, p < 0.0001) and high-grade squamous abnormalities (chi2 = 8.31, p = 0.0039) were significantly higher according to Bethesda 2001. The 2001 Bethesda System seems to reduce the number of cervical smear diagnoses of ASC, without causing any impairment in the diagnosis of HSIL thus decreasing the number of unneccesary interventions like cervical biopsy and decreasing the cost, inconvenience, anxiety and discomfort.


68Ga DOTATATE PET/CT Versus 18F-FDG PET/CT for Detecting Intramedullary Hemangioblastoma in a Patient With Von Hippel-Lindau Disease.
Von Hippel-Lindau disease is an inherited syndrome associated with several benign and malignant tumors such as central nervous system (CNS) hemangioblastoma. Herein, we report a known case of A Von Hippel-Lindau patient with a cerebral hemangioblastoma who was referred for further evaluation because of recent paraparesis. F-FDG PET/CT showed no focal uptake in the thoracic spine, which demonstrated increased Ga DOTATATE activity, owing to overexpression of somatostatin receptors, suggesting spinal cord hemangioblastoma. This case report indicates the significant role of Ga-labeled somatostatin receptor analogs in the diagnosis of hemangioblastoma.


Molecular architecture of tight junctions of periderm differs from that of the maculae occludentes of epidermis.
Occludin and claudins are tetraspan-transmembrane proteins in tight junctions. Maculae occludentes, which are less-developed tight junctions, occur in the granular cell layer of the epidermis. The periderm, which overlies the developing epidermis and functions as a protective layer for the embryo, carries developed tight junctions as observed in simple epithelia. In both periderm and epidermis, occludin is expressed at the cell-cell border. To determine the difference between tight junctions of periderm and epidermis, claudin-6 expression was examined in periderm and epidermis. Immunofluorescence staining showed claudin-6 expression at the cell-cell border of the periderm, but not in the epidermis. Reverse transcription-polymerase chain reaction confirmed that claudin-6 was not expressed in mouse adult skin, whereas immunoelectron microscopy revealed that claudin-6 was localized at tight junctions of the periderm. Furthermore, L fibroblasts with stable expression of exogenous claudin-6 formed developed tight junctions at cell-cell borders. These findings indicate that molecular architecture of tight junctions of the periderm is different from that of the maculae occludentes of the epidermis, and that claudin-6 is important in the formation of tight junctions of the periderm.


Sulphur-containing non enzymatic antioxidants: therapeutic tools against cancer.
The prevention of oxidation is an essential process in all cells, as decreased antioxidant protection may lead to cytotoxicity, mutagenicity and carcinogenicity. The mechanisms by which oxidative stress contributes to carcinogenesis include modulation of gene expression and induction of genetic modifications. Cellular methylation and antioxidant metabolism are linked by the transsulfuration pathway, which converts the methionine cycle intermediate, homocysteine, to cysteine, the limiting reagent in glutathione synthesis. Taurine can protect cells from oxidant-induced injury scavenging strong oxidant and cytotoxic agents, and lipoic acid can regenerate glutathione. N-acetylcysteine has anticancer properties such as counteractions against mutagens and prevention of tumor progression. The oxidizing agents react with the thiol group of these non enzymatic antioxidants determining cellular redox potential, and modulating several biological events, since different redox-sensitive molecules are involved in many cell responses such as proliferation, growth arrest, and death. The high metabolic activity characteristic of cancer cells often upregulates oxidative stress protection mechanisms. In fact, glutathione depletion is an early hallmark observed in apoptosis and it has been demonstrated as a common feature of cancer.


[Prognosis predictor of chronic-stage acute myocardial infarction].
An investigation of acute myocardial infarction (AMI) was performed in Obihiro City, Hokkaido from October 1.1990 to March 31.1996. Based on the recorded cases, we conducted an investigation on the progress of 194 survivors by questionnaires, and we investigated the factors affecting long-term prognosis of AMI. The mean follow-up period was 1.62 years. The mean age at onset and frequency of hypertension were higher in women than in men. On the other hand, a larger percentage of men smoked and drank alcohol. Kaplan-Meier analysis showed that survival was strongly influenced by aging, drinking, prior history of AMI or stroke, renal dysfunction, cardiac failure and early rehabilitation. Using Cox's hazard model, it was found that mortality risk increases 1) by 1.5 times for an increase of 10 years in age (2.6-times higher for people over 65 years old), 2) by 2.5 times for people with a history of AMI or stroke, 3) by 4.6 times for people with renal dysfunction, and 4) by 5.7 times for people with cardiac failure of Killip class III or IV. On the other hand, it was found that mortality risk decreases 1) by 0.3 times for people who drink alcohol, 2) by 0.1 times for people who have undergone PTCA, and 3) by 0.3 times for people who have undergone rehabilitation. The mortality risk is high for people who do not drink alcohol and those who have not undergone rehabilitation using Cox's hazard model adjusted all those factors. In conclusion, prognostic predictor in chronic-stage acute myocardial infarction are aging, drinking, prior history of AMI or stroke, renal dysfunction, cardiac failure, early rehabilitation, and PTCA. The results also indicated that, regardless of the historical and clinical characteristics, early rehabilitation is very important to increase the probability of long-term survival.


