Isotachophoresis at pH extremes: theory and experimental validation.
The evolution of an isotachophoresis (ITP) system in acidic or basic pH ranges can be quite different from that predicted by the existing theory. It was found theoretically and proved experimentally that the contribution of hydrogen or hydroxyl ion to conductivity of solution and/or its net charge changes the behavior of the ITP system, creating in the terminating electrolyte an additional zone close to the initial interfaces between electrolytes (leader and terminator). One boundary of the zone, being either sharp or dispersed, moves toward the leader; the other is always sharp and stationary and coincides with initial electrolytes' discontinuity. The latter can be registered in the presence of electroosmotic flow which delivers it to the detection point. In order to describe the dynamics of the ITP system at pH extremes an algorithm of analytical solution was developed, based on the revised Kohlrausch theory. Its predictions coincide well with computer simulations and experimental data. The results presented can help in a correct analysis of ITP data and explain some confusing phenomena which were considered to be artifacts.


A Retrospective Study of the Clinical Characteristics and Post-treatment Hearing Outcome in Idiopathic Sudden Sensorineural Hearing Loss.
The purpose of this retrospective study was to analyze the clinical characteristics and document hearing recovery in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). 122 patients diagnosed with unilateral ISSNHL, from March 2009 to December 2014, were treated with oral steroids and pentoxifylline. Hearing change was evaluated by comparing pre-treatment and post-treatment pure-tone average (PTA) (500, 1K, and 2K Hz), and categorized into complete, partial, and no recovery of hearing. T-test, Wilcoxon Signed Rank test and Regression analysis were employed to analyze the statistical significance. Of the 122 patients, seventy-one (58%) had complete recovery and 34 (28%) had partial recovery. The average pre-treatment PTA was 78.3±16.9 dB whereas post-treatment average was 47.0±20.8 dB, showing statistically significant improvement (t=24.89, P≤0.001). The factors such as presence of tinnitus (P=0.005) and initial milder hearing loss (P=0.005) were found to be significant predictors for hearing recovery. Conventional steroid regimes produced a recovery rate in ISSNHL, which exceeds the spontaneous recovery rate. The current study results highlight the importance of medical treatment in the management of ISSNHL.


Preliminary mutational analysis of the human kinin B2 receptor for nonpeptide antagonist ligands recognition.
FR173657, LF16,0335, and LF16,0687 are nonpeptide antagonists, endowed with high affinity and selectivity for the human kinin B2 receptor. The kinin B2 receptor belongs to the family of G-protein-coupled receptors with seven transmembrane (TM) helices. In the present study, we aimed, through computer-assisted modeling and mutagenesis, to identify residues in the human B2 receptor (hB2R) amino acid sequence that are involved in nonpeptide antagonist binding in order to build up experimental data as a first step towards a molecular model of nonpeptide ligands binding site. Fourteen amino acid residues within the TM segments were mutated to alanine. The wild type and mutant receptors were stably expressed in Chinese hamster ovary (dhfr-) cells and tested for their ability to bind agonist ([3H]bradykinin) and peptide antagonist ([3H]MENI 1270) radioligands. The affinity of nonpeptide ligands was determined by heterologous competition experiments using the above radioligands. We found that some mutations in TM2 (W86A) and TM7 (Y295A, N297A) impair the binding affinity of the three nonpeptide antagonists. On the other hand, some mutated residues in TM3 (S1 17A) and TM6 (W256A) reduce the affinity of LF16,0335 and LF16,0687 only. Results are discussed in order to build up a hypothesis for the likely different interactions of various nonpeptide ligands with the B2 receptor.


Sensitivity of CAPD/IPD peritonitis organisms to ciprofloxacin.
Studies have suggested that oral quinolones may be useful in the treatment of peritonitis in peritoneal dialysis. We undertook a study of organisms causing peritonitis in our IPD and CAPD populations to determine if these organisms would be susceptible in vitro to Cipro. We determined the minimal inhibitory concentrations (MIC) of 62 non-duplicate isolates from episodes of peritonitis to Cipro by standard broth microdilution. Serial dilutions were done with Cipro and MIC50 and MIC90 were determined. The isolates were as follows: S, epidermidis (17), S. aureus (14), coliforms (11), Pseudomonas (8), Enterococci (8), Diphtheroids (4). The MIC50 and MIC90 for each of the isolate groups and overall are shown below.


Short and tall stature: a new paradigm emerges.
In the past, the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis was often considered to be the main system that regulated childhood growth and, therefore, determined short stature and tall stature. However, findings have now revealed that the GH-IGF-1 axis is just one of many regulatory systems that control chondrogenesis in the growth plate, which is the biological process that drives height gain. Consequently, normal growth in children depends not only on GH and IGF-1 but also on multiple hormones, paracrine factors, extracellular matrix molecules and intracellular proteins that regulate the activity of growth plate chondrocytes. Mutations in the genes that encode many of these local proteins cause short stature or tall stature. Similarly, genome-wide association studies have revealed that the normal variation in height seems to be largely due to genes outside the GH-IGF-1 axis that affect growth at the growth plate through a wide variety of mechanisms. These findings point to a new conceptual framework for understanding short and tall stature that is centred not on two particular hormones but rather on the growth plate, which is the structure responsible for height gain.


Curved Versus Flat Monitors: Interactive Effects of Display Curvature Radius and Display Size on Visual Search Performance and Visual Fatigue.
The aim of this study is to examine the interactive effects of display curvature radius and display size on visual search accuracy, visual search speed, and visual fatigue. Although the advantages of curved displays have been reported, little is known about the interactive effects of display curvature radius and size. Twenty-seven individuals performed visual search tasks at a viewing distance of 50 cm using eight configurations involving four display curvature radii (400R, 600R, 1200R, and flat) and two display sizes (33″ and 50″). To simulate curved screens, five flat display panels were horizontally arranged with their centers concentrically repositioned following each display curvature radius. For accuracy, speed, and fatigue, 33″-600R and 50″-600R provided the best or comparable-to-best results, whereas 50″-flat provided the worst results. For accuracy and fatigue, 33″-flat was the second worst. The changes in the horizontal field of view and viewing angle due to display curvature as well as the association between effective display curvature radii and empirical horopter (loci of perceived equidistance) can explain these results. The interactive effects of display curvature radius and size were evident for visual search performance and fatigue. Beneficial effects of curved displays were maintained across 33″ and 50″, whereas increasing flat display size from 33″ to 50″ was detrimental. For visual search tasks at a viewing distance of 50 cm, 33″-600R and 50″ 600R displays are recommended, as opposed to 33″ and 50″ flat displays. Wide flat displays must be carefully considered for visual display terminal tasks.


Notes on sugar feeding and selected wild mammalian hosts of black flies (Diptera: Simuliidae) in Newfoundland.
This study, done on the Avalon Peninsula, Newfoundland, identified selected wild mammalian hosts and quantified the incidence of sugar feeding for several species (species complexes) of black flies. Female flies were taken from fox, snowshoe hare, lynx, caribou, and human baits. Simulium truncatum/venustum complex females took blood from fox, lynx, rabbit, and caribou and were frequently taken in sweep net collections around humans. Blood-fed females of the Simulium rostratum/verecundum complex were collected only from caribou, were rarely attracted to the other mammalian baits, and were not attracted to humans. Although most females had sugar-free before seeking a host, significant interspecific differences in the incidence of fructose-positive females were found among the four species (species complexes) examined (Prosimulium mixtum, 92.9%; S. truncatum/venustum complex, 87.4%; Stegopterna mutata (triploid cytospecies), 83.3%; Simulium vittatum complex, 67.4%). No significant differences were found in the proportion of sugar-fed flies among three habitats examined (forest, scrubland, and pasture) for either P. mixtum or the S. truncatum/venustum complex. However, the percentage of sugar-fed S. truncatum/venustum complex females was significantly higher in the evening than in the morning. Time of day did not influence the incidence of sugar-fed P. mixtum.


One-pot construction of functional mesoporous silica nanoparticles for the tumor-acidity-activated synergistic chemotherapy of glioblastoma.
Mesoporous silica nanoparticles (MSNs) have proved to be an effective carrier for controlled drug release and can be functionalized easily for use as stimuli-responsive vehicles. Here, a novel intelligent drug-delivery system (DDS), camptothecin (CPT)-loaded and doxorubicin (DOX)-conjugated MSN (CPT@MSN-hyd-DOX), is reported via a facile one-pot preparation for use in synergistic chemotherapy of glioblastoma. DOX was conjugated to MSNs via acid-labile hydrazone bonds, and CPT was loaded in the pores of the MSNs. At pH 6.5 (analogous to the pH in tumor tissues), a fast DOX release was observed that was attributed to the hydrolysis of the hydrazone bonds. In addition, a further burst release of DOX was found at pH 5.0 (analogous to the pH in lyso/endosomes of tumor cells), leading to a strong synergistic effect. In all, CPT and DOX could be delivered simultaneously into tumor cells, and this intelligent DDS has great potential for tumor-trigged drug release for use in the synergistic chemotherapy of tumors.


An unusual case of concordant ventriculoarterial connections, subpulmonary infundibulum, and parallel arterial trunks: a diagnostic challenge.
We present an unusual case of concordant ventriculoarterial connections, subpulmonary infundibulum, and parallel arterial trunks. This case was complicated by extreme pulmonary artery tortuosity and low arching aorta causing severe tracheal compression. We discuss the difficulty in prenatal diagnosis, necessity for advanced imaging postnatally, and associated airway complications.


[Frostbite animal model preparation specification(draft)].
Frostbite is a common disease in winter, and systemic or local injury caused by low temperature invasion. Frostbite sites are commonly face, ears, nose, hands, feet and other peripheral blood circulation parts. The main symptoms are pale skin, cold, pain and numbness, skin itching in high temperature, and severe cases may suffer from skin erosions and ulcers. Frostbite model is a pathological model mainly based on Western medicine index. Based on the analysis of clinical symptoms of frostbite in traditional Chinese medicine and western medicine, and a large number of experimental studies on the existing animal models, the animal model preparation of specifications (draft) was formulated as follows.


