Juniperus chinensis Fruits Attenuate Oxazolone- and 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis Symptoms in Mice.
Juniperus chinensis, commonly Chinese juniper, has been used for treating inflammatory diseases. This study aimed to investigate anti-atopic dermatitis (AD) effects of standardized J. chinensis fruits extract on murine oxazolone- and 2,4-dinitrochlorobenzene (DNCB)-induced models of AD. Ear swelling, epidermis thickening, and eosinophils infiltration in the oxazolone-mediated dermatitis of BALB/c mice were significantly reduced upon topical application of J. chinensis fruits 95% EtOH extract (JCE). Besides, transdermal administration of JCE to SKH-1 hairless mice inhibited the development of DNCB-induced AD-like skin lesions by suppressing transepidermal water loss and improving skin hydration. Decreased total serum immunoglobulin E (IgE) and interleukin (IL)-4 levels could be observed in atopic dorsal skin samples of JCE-treated group. According to the phytochemical analysis, JCE was found to contain isoscutellarein-7-O-β-D-xyloside, cupressuflavone, and amentoflavone as main compounds. Therapeutic attempts with the J. chinensis fruits might be useful in the treatment of AD and related skin inflammatory diseases.


Visualizing cancer and response to therapy in vivo using Cy5.5-labeled factor VIIa and anti-tissue factor antibody.
We have developed a specific technique for imaging cancer in vivo using Cy5.5-labeled factor VIIa (fVIIa), clotting-deficient FFRck-fVIIa, paclitaxel-FFRck-fVIIa, and anti-tissue factor (TF) antibody. FVIIa is the natural ligand for TF. We took advantage of the fact that vascular endothelial cells (VECs) in cancer, but not normal tissue, aberrantly express TF due to its induction by vascular endothelial growth factor (VEGF). Under physiological conditions, TF is expressed by stromal cells and outer blood vessel layers (smooth muscle and adventitia), but not by VECs. We hypothesized that labeled fVIIa or anti-TF antibodies could be used to image the tumor vasculature in vivo. To test this, Cy5.5-labeled fVIIa, FFRck-fVIIa, paclitaxel-FFRck-fVIIa, and anti-TF antibody were developed and administered to athymic nude mice carrying xenografts including glioma U87EGFRviii, pancreatic cancer ASPC-1 and Mia PaCa-2, and squamous cell carcinoma KB-V1. Cy5.5 labeled with these targeting proteins specifically localized to the tumor xenografts for at least 14 days but unconjugated Cy5.5 did not localize to any xenografts or organs. This method of imaging TF in the tumor VECs may be useful in detecting primary tumors and metastases as well as monitoring in vivo therapeutic responses.


Injectable Antiswelling and High-Strength Bioactive Hydrogels with a Wet Adhesion and Rapid Gelling Process to Promote Sutureless Wound Closure and Scar-free Repair of Infectious Wounds.
Developing injectable antiswelling and high-strength bioactive hydrogels with wet tissue adhesiveness and a rapid gelling process to meet the requirements for rapid hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds continues to have ongoing challenges. Herein, injectable, antibacterial, and antioxidant hydrogel adhesives based on poly(citric acid-co-polyethylene glycol)-g-dopamine and amino-terminated Pluronic F127 (APF) micelles loaded with astragaloside IV (AS) are prepared. The H2O2/horseradish peroxidase (HRP) system is used to cause cross-linking of the hydrogel network through oxidative coupling between catechol groups and chemical cross-linking between the catechol group and the amino group. The hydrogels exhibit a rapid gelling process, high mechanical strength, an antiswelling effect, good antioxidant property, H2O2 release behavior, and degradability. In addition, the hydrogels present good wet tissue adhesiveness, high bursting pressure, excellent antibacterial activity, long-term sustained release of AS, and good biocompatibility. The hydrogels perform good hemostasis on mouse liver, rat liver, and rabbit femoral vein bleeding models and achieve much better closure and healing of skin incisions than biomedical glue and surgical sutures. Furthermore, the hydrogel dressing significantly improved the scar-free repair of MRSA-infected full thickness skin defect wounds by modulating inflammation, regulating the ratio of collagen I/III, and improving the vascularization and granulation tissue formation. Thus, AS-loaded hydrogels show huge potential as multifunctional dressings for in vivo hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds.


