Effects of Hot-Pressure Extraction Time on Composition and Gelatin Properties of Chicken Bone Extracts.
Hot-pressure extraction was utilized in this study to extract proteins from chicken bones at 130 °C. The obtained extracts were further used to prepare gelatin gels. Results demonstrated that the extraction time can significantly affect the composition of the chicken bone extracts (P < 0.05). High-performance liquid chromatography (HPLC) analysis indicated that the protein fraction of molecular weight (MW) >30 KDa was only visible in the extracts collected between 40 and 60 min. The highest contents of hydroxyproline, imino acids, and hydrophobic amino acids were all achieved in the chicken bone extracts after 120 min of extraction, being 3.9, 7.7, and 16.0 mg/g, respectively. The prepared gelatin properties were evaluated in terms of viscosity, storage and loss modulus, stability, gel strength, and their microstructures. Results indicated that gelatins made from chicken bone extracts of 20, 40, and 60 min extraction had better properties compared to that of 90 and 120 min. Significant correlations were identified between gelatin's composition and properties (P < 0.05). The abundance of proteins with MW of <10 KDa and 10 to 30 KDa was found to be the predominant factor that can affect the gelatin's properties. This study illustrated a promising and natural way to obtain edible gelatins from chicken bones.


Epithelial-mesenchymal interactions in pulmonary fibrosis.
Pulmonary fibrosis represents the sequelae of a variety of acute and chronic lung injuries of known and unknown etiologies. Tissue specimens obtained from patients with pulmonary fibrosis, regardless of the etiology, consistently show evidence of an ongoing wound-repair response. Epithelial-mesenchymal interactions have critical roles in normal lung development, tissue repair processes, and fibrosis. Current hypotheses propose that dysregulated function of, and impaired communication between, epithelial and mesenchymal cells prevent resolution of the wound-repair response and contribute to the pathobiology of pulmonary fibrosis. This hypothesis is supported by abundant evidence from patients, animal models, and cell-culture studies demonstrating abnormalities in epithelial cell and mesenchymal cell activities including proliferation, differentiation, and survival. This article reviews the aberrant epithelial and mesenchymal cellular phenotypes found in the context of pulmonary fibrosis and discusses the mechanisms that perpetuate these cellular phenotypes.


Long-term study of large ceramic implants (porous hydroxyapatite) in dog femora.
Blocks of porous ceramic hydroxyapatite (dimensions, 2.5 X 1.25 X 0.5 cm; sintering temperature, 1300 degrees; macroporosity, 56%; average pore size 0.18 mm2) were implanted into surgically created defects in dog femora. The implants were retrieved up to 3.5 years after implantation. The implants were 3.5 years after implantation. The implants were firmly attached to the bone. Histologic evaluation suggests that optimal contact between bone and implant should be provided to accelerate bone ingrowth. Bone growth in the pores reached a maximum level after 35 weeks, at which time about one-third of the pore space was filled with bone. When measuring the relative surface areas of bone and ceramic on histologic slides, no change in ceramic mass could be detected, indicating that hydroxyapatite ceramics are not affected by biodegradation processes. The implants effectively provided a scaffold for bone growth bridging a larger bone defect.


Positive smoking cessation-related interactions with HIV care providers increase the likelihood of interest in cessation among HIV-positive cigarette smokers.
Smoking cessation has proven to be a challenge for HIV-positive smokers. Patient and provider characteristics may provide barriers to smoking cessation. We aimed to identify characteristics associated with interest in cessation as well as characterize use of, current interest in, and provider recommendations for smoking cessation modalities. Data came from 275 HIV-positive smokers recruited online. Half (49.1%) of the sample was interested in quitting; daily smoking was associated with decreased likelihood of interest in cessation, whereas making a lifetime quit attempt, receiving encouragement to quit from an HIV care provider, and greater frequency of discussions regarding cessation with HIV care providers were associated with increased likelihood of interest in cessation. Nicotine replacement therapy was the most commonly used (42.9%), generated the most interest (59.1%), and was the most commonly clinician-recommended (70.7%) cessation modality. Findings emphasize the importance of the healthcare provider-patient relationship for smoking cessation promotion in HIV-positive smokers.


[Computerized tomography and myelography findings following lumbar intervertebral disk surgery].
56 patients suspected of having suffered recurrent disc prolapse in the lumbar region were examined by CT and by myelography; the value of these examinations has been analysed. In 32 patients the findings were checked during surgery. There were difficulties in diagnosis, both for CT and myelography, where the findings were complex, i.e. in patients in whom there was postoperative fibrosis as well as disc prolapse and/or osseous spinal canal stenosis. As regards recurrence of prolapse, sensitivity for both methods was 83%. Postoperative scar formation can be clearly demonstrated by CT, but myelography produced a false positive diagnosis of recurrent prolapse in 17%. The changes were, in fact, caused by scar tissue formation.


Microbial pigments: Sources, current status, future challenges in cosmetics and therapeutic applications.
Color serves as the initial attraction and offers a pleasing aspect. While synthetic colorants have been popular for many years, their adverse environmental and health effects cannot be overlooked. This necessitates the search for natural colorants, especially microbial colorants, which have proven and more effective. Pigment-producing microorganisms offer substantial benefits. Natural colors improve product marketability and bestow additional benefits, including antioxidant, antiaging, anticancer, antiviral, antimicrobial, and antitumor properties. This review covers the various types of microbial pigments, the methods to enhance their production, and their cosmetic and therapeutic applications. We also address the challenges faced during the commercial production of microbial pigments and propose potential solutions.


Release behavior of poly(lactic acid-co-glycolic acid) implants containing phosphorothioate oligodeoxynucleotide.
The release behavior of phosphorothioate oligodeoxynucleotide, 5'-GCCGAGGTCCATGTCGTACGC-3' (ODN), from poly(lactic acid-co-glycolic acid) (PLGA) implant was studied. The pillar shape implant was fabricated by the heating mold method. About 20% of ODN were released initially, and the subsequent pseudo-zero-order release lasted for more than 20 d from a PLGA10000 implant loaded with 8.4% ODN in phosphate buffered saline, pH 7.4. The duration of ODN release did not depend on the molecular weights of PLGA, and pseudo-zero-order release may be achieved by changing the loaded amount of ODN in fabrication of the PLGA implant. Almost the same release profiles were obtained in the pH range of 7.2 to 7.6, which is known as the physiological pH of a vitreous body. Furthermore, the duration of intact ODN release in bovine vitreous was found. The implant in the present study may possibly be applicable to intravitreal implantation for the treatment of ocular disease.


Lagrangian betweenness as a measure of bottlenecks in dynamical systems with oceanographic examples.
The study of connectivity patterns in networks has brought novel insights across diverse fields ranging from neurosciences to epidemic spreading or climate. In this context, betweenness centrality has demonstrated to be a very effective measure to identify nodes that act as focus of congestion, or bottlenecks, in the network. However, there is not a way to define betweenness outside the network framework. By analytically linking dynamical systems and network theory, we provide a trajectory-based formulation of betweenness, called Lagrangian betweenness, as a function of Lyapunov exponents. This extends the concept of betweenness beyond the context of network theory relating hyperbolic points and heteroclinic connections in any dynamical system to the structural bottlenecks of the network associated with it. Using modeled and observational velocity fields, we show that such bottlenecks are present and surprisingly persistent in the oceanic circulation across different spatio-temporal scales and we illustrate the role of these areas in driving fluid transport over vast oceanic regions. Analyzing plankton abundance data from the Kuroshio region of the Pacific Ocean, we find significant spatial correlations between measures of diversity and betweenness, suggesting promise for ecological applications.


[Kidney injury associated with antitumor therapy: focus on the adverse events of modern immuno-oncological drugs].
Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death protein 1 (PD-1) or its ligand (PD-L1), are a new generation of immuno-oncological drugs that to date have demonstrated efficacy in a number of malignancies. The mechanism of ICT inhibitors action consist in the potentiation of the immune response by eliminating the tumor cells inhibitory effect on the T-lymphocytes activation. However, excessive immune system activation can cause the development of a special class of immune-related adverse events (irAEs) involved a wide variety of organs and systems, including the kidneys. Despite the fact that immuno-mediated kidney injury caused by ICI therapy develops quite rarely, it can be serious and determine the patient's prognosis, which necessitates early diagnosis and timely start of treatment. In this regard, awareness of the manifestations of ICI-associated renal irAEs is particularly relevant not only for oncologists and for nephrologists, but for doctors of other specialties. In this review, we elucidated the main variants of immuno-mediated kidney injury caused by ICI therapy, discussed possible predictors and mechanisms of their development, and considers the general principles of diagnosis and management of patients according to the severity of irAEs.


Impact of progestins on estradiol potentiation of the glutamate calcium response.
One mechanism by which estrogen may modulate cognitive function is through potentiation of glutamate-mediated rises in intracellular calcium ([Ca2+]i) with resultant effects on neuronal morphology and signaling. Since progesterone is a component of hormone replacement therapy (HRT), we sought to determine whether therapeutically relevant progestins attenuated or blocked estrogen potentiation of glutamate-induced [Ca2+]i rises. 17beta-estradiol and progesterone, alone or in combination, significantly potentiated the rise in [Ca2+]i. When co-administered, progesterone attenuated the estrogen response to the level seen with progesterone alone. In contrast, medroxyprogesterone acetate (MPA) had no effect when administered alone and completely blocked the 17beta-estradiol-induced potentiation when co-administered. These results may have important implications for effective use of HRT to maintain cognitive function during menopause and aging.