Influences of season, parity, lactation, udder area, milk yield, and clinical symptoms on intramammary infection in dairy cows.
The aim of this study was to evaluate the influences of season, parity, lactation, udder area, milk yield, and clinical symptoms on bacterial intramammary infection (IMI) in dairy cows. A total of 2,106 mastitis pathogens in 12 species were isolated from 125 dairy farms distributed in 30 different cities in China, and the information about these factors was recorded at the same time. Mastitis pathogens were isolated from 63.43% of the milk samples, whereas Streptococcus agalactiae accounted for 38.61% of all pathogens, followed by Str. dysgalactiae (28.16%), Staphylococcus aureus (19.10%), Escherichia coli (6.90%), and other pathogens (7.23%). According to our investigation, IMI was more common in spring with the isolation rate of pathogens at 81.04%, and lowest in winter (52.34%). Cows were more likely to be infected by environmental pathogens (E. coli or Str. uberis) in summer, in rear quarters and in cows with higher daily milk yield or lower somatic cell count. In addition, Str. dysgalactiae exhibited a higher prevalence with increased parity. Different clinical symptoms of quarters with bacterial IMI were seen in this study, and mastitis pathogens were isolated from healthy quarters.


The inflammatory cytokine effect of Pam3CSK4 TLR2 agonist alone or in combination with Leishmania infantum antigen on ex-vivo whole blood from sick and resistant dogs.
A wide spectrum of clinical manifestations and immune responses exist in canine L. infantum infection. Ibizan hounds are more "resistant" to disease than other dog breeds. Recognition of pathogen-associated molecule patterns by toll like receptors (TLRs) rapidly triggers a variety of anti-microbial immune responses through the induction of pro-inflammatory cytokines such as TNF-α and IL-6 which may play an important role in controlling Leishmania infection. The main objective of this study was to investigate and compare the effect of a TLR2 agonist (TLR2a) alone or in combination with L. infantum antigen (LSA) on ex vivo whole blood cytokine production from healthy seronegative IFN-γ non-producer dogs from an area of low in canine leishmaniosis endemicity (n = 11); sick seropositive dogs with low production of IFN-γ (n = 17) and healthy seronegative or low positive Ibizan hounds with a predominant IFN-γ production (n = 21) from a highly endemic area. Whole blood was stimulated with medium alone (Ø), LSA, concanavalin A, TLR2 (Pam3CSK4) receptor agonist (Ø + TLR2a) and TLR2a and LSA (LSA + TLR2a) for 48 h. Supernatants were harvested for measurement of canine TNF-α and IL-6 cytokines by ELISA. A significant increase of TNF-α was found in the supernatants of stimulated blood from all groups (Ø + TLR2a and LSA + TLR2a) when compared with medium alone. A similar pattern was observed for IL-6. Interestingly, a significant increase of TNF-α production was only observed when stimulation with LSA + TLR2a was compared with TLR2a alone in Ibizan hounds. A significant increase of TNF-α production was observed with stimulation of LSA + TLR2a when compared with LSA in all groups. Significantly higher concentrations of TNF-α and IL-6 were detected in Ibizan hounds, especially for the Ø + TLR2a and LSA + TLR2a treatments compared with other groups. This study demonstrated that TLR2a alone enhances the production of the inflammatory cytokines TNF-α and IL-6 in sick, "resistant" and healthy non-infected dogs. In addition, a combination of LSA+TLR2a promoted a synergistic pro-inflammatory effect with TNF-α in Ibizan hounds but not in seropositive sick dogs and seronegative healthy dogs. These findings might suggest the importance of Pam3CSK4 as a possible immunomodulator for CanL.


Vitamin A-coupled liposomes containing siRNA against HSP47 ameliorate skin fibrosis in chronic graft-versus-host disease.
Chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) is characterized by multiorgan fibrosis and profoundly affects the quality of life of transplant survivors. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, plays a critical role in collagen synthesis in myofibroblasts. We explored the role of HSP47 in the fibrotic process of cutaneous chronic GVHD in mice. Immunohistochemical analysis showed massive fibrosis with elevated amounts of collagen deposits and accumulation of F4/80+ macrophages, as well as myofibroblasts expressing HSP47 and retinol-binding protein 1 in the skin after allogeneic SCT. Repeated injection of anti-colony-stimulating factor (CSF-1) receptor-blocking antibodies significantly reduced HSP47+ myofibroblasts in the skin, indicating a macrophage-dependent accumulation of myofibroblasts. Vitamin A-coupled liposomes carrying HSP47 small interfering RNA (siRNA) (VA-lip HSP47) delivered HSP47 siRNA to cells expressing vitamin A receptors and knocked down their HSP47 in vitro. Intravenously injected VA-lip HSP47 were specifically distributed to skin fibrotic lesions and did not affect collagen synthesis in healthy skin. VA-lip HSP47 knocked down HSP47 expression in myofibroblasts and significantly reduced collagen deposition without inducing systemic immunosuppression. It also abrogated fibrosis in the salivary glands. These results highlight a cascade of fibrosis in chronic GVHD; macrophage production of transforming growth factor β mediates fibroblast differentiation to HSP47+ myofibroblasts that produce collagen. VA-lip HSP47 represent a novel strategy to modulate fibrosis in chronic GVHD by targeting HSP47+ myofibroblasts without inducing immunosuppression.


Total flavonoid concentrations of bryophytes from Tianmu Mountain, Zhejiang Province (China): Phylogeny and ecological factors.
The flavonoids in bryophytes may have great significance in phylogeny and metabolism research. However, to date there has been little research on bryophyte metabolites, especially flavonoids. To redress this somewhat, we determined flavonoid concentrations of bryophytes from Tianmu Mountain through a colorimetric assay and considered the factors influencing the results. This is the first time that the flavonoid contents of bryophytes have been examined in detail. The results revealed a range of total flavonoid concentrations in 90 samples collected from Tianmu Mountain from 1.8 to 22.3 mg/g (w/w). The total flavonoid contents of liverworts were generally higher than those of mosses; acrocarpous mosses had generally higher values than that of pleurocarpous mosses. The total flavonoid contents of bryophytes growing at lower light levels were general higher than those growing in full-sun. The total flavonoid contents of epiphytic bryophytes were highest, while those of aquatic bryophytes were the lowest. Total flavonoid contents of species growing at low-latitudes were much higher than those at high-latitude individuals. In conclusion, total flavonoid contents of bryophytes have some connection with plant phylogeny; more flavonoids might be contained in relatively primitive bryophytes. Meanwhile, the effects of ecological factors on total flavonoid contents of bryophytes exist; light and habitat (especially tree habitat and river habitat) might be representative factor.


Structure and function relations with a T-cell-activating polysaccharide antigen using circular dichroism.
Studies centered on understanding how molecular structure affects biological function have historically focused on proteins. Circular dichroism (CD) is commonly used to analyze protein secondary structure, yet its application to other molecules is far less explored. In fact, little is known about how glycan conformation might affect function, likely because of a lack of tools for measuring dynamic structural changes of carbohydrates. In the present study, we developed a method based on CD to monitor conformational changes in the zwitterionic T-cell-activating glycoantigen polysaccharide A1 (PSA). We found that PSA helical structure produces a CD spectrum that is strikingly similar to proteins rich in alpha-helical content and is equally sensitive to nonpolar solvents. Like conventional T-cell-dependent proteins, PSA requires processing before major histocompatibility complex class II (MHCII) binding. CD spectra of PSA fragments of varying sizes indicated that fragments smaller than three repeating units lack helical content and are incapable of MHCII binding. Likewise, neutralization of charged groups in the repeating unit resulted in major conformational changes as measured by CD, which correlated with a lack of MHCII presentation. These data represent two significant findings: CD can be used to measure conformational changes in carbohydrates and the functional epitope from PSA is dependent on a specific conformation that is stabilized by adjacent repeating units and a zwitterionic charge motif. As a result, this work demonstrates that CD is a valuable tool for use in functional glycomics efforts that seek to align chemical and conformational structure with biological activity.


Denervation of the painful temporomandibular joint.
The successful management of temporomandibular joint (TMJ) pain remains elusive. Often the initial relief of pain is complicated by recurrence of the symptoms. This time frame suggests that the pain may be related to neuromas of the nerves that innervate the TMJ. In 2003, an anatomic description of the innervation of the TMJ suggested that denervation of this joint might be the appropriate treatment for pain resistant to traditional forms of therapy. In January, 2005, this approach was used to treat recalcitrant left TMJ pain in a 21-year-old woman with congenital hearing loss who had recurrent dislocations of her TMJ articular disc. She previously had two arthroscopic surgeries and one open attempt to treat her TMJ pain. The last failed TMJ surgery created a painful neuroma that prevented her from wearing her hearing aid. A medial and lateral denervation of the TMJ joint was done. The successful results of this surgery are presented at one-year follow-up. The technical considerations of this approach and risk to the facial nerve are discussed.


Sensitive LC-MS/MS Method for the Simultaneous Determination of Bendamustine and its Active Metabolite, γ-Hydroxybendamustine in Small Volume Mice and Dog Plasma and its Application to a Pharmacokinetic Study in Mice and Dogs.
A highly sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the simultaneous quantification of bendamustine (BM) and γ-hydroxybendamustine (HBM) in small volume (20 µL) mice and dog plasma using phenacetin as an internal standard (IS) as per regulatory guidelines. Both the analytes and IS were extracted from mice and dog plasma using a liquid-liquid extraction method. Chromatography was achieved on Atlantis dC18 column using an isocratic mobile phase (0.2% formic acid:acetonitrile, 25:75) at a flow rate of 0.40 mL/min. The total chromatographic run time was 3.0 min and the elution of BM, HBM and IS occurred at ~1.2, 1.2 and 2.0 min, respectively. A linear response function was established 0.11-518 ng/mL for both the analytes in mice and dog plasma. The intra- and inter-day accuracy and precisions were in the range of 3.46-12.9 and 3.63-8.23%; 1.15-9.00 and 7.86-9.49% for BM and HBM, respectively in mice plasma and 2.15-6.49 and 1.73-13.1%; 4.35-13.9 and 4.33-10.5% for BM and HBM, respectively in dog plasma. This novel method has been applied to a pharmacokinetic study in mice and dogs.