[Efficacy of biofeedback and electrical stimulation therapy combined with Sabale capsules for chronic prostatitis / chronic pelvic pain syndrome].
To investigate the clinical effect of biofeedback and electrical stimulation therapy (BFES) combined with Sabale capsules (SC) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS). A total of 140 outpatients meeting CP/CPPS diagnostic and research criteria in the Second Affiliated Hospital of Xi'an Jiaotong University were randomly divided into groups A (blank control), B (BFES intervention), C (SC intervention) and D (BFES+SC intervention), 35 cases in each group. The patients in group A were left untreated, while those in groups B, C and D received BFES, SC and BFES+SC, respectively, all for 12 weeks. Then the patients were followed up at 30 days after treatment and the urinary flow rate and NIH-CPSI scores were obtained and compared with the baseline. In comparison with the baseline, the total NIH-CPSI scores after intervention were significantly decreased in groups B, ([27.30 ± 2.44] vs [19.43 ± 2.33]), C ([26.77 ± 2.54] vs [19.40 ± 2.75]) and D ([27.67 ± 3.69] vs [15.57 ± 1.94]) (all P < 0.05), and so were the individual item scores in pain or discomfort ([12.50 ± 1.94] vs [9.40 ± 2.01], [11.93 ± 1.64] vs [9.23 ± 1.96], and [12.33 ± 2.20] vs [7.50 ± 1.55]), urination symptoms ([6.07 ± 1.57] vs [3.83 ± 1.05], [5.97 ± 1.33] vs [3.77 ± 1.14], and [6.20 ± 1.88] vs [2.87 ± 0.94]), quality of life (QOL) ([8.73 ± 1.62] vs [6.20 ± 1.42], [8.87 ± 1.25] vs [6.40 ± 1.59], and [9.13 ± 1.70] vs [5.20 ± 1.40]) (all P < 0.05), while the maximum urinary flow rate (Qmax) was remarkably increased ([15.72 ± 2.38] vs [19.73 ± 2.85], [16.20 ± 2.44] vs [19.46 ± 2.48], and [15.83 ± 2.52] vs [22.49 ± 2.76]) (all P < 0.05), and so was the average urinary flow rate (Qavg) ([9. 282 ± 1.52] vs [11.27 ± 1.95], [8.97 ± 1.25] vs [11.16 ± 1.74], and [9.20 ± 1.36] vs [13.50 ± 2.30]) (all P < 0.05). The decrease in NIH-CPSI total and item scores and increase in Qmax and Qavg after treatment were more significant in group D than in B and C (P < 0.05), but showed no statistically significant difference between groups B and C (P > 0.05). Nor was any significant change observed in the above parameters in group A after treatment ( P > 0.05). Biofeedback and electrical stimulation therapy combined with Sabale capsules can alleviate urination dysfunction, pelvic floor tension myalgia and other symptoms and significantly improve the QOL of CP/CPPS patients.


Function of the alpha subunit of rice heterotrimeric G protein in brassinosteroid signaling.
The alpha subunit of plant heterotrimeric G proteins (Galpha) plays pivotal roles in multiple aspects of development and responses to plant hormones. Recently, several lines of evidence have shown that Galpha participates in brassinosteroid (BR) responses in Arabidopsis and rice plants. In this study, we conducted a comprehensive analysis of the roles of the rice Galpha in the responses to BR using a defective mutant of the Galpha gene, T65d1. Decreased sensitivity to 24-epi-brassinolide (24-epiBL) in the T65d1 mutant was observed in many processes examined, e.g. in the inhibition of root growth and the promotion of coleoptile elongation. The T65d1 mutant also showed similar phenotypes to those of BR-deficient mutants, such as the specifically shortened second internode and the constitutive photomorphogenic growth phenotype under dark conditions. However, a negative feedback effect by 24-epiBL on the expression of BR biosynthetic genes was observed in the T65d1 mutant, and the levels of BR intermediates did not fluctuate in this mutant. To determine the epistatic relationship between the T65d1 mutant and d61-7, a weak allele of a rice BR receptor mutant, the two mutants were crossed. The T65d1/d61-7 double mutant showed no epistasis in the elongation inhibition of the internodes, the internode elongation pattern, the leaf angle and the morphological abnormality of leaf, except for the vertical length of seed and the seed weight. Our results suggest that the rice Galpha affects the BR signaling cascade but the Galpha may not be a signaling molecule in BRI1-meditated perception/transduction.


In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice.
Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e., increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two-photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10-Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.


Simultaneous Imaging of Endogenous Survivin mRNA and On-Demand Drug Release in Live Cells by Using a Mesoporous Silica Nanoquencher.
The design of multifunctional drug delivery systems capable of simultaneous target detection, imaging, and therapeutics in live mammalian cells is critical for biomedical research. In this study, by using mesoporous silica nanoparticles (MSNs) chemically modified with a small-molecule dark quencher, followed by sequential drug encapsulation, MSN capping with a dye-labeled antisense oligonucleotide, and bioorthogonal surface modification with cell-penetrating poly(disulfide)s, the authors have successfully developed the first mesoporous silica nanoquencher (qMSN), characterized by high drug-loading and endocytosis-independent cell uptake, which is able to quantitatively image endogenous survivin mRNA and release the loaded drug in a manner that depends on the survivin expression level in tumor cells. The authors further show that this novel drug delivery system may be used to minimize potential cytotoxicity encountered by many existing small-molecule drugs in cancer therapy.