[Comparison of the biological characteristics of serum-free and fetal bovine serum-contained medium cultured umbilical cord-derived mesenchymal stem cells].
To compare the differences of biological characteristics between human umbilical cord-derived mesenchymal stem cells (UC-MSCs) cultured by serum-free medium or fetal bovine serum-contained complete medium to establish a xenogeneic protein-free UC-MSCs culture system. Healthy human umbilical cord segments were digested with collagenase. UC-MSCs were cultured by serum-free MesenCult-XF medium and FBS-based αMEM complete medium, then analyzed the morphology, immunophenotype, expansion potential, lineage differentiation potential, karyotype and immunosuppression of early passages. The average cell diameters of UC-MSCs in suspension cultured by serum-free medium and FBS-based medium were 26 (18 - 39) µm and 35 (20 - 61) µm, respectively. Cell expansion folds with serum free medium and FBS-based medium were (5.2 ± 0.2) and (3.5 ± 0.1) respectively, in the first five passages. The expansion potential of serum-free medium cultured UC-MSCs was significantly higher than FBS-based medium cultured ones (P < 0.05). A panel of markers CD29, CD44, CD90, CD73, CD105 and HLA-ABC expressed on human UC-MSCs. Hematopoietic lineage markers CD34, CD45 and HLA-DR were not detectable on UC-MSCs. The cpm were (4.57 ± 0.14)×10(4), (2.04 ± 0.16)×10(4) and (0.42 ± 0.04)×10(4), respectively when serum-free medium cultured MSCs were added to the cultures at MSCs/T cell ratios of 1:100, 1:10 and 1:5. While the cpm was (4.57 ± 0.14)×10(4), (2.04 ± 0.16)×10(4) and (0.42 ± 0.04)×10(4), respectively when serum-free medium cultured UC-MSCs were added to the cultures. The immunosuppressive potential of serum-free medium-cultured UC-MSCs was higher than serum-contained medium cultured ones at three different MSC/T cell ratios (P < 0.05). Compare with serum-contained medium cultured early passages of UC-MSCs, the cell diameter of serum-free medium cultured UC-MSCs was smaller with higher expansion potential. No xenogeneic proteins were presented in UC-MSCs preparations when cultured with serum-free medium. Human UC-MSCs suppressed T-cell proliferation in a dose-dependent manner. The immunosuppressive potential of serum-free medium cultured UC-MSCs was higher than FBS-based medium cultured ones.


Synthesis, characterization, and photocatalytic activity of TiO2/SiO2 nanoparticles loaded on carbon nanofiber web.
TiO2/SiO2 catalysts were loaded on carbon nanofibers (CNF) support by sol-gel preparation and followed by a dip-coating and heat treatment up to 900 degrees C in inert atmosphere. The photocatalytic activities of the catalysts (TiO2/SiO2)/CNF were tested by the photocatalytic degradation rate of methylene blue (MB) under UV irradiation. It was found that (TiO2/SiO2)/CNF showed a higher photocatalytic activity than TiO2/CNF only. It was analyzed that SiO2 contributed to an increase the photo catalytic activity by suppressing the phase transformation of the TiO2 crystals from anatase to rutile on the heat treatment up to 900 degrees C.


Radiographic Evaluation of Common Pediatric Elbow Injuries.
Normal variations in anatomy in the skeletally immature patient may be mistaken for fracture or injury due to the presence of secondary centers of ossification. Variations in imaging exist from patient to patient based on sex, age, and may even vary from one extremity to the other on the same patient. Despite differences in the appearance of the bony anatomy of the elbow there are certain landmarks and relationships, which can help, distinguish normal from abnormal. We review common radiographic parameters and pitfalls associated in the evaluation of pediatric elbow imaging. We also review common clinical diagnoses in this population.


Effect of postoperative analgesia on energy metabolism and role of cyclooxygenase-2 inhibitors for postoperative pain management after abdominal surgery in adults.
It is questionable whether the stress response to surgery is necessary. The objective of this study was to evaluate the effectiveness of postoperative analgesia on energy metabolism and compare cyclooxygenase-2 selective inhibitor with tramadol in postoperative pain management after major abdominal surgery. A total of 112 patients undergoing major abdominal surgery were randomly assigned to one of the 4 treatment groups before surgery. Then, patients were scheduled to receive different analgesic drugs after surgery: group parecoxib/control received intravenous parecoxib (40 mg bid) for 3 days; group parecoxib/celecoxib received intravenous parecoxib (40 mg bid) for 3 days and continued oral celecoxib (0.2 mg bid) for 4 days; group tramadol/control received intravenous tramadol (0.1 g tid) for 3 days; and group tramadol/tramadol received intravenous tramadol (0.1 g tid) for 3 days and continued oral tramadol (0.1 g tid) for 4 days. Group tramadol/tramadol showed much lower rest energy expenditure 1 week after surgery (P<0.05). The measured rest energy expenditure was significantly lower in patients treated with analgesic drugs administered from day 4 to 7 after surgery relative to control group (P<0.01). From the fourth day after surgery, groups parecoxib/celecoxib and tramadol/tramadol showed significantly lower pain intensity ratings compared with groups parecoxib/control and tramadol/control during leg raising (P<0.05). These results confirm that sufficient postoperative analgesia may be efficient to reduce some of the stress responses to operative trauma. In addition, intravenous parecoxib (40 mg bid) followed by oral celecoxib (0.2 g bid) is as effective as intravenous tramadol (0.1 g tid) with continued oral tramadol (0.1 g tid) after major abdominal surgery.


Anion A(-) • HX clusters with reduced electron binding energies: proton vs hydrogen atom relocation upon electron detachment.
Clustering an anion with one or more neutral molecules is a stabilizing process that enhances the oxidation potential of the complex relative to the free ion. Several hydrogen bond clusters (i.e., A(-) • HX, where A(-) = H2PO4(-) and CF3CO2(-) and HX = MeOH, PhOH, and Me2NOH or Et2NOH) are examined by photoelectron spectroscopy and M06-2X and CCSD(T) computations. Remarkably, these species are experimentally found to have adiabatic detachment energies that are smaller than those for the free ion and reductions of 0.47 to 1.87 eV are predicted computationally. Hydrogen atom and proton transfers upon vertical photodetachment are two limiting extremes on the neutral surface in a continuum of mechanistic pathways that account for these results, and the whole gamut of possibilities are predicted to occur.


A C-Shaped Canal in a Maxillary Second Molar: Prexion 3D Cone-Beam Computed Tomography Analysis.
The aim of this study was to present an atypical case of a C-shaped root canal that was present in the vestibular root of a permanent maxillary second molar using PreXion 3-D cone-beam computed tomography (CBCT) as a diagnostic device. A 50-year-old female patient was referred for routine examination to a private diagnostic imaging clinic in Recife-Pernambuco. During the physical examination, the presence of an unusual C-shaped anatomy in the vestibular canal with a mesiodistal interconnection that extended from the apical to the cervical third was detected in axial slices acquired with a PreXion 3-D scanner. Although C-shaped root canals are most frequently observed in the mandibular second molar, this case presented a rare finding in the permanent maxillary second molar. PreXion 3-D CBCT has emerged as a new high-resolution imaging test technology, thus assisting with the diagnosis of anatomical variations such as C-shaped root canals. However, such imaging technology is not recommended for routine use.


Synthesis of substituted isoquinolines by electrophilic cyclization of iminoalkynes.
The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I(2), ICl, PhSeCl, PhSCl, and p-O(2)NC(6)H(4)SCl to give the corresponding halogen-, selenium-, and sulfur-containing disubstituted isoquinolines and naphthyridines, respectively. This methodology accommodates a variety of iminoalkynes and affords the anticipated heterocycles in moderate to excellent yields. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. The silver-catalyzed ring closure is highly effective in cyclizing aryl-, alkenyl-, and alkyl-substituted iminoalkynes at 50 degrees C.


A comparison of rocuronium and vecuronium: the pharmacodynamic, cardiovascular and intra-ocular effects.
The aim of this study was to compare, in 30 patients, the pharmacodynamics of equipotent intubating doses of rocuronium and vecuronium and to compare their effects on heart rate, arterial pressure and intra-ocular pressure under steady state propofol anaesthesia. Baseline readings of heart rate and arterial pressure, using a Dinamap, and intra-ocular pressure, using a Tonopen, were made after induction of anaesthesia. The effects of the administration of the relaxants on these parameters were measured, recorded and compared. Rocuronium had a faster onset time than vecuronium, but had a similar duration of action. Vecuronium had no significant cardiovascular effects. Rocuronium caused a rise in mean arterial pressure (10-15%) and a slight rise in heart rate (5-10%). Both vecuronium and rocuronium caused similar falls in intra-ocular pressure. With its rapid onset time and lack of intra-ocular pressure effects, rocuronium is perhaps the relaxant of choice in patients with penetrating eye injuries requiring emergency endotracheal anaesthesia where a longer-acting relaxant is not contraindicated.


Brief ischemia causes long-term depression in midbrain dopamine neurons.
Degeneration of dopamine neurons in the substantia nigra pars compacta (SNc) plays an important role in the pathophysiology of neurodegenerative diseases like Parkinsonism and vascular dementia. SNc dopamine neurons both in vitro and in vivo show sensitivity to hypoxic/ischemic conditions and undergo degeneration. In acute brain slices, these dopamine neurons undergo hyperpolarization during hypoxia and hypoglycemia, which results in silencing of the neurons. However, the role that SNc excitatory synapses play in this process is poorly understood. Here we examined the effect of oxygen/glucose deprivation (OGD) on glutamatergic synaptic transmission in the SNc in a rat midbrain slice preparation. OGD for 5 min caused pre-synaptic ischemic long-term depression (iLTD) of glutamate transmission, as both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid- and N-methyl-D-aspartate receptor-mediated synaptic currents in SNc dopamine neurons were depressed to a similar extent. This depression began immediately after exposure to OGD and was not recovered upon washout of OGD. Pharmacological studies revealed that the iLTD was triggered by a rise in post-synaptic intracellular calcium and mediated by activation of pre-synaptic adenosine A(1) receptors, which reduced glutamate-dependent synaptic transmission by activating ATP-dependent potassium channels. Furthermore, we observed that iLTD did not occlude tetanic long-term depression (LTD) at the SNc excitatory synapses, suggesting that these two forms of LTD involve different pathways. Taken together, our results showed that brief exposure to hypoxia and hypoglycemia results in LTD of synaptic activity at glutamatergic synapses onto SNc neurons and this phenomenon could represent a protective mechanism by reducing ischemia-induced excitotoxic injury to dopamine neurons.


The effect of passive foot flexion on blood circulation in sports and clinical medicine.
The aim of the study was to analyze the effect of the passive foot flexion on peripheral and systemic blood circulations in the state of rest of persons adapted to endurance physical loads, and on patients during surgery. In the first series of experiments which included 16 males in recumbent supine position adapted to endurance physical loads, the effect of the passive foot flexion by applying a leg muscle activator on the systemic and peripheral blood circulations was analyzed. In the second series of experiments conducted with 6 males and 12 females, the passive foot flexion was aimed at preventing thromboembologenesis during the intraoperative period. After a session of the passive foot flexion applied to persons adapted to endurance physical loads, the venous reserve volume in them increased to 1.68+/-0.3 mL/100 mL (p<0.05). The maximal venous emptying rate increased to 48.3+/-8.8 mL/100 mL/min (p<0.05). After 15 min of the passive foot flexion, the indices of the systemic blood circulation were analogous to the ones before passive foot flexion. The maximal venous emptying rate in the calves of the left and right legs at the end of the surgery decreased to 59.7+/-4.7 mL/100 mL/min (p>0.05) and to 62.9+/-4.0 mL/100 mL/min (p>0.05), respectively. The passive foot flexion applied to persons adapted to endurance physical loads increases venous reserve volume and maximal venous emptying rate. During the intraoperative period, the passive foot flexion increases maximal venous emptying rate from the triceps muscle of the calf thus decreasing the possible danger of thromboembologenesis.