[Fingerprint comparison of mountain cultivated ginseng and wild ginseng by HPLC].
To establish the fingerprint of mountain cultivated ginseng by HPLC and compare the fingerprint with that of wild ginseng for the quality control. The analysis was carried out on a ZORBAX Eclipse XDB-C18 column (150 mm x 4.6 mm, 5 microm) with a mobile phase consisting of water-acetonitrile with gradient elution, and the flow rate was 1 mL/min. The column temperature was set at (30 +/- 0.15) degrees C and UV detection wavelength was set at 203 nm. There were 15 common peaks in the fingerprint of mountain cultivated ginseng. The similarities of 10 batches ginseng were between 0.90 and 1.00. This method has good characteristics and specificity, and could be used for quality control of mountain cultivated ginseng. The type and content of components in wild ginseng were slightly higher than those in mountain cultivation ones.


Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol.
Estriol acts as a weak estrogen when administered in a single dose into immature or ovariectomized laboratory animals, but produces full estrogenic responses upon chronic administration. However, when estriol is injected together with estradiol it acts as an antiestrogen. We studied the dual agonist/antagonist properties of estriol, using recombinant human estrogen receptor (hER) in ligand-binding assay, cell-free transcription assay, electrophoretic mobility shift assay with cVitII estrogen response element (ERE), and ERE-Sepharose chromatography. We show that the weak estrogenic activity of estriol results from impaired hER-ERE interaction. The antiestrogenic activity of estriol was demonstrated in a cell-free transcription assay where it reduced estradiol-dependent transcription in a dose-dependent manner. Estriol interfered with estradiol-induced positive cooperative binding and receptor dimerization, and binding of hER complexes to ERE. These effects of estriol were maximal at a 10-fold molar excess over estradiol; under these conditions estradiol-dependent transcription was decreased by 85%, although [3H]estradiol binding was reduced by only 50%. We propose that when hER, estradiol, and estriol are coequilibrated, several receptor species are formed: unliganded hER monomers and dimers; estradiol-hER monomers and dimers, estriol-hER monomers and dimers; and presumably mixed estradiol-estriol dimers. Since estrogen-hER complexes bind cooperatively to ERE sequences, the concentrations of transcriptionally active complexes (estriol- and estradiol-hER dimers) are reduced to low levels that fail to bind cooperatively with ERE and initiate transcription. We discuss our results in relation to the massive estriol production during pregnancy and to the "Estriol Hypothesis" on the protective role for estriol in opposing carcinogenic effects of estradiol.


Is Opioid-Limiting Legislation Effective for Hand Surgery Patients?
The Rhode Island State Legislature passed the Uniform Controlled Substances Act in 2016 to limit opioid prescriptions. We aimed to objectively evaluate its effect on opioid prescribing for hand surgery patients and also identify risk factors for prolonged opioid use. A 6-month period (January-June 2016) prior to passage of the law was compared with a period following its implementation (July-December 2017). Thumb carpometacarpal arthroplasty and distal radius fracture fixation were classified as "major surgery" and carpal tunnel and trigger finger release as "minor surgery." Prescription Drug Monitoring Database was used to review controlled substances filled during the study periods. A total of 1380 patients met our inclusion criteria, with 644 prelaw and 736 postlaw patients. Patients undergoing "major surgery" saw a significant decrease in the number of pills issued in the first postoperative prescription (41.1 vs 21.0) and a corresponding decrease in morphine milligram equivalents (MMEs) (318.6 vs 159.2 MMEs) after implementation. A 30% decrease in MMEs was also seen in those undergoing "major surgery" in the first 30 days postoperatively (544.7 vs 381.7 MMEs). Risk factors for prolonged opioid use included male sex and preoperative opioid use. In Rhode Island, opioid-limiting legislation resulted in a significant decrease in the number of pills and MMEs of the initial prescription and a 30% decrease in total MMEs in the 30-day postoperative period after "major hand surgery." Additional research is needed to explore the association between legislation and clinical outcomes.