Isolated cystic duct cyst with associated stones in a 4-month-old boy.
Isolated cystic duct cysts are rare entities, with few cases having been reported. We present the case of a 4-month-old male patient presenting with abdominal pain and vomiting. Ultrasonography and magnetic resonance cholangiopancreatography revealed an isolated cystic duct cyst with associated stones. The patient underwent open cholecystectomy with complete cyst excision and cystic duct transection; there were no postoperative complications. While lesions like the one described herein are extremely rare, they should be included as a separate category in classifications of choledochal cysts.


Late vascular injury following intertrochanteric fracture reduction with sliding hip screw.
A case involving late injuries to pelvic vessels caused by a sliding hip screw penetrating through the acetabulum has not been previously reported. We present the case of an 88-year-old man who presented with a retroperitoneal and extraperitoneal hematoma 4 months after open reduction and internal fixation of an intertrochanteric hip fracture. Surgical exploration showed a laceration of the left external iliac artery, which was repaired. However, the sliding hip screw was left in place. The patient's condition deteriorated, and he expired 2 days later. Postmortem examination revealed a laceration of the left internal iliac vein. Our calculations show that the compression screw utilized in the fixation may not have been properly engaged into the sliding screw.


Treatment of green table olive solutions with ozone. Effect on their polyphenol content and on Lactobacillus pentosus and Saccharomyces cerevisiae growth.
Disposition of green table olives alkaline solutions (GTOS) remains a major task for the industry with serious environmental implications. The presence of high concentrations of polyphenols in olives also presents a problem for direct brining and successful fermentation step. In this study we evaluated the effect of ozone treated GTOS on the growth of Saccharomyces cerevisiae and Lactobacillus pentosus. GTOS were treated with ozone for 24 and 72 h. The treatment caused a rapid destruction of polyphenols but did not affect sugar concentration. S. cerevisiae grew in the original and treated liquids, although its maximum specific growth rate (mu(m)) and its population size increased as the ozone treatment was longer. L. pentosus was completely inhibited in the original and 24 h ozone treated GTOS, but grew in 72 h treated solutions. Co-culture with S. cerevisiae improved L. pentosus performance. Diluting the original GTOS with distilled water in several ratios, and adding MRS medium (50 g/L) to ensure nutrient availability, showed that a complete inhibition on L. pentosus did never occur; however, its mu(m) progressively increased, and the lag phase period (lambda) decreased linearly, with increasing dilutions levels. The inhibition effect was lower in 24 h ozone treated GTOS and disappeared completely in those treated for 72 h. Furthermore, treatment of GTOS with ozone always improved microbial growth.


Men's multiple sexual partnerships in 15 Sub-Saharan African countries: sociodemographic patterns and implications.
Men's multiple sexual partnerships contribute to the spread of HIV in sub-Saharan Africa, but the social determinants of these relationships remain poorly understood. Prevailing wisdom suggests that men's institutionalized authority over women and their control of economic resources are key facilitators of multiple partnerships in this region. Men's exposure to or freedom from social control mechanisms embedded in family and village life may also play a role. This article provides insight into these issues by examining sociodemographic correlates of men's multiple sexual partnerships using data from recent Demographic and Health Surveys in 15 sub-Saharan African countries. The prevalence of self-reported multiple partnerships varies widely among countries. Sociodemographic patterns of such partnerships confirm the importance of men's control of economic resources and suggest that men's freedom from social control mechanisms may be more important than their authority over their wives.


Dietetic management of gestational diabetes in New Zealand: A cross-sectional survey.
The aim of this study was to evaluate dietetic practice in the management of gestational diabetes in New Zealand, compare this with evidence-based guidelines and determine the need for New Zealand-specific evidence-based nutrition practice guidelines for gestational diabetes. A 64-item cross-sectional online survey of New Zealand-registered dietitians providing care to women with gestational diabetes was undertaken. Participants were recruited through Dietitians New Zealand, District Health Boards and private practices across New Zealand. The survey examined dietetic service provision, management recommendations, guideline use, service evaluation, compliance with national and international guidelines and the perceived need for New Zealand-specific evidence-based guidelines for the nutritional management of gestational diabetes. Thirty-three (62%) eligible dietitians participated in the survey. There was significant variation in dietetic services and management recommendations. Nine (28%) dietitians felt the service within which they worked did not offer adequate dietetic services for women with gestational diabetes. Compliance with national and international evidence-based guidelines ranged from 28 to 100% depending on the recommendation. Twenty-five (76%) respondents felt there was a need for New Zealand-specific evidence-based nutrition practice guidelines for gestational diabetes. These results highlight differences in dietetic services and practice in New Zealand and variations in compliance with local and international evidence-based guidelines. The development of New Zealand-specific evidence-based nutrition practice guidelines for gestational diabetes is supported.