Inhibition of histone deacetylase 6 restores innate immune cells in the bone marrow in a lethal septic model.
We have previously demonstrated that Tubastatin A, a selective inhibitor of histone deacetylase 6 (HDAC6), improves survival and increases circulating monocyte count and bacterial clearance in a lethal model of cecal ligation and puncture (CLP) in mice. The aim of the present study was to characterize the effects of inhibition of HDAC6 on the bone marrow cell population. C57BL/6J mice were subjected to CLP and, 1 hour later, given an intraperitoneal injection of either Tubastatin A (70 mg/kg) dissolved in DMSO or DMSO alone (n = 9 per group). Sham-operated animals were treated in an identical fashion, without CLP. Forty-eight hours later, bone marrow cells were flushed out from the femurs and tibias. Erythrocytes were lysed, and a single-cell suspension was made for analysis. Cells were washed; blocked with antimouse CD16/32; stained with antimouse B220 PE-Cy7, CD3 APC-eFluor 780, CD11b FITC, Gr-1 PerCP-Cy5.5, and F4/80 Antigen APC; and subjected to flow cytometry. Data were acquired on an LSRII Flow Cytometer (BD Biosciences, San Jose, CA) and analyzed with FlowJo (Flowjo, LLC, Ashland, OR). In comparison with the sham group, CLP animals showed decreased percentage of innate immune cells (CD11b, 62.1% ± 3.1% vs. 32.9% ± 4.9%, p = 0.0025) and macrophages (CD11bF4/80, 44.6% ± 3.4% vs. 19.8% ± 2.6%, p = 0.0002) as well as increased percentage of T lymphocytes (CD3, 1.1% ± 0.2% vs. 3.3% ± 0.4%, p = 0.0082) in the bone marrow 48 hours after CLP. Treatment with Tubastatin A restored the innate immune cells (32.9% ± 4.9% vs. 54.0% ± 4.1%, p = 0.0112) and macrophages (19.8% ± 2.6% vs. 47.1% ± 4.6%, p = 0.0001) and increased the percentage of neutrophils (CD11bGr-1, 28.4% ± 3.9% vs. 48.0% ± 4.0%, p = 0.0075). The percentages of B (B220) and T lymphocytes were not significantly altered by Tubastatin A, compared with the vehicle-treated CLP animals. Selective inhibition of HDAC6 in this lethal septic model restored the innate immune cell and macrophage populations and increased the neutrophil composition in the bone marrow. These results may explain the previously reported beneficial effects of Tubastatin A treatment in a septic model.


The effectiveness of self-care and lifestyle interventions in primary dysmenorrhea: a systematic review and meta-analysis.
Menstrual pain is very common amongst young women. Despite the significant impact that menstrual pain has on academic attendance and performance, social activities and quality of life, most young women do not seek medical treatment but prefer to use self-care; commonly OTC analgesic medications and rest. Many women do not get significant pain relief from these methods, therefore other low cost, easy to learn self-care methods may be a valuable approach to management. This review and meta-analysis examines the evidence for participant lead self-care techniques. A search of Medline, PsychINFO, Google Scholar and CINAHL was carried out in September 2017. Twenty-three trials including 2302 women were eligible and included in the meta-analysis. Studies examined self-delivered acupressure, exercise and heat as interventions. Risk of bias was unclear for many domains. All interventions showed a reduction in menstrual pain symptoms; exercise (g = 2.16, 95% CI 0.97 to 3.35) showed the largest effect size, with heat (g = 0.73, 95% CI 0.06 to 1.40) and acupressure (g = 0.56, 95% CI 0.10 to 1.03) showing more moderate effect sizes. Exercise (g = 0.48, 95% CI 0.12 to 0.83) and heat (g = 0.48, 95% CI 0.10 to 0.87), were more effective than analgesics in reducing pain intensity, whereas acupressure was significantly less effective (g = - 0.76, 95% CI -1.37 to - 0.15). Exercise showed large effects, while acupressure and heat showed moderate effects in reducing menstrual pain compared to no treatment. Both exercise and heat are potential alternatives to analgesic medication. However, difficulties in controlling for non-specific effects, along with potential for bias, may influence study findings.


Research progress into adipose tissue macrophages and insulin resistance.
In recent years, there has been an increasing incidence of metabolic syndrome, type 2 diabetes, and cardiovascular events related to insulin resistance. As one of the target organs for insulin, adipose tissue is essential for maintaining in vivo immune homeostasis and metabolic regulation. Currently, the specific adipose tissue mechanisms involved in insulin resistance remain incompletely understood. There is increasing evidence that the process of insulin resistance is mostly accompanied by a dramatic increase in the number and phenotypic changes of adipose tissue macrophages (ATMs). In this review, we discuss the origins and functions of ATMs, some regulatory factors of ATM phenotypes, and the mechanisms through which ATMs mediate insulin resistance. We explore how ATM phenotypes contribute to insulin resistance in adipose tissue. We expect that modulation of ATM phenotypes will provide a novel strategy for the treatment of diseases associated with insulin resistance.


[Movement as a Neuromodulator: How Physical Activity Influences the Physiology of Adolescent Depression].
Movement as a Neuromodulator: How Physical Activity Influences the Physiology of Adolescent Depression Abstract: In the context of adolescent depression, physical activity is becoming increasingly recognized for its positive effects on neuropathology. Current scientific findings indicate that physical training affects the biological effects of depression during adolescence. Yet the pathophysiology of adolescent depression is not yet fully understood. Besides psychosocial and genetic influences, various neurobiological factors are being discussed. One explanation model describes a dysfunction of the hypothalamus-pituitary-adrenal axis (HPA axis) with a sustained elevation in cortisol concentration. Recent studies highlight neuroimmunological processes and a reduced concentration of growth factors as causative factors. These changes appear to lead to a dysregulation of the excitation and inhibition balance of the cerebral cortex as well as to cerebral morphological alterations. Regular physical training can potentially counteract the dysregulation of the HPA axis and normalize cortisol levels. The release of proinflammatory cytokines is inhibited, and the expression of growth factors involved in adult neurogenesis is stimulated. One should ensure the synergistic interaction of biological and psychosocial factors when designing the exercise schedule (endurance or strength training, group or individual sports, frequency, duration, and intensity). Addressing these open questions is essential when integrating physical activity into the guidelines for treating depressive disorders in children and adolescents.


Front-end Weber-Fechner gain control enhances the fidelity of combinatorial odor coding.
We showed previously (Gorur-Shandilya et al., 2017) that Drosophila olfactory receptor neurons (ORNs) expressing the co-receptor Orco scale their gain inversely with mean odor intensity according to Weber-Fechner's law. Here, we show that this front-end adaptation promotes the reconstruction of odor identity from dynamic odor signals, even in the presence of confounding background odors and rapid intensity fluctuations. These enhancements are further aided by known downstream transformations in the antennal lobe and mushroom body. Our results, which are applicable to various odor classification and reconstruction schemes, stem from the fact that this adaptation mechanism is not intrinsic to the identity of the receptor involved. Instead, a feedback mechanism adjusts receptor sensitivity based on the activity of the receptor-Orco complex, according to Weber-Fechner's law. Thus, a common scaling of the gain across Orco-expressing ORNs may be a key feature of ORN adaptation that helps preserve combinatorial odor codes in naturalistic landscapes.


Understanding M-ligand bonding and mer-/fac-isomerism in tris(8-hydroxyquinolinate) metallic complexes.
Tris(8-hydroxyquinolinate) metallic complexes, Mq3, are one of the most important classes of organic semiconductor materials. Herein, the nature of the chemical bond in Mq3 complexes and its implications on their molecular properties were investigated by a combined experimental and computational approach. Various Mq3 complexes, resulting from the alteration of the metal and substitution of the 8-hydroxyquinoline ligand in different positions, were prepared. The mer-/fac-isomerism in Mq3 was explored by FTIR and NMR spectroscopy, evidencing that, irrespective of the substituent, mer- and fac-are the most stable molecular configurations of Al(iii) and In(iii) complexes, respectively. The relative M-ligand bond dissociation energies were evaluated experimentally by electrospray ionization tandem mass spectrometry (ESI-MS-MS), showing a non-monotonous variation along the group (Al > In > Ga). The results reveal a strong covalent character in M-ligand bonding, which allows for through-ligand electron delocalization, and explain the preferred molecular structures of Mq3 complexes as resulting from the interplay between bonding and steric factors. The mer-isomer reduces intraligand repulsions, being preferred for smaller metals, while the fac-isomer is favoured for larger metals where stronger covalent M-ligand bonds can be formed due to more extensive through-ligand conjugation mediated by metal "d" orbitals.


Inhibition of Protein Synthesis Induced by CHK1 Inhibitors Discriminates Sensitive from Resistant Cancer Cells.
The DNA-damage-activated checkpoint protein CHK1 is required to prevent replication or mitosis in the presence of unrepaired DNA damage. Inhibitors of CHK1 (CHK1i) circumvent this checkpoint and enhance cell killing by DNA-damaging drugs. CHK1i also elicit single-agent cytotoxicity in a small subset of cell lines. Resolving the mechanisms underlying the single-agent activity may permit patient stratification and targeted therapy against sensitive tumors. Our recent comparison of three CHK1i demonstrated that they all inhibited protein synthesis only in sensitive cells. LY2606368, the most selective of these CHK1i, was used in the current study. Comparison across a panel of cell lines demonstrated that sensitive cells died upon incubation with LY2606368, whereas resistant cells underwent growth inhibition and/or cytostasis but failed to die. Sensitive cells exhibited inhibition of protein synthesis, elevated DNA damage, impaired DNA repair, and subsequently death. The consequence of CHK1 inhibition involved activation of cyclin A/CDK2 and MUS81, resulting in DNA damage. This damage led to activation of AMPK, dephosphorylation of 4E-BP1, and inhibition of protein synthesis. Inhibition of MUS81 prevented activation of AMPK, while inhibition of AMPK enhanced DNA repair and cell survival. The activation of AMPK may involve a combination of LKB1 and CaMKKβ. This study raises questions concerning the potential importance of the inhibition of protein synthesis in response to other drugs, alone or in combination with CHK1i. It also highlights the importance of clearly discriminating among growth inhibition, cytostasis, and cell death, as only the latter is likely to result in tumor regression.