Evaluation of standardized uptake value to assess cerebral glucose metabolism.
When the cerebral metabolic rate of glucose (CMRglc) is to be measured, arterial blood sampling is usually required for fluorine-18 fluorodeoxyglucose (FDG) and positron emission tomography (PET) studies. However, blood sampling is inconvenient because it requires several staff members and is invasive for patients. To assess cerebral glucose metabolism by a noninvasive and simplified method, the authors used the standardized uptake value (SUV), which requires no input function or blood sampling. The study participants included 18 healthy volunteers (4 men and 14 women; mean +/- SD age, 68.2+/-6.3 years), 18 patients with mild Alzheimer's disease (AD) (4 men and 14 women; mean +/- SD age, 68.8+/-7.3 years), and 18 patients with moderate AD (5 men and 13 women, mean +/- SD age, 69.5+/-8.5 years). Regional CMRglc and regional cerebral SUV were measured in the three groups using FDG PET, and the correlation between global CMRglc and global SUV was estimated. The correlation coefficients of global CMRglc and global SUV in the healthy volunteers, mild AD patients, and moderate AD patients were 0.82, 0.67, and 0.62, respectively. Compared with the healthy persons, the patients with mild AD showed significantly decreased CMRglc in the temporal, frontal, and parietal cortices, but they did not show significantly decreased SUV in any region. Patients with moderate AD had significantly decreased CMRglc in the temporal, frontal, occipital, parietal, and sensorimotor cortices and significantly decreased SUV in the temporal, frontal, occipital, and parietal cortices. The SUV would be useful as a semiquantitative index of cerebral glucose metabolism only in healthy persons or those with mild AD.


LPI-HyADBS: a hybrid framework for lncRNA-protein interaction prediction integrating feature selection and classification.
Long noncoding RNAs (lncRNAs) have dense linkages with a plethora of important cellular activities. lncRNAs exert functions by linking with corresponding RNA-binding proteins. Since experimental techniques to detect lncRNA-protein interactions (LPIs) are laborious and time-consuming, a few computational methods have been reported for LPI prediction. However, computation-based LPI identification methods have the following limitations: (1) Most methods were evaluated on a single dataset, and researchers may thus fail to measure their generalization ability. (2) The majority of methods were validated under cross validation on lncRNA-protein pairs, did not investigate the performance under other cross validations, especially for cross validation on independent lncRNAs and independent proteins. (3) lncRNAs and proteins have abundant biological information, how to select informative features need to further investigate. Under a hybrid framework (LPI-HyADBS) integrating feature selection based on AdaBoost, and classification models including deep neural network (DNN), extreme gradient Boost (XGBoost), and SVM with a penalty Coefficient of misclassification (C-SVM), this work focuses on finding new LPIs. First, five datasets are arranged. Each dataset contains lncRNA sequences, protein sequences, and an LPI network. Second, biological features of lncRNAs and proteins are acquired based on Pyfeat. Third, the obtained features of lncRNAs and proteins are selected based on AdaBoost and concatenated to depict each LPI sample. Fourth, DNN, XGBoost, and C-SVM are used to classify lncRNA-protein pairs based on the concatenated features. Finally, a hybrid framework is developed to integrate the classification results from the above three classifiers. LPI-HyADBS is compared to six classical LPI prediction approaches (LPI-SKF, LPI-NRLMF, Capsule-LPI, LPI-CNNCP, LPLNP, and LPBNI) on five datasets under 5-fold cross validations on lncRNAs, proteins, lncRNA-protein pairs, and independent lncRNAs and independent proteins. The results show LPI-HyADBS has the best LPI prediction performance under four different cross validations. In particular, LPI-HyADBS obtains better classification ability than other six approaches under the constructed independent dataset. Case analyses suggest that there is relevance between ZNF667-AS1 and Q15717. Integrating feature selection approach based on AdaBoost, three classification techniques including DNN, XGBoost, and C-SVM, this work develops a hybrid framework to identify new linkages between lncRNAs and proteins.