[Genetic diversity and phylogeographic distribution of SIV: how to understand the origin of HIV].
Emergence of human immunodeficiency viruses HIV-1 and HIV-2 results from interspecies transmission from simian viruses SIV. SIVcpzPtt infecting chimpanzees, and from which the HIV-1 (subgroups M and N) is derived is still found in the Pan troglodytes troglodytes population of south Cameroon chimpanzees. The ancestor of HIV-1 group O, is found in the Gorilla residing in Western Africa, but chimpanzees are in fact the initial reservoir of the SIV viruses SIVgor, and it is still unclear whether the group O HIV-1 has been transmitted to humans by gorillas and/or chimpanzees. At least eight interspecies transmissions between and humans implicating SIVsmm (from sooty mangabey monkeys) have occurred, corresponding to the eight VIH-2 groups. Since habits of hunting and meat preparation in the bush still persistently expose humans in Africa to SIV infection, new interspecies transmission of these viruses remains a possibility.


A randomized controlled noninferiority trial comparing radiofrequency with stripping and conservative hemodynamic cure for venous insufficiency technique for insufficiency of the great saphenous vein.
The quality of available evidence regarding new minimally invasive techniques to abolish great saphenous vein reflux is moderate. The present study assessed whether radiofrequency ablation (RFA) was noninferior to high ligation and stripping (HLS) and conservative hemodynamic cure for venous insufficiency (CHIVA) for clinical and ultrasound recurrence at 2 years in patients with primary varicose veins (VVs) due to great saphenous vein (GSV) insufficiency. We performed a randomized, single-center, open-label, controlled, noninferiority trial to compare RFA and 2 surgical techniques for the treatment of primary VVs due to GSV insufficiency. The noninferiority margin was set at 15% for absolute differences. Patients aged >18 years with primary VVs and GSV incompetence, with or without clinical symptoms, C2 to C6 CEAP (Clinical, Etiologic, Anatomic, Pathophysiologic) clinical class, and GSV diameter >4 mm were randomized with a 1:1:1 ratio to RFA, HLS, or CHIVA. The rate of clinical recurrence at 24 months was the primary endpoint and was analyzed using a delta noninferiority margin of 15%. Ultrasound recurrence, safety, and quality of life were secondary endpoints. From December 2012 to June 2015, 225 limbs had been randomized to RFA, HLS, or CHIVA (n = 74, n = 75, and n = 76). Clinical follow-up and Doppler ultrasound examinations were performed at 1 week and 1, 6, 12, and 24 months postoperatively. No differences in postoperative complications or pain were observed among the three groups. RFA was noninferior to HLS and CHIVA for clinical recurrence at 24 months, with an estimated difference in recurrence of 3% (95% confidence interval [CI], -4.8% to 10.7%; noninferiority P = .002) and -7% (95% CI, -17% to 3%; P < .001), respectively. For ultrasound recurrence, RFA was noninferior to CHIVA, with an estimated difference of -34% (95% CI, -47% to -20%; noninferiority P < .001) at 24 months. However, noninferiority could not be demonstrated compared with HLS (5.9%; 95% CI, -4.1 to 15.9; P = .073). No differences were found in quality of life among the three groups. RFA was shown to be noninferior in terms of clinical recurrence to HLS and CHIVA in the treatment of VVs due to GSV insufficiency.


Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation.
Tumor necrosis factor-alpha (TNF-alpha) is an important inflammation cytokine without known direct effect on DNA. In this study, we found that TNF-alpha can cause DNA damages through reactive oxygen species. The mutagenic effect of TNF-alpha is comparable with that of ionizing radiation. TNF-alpha treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation, and chromosomal instability. Antioxidants significantly reduced TNF-alpha-induced genetic damage. TNF-alpha also induced oxidative stress and nucleotide damages in mouse tissues in vivo. Moreover, TNF-alpha treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. As TNF-alpha is involved in chronic inflammatory diseases, such as chronic hepatitis, ulcerative colitis, and chronic skin ulcers, and these diseases predispose the patients to cancer development, our results suggest a novel pathway through which TNF-alpha promotes cancer development through induction of gene mutations, in addition to the previously reported mechanisms, in which nuclear factor-kappaB activation was implicated.


An intensive care unit in a rural area.
Factors that governed the setting up of a multipurpose, temporary Intensive Care Unit of six beds, in a remote area of Malaysia and the experience of operating it for more than two and a half years are outlined.


Addison's Disease Mimicking as Acute Pancreatitis: A Case Report.
Over past two decades there has been significant improvement in medical field in elucidating the underlying pathophysiology and genetics of Addison's disease. Adrenal insufficiency (Addison's disease) is a rare disease with an incidence of 0.8/100,000 cases. The diagnosis may be delayed if the clinical presentation mimics a gastrointestinal disorder or psychiatric illness. We report a case of Addison's disease presenting as acute pain in abdomen mimicking clinical presentation of acute pancreatitis.


Outcome of arthrodesis of the hindfoot as a salvage procedure for complex ankle pathology using the Ilizarov technique.
Achieving arthrodesis of the ankle can be difficult in the presence of infection, deformity, poor soft tissues and bone loss. We present a series of 48 patients with complex ankle pathology, treated with the Ilizarov technique. Infection was present in 30 patients and 30 had significant deformity before surgery. Outcome was assessed clinically and with patient-reported outcome measures (Modified American Orthopaedic Foot and Ankle Society (MAOFAS) scale and the Short-Form (SF-36)). Arthrodesis was achieved in 40 patients with the Ilizarov technique alone and in six further patients with additional surgery. Infection was eradicated in all patients at a mean follow-up of 46.6 months (13 to 162). Successful arthrodesis was less likely in those with comorbidities and in tibiocalcaneal fusion compared with tibiotalar fusion. These patients had poor general health scores compared with the normal population before surgery. The mean MAOFAS score improved significantly from 24.3 (0 to 90) pre-operatively to 56.2 (30 to 90) post-operatively, but there was only a modest improvement in general health; the mean SF-36 improved from 44.8 (19 to 66) to 50.1 (21 to 76). There was a major benefit in terms of pain relief. Arthrodesis using the Ilizarov technique is an effective treatment for complex ankle pathology, with good clinical outcomes and eradication of infection. However, even after successful arthrodesis general health scores remain limited.


Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.
The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol.


In vitro anti-foot-and-mouth disease virus activity of magnesium oxide nanoparticles.
Foot-and-mouth disease (FMD) is an extremely contagious viral disease of cloven-hoofed animals that can lead to huge economic losses in the livestock production. No antiviral therapies are available for treating FMD virus (FMDV) infections in animals. The antiviral effects of magnesium oxide nanoparticles (MgO NPs) on the FMDV were investigated in cell culture. The viability of the cells after MgO NP treatment was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The direct effects of MgO NPs on the FMDV in extracellular (virucidal assay) and also different stages of virus replication (antiviral assay) were evaluated by plaque reduction assay. The results showed that MgO NPs were safe at concentrations up to 250 µg/ml in the Razi Bovine kidney cell line. The treatments with NPs indicated that the MgO NPs exerted in vitro virucidal and antiviral activities. Plaque reduction assay revealed that MgO NPs can inhibit FMDV by more than 90% at the early stages of infection such as attachment and penetration but not after penetration. The results of this study suggested that NPs might be applied locally as an antiviral agent in early stages of infection in susceptible animals.


Pulmonary tumor thrombotic microangiopathy induced by ureteral carcinoma: a necropsy case report.
Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related pulmonary complication with rapidly progressing dyspnea and pulmonary hypertension that occasionally induces sudden death. We report the first case of PTTM induced by ureter carcinoma. The patient was an 80-year-old Japanese female with chief complaints of dry cough and dyspnea. An echocardiogram revealed severe pulmonary hypertension. A chest radiograph showed ground glass opacity of bilateral lower lung field predominance, and an abdominal computed tomography scan revealed a left ureter mass suggestive of ureter carcinoma. The patient died of respiratory failure on the eighth day of hospitalization. Postmortem examination indicated that the primary lesion was a left ureter cancer with tumor microemboli extending to both lungs through the right side of the heart. The final diagnosis of this case was PTTM induced by ureter carcinoma. The pathogenesis and pathophysiology of PTTM remains obscure with no effective management available. In cases of rapidly progressing respiratory failure with pulmonary hypertension, it is necessary to consider PTTM in the differential diagnosis.


Standard versus extralevator abdominoperineal excision and oncologic outcomes for patients with distal rectal cancer: A meta-analysis.
The role of extralevator abdominoperineal excision (ELAPE) for distal rectal cancer remains controversial, and the procedure is not widely accepted or practiced. An electronic search of Medline, EMBASE, Web of Science, and similar databases for articles in English was performed from the inception of the study until October 31, 2017. Two reviewers extracted information and independently assessed the quality of included studies by the methodological index for nonrandomized studies, then data were analyzed with Review Manager 5.3 software and Stata version 12.0 software. Our meta-analysis included 17 studies with 3479 patients, of whom 1915 (55.0%) underwent ELAPE and 1564 (44.0%) underwent abdominoperineal excision (APE). Compared with patients undergoing APE, patients undergoing ELAPE had a significant reduced risk of no more than 3 years local recurrence (LR) (risk ratio [RR] = 0.27, 95% confidence interval [CI] = 0.08-0.94), 3-year mortality (odds ratio [OR] = 0.45, 95% CI = 0.20-0.97), intraoperative bowel perforation (IBP) involvement (RR = 0.48, 95% CI = 0.31-0.74), and circumferential resection margin (CRM) positivity (RR = 0.66, 95% CI = 0.43-1.00) at the threshold level. The application of ELAPE is more effective in reducing the chance of 3 years LR, mortality, IBP involvement and CRM positivity than conventional APE, and worthy of being widely applied in surgical treatment of the distal rectal cancer.


Beta-hydroxyaspartic acid in vitamin K-dependent plasma proteins from scorbutic and warfarin-treated guinea pigs.
beta- Hydroxyaspartic acid is a rare amino acid, present in all vitamin K-dependent plasma proteins except prothrombin, and is formed by a post-translational hydroxylation of aspartic acid. We have now investigated whether this hydroxylation, like that of proline in collagen, is vitamin C-dependent. The vitamin K-dependent plasma proteins were isolated from normal and scorbutic guinea pig plasma by barium citrate adsorption and the beta- hydroxyaspartic acid content was determined. Compared with normal animals, scorbutic animals showed no significant reduction of beta- hydroxyaspartic acid content. In warfarin-treated animals there was a decreased content of both beta- hydroxyaspartic acid and gamma-carboxyglutamic acid in the barium citrate adsorbed fraction. It was concluded that the post-translational hydroxylation of aspartic acid is unlikely to be vitamin C-dependent.