Detox shampoos for EtG and FAEE in hair - Results from in vitro experiments.
The assessment of alcohol consumption behavior in hair is well established in forensic toxicology. The Society of Hair Testing (SoHT) recommends the direct alcohol markers ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE) for the detection of past alcohol consumption. In this study, we investigated if detox shampoos which are sold online can have an impact on EtG or FAEE concentrations in hair. According to customer reviews, positive drug testing results could be avoided after long-term incubation with shampoo under a swimming cap. To evaluate the potential of four detox shampoos, we incubated distal hair samples from three subjects, obtained during a standard haircut, for 2.5, 5, 7.5, and 10 hours. For EtG, three shampoos performed similar to deionized water. The fourth shampoo showed additional heavy washout effects with a decrease of up to 86% after 2.5 hours. For the apolar FAEE, no washout was observed. Incubation with two shampoos resulted in increases in FAEE concentrations due to FAEE being present as shampoo ingredients. Further investigation of EtG washout in proximal forensic hair samples (n = 9) with the most potent shampoo showed a mean decrease in deionized water of 23% ± 25%, and a decrease by the use of detox shampoo of 73% ± 12%, compared to non-incubated hair after 8 hours. In conclusion, detox shampoos proved to have the potential to alter EtG and FAEE concentrations in hair during in vitro experiments.


Functional polymorphisms in monocyte chemoattractant protein-1 are associated with increased susceptibility to ovarian cancer.
Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. Monocyte chemoattractant protein-1 (MCP-1) is highly expressed in various malignancies and promotes carcinogenesis. The aim of the study was to investigate the association between MCP-1 genetic polymorphisms and the susceptibility to ovarian cancer. MCP-1 rs1024611A/G and rs3760396C/G polymorphisms were examined in 257 ovarian cancer patients and 273 healthy controls. We found that distributions of rs1024611GG genotype and rs3760396GG genotype were clearly increased in ovarian cancer cases compared to healthy donors (odds ratio [OR]=1.93, 95% confidence interval [CI]: 1.13-3.29, p=0.015; OR=3.89, 95% CI: 1.63-9.33, p=0.001). Stratification analyses revealed that patients with serous papillary type had further increased percentage of rs3760396GG genotype than those with other types (OR=3.89, 95% CI: 1.11-13.66, p=0.024). In addition, we evaluated the possible effect of MCP-1 polymorphisms on gene expression by examining the serum level of MCP-1 in patients and controls. Data revealed that subjects carrying rs1024611AG and GG genotypes had a significantly higher serum level of MCP-1 than those with AA genotype. These data suggest that MCP-1 rs1024611A/G and rs3760396C/G polymorphisms are associated with increased susceptibility to ovarian cancer, in which rs1024611A/G may increase serum level of MCP-1 in the Chinese population.


A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas.
This phase I trial evaluated the safety, tolerability, and preliminary activity of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas. Nineteen patients received at least one dose of both study drugs. Dose-limiting toxicities consisted of thrombocytopenia, hypertriglyceridemia, oral mucositis, clinical deterioration, and the inability to receive at least three doses of temsirolimus during cycle 1. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (n = 8), neutropenia (n = 5), and two patients each hyperphosphatemia, lymphopenia, and hypertriglyceridemia. The recommended phase II dose was inotuzumab ozogamicin 0.8 mg/m2 on day 1 in combination with temsirolimus 10 mg on days 8, 15, and 22 every 28 days. Among 18 patients evaluable, seven (39%) with follicular lymphoma had a partial remission. This drug combination is not possible within a therapeutically useful range of doses due to toxicities. Antitumor activity was observed in heavily pretreated patients (ClinicalTrials.gov, Identifier NCT01535989).


Resting energy expenditure, cardiovascular risk factors and insulin resistance in obese patients.
The aim of our study was to determine whether energy expenditure modified by increasing body mass over the wide range of body mass index (BMI) was related to insulin resistance, cardiovascular risk factors and dietary intakes. A population of 87 obese non-diabetic outpatients was analyzed prospectively. Indirect calorimetry, tetrapolar electrical bioimpedance, serial assessment of nutritional intake using written 3-day food records and biochemical analyses were performed. The mean age was 45.1 +/- 16.7 years and the mean BMI was 35.2 +/- 5.2. Indirect calorimetry showed a resting metabolic rate (RMR) of 1,732.2 +/- 406.6 kcal/day and oxygen consumption of 266.2 +/- 63.3 ml/min. RMR corrected by fat-free mass was 36.8 +/- 14.1 kcal/day/kg. Serial assessment of nutritional intake using written 3-day food records showed a calorie intake of 1,660 +/- 551.7 cal/day, a carbohydrate intake of 168.63 +/- 76.6 g/day, a fat intake of 72.1 +/- 26.42 g/day and a protein intake of 81.1 +/- 23.3 g/day. Insulin, HOMA, systolic blood pressure, diastolic blood pressure, waist circumference, fat mass, waist-to-hip ratio were higher in the third BMI tertile than in the first and second tertiles. No differences were detected in calorie intake, carbohydrate intake, fat intake, protein intake, drinking and alcoholic habit among BMI tertiles. RMR was similar in the different tertiles and the corrected RMR by fat-free mass was higher in first tertile than in the second and third tertiles (44.2 +/- 20.7 vs. 34.5 +/- 9.1 vs. 33.1 +/- 8.5 kcal/kg/day; p < 0.05). In multivariate analysis with a dependent variable (RMR), the fat-free mass remained in the model (F = 7.8; p < 0.05), with an increase of 10.1 (95% CI 3.6-17.5) kcal/day with each 1 kg of fat-free mass adjusted by age and sex. Resting energy expenditure in obese patients is not related to the BMI, insulin resistance and dietary intake. RMR is related to fat-free mass in a multivariant model.


Nucleotide sequence of the ribosomal RNA gene of Physarum polycephalum: intron 2 and its flanking regions of the 26S rRNA gene.
The 26S ribosomal RNA gene of Physarum polycephalum is interrupted by two introns, and we have previously determined the sequence of one of them (intron 1) (Nomiyama et al. Proc.Natl.Acad.Sci.USA 78, 1376-1380, 1981). In this study we sequenced the second intron (intron 2) of about 0.5 kb length and its flanking regions, and found that one nucleotide at each junction is identical in intron 1 and intron 2, though the junction regions share no other sequence homology. Comparison of the flanking exon sequences to E. coli 23S rRNA sequences shows that conserved sequences are interspersed with tracts having little homology. In particular, the region encompassing the intron 2 interruption site is highly conserved. The E. coli ribosomal protein L1 binding region is also conserved.


Marginal microleakage of alternative restorative treatment and conventional glass ionomer restorations in extracted primary molars.
The objective of this study was to compare the marginal leakage of cervical glass ionomer restorations made using alternative restorative treatment (ART) and conventional restoration techniques. Twenty primary molars with Class V carious dentin on the buccal surfaces were prepared using ART, and a second set of 20 noncarious molars had Class V preparations made with a high-speed handpiece. The occlusal margin was located in enamel and the gingival margin in dentin/cementum. All teeth were restored with high-density glass ionomer cement (GIC; Fuji IXgp) according to manufacturers' instructions, thermally stressed for 300 cycles, and stained with methylene blue. Samples were sectioned and evaluated for microleakage. One-way analysis of variance revealed no statistically significant difference between leakage at margins of ART and conventional restorations. (P=.92) There was no significant difference between leakage at the enamel and dentin margins. Alternative restorative treatment with high-density glass ionomer cement provides enamel and dentin margins that show marginal leakage comparable to conventionally restored primary teeth. These results show the potential of ART in conjunction with high-density GIC in providing treatment for children and adolescents in situations where traditional cavity preparation and restoration is not possible.


Safety Evaluation of a Novel Strain of Bacteroides fragilis.
Commensal non-toxigenic Bacteroides fragilis confers powerful health benefits to the host, and has recently been identified as a promising probiotic candidate. We previously isolated B. fragilis strain ZY-312 and identified it as a novel strain based on 16S rRNA sequencing and morphological analyses. We also determined that ZY-312 displayed desirable probiotic properties, including tolerance to simulated digestive fluid, adherence, and in vitro safety. In this study, we aim to investigate whether ZY-312 meets the safety criteria required for probiotic bacteria through comprehensive and systematic evaluation. Consequently, the fatty acid profile, metabolite production, and biochemical activity of strain ZY-312 were found to closely resemble descriptions of B. fragilis in Bergey's manual. Taxonomic identification of strain ZY-312 based on whole genome sequencing indicated that ZY-312 and ATCC 25285 showed 99.99% similarity. The 33 putative virulence-associated factors identified in ZY-312 mainly encoded structural proteins and proteins with physiological activity, while the lack of bft indicated that ZY-312 was non-toxigenic. In vivo safety was proven in both normal and immune-deficient mice. The 11 identified antibiotic resistance genes were located on the chromosome rather than on a plasmid, ruling out the risk of plasmid-mediated transfer of antibiotic resistance. In vitro, ZY-312 showed resistance to cefepime, kanamycin, and streptomycin. Finally, and notably, ZY-312 exhibited high genetic stability after 100 passages in vitro. This study supplements the foundation work on the safety evaluation of ZY-312, and contributes to the development of the first probiotic representative from the dominant Bacteroidetes phylum.


Detection of novel beta 2-microglobulin in the serum of hemodialysis patients and its amyloidogenic predisposition.
Serum from 8 undialyzed patients and 30 dialyzed patients was examined by immunoblotting using anti beta 2-microglobulin (beta 2M) serum after two-dimensional gel electrophoresis (2.DE). One major spot and three minor spots were detected in the ultrafiltrate as well as in the serum. One major spot was determined to be native beta 2M and three minor spots were found to be novel beta 2M. Novel beta 2M had a lower molecular weight (MW) and a higher acidic isoelectric point (pI). Novel beta 2M was recognized in the sera of 5 out of 20 hemodialysis (HD) patients without carpal tunnel syndrome (CTS), 2 of whom had been on HD from 5 to 10 years and 3 for more than 10 years, as well as in the sera of all 10 patients with CTS. By chromatofocusing, pI of novel beta 2M was 5.2, while pI of native beta 2M was 5.7. When the tissue specimen of transverse carpal ligament of 2 HD patients with CTS was examined by immunoblotting after 2.DE, the spot of novel beta 2M was larger than that of native beta 2M. It is possible that some metabolic abnormality of beta 2M occurs through long-term hemodialysis, and it is possible that novel beta 2M might relate to amyloidogenic predisposition.