A class III PDZ binding motif in the myotilin and FATZ families binds enigma family proteins: a common link for Z-disc myopathies.
Interactions between Z-disc proteins regulate muscle functions and disruption of these interactions results in muscle disorders. Mutations in Z-disc components myotilin, ZASP/Cypher, and FATZ-2 (calsarcin-1/myozenin-2) are associated with myopathies. We report here that the myotilin and the FATZ (calsarcin/myozenin) families share high homology at their final C-terminal five amino acids. This C-terminal E[ST][DE][DE]L motif is present almost exclusively in these families and is evolutionary conserved. We show by in vitro and in vivo studies that proteins from the myotilin and FATZ (calsarcin/myozenin) families interact via this novel type of class III PDZ binding motif with the PDZ domains of ZASP/Cypher and other Enigma family members: ALP, CLP-36, and RIL. We show that the interactions can be modulated by phosphorylation. Calmodulin-dependent kinase II phosphorylates the C terminus of FATZ-3 (calsarcin-3/myozenin-3) and myotilin, whereas PKA phosphorylates that of FATZ-1 (calsarcin-2/myozenin-1) and FATZ-2 (calsarcin-1/myozenin-1). This is the first report of a binding motif common to both the myotilin and the FATZ (calsarcin/myozenin) families that is specific for interactions with Enigma family members.


Chromium(II) Metal-Organic Polyhedra as Highly Porous Materials.
Herein we report for the first time the synthesis of Cr(II)-based metal-organic polyhedra (MOPs) and the characterization of their porosities. Unlike the isostructural Cu(II)- or Mo(II)-based MOPs, Cr(II)-based MOPs show unusually high gas uptakes and surface areas. The combination of comparatively robust dichromium paddlewheel units (Cr2 units), cage symmetries, and packing motifs enable these materials to achieve Brunauer-Emmett-Teller surface areas of up to 1000 m2/g. Reducing the aggregation of the Cr(II)-based MOPs upon activation makes their pores more accessible than their Cu(II) or Mo(II) counterparts. Further comparisons of surface areas on a molar (m2/mol cage) rather than gravimetric (m2/g) basis is proposed as a rational method of comparing members of a family of related molecular materials.


High-Efficiency and Durable Water Oxidation under Mild pH Conditions: An Iron Phosphate-Borate Nanosheet Array as a Non-Noble-Metal Catalyst Electrode.
It is highly desired but still remains a key challenge to develop iron-based large-surface-area arrays as heterogeneous water oxidation catalysts that perform efficiently and durably under mild pH conditions for solar-to-hydrogen conversion. In this work, we report the in situ derivation of an iron phosphate-borate nanosheet array on carbon cloth (Fe-Pi-Bi/CC) from an iron phosphide nanosheet array via oxidative polarization in a potassium borate (KBi) solution. As a 3D catalyst electrode for water oxidation at mild pH, such a Fe-Pi-Bi/CC shows high activity and strong long-term electrochemical durability, and it only demands an overpotential of 434 mV to drive a geometrical catalytic current density of 10 mA cm-2 with maintenance of its activity for at least 20 h in 0.1 M KBi. This study offers an attractive earth-abundant catalyst material in water-splitting devices toward the large-scale production of hydrogen fuels under benign conditions for application.