Eradicating Barriers to Mental Health Care Through Integrated Service Models: Contemporary Perspectives for Psychiatric-Mental Health Nurses.
There has been renewed, global interest in developing new and transformative models of facilitating access to high-quality, cost-effective, and individually-centered health care for severe mentally-ill (SMI) persons of diverse racial/ethnic, cultural and socioeconomic backgrounds. However, in our present-day health-service delivery systems, scholars have identified layers of barriers to widespread dispersal of well-needed mental health care both nationally and internationally. It is crucial that contemporary models directed at eradicating barriers to mental health services are interdisciplinary in context, design, scope, sequence, and best-practice standards. Contextually, nurses are well-positioned to influence the incorporation and integration of new concepts into operationally interdisciplinary, evidence-based care models with measurable outcomes. The aim of this concept paper is to use the available evidence to contextually explicate how the blended roles of psychiatric mental health (PMH) nursing can be influential in eradicating barriers to care and services for SMI persons through the integrated principles of collaboration, integration and service expansion across health, socioeconomic, and community systems. A large body of literature proposes that any best-practice standards aimed at eliminating barriers to the health care needs of SMI persons require systematic, well-coordinated interdisciplinary partnerships through evidence-based, high-quality, person-centered, and outcome-driven processes. Transforming the conceptual models of collaboration, integration and service expansion could be revolutionary in how care and services are coordinated and dispersed to populations across disadvantaged communities. Building on their longstanding commitment to individual and community care approaches, and their pivotal roles in research, education, leadership, practice, and legislative processes; PMH nurses are well-positioned to be both influential and instrumental in the development of innovative, revolutionary, and transformative paradigmatic models aimed at eradicating treatment barriers, promoting well-being, and reducing preventable mortalities and morbidities among SMI persons.


Severe in utero under-virilization in a 46,XY patient with Silver-Russell syndrome with 11p15 loss of methylation.
Background Silver-Russell syndrome (SRS) is characterized by growth retardation and variable features including macrocephaly, body asymmetry, and genital manifestations such as cryptorchidism in 46,XY patients. Case presentation The patient was born at 39 weeks with a birth weight of 1344 g. Subtle clitoromegaly warranted a thorough evaluation, which disclosed 46,XY karyotype, bilateral undescended testes, and a rudimentary uterus. Because of severe under-virilization, the patient was assigned as female. Failure to thrive, macrocephaly, and body asymmetry led to the diagnosis of SRS, confirmed by marked hypomethylation of H19/IGF2 intergenic differentially methylated region (IG-DMR). From age 9 years, progressive virilization occurred, which necessitated luteinizing hormone-releasing hormone analog (LHRHa) treatment. Gonadal resection at 15 years revealed immature testes with mostly Sertoli-cell-only tubules. Panel analysis for 46,XY-differences of sex development (DSD) failed to detect any pathogenic variants. Conclusions This is the second reported case of molecularly proven 46,XY SRS accompanied by severe under-virilization. SRS should be included in the differential diagnosis of 46,XY-DSD.


Removal of lignin and reuse of cellulases for continuous saccharification of lignocelluloses.
Method of the removal of lignin and reuse of cellulases for a continuous saccharification of lignocelluloses were investigated. Only lignin could be separated from hydrolysates by differences in the settling velocity; it was removed from the saccharification process by flocculation with chitosan without loss of cellulases. The ultra-filtration membrane PM10 (Amicon) could be used for recovery of cellulases, but the membrane UH-1 (Toyo Roshi) was better for this purpose, because no cellulases leaked from the membrane, and the amount of cellulase adsorbed to the membrane was less. The cellulases were inactivated by vigorous agitation of the solution in an ultra-filtration device. The loss of cellulase activity by such agitation increased with agitation time, but could be controlled by recovery at a low speed of agitation, so the cellulases could be reused.


Characterization and strain identification of a potato virus Y isolate non-reactive with monoclonal antibodies specific to the ordinary and necrotic strains.
An isolate of potato virus Y, named PVY-36, reacted with polyclonal antibody against PVY-O (an ordinary strain), but not with any of eight monoclonal antibodies (MAbs) specific to PVY-O or with two MAbs specific to PVY-T (a necrotic strain). From its host range and symptomatology, PVY-36 belongs to the PVYO group. The nucleotide sequence of the coat protein (CP) coding region of the PVY-36 genome was determined and the amino acid sequence was predicted. Based on the CP amino acid sequence, PVY-36 is more closely related to PVY-O than to PVY-T. There were eight amino acid differences between the CPs of PVY-36 and PVY-O in the N-terminal 30 amino acids. It is suggested that amino acids 8-15 and/or 26-30 from the N-terminus may determine a PVY-O-specific epitope (or epitopes).


The dental care of U.S. children: access, use and referrals by nondentist providers, 2003.
Improvements in oral health care services have not reached evenly across every segment of American society. The authors examine the role of nondentist practitioners in referring child patients for dental care by analyzing data from the 2003 Medical Expenditure Panel Survey conducted by the Agency for Healthcare Research and Quality and the National Center for Health Statistics. The authors provide national estimates of the percentage of the civilian noninstitutionalized population of the United States aged 2 through 17 years who had a dental visit, who had a dental checkup and who received advice from a nondentist health care provider to have a dental checkup. Overall, 38 percent of all poor, near-poor or low-income children and 60 percent of all middle- or high-income children aged 2 through 17 years reported having had a dental checkup during 2003. The authors observed no significant differences between poor, near-poor and low-income children and higher-income children in terms of having been advised by a nondentist health care provider to have a dental checkup. Although income may not predict the likelihood of patients' receiving advice from a nondentist health care provider to have a dental checkup, children from families with higher levels of income were more likely to seek dental care than were children from families with lower levels of income. Practice Implications. Efforts to increase access to dental care should aim to maximize the benefit of advice provided by nondentist health care practitioners to receive a dental checkup, so that children from families with limited income are as likely to receive a dental checkup as are children from families with higher levels of income.


Bone mineral deficiency as the main factor of dolichocephalic head flattening in very-low-birth-weight infants.
We hypothesized that the postnatally reduced rate of bone mineralization observed in many very-low-birth-weight (VLBW) infants is the main cause of dolichocephalic flattening of the head in this group of newborns. We measured head shape by using the ratio of the frontooccipital and biparietal diameters, bone mineral content (BMC) at the right midhumerus, birth weight, body weight, and postnatal age at the time of BMC measurement in 85 newborn infants during the first 5 d of life (gestational age: median 34 wk, range 24-40 wk; birth weight: median 1.590 g, range 430-6.730 g) and in 269 VLBW infants at transfer to other hospitals or discharge. The head shape shortly after birth was not influenced by gestational age. Mean frontooccipital diameter/biparietal diameter was 1.27 +/- 0.73 SD (range 1.13-1.59). Stepwise multiple regression analysis from 315 measurements made in 46 VLBW infants during the first 5 d after birth and the 269 infants at discharge revealed a 27% contribution of BMC/body weight to the variation in head shape. The other variables had only a small effect (gestational age 4%, body weight 1%) or no observable effect on head shape. At discharge, the ratio of BMC to body weight was significantly lower than in the reference fetuses of the same body weight. The results support the hypothesis, and we speculate that there is a causal relationship between the head shape of VLBW infants at discharge and the amount of calcium and phosphorus given as a supplement until that time.


Influences on children's attitudes toward alcohol consumption.
To determine whether children's attitudes toward alcohol consumption changed as they grew older and to what extent peers might influence the decision to drink alcoholic beverages. A cross-sectional descriptive study of 500 children ages 8-15 years was performed using a questionnaire. Data analysis included descriptive statistics and contingency analysis. Age was the only variable significantly related to decision making. Attitudes toward alcohol were more favorable in older children. Peer influence did not appear to affect drinking behavior. Older children (ages 14-15) are more favorably disposed to drinking than younger children. Children may be more influenced by parents than is realized. Parental guidance just prior to age 14 may be an effective intervention.


Xinping Wang.
"Chemistry is fun because it is a changing art. … My favorite time of day is sunset …" Find out more about Xinping Wang in his Author Profile.


A Feasibility Study of Quantitative Motor Assessments in Children Using the Q-Motor Suite.
Q-Motor is utilized across various clinical trials in adults with Huntington's disease (HD) to provide quantitative, reliable assessments of motor abilities. With gene-knockdown therapies entering the clinic, development of preventative therapies for pediatric carriers of the HD mutation seems imminent. It is currently unclear if Q-Motor is useful for tracking changes in motor abilities in pediatric HD patients or at-risk youth, as most assessments have never been administered in children. We demonstrate the feasibility of administering Q-Motor tasks in a sample of children recruited from the community, and we show that Q-Motor is sensitive to age-related changes in motor abilities.


Mfge8 is expressed by pericytes in gastric antrum submucosa from patients with obesity.
The main function of the stomach is to digest ingested food. Gastric antrum muscular contractions mix ingested food with digestive enzymes and stomach acid and propel the chyme through the pyloric sphincter at a rate in which the small intestine can process the chyme for optimal nutrient absorption. Mfge8 binding to α8β1 integrins helps regulate gastric emptying by reducing the force of antral smooth muscle contractions. The source of Mfge8 within gastric muscles is unclear. Since Mfge8 is a secreted protein, Mfge8 could be delivered via the circulation, or be locally secreted by cells within the muscle layers. In this study, we identify a source of Mfge8 within human gastric antrum muscles using spatial transcriptomic analysis. We show that Mfge8 is expressed in subpopulations of Mef2c+ perivascular cells within the submucosa layer of the gastric antrum. Mef2c is expressed in subpopulations of NG2+ and PDGFRB+ pericytes. Mfge8 is expressed in NG2+/Mef2c+ pericytes, but not in NG2+/Mef2c-, PDGFRB+/Mef2c-, or PDGFRB+/Mef2c+ pericytes. Mfge8 is absent from CD34+ endothelial cells but is expressed in a small population of perivascular ACTA2+ cells. We also show that α8 integrin is not expressed by interstitial cells of Cajal (ICC), supporting the findings that Mfge8 attenuates gastric antrum smooth muscle contractions by binding to α8β1 integrins on enteric smooth muscle cells. These findings suggest a novel, supplementary mechanism of regulation of gastric antrum motility by cellular regulators of capillary blood flow, in addition to the regulation of gastric antrum motility by the enteric nervous system and the SMC, ICC, and PDGFRα+ cell (SIP) syncytium.