Factors associated with quality of life and mood in adults with strabismus.
To explore the factors associated with the mood and quality of life (QoL) of patients with strabismus due to undergo realignment surgery. A cross-sectional study was undertaken with adult patients. Along with demographic, clinical and psychosocial process variables, the Hospital Anxiety and Depression Scale and AS-20 QoL measures were administered. Regression models were used to identify the factors associated with QoL and mood. Of the 220 participants, 11% were experiencing clinical levels of depression, and 24% clinical anxiety. This is in line with other forms of facial disfigurement but higher than other chronic diseases. Although mood and QoL were associated with age and diplopia, it was beliefs and cognitions which were more consistently associated with well-being. This included feelings of social anxiety and avoidance, a belief that strabismus has negative consequences, poor understanding of strabismus, social support, fear of negative evaluation and the perceived visibility of their condition. Psychosocial rather than clinical characteristics were identified as determinants of well-being in this population. It is important for clinicians planning surgery to be aware of these factors which could influence outcomes. Longitudinal studies need to be conducted to explore the direction of causality before interventions to improve well-being are developed and evaluated.


Regulation of telomerase activity by interferon regulatory factors 4 and 8 in immune cells.
Telomerase activity is downregulated in somatic cells but is upregulated during the activation of cells of the immune system. The mechanism of this reactivation is not well understood. In this study, we demonstrated that interferon regulatory factor 4 (IRF-4) and, to a lesser extent, IRF-8 induce telomerase activity. The suppression of IRF-4 results in decreased levels of TERT (telomerase reverse transcriptase) mRNA and telomerase activity and reduces cell proliferation. The overexpression of TERT compensates for this proliferation defect, suggesting that telomerase contributes to the regulation of cell proliferation by IRF-4. The induction of telomerase by IRF-4 and IRF-8 correlates with the activation of the TERT promoter. IRF-4 binds the interferon response-stimulated element and the gamma interferon-activated sequence composite binding site in the TERT core promoter region in vivo. Additionally, the binding of Sp1, Sp3, USF-1, USF-2, and c-Myc to the TERT promoter is elevated in cells expressing IRF-4. IRF-4, but not IRF-8, synergistically cooperates with Sp1 and Sp3 in the activation of the TERT promoter. Collectively, these results indicate that IRF-4 and IRF-8, two lymphoid cell-specific transcription factors, increase telomerase activity by activating TERT transcription in immune cells.


Application of size exclusion electrochromatography to the microanalytical determination of the molecular mass distribution of celluloses from objects of cultural and historical value.
The molecular mass distributions (MMD) of celluloses from paper and other sources were determined by size exclusion electrochromatography (SEEC). Prior to the separation the celluloses were chemically modified with phenyl isocyanate into their tricarbanilate derivatives (CTC). Sensitive UV detection of the CTC could be performed at a wavelength of 210 nm. The solvent used for separation was acetone. With this solvent, a high electroosmotic flow could be generated in columns packed with bare silica particles. With a column packed with particles with a nominal pore size of 30 nm, use of a mobile phase with a salt concentration of 0.1 mM was found to be optimal with respect to mass selectivity and efficiency. The workable mass range under these conditions was from 2 kDa to at least 500 kDa for (native) celluloses. The SEEC method was compared to classical pressure-driven size exclusion chromatography (PD-SEC). It is shown that the two methods give comparable results for the MMD of celluloses, while SEEC has important advantages in terms of speed and sample consumption. With SEEC, the analysis time was less than 20 min. The method was applied for the study of cellulose degradation during (artificial) aging of paper samples. A clear reduction of the average molecular mass of cellulose during aging was observed. With SEEC, the required sample amount is strongly reduced compared to classical PD-SEC. With a single paper fiber (after derivatization), multiple analyses could be carried out. It is argued that this is not only important for the analysis of unique objects but that it also allows the detection of MMD heterogeneities on a microscale. The strong reduction in sample size may be relevant when local heterogeneities in other types of polymer samples are studied.


Leukocyte zinc in the assessment of zinc status.
The problems of assessment of human zinc status are reviewed, with particular emphasis on the limitations to each of the current available measurements. The advantages and limitations of leukocytes are then described. Methods of preparation and potential problems in the assay for zinc are described in detail. The data so-far produced by this method are reviewed.


Lick Observatory Optical SETI: targeted search and new directions.
Lick Observatory's Optical SETI (search for extraterrestrial intelligence) program has been in regular operation for 4.5 years. We have observed 4,605 stars of spectral types F-M within 200 light-years of Earth. Occasionally, we have appended objects of special interest, such as stars with known planetary systems. We have observed 14 candidate signals ("triple coincidences"), all but one of which are explained by transient local difficulties. Additional observations of the remaining candidate have failed to confirm arriving pulse events. We now plan to proceed in a more economical manner by operating in an unattended drift scan mode. Between operational and equipment modifications, efficiency will more than double.


Roles of acyl-CoA synthetase long-chain family member 5 and colony stimulating factor 2 in inhibition of palmitic or stearic acids in lung cancer cell proliferation and metabolism.
Lung cancer is a heterogeneous and complex disease with the highest incidence and mortality rate. The present study aims at defining the lung cancer phenome specificity of lipidomic profiles, screening target lipid-dependent transcriptional alternations, identifying target lipid-associated target genes, and exploring molecular mechanisms. Lung cancer-specific and lung cancer subtype-specific target lipids palmitic acid (C16:0) and stearic acid (C18:0) were found as target lipids by integrating clinical phenomics, lipidomics, and transcriptomics and exhibited antiproliferative effects in sensitive cells. The metabolism-associated gene ACSL5 or inflammation-associated gene CCL3 was identified in lung adenocarcinoma or small lung cancer cells, respectively. C16:0 or C18:0 could upregulate ACSL5 or CSF2 expression in a time- and dose-dependent pattern, and the deletion of both genes led to the insensitivity of cells. Target lipids increased the expression of PDK4 gene in different patterns and inhibited cell proliferation through alterations of intracellular energy. Thus, our data provide a new strategy to investigate the trans-points between clinical and phenomics and lipidomics and target lipid-associated molecular mechanisms to benefit from the discovery of new therapies.


Periorbital ecchymosis as a sign of perforating injury of the globe.
The distinction between penetrating eye injury with retained intraocular foreign body and perforating globe injuries is not always easy clinically. The case is presented of a 25-year-old man who sustained a perforating eye injury that was through a clear self-sealing corneal entry site and had no conjunctival or periorbital injury. He had periorbital ecchymosis on presentation suggesting that the globe had been perforated with resulting retro-orbital blood tracking to the periorbital region. This sign would not be expected had the foreign body remained intraocular. The management options of these cases are discussed.


Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity.
Early control of virus replication by the innate immune response is essential to allow time for the generation of a more effective adaptive immune response. As an important component of innate immunity, complement has been shown to be necessary for protection against numerous microbial infections. This study was undertaken to investigate the role of complement in neutralizing influenza virus. Results demonstrated that the classical pathway of complement mediated serum neutralization of influenza virus. Although nonimmune serum neutralized influenza virus, the mechanism of virus neutralization (VN) required antibody, as sera from RAG1-deficient mice lacked VN activity; moreover, purified natural immunoglobulin M (IgM) restored VN activity to antibody-deficient sera. The mechanism of VN by natural IgM and complement was associated with virion aggregation and coating of the viral hemagglutinin receptor; however, viral lysis did not significantly contribute to VN. Additionally, reconstitution of RAG1-deficient mice with natural IgM resulted in delayed morbidity during influenza virus infection. Collectively, these results provide evidence that natural IgM and the early components of the classical pathway of complement work in concert to neutralize influenza virus and that this interaction may have a significant impact on the course of influenza viral pneumonia.


Neuropeptide FF receptors have opposing modulatory effects on nociception.
The role of neuropeptide FF (NPFF) and its analogs in pain modulation is ambiguous. Although NPFF was first characterized as an antiopioid peptide, both antinociceptive and pronociceptive effects have been reported, depending on the route of administration. Currently, two NPFF receptors, termed FF1 and FF2, have been identified and cloned, but their roles in pain modulation remain elusive because of the lack of availability of selective compounds suitable for systemic administration in in vivo models. Ligand-binding studies confirm ubiquitous expression of both subtypes in brain, whereas only FF2 receptors are expressed spinally. This disparity in localization has served as the foundation of the hypothesis that FF1 receptors mediate the pronociceptive actions of NPFF. We have identified novel small molecule NPFF receptor agonists and antagonists with varying degrees of FF2/FF1 functional selectivity. Using these pharmacological tools in vivo has allowed us to define the roles of NPFF receptor subtypes as pertains to the modulation of nociception. We demonstrate that selective FF2 agonism does not modulate acute pain but instead ameliorates inflammatory and neuropathic pains. Treatment with a nonselective FF1/FF2 agonist potentiates allodynia in neuropathic rats and increases sensitivity to noxious thermal and to non-noxious mechanical stimuli in normal rats in an FF1 antagonist-reversible manner. Treatment with FF1 antagonists reversed established mechanical allodynia, indicating the possibility of increased NPFF tone through FF1 receptors. In conclusion, we provide evidence for the opposing roles of NPFF receptors and highlight selective FF2 agonism and/or selective FF1 antagonism as potential targets warranting further investigation.


Effects of ellipticine on cell survival and cell cycle progression in cultured mammalian cells.
The effects of ellipticine [5,11-dimethyl-6H-pyrido(4,3-b)carbazole; NSC 71795] on cell viability, growth, and colony formation were investigated in suspension (Friend leukemia and L1210) and adherent [Chinese hamster ovary (CHO)]tumor cell systems as well as in mitogen-stimulated human peripheral blood lymphocyte cultures. Cell cycle progression and the terminal point of action of the drug were monitored by flow cytometry. Ellipticine was cytostatic for all cell lines tested, blocking cells in G2 phase following 24 hr constant exposure at concentrations in the range of 1.0 microgram/ml. A 10 times higher drug concentration was required to block cells in G2 if the cells were exposed for only 30 min to the drug followed by 23.5 hr culture in drug-free medium. Formation of CHO cell colonies was inhibited by 50% following exposure to ellipticine for 2 hr at 6.0 microgram/ml or for 24 hr at 0.3 microgram/ml. Fifty % cell kill in asynchronously growing Friend leukemia and L1210 cells was obtained following exposure to ellipticine for 24 hr at 2.0 microgram/ml and 1.15 microgram/ml, respectively, whereas human peripheral blood lymphocytes required 66 hr exposure to 1.0 microgram/ml to kill 50% of the cells. Phytohemagglutinin-stimulated lymphocytes were remarkably resistant to the cytotoxic effect of ellipticine but did display a dose-dependent inhibition of stimulation and accumulation in G2 whether the drug was added prior to our during active cell proliferation. Ellipticine, at cytostatic concentrations, had a marked effect on cellular RNA content. Friend leukemia cells, blocked in G2 by the drug, doubled their RNA content compared to control cells. L1210 and CHO cells, but not lymphocytes, also increased in RNA content following ellipticine treatment. Drug concentrations which blocked cells in G2 also led in the case of Friend leukemia and L1210 but not CHO cells to an increase in the proportion of cells with greater than 4C amounts of DNA.