Clinical characteristics and prognostic factors in Chinese patients with classical Hodgkin's lymphoma involving extranodal sites: a retrospective single-center.
Objectives: To analyze the clinical characteristics and prognostic factors in Chinese patients with classical Hodgkin's lymphoma (cHL) involving extranodal sites. Methods: Clinical features and outcomes of 68 patients diagnosed with cHL involving extranodal sites from April 2003 to November 2017 were analyzed retrospectively. The data was compared with that of 76 cHL patients without extranodal involvement in the same period. Results: (1) Extranodal involvement was common in Chinese cHL patients. The most common sites were lung (44.1%) and bone (33.8%), followed by bone marrow, liver, pericardium, pleura and other sites. (2) With a median follow-up period of 4.58 years, the 5-year overall survival (OS) of 68 patients with extranodal involvement was significantly poorer than that of 76 patients with only nodal involvement (81.4% vs. 92.8%, p = 0.018). (3) In univariate analysis, lymphocytopenia (p = 0.027), elevated lactate dehydrogenase (LDH) (p = 0.026) and involved lymph node region (LNR) ≥4 (p = 0.044) predicted inferior freedom from progression (FFP) with significant difference. Elder age (p = 0.010), elevated LDH (p = 0.013), elevated platelet (p = 0.044), involved LNR ≥ 4 (p = 0.047) were also statistically significant in OS. Extranodal sites and number of extranodal sites showed no significant difference in FFP and OS. Factors with p-value smaller than 0.100 were evaluated in multivariate analysis, turning out that lymphocytopenia was the only independent adverse prognostic factor in FFP (p = 0.039; HR = 2.595) and OS (p = 0.028; HR = 4.993). Conclusion: Extranodal involvement was frequent in Chinese cHL patients, with lung to be the most commonly involved site. Lymphocytopenia was the only independent adverse prognostic factor.


Prelaminated Temporoparietal Osteofascial Flap: A Novel Nasal Reconstruction Technique.
Nasal reconstruction can be a difficult task to perform. It is a challenge when the defect to be reconstructed is extensive and involves the entire thickness of the nose. The difficulty is further increased when a recurrent tumor is removed, where other flaps were previously used to reconstruct the initial defect. A therapeutic option is microsurgical reconstruction; however, sometimes this cannot be performed. Furthermore, free flaps such as the anterolateral thigh or the antebrachialis radial tend to be very thick for the integuments of the face. Therefore, it is important to think of another reconstructive option to solve this problem. We present a case of nasal reconstruction with a prelaminated temporoparietal osteofascial flap, after full-thickness excision for recurrent carcinoma.


Maternal renal artery Doppler velocimetry in normotensive pregnancies and pregnancies complicated by hypertensive disorders.
Hypertensive disorders in pregnancy contribute to substantial maternal and perinatal morbidity and mortality. Clinically, these disorders are characterized by hypertension and proteinuria. However, these signs appear some time after the physiologic derangements have been initiated. The primary objectives of this study were as follows: 1) to establish baseline values for the maternal renal artery systolic-diastolic ratio (S/D) as a function of gestational age in normal pregnancies, and 2) to determine whether renal artery blood flow indices can accurately identify those pregnancies complicated by, or destined to develop, hypertensive disorders. Using a pulsed Doppler scanner, maternal renal artery duplex evaluation was performed in four groups of women: normotensive nonpregnant, normotensive pregnant, chronic hypertensive pregnant, and preeclamptic. In 30 normotensive pregnant women followed longitudinally, no change was noted in the renal artery S/D as gestational age advanced, with mean (+/- SD) values of 2.5 +/- 0.20 and 2.6 +/- 0.21 for the left and right sides, respectively. No clinically meaningful discriminations were detected when the four groups were compared. We conclude that maternal renal artery Doppler waveforms are not significantly altered by either pregnancy or hypertensive complications in pregnancy.


Association of HLA-DQw4 with IgA nephropathy in the Japanese population.
We have studied HLA-A, B, DR and DQ phenotypes in 50 Japanese patients with IgA nephropathy. The antigen frequency of HLA-DQw4, which is known to be associated with DR4/Dw15 specificity, was increased in the patient group as well as in those of B35 and DR4. The increase of DQw4 (36.0%) was significantly different from that of national controls (corrected p less than 0.004).