Developmental etiology for neuroanatomical and cognitive deficits in mice overexpressing Galphas, a G-protein subunit genetically linked to schizophrenia.
Schizophrenia is a widespread psychiatric disorder, affecting 1% of people. Despite this high prevalence, schizophrenia is not well treated because of its enigmatic developmental origin. We explore here the developmental etiology of endophenotypes associated with schizophrenia using a regulated transgenic approach in mice. Recently, a polymorphism that increases mRNA levels of the G-protein subunit Galphas was genetically linked to schizophrenia. Here we show that regulated overexpression of Galphas mRNA in forebrain neurons of mice is sufficient to cause a number of schizophrenia-related phenotypes, as measured in adult mice, including sensorimotor gating deficits (prepulse inhibition of acoustic startle, PPI) that are reversed by haloperidol or the phosphodiesterase inhibitor rolipram, psychomotor agitation (hyperlocomotion), hippocampus-dependent learning and memory retrieval impairments (hidden water maze, contextual fear conditioning), and enlarged ventricles. Interestingly, overexpression of Galphas during development plays a significant role in some (PPI, spatial learning and memory and neuroanatomical deficits) but not all of these adulthood phenotypes. Pharmacological and biochemical studies suggest the Galphas-induced behavioral deficits correlate with compensatory decreases in hippocampal and cortical cyclic AMP (cAMP) levels. These decreases in cAMP may lead to reduced activation of the guanine exchange factor Epac (also known as RapGEF 3/4) as stimulation of Epac with the select agonist 8-pCPT-2'-O-Me-cAMP increases PPI and improves memory in C57BL/6J mice. Thus, we suggest that the developmental impact of a given biochemical insult, such as increased Galphas expression, is phenotype specific and that Epac may prove to be a novel therapeutic target for the treatment of both developmentally regulated and non-developmentally regulated symptoms associated with schizophrenia.


Clinical features and management of pancreatic solid pseudopapillary tumor.
Solid pseudopapillary tumor (SPT) is a rare pancreatic tumor with low malignant potential. Between February 2006 and May 2013, six patients were affected by SPT. Two patients were male and four were female. Median age of the patients was 31.5 years (range, 13 to 47 years). One patient was preoperatively diagnosed by an endoscopic ultrasound-guided fine-needle aspiration biopsy. Pancreaticoduodenectomy was performed in two and distal pancreatectomy was done in four. One operation of those was laparoscopic distal pancreatectomy. In this series, recurrence or distant metastasis was not reported and successful outcome was achieved in all patients. In conclusion, whereas diagnosis of SPT is difficult, it can be diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy preoperatively. It should be treated by surgery, and laparoscopic operation can be considered.


Relationship between cerebrospinal fluid biomarkers of inflammation and tissue damage in primary progressive multiple sclerosis.
It is unclear to what extent intrathecal inflammation contributes to the pathogenesis in primary progressive multiple sclerosis (PPMS). We conducted an exploratory study to investigate the degree of intrathecal inflammation and its association with biomarkers of disease activity and severity in patients with PPMS. We included patients with PPMS who participated in a randomized controlled trial conducted at the Danish Multiple Sclerosis Center, patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls. We analyzed concentrations of a panel of cytokines in CSF using electrochemiluminescence assays. We then explored the relationship between cytokines found in increased CSF concentrations in patients with PPMS (compared with healthy controls) with CSF concentrations of neurofilament light chain (NFL) and myelin basic protein (MBP), IgG-index, and magnetic resonance imaging (MRI) metrics (volume, magnetization transfer ratio and diffusion tensor imaging) from lesions, normal-appearing white matter, and cortical grey matter. We included 59 patients with PPMS, 40 patients with RRMS, and 21 healthy controls. In patients with PPMS, CSF concentrations of CC chemokine ligand 3 (CCL-3), CXC chemokine ligand 8 (CXCL-8), CXCL-10, interleukin (IL)-10, IL-15, and vascular endothelial growth factor (VEGF)-A were increased compared with healthy controls and comparable with CSF concentrations in patients with RRMS. In addition, patients with PPMS had increased CSF concentrations of IL-12p40, IL-17A, tumor necrosis factor (TNF)-α, and lymphotoxin (LT)-α compared with healthy controls, but concentrations of these cytokines were even higher in patients with RRMS. For the remaining seven cytokines (CCL22, interferon-γ, IL-5, IL-7, IL-16, IL-22, IL-27), we found no difference between patients with PPMS and healthy controls. CSF concentrations of NFL and MBP correlated weakly with concentrations of IL-15, while the remaining proinflammatory cytokines were not associated with CSF concentrations of NFL or MBP. The IgG-index correlated with four cytokines (IL-10, IL-12p40, TNF-α, and LT-α). We did not observe any significant associations between MRI metrics and CSF biomarkers of inflammation. In this exploratory study, we found few and weak associations between intrathecal inflammation and the extent of neuroaxonal damage and demyelination, and no associations between intrathecal inflammation and MRI metrics, in patients with PPMS. Our findings suggest that, for patients with PPMS, these measures of intrathecal inflammation are not associated with the extent of neuroaxonal injury, demyelination, and disease severity, and these processes may therefore have less relevance in PPMS than in relapsing forms of MS.


Development and Validation of the System Trustworthiness Scale.
We created and validated a scale to measure perceptions of system trustworthiness. Several scales exist in the literature that attempt to assess trustworthiness of system referents. However, existing measures suffer from limitations in their development and validation. The current study sought to develop a scale based on theory and methodological rigor. We conducted exploratory and confirmatory factor analyses on data from two online studies to develop the System Trustworthiness Scale (STS). Additional analyses explored the manipulation of the factors and assessed convergent and divergent validity. The exploratory factor analyses resulted in a three-factor solution that represented the theoretical constructs of trustworthiness: performance, purpose, and process. Confirmatory factor analyses confirmed the three-factor solution. In addition, correlation and regression analyses demonstrated the scale's divergent and predictive validity. The STS is a psychometrically valid and predictive scale for assessing trustworthiness perceptions of system referents. The STS assesses trustworthiness perceptions of systems. Importantly, the scale differentiates performance, purpose, and process constructs and is adaptable to a variety of system referents.


Glutathione-Mediated Clearable Nanoparticles Based on Ultrasmall Gd2O3 for MSOT/CT/MR Imaging Guided Photothermal/Radio Combination Cancer Therapy.
Recently, multifunctional clearable inorganic theranostic nanoparticles have been attracting more and more attention. Protein-based nanoparticles can be cleared by the hepatobiliary system efficiently. In this work, ultrasmall gadolinium oxide (Gd2O3) nanoparticles, which possess the advantage of high longitudinal relaxation rate, were coated with bovine serum albumin (BSA). After the Gd2O3/BSA nanoparticles were linked with two-dimensional photothermal MoS2 nanomaterials, the nanoparticles were also modified with hyaluronic acid (HA) through the disulfide bonds for tumor-targeting effect. As indicated by in vitro and in vivo studies, these Gd2O3/BSA@MoS2-HA nanoparticles could be rapidly degraded and excreted after reacting with glutathione (GSH) by the redox response, thus avoiding long-term toxicity. In addition, the cellular uptake study and in vivo multispectral optoacoustic tomography (MSOT), X-ray computed tomography (CT), and magnetic resonance (MR) triple-modal images demonstrated that Gd2O3/BSA@MoS2-HA nanoparticles exhibited a high tumor uptake effect after intravenous injection. Consequently, such clearable theranostic nanoparticles with multiple functions, which are applicable in multimodal imaging-guided cancer therapy, might show promise for applications in nanomedical science.


[Age features of bioregulatory therapy of dental diseases.]
The article presents data on the use of peptide bioregulators of cell homeostasis and the protective functions of the body in various dental diseases and pathology of organs and tissues of the maxillofacial region. Issues related to the immunopharmacological effect and clinical use of natural and synthetic peptide thymomimetics (thymalin, thymogen, vilon, epithalamin, cortexin) and peptide bioregulators from cartilaginous (sigumir, chondrolux) and other tissues in case of trauma, as well as inflammatory, inflammatory and other pathological processes of tissues of the oral cavity and maxillofacial region. Particular attention is paid to their use in the complex treatment of dental diseases in the elderly.


Cardiac arrest due to a vagal reflex potentiated by thoracic epidural analgesia.
Reflex bradycardia and cardiac arrest may be the result of a vagal reflex, which can occur during a variety of surgical procedures. We report a patient who developed cardiac arrest as a result of a vagal reflex that was potentiated by thoracic epidural analgesia during general anaesthesia. A 53-year-old man was scheduled for subtotal gastrectomy because of an early gastric adenocarcinoma. After an epidural catheter had been inserted, general anaesthesia was induced. During surgery, an abdominal self-retaining retractor was set up but bradycardia and cardiac arrest developed. The patient returned to a normal sinus rhythm after successful resuscitation. We conclude that bradycardia as a result of a vagal reflex is mediated by potent abdominal wall traction and is potentiated by epidural analgesia. Early diagnosis and proper treatment can allow a full recovery, even in high-risk patients.


Contraceptive insurance mandates and consistent contraceptive use among privately insured women.
Half of the states in the United States mandate that health insurers cover contraceptives. Health care reform includes recommendations to extend these mandates nationally through the essential benefits package. This study evaluates the association of state-level insurance mandates and consistent contraceptive use among privately insured women aged 15-44. The National Survey of Family Growth (2006-2008) included 2276 privately insured women at risk for unintended pregnancy. Multilevel logistic regression models provided estimates of the association between state-level insurance coverage mandates and consistent contraceptive use. Among privately insured women, 18% reported a ≥1-month gap in contraceptive use. Compared with women living in states with no mandates, those in states with comprehensive mandates had increased odds of consistent contraceptive use among privately insured women [adjusted odds ratio (aOR), 1.64; 95% confidence interval (CI), 1.08-2.50], but not uninsured women (aOR, 0.77; 95% CI, 0.38-1.55). Partial mandates were not associated with consistent contraceptive use. Consistent contraceptive use among women with private insurance is higher in the states with mandates compared with those without mandates.