Approach to Study the Efficacy and Safety of New Complementary and Alternative Medicine Formulations: Lesson during COVID-19 from Sri Lanka.
COVID-19 affected Sri Lanka from early 2020, a time of considerable ignorance accompanied by wide media coverage of a devastating epidemic in Italy and Europe. Many were attracted to complementary and alternative medicine (CAM) or traditional medicine (TM) in this desperate situation. Several preparations were claimed to be effective against COVID-19 globally. Dammika Bandara Syrup© was one such preparation promoted for preventing and treating SARS-CoV-2 infection. It was based on bees' honey, pericarp and mace of Myristica fragrans (nutmeg), the seed of Foeniculum vulgare and fresh rhizome of Zingiber officinale, all believed to have anti-viral properties. Following an unpublished clinical study claiming efficacy, Dammika Bandara Syrup© gained wide media publicity and political patronage. The producer claimed of Goddess Kali revealing the formula added an anthropological, cultural, and religious complexity to the issue. The demand for the product increased rapidly as a debate raged both in public and in the parliament on utilizing such products in combating COVID-19. The Department of Ayurveda, which is statutorily responsible for regulating CAM/TM had to respond to the situation. The legislation to regulate such indigenous medicinal products was weak, and the crisis deepened as thousands converged to the production facility, defying mobility restrictions introduced to control COVID-19. This led to the Ministry of Health requesting academics to form a team and conduct a clinical trial to prove its efficacy. This paper outlines the process and issues faced during the regulatory approval for the trial in a polarized political environment. Some health professionals accused the researchers of bowing to political pressure and questioned the scientific justification for the trial. However, the team considered this as an opportunity to streamline a path for research into CAM/TM therapies in situations such as COVID-19. Several processes were identified and addressed, such as the provisional registration of CAM preparations, assessing the potential efficacy of a CAM product, confirmation of authenticity and safety, standardization and supervision of production respecting cultural identities, obtaining approval for human use, choice of comparators, and ethical issues. We believe the study has helped set standards and a benchmark for CAM and TM research in Sri Lanka.


Assessment of season-dependent body condition scores in relation to faecal glucocorticoid metabolites in free-ranging Asian elephants.
We studied seasonal and annual changes in visual body condition scores (BCSs), and assessed how these scores were related to levels of faecal glucocorticoid metabolites (fGCMs) in free-ranging Asian elephants (Elephas maximus) in the seasonally dry tropical forests of the Mysore and Nilgiri Elephant Reserves in southern India. We assessed the animals' BCS visually on a scale of 1 to 5; where 1 represents a very thin and 5 represents a very fat elephant. To understand the influence of seasonality on BCS, we sampled the population during dry (n = 398) and wet seasons (n = 255) of 2013 and 2015 while, for annual changes in BCS, we sampled nine free-ranging adult females from different family groups that had been repeatedly sighted over seven years. To evaluate the influence of body condition on fGCM, 307 faecal samples were collected from 261 different elephants and were analysed. As a parameter of adrenocortical activity, and thus stress, fGCM was measured (μg/g) in the ethanol-extracted samples using a group-specific 11-oxoaetiocholanolone EIA (antibody raised against 11-oxoaetiocholanolone-17-CMO:BSA and biotinylated-11-oxoaetiocholanolone as a label). Effect of age and season on BCS in relation to fGCM was also studied. A seasonal shift in BCS was observed as expected, i.e. individuals with low BCS were more frequent during the dry season when compared with the wet season. Concentrations of fGCM were highest in individuals with lowest BCS (BCS 1) and then significantly declined till BCS 3. fGCM levels were almost comparable for BCS 3, 4 and 5. This pattern was more conspicuous in female than in male elephants. Season-dependent BCS, hence, reflect the stress status as measured by fGCM, especially in female Asian elephants. This could be used as an important non-invasive approach to monitor the physiological health of free-ranging elephant populations.


Impact of a statewide trauma system on the triage, transfer, and inpatient mortality of injured patients.
In 2009, Arkansas implemented a statewide trauma system to address the high rates of mortality and morbidity due to trauma. The principal objective of the Arkansas Trauma System is to transport patients to the appropriate facility based on the injuries of the patients. This study evaluated four metrics that were crucial to system health. These measures included: treatment location, scene triage, admission to nondesignated facilities, and inpatient mortality. Furthermore, the authors sought to quantify how the system is selective toward the severely injured regarding triage and treatment location. The authors hypothesized that system implementation should increase the proportion of patients, particularly the severely injured, treated at Level I/II facilities. The system should increase the proportion of patients, especially the severely injured, admitted to Level I/II facilities directly from the scene. The system should result in fewer patients admitted to nondesignated facilities. Lastly, system implementation should result in fewer inpatient deaths. A pre-post study design was used for this evaluation. Data from the Arkansas Hospital Discharge data set (2007 through 2012) identified patients who were admitted as a result of their injuries. The ICD-MAP software was used to categorize those with and without severe injuries based on an Injury Severity Score of 16 or greater or head Abbreviated Injury Scale score of 3 or greater. The results indicate that while there was an overall increase in odds of patients being admitted to Level I/II facilities, those with severe injuries were associated with an even greater odds of admission to Level I/II facilities (p < 0.0001). System implementation was also associated with more severely injured patients admitted to Level I/II facilities from the scene. There were also fewer patients admitted to nondesignated hospitals after system implementation (p < 0.0001). System implementation was associated with fewer inpatient deaths (p = 0.02). Two years after implementation, the trauma system showed significant progress. The measures evaluated in this study are believed to support the effectiveness of the trauma system. Therapeutic study, level IV.