Fluid therapy for acute bacterial meningitis.
Acute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially among infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over- and under-hydration are associated with adverse outcomes. This is the latest update of a review first published in 2005 and updated in 2008 and 2014. To evaluate treatment of acute bacterial meningitis with differing volumes of initial fluid administration (up to 72 hours after first presentation) and the effects on death and neurological sequelae. For this 2016 update we searched the following databases up to March 2016: the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, CINAHL, Global Health, and Web of Science. Randomised controlled trials (RCTs) of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion. All four of the original review authors extracted data and assessed trials for quality in the first publication of this review (one author, ROW, has passed away since the original review; see Acknowledgements). The current authors combined data for meta-analysis using risk ratios (RRs) for dichotomous data or mean difference (MD) for continuous data. We used a fixed-effect statistical model. We assessed the overall quality of evidence using the GRADE approach. We included three trials with a total of 420 children; there were no trials in adult populations. The largest of the three trials was conducted in settings with high mortality rates and was judged to have low risk of bias for all domains, except performance bias which was high risk. The other two smaller trials were not of high quality.The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% confidence interval (CI) 0.53 to 1.27; 407 participants; low quality of evidence) or acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08; 407 participants; low quality of evidence). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group for spasticity (RR 0.50, 95% CI 0.27 to 0.93; 357 participants); and seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83; 357 participants) and 14 days (RR 0.19, 95% CI 0.04 to 0.88; 357 participants). There was very low quality of evidence favouring maintenance fluid over restrictive fluid for chronic severe neurological sequelae at three months follow-up (RR 0.42, 95% CI 0.20 to 0.89; 351 participants). The quality of evidence regarding fluid therapy in children with acute bacterial meningitis is low to very low and more RCTs need to be conducted. There is insufficient evidence to guide practice as to whether maintenance fluids should be chosen over restricted fluids in the treatment of acute bacterial meningitis.


Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro.
Neutrophils (PMN) are best known for their phagocytic functions against invading pathogens and microorganisms. They have the shortest half-life amongst leukocytes and in their non-activated state are constitutively committed to apoptosis. When recruited to inflammatory sites to resolve inflammation, they produce an array of cytotoxic molecules with potent antimicrobial killing. Yet, when these powerful cytotoxic molecules are released in an uncontrolled manner they can damage surrounding tissues. In recent years however, neutrophil versatility is increasingly evidenced, by demonstrating plasticity and immunoregulatory functions. We have recently identified a new neutrophil-derived subpopulation, which develops spontaneously in standard culture conditions without the addition of cytokines/growth factors such as granulocyte colony-stimulating factor (GM-CSF)/interleukin (IL)-4. Their phagocytic abilities of neutrophil remnants largely contribute to increase their size immensely; therefore they were termed giant phagocytes (Gϕ). Unlike neutrophils, Gϕ are long lived in culture. They express the cluster of differentiation (CD) neutrophil markers CD66b/CD63/CD15/CD11b/myeloperoxidase (MPO)/neutrophil elastase (NE), and are devoid of the monocytic lineage markers CD14/CD16/CD163 and the dendritic CD1c/CD141 markers. They also take-up latex and zymosan, and respond by oxidative burst to stimulation with opsonized-zymosan and PMA. Gϕ also express the scavenger receptors CD68/CD36, and unlike neutrophils, internalize oxidized-low density lipoprotein (oxLDL). Moreover, unlike fresh neutrophils, or cultured monocytes, they respond to oxLDL uptake by increased reactive oxygen species (ROS) production. Additionally, these phagocytes contain microtubule-associated protein-1 light chain 3B (LC3B) coated vacuoles, indicating the activation of autophagy. Using specific inhibitors it is evident that both phagocytosis and autophagy are prerequisites for their development and likely NADPH oxidase dependent ROS. We describe here a method for the preparation of this new subpopulation of long-lived, neutrophil-derived phagocytic cells in culture, their identification and their currently known characteristics. This protocol is essential for obtaining and characterizing Gϕ in order to further investigate their significance and functions.