Neuronal responses in mouse inferior colliculus correlate with behavioral detection of amplitude-modulated sound.
Amplitude modulation (AM) is a common feature of natural sounds, including speech and animal vocalizations. Here, we used operant conditioning and in vivo electrophysiology to determine the AM detection threshold of mice as well as its underlying neuronal encoding. Mice were trained in a Go-NoGo task to detect the transition to AM within a noise stimulus designed to prevent the use of spectral side-bands or a change in intensity as alternative cues. Our results indicate that mice, compared with other species, detect high modulation frequencies up to 512 Hz well, but show much poorer performance at low frequencies. Our in vivo multielectrode recordings in the inferior colliculus (IC) of both anesthetized and awake mice revealed a few single units with remarkable phase-locking ability to 512 Hz modulation, but not sufficient to explain the good behavioral detection at that frequency. Using a model of the population response that combined dimensionality reduction with threshold detection, we reproduced the general band-pass characteristics of behavioral detection based on a subset of neurons showing the largest firing rate change (both increase and decrease) in response to AM, suggesting that these neurons are instrumental in the behavioral detection of AM stimuli by the mice.NEW & NOTEWORTHY The amplitude of natural sounds, including speech and animal vocalizations, often shows characteristic modulations. We examined the relationship between neuronal responses in the mouse inferior colliculus and the behavioral detection of amplitude modulation (AM) in sound and modeled how the former can give rise to the latter. Our model suggests that behavioral detection can be well explained by the activity of a subset of neurons showing the largest firing rate changes in response to AM.


Facile Ball Milling Preparation of Flame-Retardant Polymer Materials: An Overview.
To meet the growing needs of public safety and sustainable development, it is highly desirable to develop flame-retardant polymer materials using a facile and low-cost method. Although conventional solution chemical synthesis has proven to be an efficient way of developing flame retardants, it often requires organic solvents and a complicated separation process. In this review, we summarize the progress made in utilizing simple ball milling (an important type of mechanochemical approach) to fabricate flame retardants and flame-retardant polymer composites. To elaborate, we first present a basic introduction to ball milling, and its crushing, exfoliating, modifying, and reacting actions, as used in the development of high-performance flame retardants. Then, we report the mixing action of ball milling, as used in the preparation of flame-retardant polymer composites, especially in the formation of multifunctional segregated structures. Hopefully, this review will provide a reference for the study of developing flame-retardant polymer materials in a facile and feasible way.


Impact of pneumococcal conjugate vaccine (PCV7 and PCV13) on pneumococcal invasive diseases in Italian children and insight into evolution of pneumococcal population structure.
The use of PCV7 for children immunization was gradually implemented in the Italian regions starting from 2006 and was replaced by PCV13 in 2010-2011. In this study we aimed to assess the PCV impact on invasive pneumococcal diseases (IPD) incidence, serotype distribution and antibiotic resistance in Italian children under 5years old. All IPD cases in children from 5 Italian regions (Emilia-Romagna, Lombardia, A. P. Bolzano, A. P. Trento, and Piemonte) reported through the nationwide surveillance system during 2008-2014 were included in this study. Pneumococcal isolates were subjected to serotyping, antibiotic susceptibility testing, and clonal analysis according to standard methods. During the study period overall IPD incidence decreased from 7.8 cases/100,000 inhabitants in 2008 to 3.0 cases/100,000 in 2014 (61% decrease, P<0.001). In particular, from 2008 to 2014, PCV7-type IPD decreased from 2.92 to 0.13 cases/100,000 inhabitants (95% decrease, P<0.001) while PCV13-non-PCV7 type IPD decreased from 3.2 to 0.89 cases/100,000 inhabitants (72% decrease, P=0.008). Conversely, non-vaccine serotype (NVS) IPD increased overtime, becoming more common than PCV13 serotype IPD in 2013-2014. Emergent NVS 24F and 12F were the most prevalent in 2014. Antibiotic resistance testing revealed an overall increasing trend in penicillin resistance, from 14% in 2008 to 23% in 2014. Erythromycin resistance showed a downward trend, from 38% in 2008 to 27% in 2014. While in 2008 PCV13 serotypes were the major responsible for antibiotic resistance, during the following years antimicrobial resistance due to NVS increased, mainly as a result of expansion of pre-existing clones. Both PCVs led to a substantial decrease in vaccine-related IPD incidence in the children population. However NVS-related IPD increased, becoming the most prevalent in the last two-years period. Continuous surveillance is an essential tool to monitor evolution of pneumococcal population causing IPD in children.


Design and development of the first exoskeletal garment to enhance arm mobility for children with movement impairments.
Children with a variety of diagnoses have impairments that limit their arm function. Despite the fact that arm function is important for early learning and activities of daily living, there are few tools to assist movement for these children, and existing devices have challenges related to cost, accessibility, comfort, and aesthetics. In this article, we describe the design process and development of the first garment-based exoskeleton to assist arm movement in young children with movement impairments: the Playskin LiftTM. We outline our design process, which contrasts with the traditional medical model in that it is interdisciplinary, user-centered, and addresses the broad needs of users, rather than device function alone. Then we report the results of field-testing with the initial prototype with respect to our design metrics on a toddler with significant bilateral arm movement impairments. Finally, we summarize our ongoing development aimed at increasing comfort, aesthetics, and accessibility of the garment. The interdisciplinary, user-centered approach to assistive technology design presented here can result in innovative and impactful design solutions that translate to the real world.


Wrist pain.
Acute and chronic wrist pain are problems frequently seen by primary care physicians. The impact of wrist pain on function is substantial and requires prompt attention and treatment by physicians. In this article we summarize the causes of wrist problems, provide an approach to wrist pain, and discuss some of the common disorders seen by primary physicians.


UK-2A, B, C, and D, novel antifungal antibiotics from Streptomyces sp. 517-02 VII. Membrane injury induced by C9-UK-2A, a derivative of UK-2A, in Rhodotorula mucilaginosa IFO 0001.
UK-2A is a potent antifungal antibiotic and its structure is highly similar to that of antimycin A3 (AA). UK-2A and AA inhibit mitochondrial electron transport at complex III. However, the antifungal activities of UK-2A and AA disappear after 48-hour treatment. In an attempt to improve the duration of the antifungal activity of UK-2A, several UK-2A derivatives were prepared by substituting its nine-membered dilactone ring with an n-alkyl or an isoprenyl moiety. Among all the derivatives tested, C9- and C10-UK-2A showed the most potent and durable antifungal activities against a strict aerobic yeast, Rhodotorula mucilaginosa IFO 0001. C9-UK-2A, in particular, continued to demonstrate its broad-spectrum antifungal activity after 120-hour treatment. Therefore, we focused on C9-UK-2A to further examine its mode of action against the yeast. Interestingly, C9-UK-2A did not inhibit cellular respiration of the cells even at concentrations greater than 100 microg/ml. C9-UK-2A gradually induced the efflux of potassium ions from the cells. Moreover, C9-UK-2A gradually induced the release of glucose from glucose-encapsulating liposomes. The patterns of efflux and release induced by C9-UK-2A were not as rapid as those seen with amphotericin B. These results suggest a membrane injury caused by C9-UK-2A in R. mucilaginosa IFO 0001.


A statewide characterization of hospital infection control practices and practitioners.
Selected features of infection control programs among the 163 general hospitals in Tennessee were surveyed in 1976 and 1979. Each hospital but one had a designated infection control practitioner. Three-fourths of the hospitals had fewer than 200 beds and most were in rural areas. The practitioners in these small hospitals worked in an isolated professional milieu: few (4%) had attended a basic training course or were members of a national (11%) or local (16%) infection control association. They also had significantly less access to standard infection control resource publications than did practitioners in large hospitals. Use of aqueous quaternary ammonium compounds for disinfection was reported by 37% of all hospitals in 1979; 68% of hospitals routinely performed bacteriologic cultures of personnel or the environment. In contrast, only 3% of hospitals did not have a policy specifying the use of sterile closed-system drainage of indwelling bladder catheters. Although these practices varied somewhat by hospital size, the differences were not statistically significant. Modest improvement in each parameter was noted since 1976. Pathology was the most common medical specialty (34%) among chairman of infection control committees; internal medicine and pediatrics accounted for only 13%. The practice of routine microbiologic monitoring was significantly more common among hospitals with chairmen who were pathologists. The implications of these findings for national priorities in hospital infection control are discussed.


Immunosuppressant-related hip pain after orthotopic liver transplant.
Immunosuppressant-related hip pain can greatly affect a patient's mobility and increase the number of total hip arthroplasties. We investigated risk factors and causes of hip pain after orthotopic liver transplant. The medical records of 175 adult orthotopic liver transplant patients, who were followed-up for more than 2 years, were retrospectively reviewed. Data collected from the records included primary disease, medications, biochemical results, Child-Turcotte-Pugh score, death, rejection, and complications related to liver transplant. A total of 11 patients (6.3%) complained of hip pain, which was diagnosed as calcineurin-inhibitor-induced pain syndrome in 4 patients (2.3%), osteonecrosis of the femoral head in 3 patients (1.7%), and osteoporosis in 2 patients (1.1%). The incidence of calcineurin-inhibitor-induced pain syndrome was related to the dosage of tacrolimus (P > .05) but independent of methylprednisolone use. The occurrence of osteonecrosis of the femoral head was independent of the dosage and early withdrawal of methylprednisolone (P > .05). Patients with methylprednisolone withdrawal within 6 months had significantly longer survival than those using methylprednisolone for more than 6 months (50 ± 15 vs 41 ± 18 mo; P = .007). Calcineurin-inhibitor-induced pain syndrome and osteonecrosis of the femoral head are main causes of hip pain in adult orthotopic liver transplant patients. Osteonecrosis of the femoral head was not common, but the incidence of hip pain owing to calcineurin-inhibitor-induced pain syndrome was relatively high in orthotopic liver transplant patients. Early withdrawal of methylprednisolone could benefit the patients' survival.