Pretreatment episode count and response to lithium treatment in manic-depressive illness.
Factors that reliably predict treatment response in bipolar disorder are much needed, particularly since no available treatment routinely affords complete protection from future illness. The number of pretreatment episodes (PTEs) is a proposed predictor, but its value remains uncertain. We therefore reviewed available research on this topic. Based on a computer-assisted search of the literature, we identified 28 reports providing data on response to lithium treatment and on history of past illness. We evaluated their methods and findings to test the hypothesis that greater PTE count predicts inferior clinical response to lithium. Most studies (68%) found no support for the predicted relationship, and those that did or did not find the hypothesized relationship differed nonsignificantly in ratings of overall study quality and individual factors, including study size, previous lithium use, diagnostic criteria, and outcome measures. The concept that PTE count strongly and consistently predicts inferior clinical response to lithium treatment in manic-depressive disorders is not supported by available research, thus adding to emerging uncertainties about the relationship of past history and later course of these often severe, disabling, and life-threatening illnesses.


A novel kavalactone derivative protects against H2O2-induced PC12 cell death via Nrf2/ARE activation.
Oxidative stress is involved in the pathogenesis of neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Natural kavalactones isolated from Piper methysticum (Piperaceae) are capable of activating the Nrf2/ARE (antioxidant response element) pathway and thus enhancing the expression of phase II antioxidant enzymes such as heme oxygenase-1 (HO-1). In an attempt to identify kavalactone derivatives that are more potent in Nrf2/ARE activation than natural compounds, we synthesized a series of chemically-modified kavalactones and studied their effects on the ARE enhancer activity in rat pheochromocytoma PC12 cells. Among 81 compounds tested, a kavalactone derivative, 2',6'-dichloro-5-methoxymethyl-5,6-dehydrokawain [(E)-6-(2',6'-dichlorostyryl)-4-methoxy-5-(methoxymethyl)-2H-pyran-2-one] (1), exhibited the strongest ARE enhancer activity. The ARE activation and HO-1 protein induction by the compound 1 were higher than those by natural kavalactones. The compound did not affect cell viability and induced expression of various phase II enzymes. Nuclear translocation of Nrf2 after treatment with 1 was preceded by phosphorylation of ERK1/2 and p38. The compound transiently increased intracellular ROS levels. Finally, pretreatment with the compound ameliorated H(2)O(2)-induced cell death, which was associated with increased expression of HO-1. These results suggest that the compound 1 protects against oxidative stress-induced neuronal cell death via a preconditioning effect on the Nrf2/ARE activation.


Purification of alkaline phosphatase of the halotolerant yeast Debaryomyces hansenii.
Alkaline phosphatase (orthophosphoric monoester phosphohydrolase, EC 22.214.171.124) of the halotolerant yeast Debaryomyces hansenii was purified by a procedure involving cell disruption, DNAase treatment, ethanol precipitation, gel filtration, chromatography on DEAE-Sephadex, and preparative polyacrylamide gel electrophoresis. The specific activity was increased 1250-fold as compared to the activity of cell free extract. The total recovery was 30%. Various modifications of the growth conditions had slight or no effect on the yield of enzyme.


Soft Tissue Mobilization to Resolve Chronic Pain and Dysfunction Associated With Postoperative Abdominal and Pelvic Adhesions: A Case Report.
Case report. Common complications from abdominal and pelvic surgery include adhesions and chronic pain. Laparoscopic adhesiolysis is sometimes used to reduce adhesions and related pain. Physical therapy interventions, such as soft tissue mobilization (STM), may be used for this condition; however, evidence to support its effectiveness is lacking. A 28-year-old woman with a history of 5 abdominal/pelvic surgeries presented with right-sided lower abdominal and anterior hip pain, which had been present since she had undergone a laparoscopic appendectomy with a right ovarian cystectomy surgery 1 year earlier. As an active-duty member in the US Navy, due to pain and weakness, she was unable to perform required curl-ups for her fitness test. Though she had been previously treated both surgically with laparoscopic adhesiolysis and nonsurgically with physical therapy consisting of stretching and strengthening exercises, her pain and function did not improve. She was again evaluated and treated with physical therapy and, based on the examination findings, STM was used to address her pain and dysfunction, which were thought to be related to intra-abdominal adhesions. Following 5 sessions of physical therapy over a 3-week period that included STM and therapeutic exercises, followed by 5 additional sessions over a 4-week period that focused on therapeutic exercises, the patient reported substantially decreased pain, improved function, and a full return to previous level of activity, including unrestricted physical training in a military setting. The outcomes for this patient suggest that STM may be effective as a conservative treatment option for pain and dysfunction related to intra-abdominal adhesions from abdominal/pelvic surgery. Studies with a higher level of evidence, including potential comparison between STM and traditional laparoscopic adhesiolysis, are needed to further determine benefits of nonsurgical care for this condition.