End-to-end azide-bridged manganese(III) chain compounds: field-induced magnetic phase transitions and variation of T(C) to 38 K depending on the side groups of the Schiff bases.
Three one-dimensional coordination polymers [Mn(L)(N(3))](n) [L = L1 (1), L2 (2), L3 (3); L1H(2) = N,N'-bis(5-chlorosalicylideneiminato)-1,3-diaminopentane, L2H(2) = N,N'-bis(5-bromosalicylideneiminato)-1,3-diaminopentane, L3H(2) = N,N'-bis(5-bromosalicylideneiminato)-1,3-diamino-2-dimethylpropane] bridged by end-to-end azides were prepared. The crystal systems differ according to the Schiff bases used. Each Mn atom adopts a typical Jahn-Teller distortion. The helicity of the chains occurs in a racemic manner only for 2. No noncovalent forces are relevant in 2, while π-π contacts are visible in 1 and 3. Magnetic measurements show the presence of apparent spin canting. Complexes 1 and 3 exhibit a field-induced metamagnetic transition from an antiferromagnetic state to a weak ferromagnetic phase, whereas 2 embraces a field-induced two-step magnetic phase transition. The critical temperature is observed at 38 K for 2, which is relatively higher than those for 1 (11 K) and 3 (10 K). The pronounced long-range order may contribute from intrachain exchange couplings and through-space dipolar interactions between adjacent chains.


Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity.
Previous studies have shown that heteroconjugates of monoclonal antibodies in which one of the component antibodies is directed at the T-cell receptor and the other is directed against any chosen site can focus effector T cells to function at the targeted site. We report here the production of a hybrid hybridoma cell line, H184.108.40.206, which secretes large amounts of a bispecific hybrid antibody of the IgG2a class, that can focus T-cell activity. The parental hybridoma lines for the secondary fusion were F23.1, which secretes an antibody specific for an allotypic determinant on the T-cell receptor of most mouse strains, and 19E12, secreting an anti-Thy-1.1 antibody. The bispecific hybrid antibody was partially purified by hydroxylapatite chromatography and characterized by isoelectric focusing. It efficiently targets Thy-1.1-expressing tumor cells for lysis by F23.1 receptor-positive cytotoxic T-cell clones in vitro. Such hybrid antibodies produced by hybrid hybridoma cell lines may have application in the therapeutic targeting of tumors or sites of viral infections for attack by T cells.


Vascular morphology and blood flow signatures for differential artery-vein analysis in optical coherence tomography of the retina.
Differential artery-vein (AV) analysis is essential for retinal study, disease detection, and treatment assessment. This study is to characterize vascular reflectance profiles and blood flow patterns of retinal artery and vein systems in optical coherence tomography (OCT) and OCT angiography (OCTA), and establish them as robust signatures for objective AV classification. A custom designed OCT was employed for three-dimensional (3D) imaging of mouse retina, and corresponding OCTA was reconstructed. Radially resliced OCT B-scans revealed two, i.e. top and bottom, hyperreflective wall boundaries in retinal arteries, while these wall boundaries were absent in OCT of retinal veins. Additional OCTA analysis consistently displayed a layered speckle distribution in the vein, which may indicate the venous laminar flow. These OCT and OCTA differences offer unique signatures for objective AV classification in OCT and OCTA.


Irreversible alteration of extracellular vesicle and cell-free messenger RNA profiles in human plasma associated with blood processing and storage.
The discovery and utility of clinically relevant circulating biomarkers depend on standardized methods that minimize preanalytical errors. Despite growing interest in studying extracellular vesicles (EVs) and cell-free messenger RNA (cf-mRNA) as potential biomarkers, how blood processing and freeze/thaw impacts the profiles of these analytes in plasma was not thoroughly understood. We utilized flow cytometric analysis to examine the effect of differential centrifugation and a freeze/thaw cycle on EV profiles. Utilizing flow cytometry postacquisition analysis software (FCMpass) to calibrate light scattering and fluorescence, we revealed how differential centrifugation and post-freeze/thaw processing removes and retains EV subpopulations. Additionally, cf-mRNA levels measured by RT-qPCR profiles from a panel of housekeeping, platelet, and tissue-specific genes were preferentially affected by differential centrifugation and post-freeze/thaw processing. Critically, freezing plasma containing residual platelets yielded irreversible ex vivo generation of EV subpopulations and cf-mRNA transcripts, which were not removable by additional processing after freeze/thaw. Our findings suggest the importance of minimizing confounding variation attributed to plasma processing and platelet contamination.


Challenges to miniaturizing cold atom technology for deployable vacuum metrology.
Cold atoms are excellent metrological tools; they currently realize SI time and, soon, SI pressure in the ultra-high (UHV) and extreme high vacuum (XHV) regimes. The development of primary, vacuum metrology based on cold atoms currently falls under the purview of national metrology institutes. Under the emerging paradigm of the "quantum-SI", these technologies become deployable (relatively easy-to-use sensors that integrate with other vacuum chambers), providing a primary realization of the pascal in the UHV and XHV for the end-user. Here, we discuss the challenges that this goal presents. We investigate, for two different modes of operation, the expected corrections to the ideal cold-atom vacuum gauge and estimate the associated uncertainties. Finally, we discuss the appropriate choice of sensor atom, the light Li atom rather than the heavier Rb.