Genetic diversity and in silico evidence of target-site mutation in the EPSPS gene in endowing glyphosate resistance in Eleusine indica (L.) from Malaysia.
Glyphosate-resistant populations of Eleusine indica are widespread in several states of Malaysia. A whole-plant bioassay confirmed that eight out of the 17 populations tested were resistant to glyphosate at double the recommended rate of 2.44 kg ha-1. Screening with allele-specific PCR (AS-PCR) revealed that resistant plants contained an EPSPS gene with either the homozygous S/S-106 or the heterozygous P/S-106 alleles. All susceptible plants contained only the homozygous P/P-106 allele. In addition, DNA sequences of the full-length EPSPS gene from one susceptible (SB) and four resistant (R2, R6, R8 and R11) populations revealed an amino acid substitution of T102I in all the resistant plants, while another substitution of P381L was only found in resistant populations R6 and R11. The significance of the P381L mutation was examined by Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) and residue interaction network (RIN) analyses, which suggests the P381L mutation may contribute to resistance. Mutations at 102 and 106 occur widely in the EPSPS gene of glyphosate-resistant E. indica populations from Malaysia with the TIPS mutation. In addition, the P381L mutation could also contribute to resistance.


The Adverse Effects and Treatment Results of Smoking Cessation Pharmacotherapy During Fasting/Non-Fasting State.
Cigarette smoking is one of the most common addictions worldwide. Muslim smokers reduce the number of cigarettes they smoke during Ramadan due to the long fasting hours. We aimed to share our experience in a smoking cessation clinic during Ramadan by analyzing the efficacy and adverse effects of once-daily dosing of bupropion or varenicline in a fasting group compared with conventional dosing in a non-fasting group. We analyzed 57 patients who attended our smoking cessation clinic during Ramadan of 2014 and 2015, and at least one follow-up visit. For the fasting patients, we prescribed bupropion or varenicline after dinner (once daily) as the maintenance therapy. We recorded demographic characteristics of the patients, fasting state, drugs taken for smoking cessation, and the dosage of the medication. At the first follow-up visit, adverse effects seen with the treatment were recorded. We conducted telephone interviews 6 months after the first visits of the patients to learn the current smoking status of the groups. Of the total 57 patients, 20 (35.1%) were fasting and 37 (64.9%) were not fasting. Fasting and non-fasting patients were similar for sex, age, smoking pack-years, marital status, educational status, and mean Fagerström scores (p >.05). Adverse effects and quit rates after 6 months of follow-up were similar between the fasting and non-fasting groups (p >.05). Although our sample size was small, we found no difference in the rates of adverse effects or smoking cessation using a single daily oral dose of bupropion or varenicline between a fasting group and a non-fasting group that received conventional dosing.


Mitochondria as a pharmacological target: magnum overview.
Mitochondria, responsible for energy metabolism within the cell, act as signaling organelles. Mitochondrial dysfunction may lead to cell death and oxidative stress and may disturb calcium metabolism. Additionally, mitochondria play a pivotal role in cardioprotective phenomena and a variety of neurodegenerative disorders ranging from Parkinson's to Alzheimer's disease. Mitochondrial DNA mutations may lead to impaired respiration. Hence, targeting the mitochondria with drugs offers great potential for new therapeutic approaches. The purpose of this overview is to present the recent state of knowledge concerning the interactions of various substances with mitochondria.


Nuclear localization of a DNA-binding C-terminal domain from Balbiani ring coded secretory protein.
All known Balbiani ring (BR) genes in Chironomus tentans, coding for giant secretory proteins, the sp-I family, end with a short (110 codons) 3'-end exon which is highly conserved in evolution and is structurally unrelated to the sequences characterizing the core of these proteins. We find that the expressed product, the C-terminal domain, shows sequence-specific DNA binding and that it is likely to be absent in one of the sp-I components, sp-Ib, believed to be coded by the BR2.2 gene. Immunohistochemistry shows that material with reactivity towards antibody against the C-terminal domain is present in the nuclei, and specifically enriched in Balbiani ring 1 and 2. Western blotting of extracts from isolated nuclei demonstrates a component with the same antibody reactivity and of an apparent size somewhat larger than that of the domain. The possibility is discussed that the C-terminal part, which is part of the secretion when derived from some of the BR genes, might be cleaved off and function as a feedback signal to control BR gene activity when derived from the BR2.2 gene.


Coexistence of ice clusters and liquid-like water clusters on the Ru(0001) surface.
The RAIRS spectra of water adsorbed on Ru(0001) at 85 K are recorded from 600 cm-1 to 4000 cm-1. Measured at water coverages from 0.13 ML to 2.0 ML, the RAIRS spectra suggest that chemisorption of water on Ru(0001) depends on coverage. Water adsorbs on a clean Ru surface as chemisorbed ice-like clusters (likely through an O-Ru bond) up to 0.33 ML. Above this coverage, the chemisorbed layer saturates. Upon more exposure, water adsorbs as a liquid-like H-bonded layer without bonding to the Ru substrate. The chemisorbed water absorbs 7 times less IR per molecule than the liquid-like structure, which indicates that the orientation of the chemisorbed water is more parallel to the surface. Additionally, the influence of water-Ru bonding on H-bonding is reflected in the OH symmetric stretching mode. Under perturbation from water-Ru bonding, a large red shift (40 cm-1) in the free OH stretching frequency is observed in the chemisorbed clusters. By deconvoluting the main H-bonded OH stretching peak into five Gaussian sub-bands at 2945 ± 5 cm-1, 3210 ± 5 cm-1, 3300 ± 15 cm-1, 3430 ± 5 cm-1 and 3570 ± 10 cm-1, changes in the H-bonding network are rationalized in terms of H-bonding motifs. The donor-acceptor-acceptor motif is significant only in the chemisorbed clusters. On the other hand, the donor-acceptor motif dominates in the liquid-like structure, which increases the disorder present in the adlayer. Although chemisorption is suppressed above 0.33 ML, no structural changes in the ice-like clusters are observed up to multilayer coverage. Therefore, ice-like and liquid-like water coexist in a meta-stable state at 85 K.


Characterization of the ABA-deficient tomato mutant notabilis and its relationship with maize Vp14.
The notabilis (not) mutant of tomato has a wilty phenotype due to a deficiency in the levels of the plant hormone abscisic acid (ABA). The mutant appears to have a defect in a key control step in ABA biosynthesis--the oxidative cleavage of a 9-cis xanthophyll precursor to form the C15 intermediate, xanthoxin. A maize mutant, viviparous 14 (vp14) was recently obtained by transposon mutagenesis. This maize genetic lesion also affects the oxidative cleavage step in ABA synthesis. Degenerate primers for PCR, based on the VP14 predicted amino acid sequence, have been used to provide probes for screening a wilt-related tomato cDNA library. A full-length cDNA clone was identified which is specific to the not gene locus. The ORFs of the tomato cDNA and maize Vp14 are very similar, apart from parts of their N-terminal sequences. The not mutation has been characterized at the DNA level. A specific A/T base pair deletion of the coding sequence has resulted in a frameshift mutation, indicating that not is a null mutant. This observation is discussed in connection with the relatively mild phenotype exhibited by not mutant homozygotes.


Determination of the sources of indoor PM2.5 in Amsterdam and Helsinki.
Daily PM2.5 samples were repeatedly collected (1-8 times) in the homes of elderly nonsmoking individuals with coronary heart disease in Amsterdam, The Netherlands (33 individuals) and Helsinki, Finland (44 individuals). Sources of indoor PM2.5 were evaluated using a two-way multilinear engine model. Because the indoor elemental data lacked a traffic marker, separation of traffic related PM was attempted by combining the indoor data with fixed site outdoor data that also contained NO. Six outdoor sources, including long-range transport (LRT), urban mixture, oil combustion, traffic, sea-salt, and soil were identified, and three indoor sources were resolved: resuspension, potassium-rich and copper-rich sources. The average contribution of the indoor factors was 6% (1.1 microg m(-3)) and 22% (2.4 microg m(-3)) in Amsterdam and Helsinki, respectively. The highest longitudinal correlations between source-specific outdoor and indoor PM2.5 concentrations were found for LRT and urban mixture; the median R was above 0.6 for most sources. The longitudinal correlations were lower in Helsinki than in Amsterdam. Indoor-generated PM2.5 was not related to ambient concentrations. We conclude that using outdoor and indoor data together improved the source apportionment of indoor PM2.5. The results support the use of fixed site outdoor measurements in epidemiological time-series studies on outdoor air pollution.


Insect-specific production of new GameXPeptides in photorhabdus luminescens TTO1, widespread natural products in entomopathogenic bacteria.
Discovery of new natural products by heterologous expression reaches its limits, especially when specific building blocks are missing in the heterologous host or the production medium. Here, we describe the insect-specific production of the new GameXPeptides E-H (5-8) from Photorhabdus luminescens TTO1, which can be produced heterologously from expression of the GameXPeptide synthetase GxpS only upon supplementation of the production media with the missing building blocks, and thus must be regarded as the true natural products under natural conditions.


A potential Cu/V-organophosphonate platform for tailored void spaces via terpyridine mold casting.
The reaction of appropriate copper and vanadium salts with tetratopic methane tetra-p-phenylphosphonic acid (MTPPA) in the presence of 2,2':6':2''-terpyridine (terpy) yielded the three-dimensional bimetallic copper vanadium phosphonate framework [{Cu(terpy)}4Cu(VO2)4(MTPPA-H)2]·4H2O (1). Terpy has no net contribution to the three-dimensional structure providing a potential platform for void space formation via mold-casting. The structure was characterized by single-crystal X-ray diffraction and thermogravimetric analysis (TGA). Magnetic measurements were performed using a SQUID magnetometer. The crystal structure of the methanol solvate of the free ligand, MTPPA·MeOH, was analysed using Hirshfeld surfaces and fingerprint plots.


A case of donepezil-related torsades de pointes.
An 80-year-old woman with Alzheimer's dementia presented with diarrhoea, vomiting and worsening confusion following an increase in donepezil dose from 5 to 10 mg. The ECG revealed prolongation of QTc interval. Soon after admission, she became unresponsive with polymorphic ventricular tachycardia (VT). Cardiopulmonary resuscitation with a 200 J shock was successful in establishing cardiac output. Following the discontinuation of donepezil, the QTc interval normalised and no further arrhythmias were recorded. Treatment with anticholinesterase inhibitors may result in life-threatening VT. Vigilance is required for the identification of this condition in patients presenting with presyncope, syncope or seizures.