Transition from methadone to subcutaneous buprenorphine depot in patients with opioid use disorder in custodial setting - a case series.
Methadone, a full opioid agonist, and buprenorphine, a partial agonist at the opioid receptor, are established first-line medications for opioid maintenance therapy. Transition from methadone to sublingual buprenorphine may precipitate withdrawal and is usually performed only in patients on low dose of methadone (<30-40 mg). Transition from methadone to a novel subcutaneous buprenorphine depot (Buvidal) has not been previously described. To test the hypothesis that a rapid transition from methadone to buprenorphine depot after a single dose of buprenorphine 4 mg sublingual is safe and well tolerated. Retrospective chart analysis of a case series of seven opioid users under custodial setting (prison) who were switched from methadone to buprenorphine depot (initial dose 16 mg weekly subcutaneously) after an initial test dose of buprenorphine 4 mg sublingual within 48 hours. Clinical data indicate that a rapid transition from methadone to depot buprenorphine is feasible (six patients within 48 hours, one within 4 days). All patients were successfully switched to buprenorphine depot and the transfer period was completed without dropouts or major medical problems. Further dose adjustments were performed in 4 of 7 patients. Transition of opioid users from methadone to buprenorphine depot is feasible and safe via 4 mg buprenorphine sublingual. This procedure may facilitate induction of buprenorphine depot formulations in patients treated with methadone.


Tumor-promoting phorbol esters suppress receptor-stimulated inositol phospholipid degradation and Ca2+ mobilization in mouse lymphocytes.
Anti-immunoglobulin antibodies (anti-Ig) provoke the rapid breakdown of phosphatidylinositol bisphosphate (PIP2), elevation of cytoplasmic Ca2+ levels ([Ca2+]i) and activation of protein kinase C (PKC) in B lymphocytes. Tumor-promoting phorbol esters, like phorbol myristate acetate, also activate PKC, but inhibit anti-Ig-induced B cell proliferation. To investigate the basis of the latter effect, we studied the influence of phorbol esters on PIP2 degradation and [Ca2+]i in murine B cells. The results show that PKC-activating phorbol esters cause marked inhibition of anti-Ig-stimulated PIP2 breakdown and Ca2+ mobilization. In addition, these agents inhibit concanavalin A-provoked Ca2+ influx, lower resting cytoplasmic Ca2+ levels and reduce ionophore-induced Ca2+ influx in B cells. Apparently, PKC stimulation causes feedback inhibition of receptor signalling, not only by suppressing PIP2 degradation, but also by exerting additional complex effects on the control of [Ca2+]i in B cells. It is, however, not clear how these findings relate to the anti-proliferative effects of phorbol esters on B cells.


Early Experience in Starting a Laparoscopic Liver Resection Program in Greece.
Laparoscopic liver resections (LLRs) have gained wider acceptance during the decade as safe and efficient procedures in the management of several benign and malignant diseases when performed by experienced surgeons. We report our initial institutional experience with LLRs performed by 1 certified hepatobiliary surgeon. Patients undergoing LLRs by 1 senior hepatobiliary surgeon in our Institution during the period from January 2012 through January 2017 were prospectively sampled and retrospectively analyzed for the purposes of this study. Forty-two of 175 patients (24%) who had surgery for liver tumors underwent LLR. Median age was 64 years; median body mass index and Charlson comorbidity index were 27.3 kg/m2 and 6.5, respectively. Patients underwent resections for benign (n = 22) or malignant (n = 20) lesions. Median total operating time was 115 minutes and liver resections included: 1 left hepatectomy, 11 bisegmentectomies, 7 segmentectomies, 5 wide wedge resections, 1 left lateral sectionectomy combined with segmentectomy and radiofrequency ablation, 15 liver cyst unroofing, 1 laparoscopic drainage of a pyogenic liver abscess, and 1 laparoscopic drainage of a hepatic hydatid cyst. Blood transfusion was needed in 10 patients. Six patients (14%) had postoperative complications, none of which necessitated reoperation. None of the patients was admitted to the intensive care unit after surgery, and the median hospital stay was 4 days. The tumor-free resection margin was documented in all primary or secondary oncologic cases. Careful patient selection and compliance with the international recommendations are the keys for the successful introduction and evolution of an LLR program with a certified hepatobiliary surgeon with laparoscopic experience.