Caudal and even-skipped in the annelid Platynereis dumerilii and the ancestry of posterior growth.
In order to address the question of the conservation of posterior growth mechanisms in bilaterians, we have studied the expression patterns of the orthologues of the genes caudal, even-skipped, and brachyury in the annelid Platynereis dumerilii. Annelids belong to the still poorly studied third large branch of the bilaterians, the lophotrochozoans, and have anatomic and developmental characteristics, such as a segmented body plan, indirect development through a microscopic ciliated larva, and building of the trunk through posterior addition, which are all hypothesized by some authors (including us) to be present already in Urbilateria, the last common ancestor of bilaterians. All three genes are shown to be likely involved in the building of the anteroposterior axis around the slit-like amphistomous blastopore as well as in the patterning of the terminal anus-bearing piece of the body (the pygidium). In addition, caudal and even-skipped are likely involved in the posterior addition of segments. Together with the emerging results on the conservation of segmentation genes, these results reinforce the hypothesis that Urbilateria had a segmented trunk developing through posterior addition.


Binding of A/T-rich DNA by three high mobility group-like domains in c-Abl tyrosine kinase.
The c-Abl tyrosine kinase has been shown previously to bind DNA. Using polymerase chain reaction-based binding site-selection methods, no consensus high affinity binding site for c-Abl was found. Instead, oligonucleotides with runs of A/T sequences were isolated, and purified c-Abl was shown to bind A/T-containing oligonucleotides better than those without A/T sequences. DNA binding of c-Abl was dependent on three high mobility group 1-like boxes (HLBs), which bound cooperatively to the A/T-rich oligonucleotides. To distinguish binding to A/T sequences per se from binding to nonspecific DNA with a bend at the A/T-rich region, two oligonucleotides were compared for binding to c-Abl. Both oligonucleotides contained A/T sequences. In one, the A/T motif was part of an 80-mer duplex DNA. In another, the A/T motif was in the duplex arm of an 80-mer "bubble DNA" containing an internal unpaired 20-mer region to provide a flexible hinge. Interestingly, the HLBs of c-Abl bound better to the oligonucleotide containing the bubble, suggesting a higher affinity for bent DNA rather than A/T sequences per se. Taken together, these observations define a new class of DNA binding domains, the HLBs, which do not bind DNA with a high degree of sequence specificity, but may selectively bind to bent DNA or to sequences that are easier to distort.


Accuracy of a Mobile 2D Imaging System for Body Volume and Subsequent Composition Estimates in a Three-Compartment Model.
The purpose of the study was to compare a single two-dimensional image processing system (IMAGE) to underwater weighing (UWW) for measuring body volume (BV) and subsequently estimating body fat percentage (%Fat), fat mass (FM), and fat-free mass (FFM) via a 3-compartment (3C) model. A sample of participants age 18-39 yr was recruited for this study (n = 67, 47.8% female). BV was measured with UWW and predicted via the IMAGE software. The BV estimates from UWW (3CUWW) and IMAGE (3CIMAGE) were separately combined with constant total body water and body mass values for 3C model calculation of %Fat, FM, and FFM. BV obtained from the IMAGE was 67.76 ± 12.19 and 67.72 ± 12.04 L from UWW, which was not significantly different (P = 0.578) and very largely correlated (r = 0.99, P < 0.001). When converted to %Fat (3CUWW = 21.01% ± 7.30%, 3CIMAGE = 21.08% ± 7.04%, P = 0.775), FM (3CUWW = 14.68 ± 5.15 kg, 3CIMAGE = 14.78 ± 5.08 kg, P = 0.578), and FFM (3CUWW = 57.00 ± 13.20 kg, 3CIMAGE = 56.90 ± 12.84 kg, P = 0.578) with the 3C model, no significant mean differences and very large correlations (r values ranged from 0.96 to 0.99) were observed. In addition, the standard error of estimate, total error, and 95% limits of agreement for all three metrics were small and considered acceptable. An IMAGE system provides valid estimates of BV that accurately estimates body composition in a 3C model.