A new method for detecting and localizing cell markers endocytosed by fibroblasts in epoxy resin semi-thin sections using scanning electron microscopy combined with energy dispersive X-ray microanalysis after ion-etching.
Cell marking is widely used to examine cell development and differentiation in developmental biology. We developed a new method for localizing cell markers in a semi-thin epoxy section with scanning electron microscopy. Cultured fibroblasts ingesting carbon particles were autologously transplanted into a rabbit transparent ear chamber, 6 mm in diameter and 100 microm in depth. Eight days after the transplantation, tissues in the chamber were fixed and embedded in epoxy resin. Semi-thin sections were cut and stained with toluidine blue. Fibroblasts in connective tissues which contained black spots were observed with a light microscope. These sections were subsequently ion-etched with an ion-coater and coated with platinum. The same fibroblasts were then visualized by secondary electron imaging using a scanning electron microscope. A nucleus with nuclear envelope, nuclear pores, a nucleolus and heterochromatin, mitochondria with cristae and rough endoplasmic reticulum were observed in the fibroblasts. The black spots in the fibroblasts were identified as bright bodies with the scanning electron microscope. The bright bodies were found to be a lump of tiny particles less than 100 nm in diameter. In order to analyse such particles with energy dispersive X-ray microanalysis, ion-etched sections were coated with carbon. X-ray energy spectrometry clearly demonstrated that these were carbon particles, which had been endocytosed by the fibroblast. This suggests that scanning electron microscopy combined with energy dispersive X-ray microanalysis is useful for detecting carbon particles in the cytoplasm at an ultrastructural level in semi-thin epoxy sections subsequent to ion etching and that this method may be applicable to other cell markers, such as gold particles to track cells in the field of cell development and cell differentiation.


Studies of 7 beta-[2-(aminoaryl)acetamido]-cephalosporin derivatives. I. Synthesis and structure-activity relationships in the aminopyridine series.
The synthesis and in vitro activity of 7 beta-(2-aminopyridyl-2-alkoxyiminoacetamido)cephalosporins with various substituents at the 3-position are described. The effects of substitution pattern on the pyridine ring, oxime substituent and 3-substituent were studied as a function of the MIC values. Of these various kinds of derivatives, 7 beta-[2-(2-aminopyridin-6-yl)-2-alkoxyiminoacetamido]cephalo sporins exhibited significantly higher activity against most of micro-organisms.


Hamulonema gen. nov. for Teladorsagia hamata and Ostertagia kenyensis in the ostertagiine fauna (Nematoda: Trichostrongyloidea) from African ungulates.
Hamulonema gen. nov. is proposed for Teladorsagia hamata and Ostertagia kenyensis in the ostertagiine nematode fauna found in artiodactyl hosts from Africa. Monomorphic species representing this genus are characterized by a bilaterally symmetrical and parallel synlophe in males and females, a 2-2-1 bursal formula, an accessory bursal membrane that is strongly cuticularized and reduced, a strongly reduced dorsal lobe and ray, and robust spicules with a simple, weakly pointed, ventral process, and curved, hooklike dorsal process. Species referred to Hamulonema nov. gen. are immediately distinguished from those of Camelostrongylus, Longistrongylus, Marshallagia, Orloffia, Ostertagia, and Pseudomarshallagia in which the bursal formula is 2-1-2 in males. Hamulonema nov. gen. is distinguished from those genera having a 2-2-1 bursa, including Africanastrongylus, Cervicaprastrongylus, Hyostrongylus, Mazamastrongylus, Sarwaria, Spiculopteragia, and Teladorsagia by the structure of the synlophe, bursa, genital cone, "0" and "7" papillae, dorsal lobe, and spicules in specific instances. In the global fauna, 4 of 14 ostertagiine genera are endemic to Africa. African genera may represent morphologically divergent and discrete or historically isolated lineages reflecting a pattern of geographic and host colonization as a driver for diversification since the Miocene.


Blood Collection and Cell-Free DNA Isolation Methods Influence the Sensitivity of Liquid Biopsy Analysis for Colorectal Cancer Detection.
During colorectal cancer (CRC) development tumor-derived cell-free DNA (cfDNA) can be released into the bloodstream. Many different cfDNA isolation methods and specific blood collection tubes preventing the release of genomic DNA and stabilizing cfDNA with preservative reagents became available. These factors may affect greatly on the further liquid biopsy analyses. Our aim was to test different blood collection tubes and cfDNA isolation methods to determine whether these factors influence the cfDNA amount and the promoter methylation of four previously described hypermethylated biomarkers. Three manual isolation methods (High Pure Viral Nucleic Acid Large Volume Kit; Epi proColon 2.0 Kit; Quick-cfDNA™ Serum & Plasma Kit) and automated sample preparation systems (InviGenius and InviGenius PLUS) were examined. Furthermore, K3EDTA Vacuette tubes and Streck Cell-Free DNA BCT® tubes were compared. After cfDNA isolation and bisulfite conversion of samples, the methylation level of SFRP1, SFRP2, SDC2, and PRIMA1 were defined with MethyLight assays. We have ascertained that there are differences between the cfDNA amounts depending on the isolation methods. Higher cfDNA yield was observed using InviGenius system than column-based manual isolation method; however, InviGenius PLUS has produced lower cfDNA amounts. No remarkable variance could be found between K3EDTA and Streck tubes; slightly higher cfDNA quantity was detected in 60% of plasma samples using Streck tubes. In point of methylation level and frequency, manual column-based isolation produced more consistent results. Automated cfDNA extraction systems are easy-to-use and high-throughput; however, further improvements in the isolation protocols might lead to the increase of the sensitivity of further methylation analysis.


What the Distribution of Cell Lengths in the Root Meristem Does and Does Not Reveal About Cell Division.
Roots have long been realized to be useful material for studies of cell division. Despite this long history of use, the behavior of cells in the meristem is often misinterpreted. A common error is to argue that differences in cell length reflect differences in cell division rate. In this article we explain the fallacy behind this argument and show how the analysis of cell length distribution can lead to insight about the root meristem. These observations support a model for the root meristem where cells of various tissues grow at the same relative growth rate and divide at the same frequency, indicating that these growth parameters are built into the cells at a fundamental level. The differences in cell length between various tissues appear to arise at their formation, first at the tissue initials and ultimately in the seed. Length differences among mature cells may be enhanced by differences in the location within the meristem where division ceases. Discovering mechanisms regulating the length of initial cells and the position where cells cease division requires a realistic understanding of how growth constrains the division behavior of dividing cells.


The effect of perioperative portal venous injection of donor spleen cells on renal allograft survival in dogs.
Preoperative portal venous injection of donor lymphocytes has been shown to extend allograft survival in inbred animals. However, the effect of perioperative injection in a large animal model has not been carefully studied. We examined the effect of perioperative (day 0) donor spleen cell administration in a canine kidney transplant model using both a double-donor transplantation and a single-donor survival study. In the double-donor model, two kidneys from two separate donors were transplanted into a single recipient. Spleen cells obtained from only one of the donors were injected through the portal vein immediately after reperfusion of the allografts. Both allografted kidneys were resected 14 days after transplantation and studied. There was only a slight cellular infiltrate in the kidney derived from the donor from whom spleen cells had been obtained, whereas a much more extensive cellular infiltrate as well as edema and hemorrhage were present in the other kidney. In a survival study of single allografts, the injection of 2 x 10(9) spleen cells significantly prolonged the mean survival time (15.0 +/- 3.4 days) compared with untreated recipients (6.6 +/- 2.2 days). Addition of cyclosporine did not significantly prolong survival in the spleen cell inoculated animals. These findings suggest that perioperative protal venous injection of donor cells may be a specific immunosuppressive method useful in clinical organ transplantation.


A report from The Liver Meeting 2014 (November 7-11 - Boston, Massachusetts, USA).
The first waves of winter cold were sweeping across Massachusetts at the time this year's American Academy for the Study of Liver Diseases' Liver Meeting opened gates to a crowd of scientists and researchers from across the globe. The Hynes Convention Center acted as the liver through which new research from many different sources, shaped as oral and poster presentations, was transformed into a story of hope for new, more effective treatments for common liver diseases, particularly viral hepatitis infection and nonalcoholic steatohepatitis. As summarized in the following report, novel research was also reported emphasizing novel potential therapies for liver cancer as well as a broad range of liver diseases.


Biosensing Intestinal Alkaline Phosphatase by Pregnancy Test Strips Based on Target-Triggered CRISPR-Cas12a Activity to Monitor Intestinal Inflammation.
With an increasing incidence worldwide, inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal tract, which impairs the life quality of patients. Therefore, it is of great significance to construct a sensitive, simple, and convenient biosensor to analyze IBD-associated biomarkers for an auxiliary diagnosis of IBD. Intestinal alkaline phosphatase (IAP), expressed by the intestinal epithelium, is an endogenous protein that is thought to play a vital role in maintaining intestinal homeostasis and is considered a potential biomarker for IBD. Here, an IAP detection method was developed using pregnancy test strips by dephosphorylation. Initially, a double-stranded DNA (dsDNA) was designed to respond to IAP and acted as an activator of Cas12a. In the presence of IAP, the designed dsDNA was not digested by lambda exonuclease (λ exo), which hybridized to the Cas12a-crRNA duplex and resulted in the activation of the trans-cleavage of Cas12a. Further, the activated Cas12a cleaved the single-strand DNA (ssDNA) linker in the MBs-ssDNA-hCG probe, triggering the release of hCG. With magnetic separation, the released hCG could be quantitatively detected by pregnancy test strips. IAP levels were analyzed in feces from colitis and healthy mice by pregnancy test strips. The results showed that the IAP level of colitis mice (3.89 ± 1.92 U/L) was much lower than that of healthy mice (39.64 ± 24.93 U/L), indicating the correlation between IAP and intestinal inflammation. Taken together, a sensitive, user-friendly detection assay based on pregnancy test strips was constructed to monitor IAP and used as an auxiliary diagnostic approach for IBD in a clinical scene.