Synthesis of 6-Substituted Piperidin-3-ones via Rh(II)-Catalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles with Electron-Rich Aromatic Nucleophiles.
A highly diastereoselective rhodium(II)-catalyzed transannulation of aldehyde-tethered N-sulfonyl triazoles with electron-rich aromatic nucleophiles is reported for the first time to afford functionalized 6-substituted piperidin-3-ones. The reaction has a broad substrate scope including both aliphatic and aromatic N-sulfonyl-1,2,3-triazoles together with various aromatic nucleophiles. The addition of a catalytic amount of Lewis acid has proven to be crucial for the yield improvement. By employing this methodology, hardly accessible piperidin-3-ones bearing quaternary carbons could be obtained.


Symmetrical Facial Giant Plaque-Type Juvenile Xanthogranuloma: Case Report and Review of the Literature.
Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis. JXG is a rare benign tumor, which may be present at birth or develop later. The classical form of JXG is characterized by a red-yellowish benign papule or nodule with predilection sites on the head, neck, and trunk, although lesions can appear on extremities or extracutaneous sites. In most cases there is only one lesion, whereas numerous papules or nodules may occur. Special forms of JXG such as mixed, giant, subcutaneous, eruptive, clustered, and plaque-like have been reported and associations between JXG and systemic diseases have been made. Diagnosis mainly relies on the clinical appearance, and histology usually can confirm the disease. Here we present a very rare case of symmetrical giant facial plaque-type juvenile xanthogranuloma (SGFP-JXG) and compare it with classical JXG, variations of JXG, and discuss the differential diagnosis. A 4-year-old Caucasian female presented with plaque-like lesions composed of yellowish confluent papules on both the cheeks. The histological evaluation revealed a histiocytic lesion with a formation of Touton giant cells and immunohistochemistry results confirmed the diagnosis of the SGFP-JXG. In comparison to classical JXG, the onset of SGFP-JXG sometimes occurs later and the spontaneous resolution period may be prolonged. No associated diseases and no systemic involvements were observed. Histopathology is required to differentiate this form of JXG from other histiocytosis. To the best of our knowledge, only four cases of SGFP-JXG have been reported in the literature so far.


Phosphorus and nitrogen runoff from a forested watershed fertilized with biosolids.
Municipal biosolids are typically not used on the steepest of forested slopes in the U.S. Pacific Northwest. The primary concern in using biosolids on steep slopes is movement of biosolids particles and soluble nutrients to surface waters during runoff events. We examined the pattern and extent of P and N runoff from a perennial stream draining a small, forested 21.4-ha watershed in western Washington before and after biosolids application. In this study, we applied biosolids at a rate of 13.5 Mg ha(-1) (700 kg N ha(-1) and 500 kg P ha(-1)) to 40% of the watershed following nearly 1.5 years of pre-application water sampling and 1.5 years thereafter. There was no evidence of direct runoff of P or N from biosolids into surface water. Elevated surface water discharge did not change the concentration of PO4-P, biologically available phosphorus (BAP), bioavailable particulate phosphorus (BPP), or total P nor did it affect the concentration-discharge relationship. Some instances of total P concentrations exceeding the USEPA surface water standard of 0.1 mg L(-1) were observed following biosolids application. However, total P in 27 Creek was predominately in particulate form and not labile, suggesting that detritus moving into the main creek channel and ephemeral drainage courses may be the principal P source. Ammonium N concentrations in runoff water were consistent before and after biosolids application, ranging from below detection limits (0.01 mg L(-1)) to 0.1 mg L(-1); no concentration-discharge relationship existed. Biosolids application changed the 27 Creek concentration-discharge relationship for NO3(-)-N. Before application, no relationship existed. Beginning nine months after biosolids application, increases in discharge were positively related to increases in NO3(-)-N concentrations. Nitrate concentrations in runoff following biosolids application were approximately 10 times less than the USEPA drinking water standard of 10 mg L(-1).


[Experimental studies on the symptom-complex mechanism of pi man zao shi of dachengqi decoction].
Experiments have shown that Dachengqi Decoction can inhibit the activity of G-germs which commonly grow in the intestinal tract, inactivate the endotoxin directly in vitro, reduce the amplitude of fever caused by endotoxin injected intravenously, promote the gastric secretion and gastric retaining in rats, and increase the level of glycogen in liver. It also has some other effects. All these actions contribute to the explanation on the efficacy of Dachengqi Decoction to purge off the internal heat.


Effect of a homologous beta-interferon preparation on degradation of Escherichia coli and on lysosomal enzyme activities in mouse peritoneal macrophages.
The degradation of 32P-labelled E. coli and the activity of three lysosomal enzymes, acid phosphatase, cathepsin D and beta-glucuronidase, in mouse peritoneal macrophages (MPM) were tested after cultivation of the cells for 24 or 48 hours with 10(1) - 10(4.7) U per ml of a homologous beta-interferon preparation (IFN-beta). Low to moderate concentrations of IFN-beta did not influence bacterial degradation in MPM. However, a reduction in bacterial degradation by 20 per cent or more was seen when the MPM were pre-treated with 10(4.7) U per ml for 24 hours or 10(3) U per ml of IFN-beta for 48 hours. Cultivation of the MPM with 10(2) U per ml of IFN-beta suppressed the activities of the lysosomal enzymes, provided that the cells were treated for 48 hours. The beta--glucuronidase activity was significantly reduced also after 24 hours. Increased release of beta-glucuronidase from MPM to the medium during cultivation with 10(2) U per ml of IFN-beta was also observed. Specific anti-IFN-beta globulin abolished the suppression by IFN-beta on the lysosomal enzyme activities. A human IFN-alpha preparation did not influence bacterial degradation or lysosomal enzyme activities in MPM.


Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature).
Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses.


A Deep Learning Approach for Fusing Sensor Data from Screw Compressors.
Chillers are commonly used for thermal regulation to maintain indoor comfort in medium and large buildings. However, inefficiencies in this process produce significant losses, and optimization tasks are limited because of accessibility to the system. Data analysis techniques transform measurements coming from several sensors into useful information. Recent deep learning approaches have achieved excellent results in many applications. These techniques can be used for computing new data representations that provide comprehensive information from the device. This allows real-time monitoring, where information can be checked with current working operation to detect any type of anomaly in the process. In this work, a model based on a 1D convolutional neural network is proposed for fusing data in order to predict four different control stages of a screw compressor in a chiller. The evaluation of the method was performed using real data from a chiller in a hospital building. Results show a satisfactory performance and acceptable training time in comparison with other recent methods. In addition, the model is capable of predicting control states of other screw compressors different than the one used in the training. Furthermore, two failure cases are simulated, providing an early alarm detection when a continuous wrong classification is performed by the model.


SAC-1 ensures epithelial endocytic recycling by restricting ARF-6 activity.
Arf6/ARF-6 is a crucial regulator of the endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) pool in endocytic recycling. To further characterize ARF-6 regulation, we performed an ARF-6 interactor screen in Caenorhabditis elegans and identified SAC-1, the homologue of the phosphoinositide phosphatase Sac1p in yeast, as a novel ARF-6 partner. In the absence of ARF-6, basolateral endosomes show a loss of SAC-1 staining in epithelial cells. Steady-state cargo distribution assays revealed that loss of SAC-1 specifically affected apical secretory delivery and basolateral recycling. PI(4,5)P2 levels and the endosomal labeling of the ARF-6 effector UNC-16 were significantly elevated in sac-1 mutants, suggesting that SAC-1 functions as a negative regulator of ARF-6. Further analyses revealed an interaction between SAC-1 and the ARF-6-GEF BRIS-1. This interaction outcompeted ARF-6(guanosine diphosphate [GDP]) for binding to BRIS-1 in a concentration-dependent manner. Consequently, loss of SAC-1 promotes the intracellular overlap between ARF-6 and BRIS-1. BRIS-1 knockdown resulted in a significant reduction in PI(4,5)P2 levels in SAC-1-depleted cells. Interestingly, the action of SAC-1 in sequestering BRIS-1 is independent of SAC-1's catalytic activity. Our results suggest that the interaction of SAC-1 with ARF-6 curbs ARF-6 activity by limiting the access of ARF-6(GDP) to its guanine nucleotide exchange factor, BRIS-1.


The Emerging Role of the Mammalian Glycocalyx in Functional Membrane Organization and Immune System Regulation.
All cells in the human body are covered by a dense layer of sugars and the proteins and lipids to which they are attached, collectively termed the "glycocalyx." For decades, the organization of the glycocalyx and its interplay with the cellular state have remained enigmatic. This changed in recent years. Latest research has shown that the glycocalyx is an organelle of vital significance, actively involved in and functionally relevant for various cellular processes, that can be directly targeted in therapeutic contexts. This review gives a brief introduction into glycocalyx biology and describes the specific challenges glycocalyx research faces. Then, the traditional view of the role of the glycocalyx is discussed before several recent breakthroughs in glycocalyx research are surveyed. These results exemplify a currently unfolding bigger picture about the role of the glycocalyx as a fundamental cellular agent.


Adult eosinophilic esophagitis and advances in its treatment.
Eosinophilic esophagitis (EoE) is a chronic eosinophil inflammation that seems to be T helper type 2 antigen-driven. The disease is one of several eosinophilic gastrointestinal disorders in which there appears to be inflammation of the gastrointestinal tract without any apparent underlying causes. Differential diagnosis needs to be made with gastroesophageal reflux, which is characterized by chronic inflammation due to gastric refluxate from disorders related to motility. EoE, however, is considered a chronic allergic inflammatory disorder related to destructive tissue remodeling. There seems to be a higher prevalence of EoE in Western countries. It is typically found in atopic male individuals. Physiopathological risk factors include atopy, environmental factors, esophageal epithelial barrier dysfunctions, etc. EoE can cause several symptoms that include retrosternal burning sensation, dysphagia, food impaction, chronic reflux symptoms, nausea, and vomiting. Early diagnosis, which requires a biopsy to assess for esophageal inflammation, is essential for proper treatment. The aim of our brief overview is to summarize the current literature regarding the characteristics, diagnosis, complications, mechanisms of pathology, clinical features, influence of comorbidities, and treatment in patients with EoE.