An intervention to increase safety behaviors of abused women: results of a randomized clinical trial.
Although intimate partner violence is recognized as a major threat to women's health, few interventions have been developed or tested. To test an intervention administered to abused women in order to increase safety-seeking behaviors. A two-group clinical trial randomized 75 abused women to receive six telephone intervention sessions on safety behaviors. A control group of 75 women received standard care. Women in both groups were re-interviewed at 3 months and 6 months post-initial measurement. Using repeated measures analysis of variance (ANOVA), we found significantly [F (2,146) 5.11, =.007] more adopted safety behaviors reported by women in the intervention group than by women in the control group at both the 3-month [F (91,74) = 19.70, <.001] and 6-month [F (1,74) = 15.90, <.001] interviews. The effect size (ES) of the intervention was large at 3 months (ES = 1.5) and remained substantial at 6 months (ES = 0.56). These findings demonstrate that an intervention to increase safety behaviors of abused women is highly effective when offered following an abusive incident and remains effective for 6 months.


Deinococcus saudiensis sp. nov., isolated from desert.
Two gamma- and UV-radiation-resistant, pink-coloured bacterial strains, designated YIM F302T and YIM F235, were isolated from the desert of Yanbu' al Bahr located in west of Saudi Arabia. Taxonomic positions of the two isolates were investigated by polyphasic taxonomic approaches. Cells of the two strains were Gram-stain-negative, aerobic and rod-shaped. They were able to grow at 15-45 °C and pH 6.0-8.0 and had a NaCl tolerance limit of 1 % (w/v). Phylogenetic analyses based on 16S rRNA gene sequences revealed that strains YIM F302T and YIM F235 represent members of the genus Deinococcus, sharing highest sequence similarities of 98.3 and 98.4 %, respectively, with Deinococcus grandis DSM 3963T. The strains were found to contain MK-8 as the respiratory menaquinone. Major fatty acids (>10 %) of the two strains were C15 : 1ω6c, C16 : 0 and C16 : 1ω7c. DNA-DNA hybridization values of the two isolates against the closely related type strains were significantly below the 70 % limit for species delineation. Genomic DNA G+C contents of strains YIM F302T and YIM F235 were 69.3 and 69.0 mol%, respectively. Based on the phenotypic and genotypic characteristics recorded, it is determined that the two isolates represent a novel species of the genus Deinococcus, for which the name Deinococcus saudiensis sp. nov. is proposed. The type strain is YIM F302T (=CGMCC 1.15089T=DSM 29933T).


Mesoporous TiO(2) nanocrystal clusters for selective enrichment of phosphopeptides.
Protein phosphorylation plays a key role in most cellular processes. Studying phosphopeptides in complex biological samples has been a great challenge due to their low abundance as well as the coexistence of excessive amounts of salts or surfactants. In this work we demonstrate a general approach for selective separation of phosphopeptides using a class of novel mesoporous nanostructured materials. TiO(2) nanocrystals are first self-assembled into submicrometer clusters containing relatively uniform mesoscale pores and then stabilized by coating with a thin layer of silica. Calcination of the materials at high temperatures connects the neighboring nanocrystals together and enhances the mechanical stability of the clusters and at the same time removes the organic surfactants and makes the TiO(2) surface fully accessible to phosphopeptides. By coating the nanocrystal clusters with a layer of silica before calcination and removing it afterward through chemical etching, we have been able to make the cluster surface hydrophilic and negatively charged, thus enhancing the water dispersibility of the clusters and eventually their accessibility to phosphopeptides. The high selectivity and capacity of these mesoporous TiO(2) clusters have been demonstrated by effectively enriching phosphopeptides from digests of phosphoprotein (alpha- or beta-casein), protein mixtures of beta-casein and bovine serum albumin, milk, and human serum samples. We also demonstrate that the self-assembly process brings the flexibility of incorporation of multiple components, such as superparamagnetic nanocrystals, to further facilitate the peptide separation.


How Important Is Protein Diffusion in Prokaryotes?
That diffusion is important for the proper functioning of cells is without question. The extent to which the diffusion coefficient is important is explored here for prokaryotic cells. We discuss the principles of diffusion focusing on diffusion-limited reactions, summarize the known values for diffusion coefficients in prokaryotes and in in vitro model systems, and explain a number of cases where diffusion coefficients are either limiting for reaction rates or necessary for the existence of phenomena. We suggest a number of areas that need further study including expanding the range of organism growth temperatures, direct measurements of diffusion limitation, expanding the range of cell sizes, diffusion limitation for membrane proteins, and taking into account cellular context when assessing the possibility of diffusion limitation.