Influence of thermal expansion mismatch and fatigue loading on phase changes in porcelain veneered Y-TZP zirconia discs.
There is a rapidly growing interest for the use of Y-TZP zirconia as core material in veneered all-ceramic prostheses. It was hypothesized that a mismatch in coefficient of thermal expansion between the veneering porcelain and the Y-TZP zirconia core of these prostheses causes transformation of the tetragonal to the monoclinic structure in Y-TZP zirconia at the interface boundary when exposed to fatigue loading, resulting in fracture at the interface boundary. Y-TZP zirconia discs were veneered with three porcelains differing in coefficient of thermal expansion. Finite element analysis was used to investigate the stress distribution in the bi-layered discs because of the mismatch in thermal expansion. Two of these three groups were fatigued with the veneering ceramic in tension. X-ray diffraction was used to measure the intensity of monoclinic and tetragonal zirconia phase present at the zirconia core surface after sintering, airborne abrasion, veneering, and fatigue loading. It was found that the sintered tetragonal structure was converted to monoclinic up to a depth of 27 mum after airborne abrasion, and reversed back to tetragonal after porcelain veneering with porcelain. Fatigue loading of veneered discs did not, even with the highest possible thermal mismatch stress, cause any conversion from tetragonal to monoclinic phase.


Cardiac beta-adrenergic receptors in diabetic rats: alteration of guanyl nucleotide regulation.
Cardiac beta-adrenergic receptors (beta AR) were studied in rats after 4 months of diabetes induced by streptozotocin (50 mg/kg, i.v.). Saturation binding studies performed using [125I]-iodocyanopindolol (ICYP) as an antagonist ligand showed that the number and affinity of beta AR were not significantly altered. Analysis of competition curves of ICYP binding by the agonist (-)-isoproterenol showed that diabetes induces an increase in the (-)-isoproterenol IC50 and a steepening of the curve ("pseudo-Hill" coefficient not significantly different from 1) in the absence of Gpp(NH)p, while these parameters were not significantly modified in the presence of Gpp(NH)p (10(-4) M). These results indicates that beta AR were not significantly reduced in number but altered in their capacity to efficiently couple with the GTP-binding protein of adenylate cyclase (AC). These data can be correlated to the alteration of beta-adrenergic stimulation of cardiac AC previously observed after 4 months of diabetes. The characteristics of beta AR alteration at this stage of the disease are similar to those of a first step of a beta AR desensitization process due to overstimulation.


A cell-level quality control workflow for high-throughput image analysis.
Image-based high throughput (HT) screening provides a rich source of information on dynamic cellular response to external perturbations. The large quantity of data generated necessitates computer-aided quality control (QC) methodologies to flag imaging and staining artifacts. Existing image- or patch-level QC methods require separate thresholds to be simultaneously tuned for each image quality metric used, and also struggle to distinguish between artifacts and valid cellular phenotypes. As a result, extensive time and effort must be spent on per-assay QC feature thresholding, and valid images and phenotypes may be discarded while image- and cell-level artifacts go undetected. We present a novel cell-level QC workflow built on machine learning approaches for classifying artifacts from HT image data. First, a phenotype sampler based on unlabeled clustering collects a comprehensive subset of cellular phenotypes, requiring only the inspection of a handful of images per phenotype for validity. A set of one-class support vector machines are then trained on each biologically valid image phenotype, and used to classify individual objects in each image as valid cells or artifacts. We apply this workflow to two real-world large-scale HT image datasets and observe that the ratio of artifact to total object area (ARcell) provides a single robust assessment of image quality regardless of the underlying causes of quality issues. Gating on this single intuitive metric, partially contaminated images can be salvaged and highly contaminated images can be excluded before image-level phenotype summary, enabling a more reliable characterization of cellular response dynamics. Our cell-level QC workflow enables identification of artificial cells created not only by staining or imaging artifacts but also by the limitations of image segmentation algorithms. The single readout ARcell that summaries the ratio of artifacts contained in each image can be used to reliably rank images by quality and more accurately determine QC cutoff thresholds. Machine learning-based cellular phenotype clustering and sampling reduces the amount of manual work required for training example collection. Our QC workflow automatically handles assay-specific phenotypic variations and generalizes to different HT image assays.


Orientational changes of white matter fibers in Alzheimer's disease and amnestic mild cognitive impairment.
White matter abnormalities represent early neuropathological events in neurodegenerative diseases such as Alzheimer's disease (AD), investigating these white matter alterations would likely provide valuable insights into pathological changes over the course of AD. Using a novel mathematical framework called "Director Field Analysis" (DFA), we investigated the geometric microstructural properties (i.e., splay, bend, twist, and total distortion) in the orientation of white matter fibers in AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) individuals from the Alzheimer's Disease Neuroimaging Initiative 2 database. Results revealed that AD patients had extensive orientational changes in the bilateral anterior thalamic radiation, corticospinal tract, inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus in comparison with CN. We postulate that these orientational changes of white matter fibers may be partially caused by the expansion of lateral ventricle, white matter atrophy, and gray matter atrophy in AD. In contrast, aMCI individuals showed subtle orientational changes in the left inferior longitudinal fasciculus and right uncinate fasciculus, which showed a significant association with the cognitive performance, suggesting that these regions may be preferential vulnerable to breakdown by neurodegenerative brain disorders, thereby resulting in the patients' cognitive impairment. To our knowledge, this article is the first to examine geometric microstructural changes in the orientation of white matter fibers in AD and aMCI. Our findings demonstrate that the orientational information of white matter fibers could provide novel insight into the underlying biological and pathological changes in AD and aMCI.


Agricultural Conservation Planning Framework: 3. Land Use and Field Boundary Database Development and Structure.
Conservation planning information is important for identifying options for watershed water quality improvement and can be developed for use at field, farm, and watershed scales. Translation across scales is a key issue impeding progress at watershed scales because watershed improvement goals must be connected with implementation of farm- and field-level conservation practices to demonstrate success. This is particularly true when examining alternatives for "trap and treat" practices implemented at agricultural-field edges to control (or influence) water flows through fields, landscapes, and riparian corridors within agricultural watersheds. We propose that database structures used in developing conservation planning information can achieve translation across conservation-planning scales, and we developed the Agricultural Conservation Planning Framework (ACPF) to enable practical planning applications. The ACPF comprises a planning concept, a database to facilitate field-level and watershed-scale analyses, and an ArcGIS toolbox with Python scripts to identify specific options for placement of conservation practices. This paper appends two prior publications and describes the structure of the ACPF database, which contains land use, crop history, and soils information and is available for download for 6091 HUC12 watersheds located across Iowa, Illinois, Minnesota, and parts of Kansas, Missouri, Nebraska, and Wisconsin and comprises information on 2.74 × 10 agricultural fields (available through /). Sample results examining land use trends across Iowa and Illinois are presented here to demonstrate potential uses of the database. While designed for use with the ACPF toolbox, users are welcome to use the ACPF watershed data in a variety of planning and modeling approaches.


[Clinical efficiency in children treated with intravenous drip infusion of peramivir].
The clinical effect of peramivir was examined retrospectively in 30 children aged 23 days to 8 years; they had been treated with peramivir at our hospital within 48 hours after the onset of influenza from November 2010 to April 2011. Intravenous dripping of peramivir at a dose of 10 mg/kg was performed only once for 15 to 30 minutes. To examine the clinical effect of peramivir, the time from dosing to defervescence (body temperature <37.5 degrees C) was evaluated. To compare the clinical effects of peramivir and oseltamivir, the time required for the defervescence was evaluated in a similar manner in 30 children aged 7 months to 8 years who had been treated for influenza with oseltamivir at a dose of 4 mg/kg/day. The influenza type was type A (n=25) and type B (n=5) in the peramivir group and type A (n=26) and type B (n=4) in the oseltamivir group. In the peramivir group, 5 (16.7%), 16 (53.3%), and 24 (80.0%) patients achieved defervescence within 6, 12, and 24 hours, respectively. In the oseltamivir group, 3 (10.0%) and 6 (20.0%) patients had defervescence within 12 and 24 hours, respectively. The difference between these groups was statistically significant (p<0.05). An increase in the levels of AST and ALT was observed as an adverse reaction in 1 patient. Thus, peramivir was determined to be effective to influenza in children.


CATCHing putative causative variants in consanguineous families.
Consanguinity is an important risk factor for autosomal recessive (AR) disorders. Extended genomic regions identical by descent (IBD) in the offspring of consanguineous parents give rise to recessive disorders with identical (homozygous) pathogenic variants in both alleles. However, many clinical phenotypes presenting in the offspring of consanguineous couples are still of unknown etiology. Nowadays advances in High Throughput Sequencing provide an excellent opportunity to achieve a molecular diagnosis or to identify novel candidate genes. To exploit all available information from the family structure we developed CATCH, an algorithm that combines genotyped SNPs of all family members for the optimal detection of Runs Of Homozygosity (ROH) and exome sequencing data from one affected individual to identify putative causative variants in consanguineous families. CATCH proved to be effective in discovering known or putative new causative variants in 43 out of 50 consanguineous families. Among them, novel variants causative of familial thrombocytopenia, sclerosis bone dysplasia and the first homozygous loss-of-function mutation in FGFR3 in human causing severe skeletal deformities, tall stature and hearing impairment were identified.


Mitochondrial changes in leukocytes of patients with optic neuritis.
Optic neuritis (ON) is a demyelinating disorder affecting optic nerves. It has certain similarities to Leber hereditary optic neuropathy (LHON) and other spontaneous optic neuropathies known to be associated with mitochondriopathies. We evaluated patients with optic neuritis for evidence of systemic mitochondrial abnormalities. Patients were selected who had ON affecting one or both eyes. We performed clinical examinations and neuroimaging on the participants. We sequenced the entire mitochondrial DNA (mtDNA) genome except for the D-loop in leukocytes of all patients; assessed relative mtDNA content; measured mitochondrial respiratory function in 15 patients; and sequenced OPA1 and OPA3 genes, where mutations have been associated with dominant and recessive optic nerve atrophy, respectively. Twenty-six patients (11 males and 15 females; average age at onset 23.4+/-8.1 years) met inclusion and exclusion criteria. Eleven patients had neuroimaging evidence of disseminated demyelination, and six had clinically definite multiple sclerosis. No patient had a primary LHON mutation or a pathologic sequence change in OPA1 or OPA3 genes. Sixteen patients had potentially pathologic mtDNA changes, and after recovery these patients had significantly worse visual acuity (p=0.002) and color vision (p = 0.009) than other patients. Mean relative mtDNA content was significantly increased in ON patients compared to controls (2.39 versus 1.03; p<0.001), while mitochondrial respiratory activity was significantly decreased (16.78 versus 22.53; p<0.001). The presence of these systemic mitochondrial abnormalities in patients with ON suggests that mitochondrial abnormalities may constitute risk factors for the occurrence and severity of ON.


Psychometric properties of the Turkish version of the Internet Addiction Test (IAT).
Of many instruments developed to assess Internet addiction, the Internet Addiction Test (IAT), an expanded version of the Internet Addiction Diagnostic Questionnaire (IADQ), has been the most widely used scale in English and non-English speaking populations. In this study, our aim was to investigate the psychometric properties of short and expanded versions of the IAT in a Turkish undergraduate sample. Overall, 455 undergraduate students from Turkey aged between 18 and 30 participated in the study (63.53% were females). Explanatory and confirmatory factor analytic procedures investigated factor structures of the IADQ and IAT. The Internet Addiction Scale (IAS), Coping Inventory for Stressful Situations (CISS), Obsessive Compulsive Inventory-Revised (OCI-R) and Dissociative Experiences Scale (DES) were administered to assess convergent and divergent validities of the IADQ and IAT. Internal consistency and 15-day test-retest reliability were computed. In the factorial analytic investigation, we found a unidimensional factor structure for each measure fit the current data best. Significant but weak to moderate correlations of the IADQ and the IAT with the CISS, OCI-R and DES provided empirical evidence for divergent validity, whereas strong associations with the subscales of the IAS pointed to the convergent validity of Young's Internet addiction construct. Internal consistency of the IADQ was weak (α=0.67) and of the IAT was high (α=0.93). Temporal reliability of both instruments was very high (α=0.81 and α=0.87; respectively). The IAT revealed promising and sound psychometric properties in a Turkish sample.


Silver nanoparticle-mediated enhancement in growth and antioxidant status of Brassica juncea.
Metal nanoparticles can potentially be used as tools for engineering biological redox reactions. Present study underlines the effect of silver metal nanoparticles (at 0, 25, 50, 100, 200 and 400 ppm) on the growth and antioxidant status of 7-day-old Brassica juncea seedlings. Fresh weight, root and shoot length, and vigor index of seedlings is positively affected by silver nanoparticle treatment. It induced a 326 % increase in root length and 133 % increase in vigor index of the treated seedlings. Improved photosynthetic quantum efficiency and higher chlorophyll contents were recorded in leaves of treated seedlings, as compared to the control seedlings. Levels of malondialdehyde and hydrogen peroxide decreased in the treated seedlings. Nanoparticle treatment induced the activities of specific antioxidant enzymes, resulting in reduced reactive oxygen species levels. Decrease in proline content confirmed the improvement in antioxidant status of the treated seedlings. The observed stimulatory affects of silver nanoparticles are found to be dose dependent, with 50 ppm treatment being optimum for eliciting growth response. Present findings, for the first time indicate that silver nanoparticles promote the growth of B. juncea seedlings by modulating their antioxidant status.


Endovascular repair of a giant common hepatic aneurysm.
Hepatic artery aneurysms are a rare phenomenon but their diagnosis and prompt treatment are imperative due to a high risk of mortality and complications. Appropriate management depends on patient characteristics, anatomical location of the aneurysm, operative risk and collateral arterial supply. Management options include surgical and endovascular approaches. The endovascular approach has gained popularity over recent years as it is an effective and less invasive alternative to surgical management. In this case report, we present a giant common hepatic artery aneurysm and its successful endovascular management. The patient had a complete resolution of symptoms after the procedure and remained well 8 months postprocedure.


Machine-learning approach to holographic particle characterization.
Holograms of colloidal dispersions encode comprehensive information about individual particles' three-dimensional positions, sizes and optical properties. Extracting that information typically is computationally intensive, and thus slow. Here, we demonstrate that machine-learning techniques based on support vector machines (SVMs) can analyze holographic video microscopy data in real time on low-power computers. The resulting stream of precise particle-resolved tracking and characterization data provides unparalleled insights into the composition and dynamics of colloidal dispersions and enables applications ranging from basic research to process control and quality assurance.


Natural killer cells in immunodefense against infective agents.
Following the discovery of innate immune receptors, the topics of innate immunity and its role in defense against infective agents have recently blossomed into very active research fields, after several decades of neglect. Among innate immune cells, natural killer (NK) cells are endowed with the unique ability to recognize and kill cells infected with a variety of pathogens, irrespective of prior sensitization to these microbes. NK cells have a number of other functions, including cytokine production and immunoregulatory activities. Major advances have recently been made in the understanding of the role of NK cells in the physiopathology of infectious diseases. The cellular and molecular mechanisms regulating the acquisition of effector functions by NK cells and their triggering upon pathogenic encounters are being unraveled. The possibility that the power of NK cells could be harnessed for the design of innovative treatments against infections is a major incentive for biologists to further explore NK cell subset complexity and to identify the ligands that activate NK cell receptors.


A case of intravascular large B cell lymphoma with brain involvement mimicking progressive multifocal leukoencephalopathy.
Intravascular large B-cell lymphoma (IVLBCL) is a very rare form of extranodal lymphoma, characterized by the proliferation of neoplastic B cells within the lumen of small vessels. Due to its high aggressivity, for years the prognosis had been really poor with only anectodical cases of remission after traditional chemotherapy. More recently, new therapeutic protocols allowed a significant increase in overall survival. It can virtually involve every organ, being skin and central nervous system the most affected. The clinical presentation is often unspecific and insidious; therefore, diagnosis can be challenging. Tissue biopsy, in particular random deep skin biopsy, is the gold standard for definitive diagnosis. We describe the case of a 58-year-old woman with a previous diagnosis of myelofibrosis, who presented with a rapidly progressive neurological deterioration and a brain MRI suggestive of Progressive Multifocal Leukoencephalopathy. Due to the absence of BK and JC viruses in cerebrospinal fluid and the presence of severe myalgias and subcutaneous nodules, a skin and muscle biopsy was performed, allowing diagnosis of IVLBCL. We describe the diagnostic pitfalls of this case, briefly reviewing existing literature about IVLBCL.


Demographic and clinical profiles of type 2 diabetes mellitus patients initiating sitagliptin in the real-world setting.
Dipeptidyl peptidase-4 (DPP-4) inhibitors have been used for the management of type 2 diabetes (T2D) for over a decade; however, there is a limited understanding of the evolution of their use in the real-world setting over this time period. This study evaluated the demographics and clinical characteristics of patients initiating sitagliptin over a 10 year period in the United States. Quintiles electronic medical records database was used to identify adults with a new prescription of sitagliptin over two 5 year time periods: 2006-2010 (n = 57,604), and 2011-2015 (n = 147,326). In addition, we also evaluated how the most recent (year 2015) profile of sitagliptin initiators (n = 29,295) compares to the treated T2D patients (N = 474,877) in 2015. No outcomes were assessed. Descriptive statistics were used to summarize baseline patient characteristics. The overall demographics and clinical characteristics of patients initiating sitagliptin were generally similar over the two time periods; however, baseline HbA1c (median) was higher in the later time period: 7.6% vs. 7.9% respectively. Sitagliptin was initiated in patients across a broad range of age (18-79) years, body mass index (BMI) (10-70) kg/m2 and HbA1c (3-20) %. The most prevalent comorbidities observed in these patients were hypertension (93%), hyperlipidemia (81%), obesity (55%), chronic kidney disease (22%) and cardiovascular disease (21%). Additionally, when we assessed the treated T2D patients and patients initiating sitagliptin in 2015, several characteristics were comparable such as age (median) (64 vs. 63) years and BMI (33 vs. 33) kg/m2, and the most prevalent comorbidities were hypertension (97 vs. 95) %, and hyperlipidemia (86 vs. 81) % respectively. The overall demographic and comorbidity profile of patients initiating sitagliptin did not substantially change over the last decade and is similar to the treated T2D population.


Jaw muscle activity during chin-tapping.
Electromyographic (EMG) activity was recorded from the masseter, the anterior temporal and the anterior digastric muscle on the right side of ten dental students when taps were administered upwards or downwards to the chin. The experiment was performed both with relaxed jaw muscles and with contracting depressor muscles. Pairs of intracutaneous platinum hook electrodes were used for the masseter and temporal muscles while concentric needle electrodes were inserted into the anterior digastric muscles. The mean latency of the jaw-jerk elicited in the relaxed masseter muscle when tapping downwards on the chin was 7.8 msec and in the temporal muscle 8.4 msec. The corresponding values of the latency during jaw opening against resistance from the investigator's finger was 8.2 msec and 9.0 msec. During upward tapping on the chin recordings from the anterior digastric muscle showed obvious changes in EMG activity, the latency ranging from 13 to 34 msec. Thus, compared to the latency of the jaw-jerk in the masseter and temporal muscles, which contain numerous muscle spindles, recordings from the anterior digastric muscle, where muscle spindles are thought to be either lacking or few in number, showed no signs of a monosynaptic reflex.


Serum interferon levels in patients with systemic lupus erythematosus.
Levels of interferon (IFN) were measured in 81 serum samples from 23 patients with systemic lupus erythematosus (SLE) by a plaque-reduction method and correlated retrospectively with clinical records of disease activity, anti-DNA binding, and serum complement measurements. IFN titers were found to correlate with both clinical disease activity and anti-DNA binding, but no relation was found to serum complement. Most (76.6%, 31 of 41) serum samples obtained during periods of active disease contained measureable amounts of IFN, but only 9.1% (2 of 22) of results of tests on samples obtained during periods of disease quiescence were positive (P less than 0.005). Of samples with clearly elevated anti-DNA binding (greater than 40%), 69.7% (23 of 33) had positive results for IFN, but 57.1% (8 of 14) had negative results when the anti-DNA binding was normal (less than 20%) (P less than 0.005). Measurement of serum IFN titers in patients with SLE, therefore, provides another serologic marker of disease activity. Contrary to the findings of previous studies, the IFN found in the present study was characterized as IFN-alpha, or Type I IFN, on the basis of acid stability and neutralization by antibody to IFN-alpha. Of interest are the questions raised about the origin of IFN in the sera of patients with SLE and what role IFN might have in the pathogenesis of the autoimmune disease in view of the many documented immunomodulating effects of IFN.