Stereoselective synthesis of (E)-mannosylidene derivatives using the Wittig reaction.
Stabilized ylides Bu(3)P=CH(EWG), where EWG is an ester or nitrile group, react with 2,3,4,6-tetra-O-benzylmannono-1,5-lactone giving high yields of mannosylidene derivatives; in contrast to the glucose and galactose analogues, the (E)-mannosylidenes are predominant (E:Z > 9:1), thus minimizing dipole-dipole repulsions in the Wittig reactions. NMR indicates chair-like conformations for solutions of the (E)-mannopyranosylidenes, but not for those (Z)-isomers where data are available (EWG = CN or CO(2)Et). X-ray crystallography shows an approximately twist-boat conformation for the tetra-O-benzyl-protected (Z)-mannosylideneacetonitrile.


Acute myocardial infarction in a patient with normal coronary arteries after an allergic reaction.
The case is described of a man aged 51 years who, one hour after a coronary angiographic examination that showed coronary arteries without lesions, suffered an acute inferior myocardial infarction as the result of an acute allergic reaction, probably to the iodinated contrast agent that was used. Acute myocardial infarction following an allergy is an extremely rare clinical entity that, according to existing data, is due to the local release of vasoconstrictive substances as a result of the allergic reaction.


Effect of osmotic pressure on uptake of chemotherapeutic agents by carcinoma cells.
Intraperitoneal chemotherapy has been used to treat cancers which are confined to the abdominal cavity. Several variables which affect drug delivery into tumor cells have been identified, but the effect of osmotic pressure has not been studied. Tumor cell lines were used to evaluate the effect of fluid tonicity on drug uptake. HeLa cells and a murine teratoma cell line were suspended in solutions of tonicities 154, 308, and 616 mosM, each containing the same quantity of 5-fluorouracil, and uptake of the drug was measured at different intervals over 30 min. At all time points the amount of 5-fluorouracil taken up by cells in solutions of 154 mosM was greater than that in 310 mosM solutions, which was greater than the uptake in 616 mosM solutions, each by an average of 40-50%. Incorporation of drug into tumor cells was also assayed in vivo using a teratoma cell line propagated i.p. in mice. Tumor cell uptake of doxorubicin was increased to a similar extent when this drug was administered in hypotonic solutions of 154 mosM and was decreased by administration in hypertonic solutions of 465 mosM, as compared to solutions of 310 mosM. These results demonstrate that the uptake of chemotherapeutic agents into tumor cells is increased significantly when these drugs are infused in solutions of lower osmolalities, a finding which may be exploited in clinical situations.


Role of three-dimensional imaging integration in atrial fibrillation ablation.
Atrial fibrillation is the most common arrhythmia and in symptomatic patients with a drug-refractory form, catheter ablation aimed at electrically disconnecting the pulmonary veins (PVs) has proved more effective than use of antiarrhythmic drugs in maintaining sinus rhythm during follow-up. On the other hand, this ablation procedure is complex, requires specific training and adequate clinical experience. A main challenge is represented by the need for accurate sequential positioning of the ablation catheter around each veno-atrial junction to deliver point-by-point radiofrequency energy applications in order to achieve complete and persistent electrical disconnection of the PVs. Imaging integration is a new technology that enables guidance during this procedure by showing a three-dimensional, pre-acquired computed tomography or magnetic resonance image and the relative real-time position of the ablation catheter on the screen of the electroanatomic system. Reports in the literature suggest that imaging integration provides accurate visual information with improvement in the procedure parameters and/or clinical outcomes of the procedure.


Polychlorinated Dibenzo-p-dioxins and Dibenzofurans in Sediments from Siskiwit Lake, Isle Royale.
Polychlorinated dibenzo-p-dioxins and dibenzofurans were found in sediment from Siskiwit Lake on Isle Royale, Lake Superior, a location which can receive only atmospheric inputs. The source of these compounds is the atmospheric transport of dioxins and furans formed by combustion of domestic and chemical waste.


[Impact of the guidelines on clinical practice of artificial nutrition in intensive care unit after cardiovascular and thoracic surgery].
To analyze the impact of an artificial nutrition program in post-anaesthesia intensive care unit. Observational study. Patients with length of stay greater than 8 days after cardiovascular and thoracic surgery: Group 1: 34 patients (4-month period in 2000); group 2: 15 patients (2-month period in 2001); group 3: 40 patients (4-month period in 2003). Between these 3 periods, informations of physicians and written protocol in order to improve their nutritional knowledge. After analysis of variance (P<0.05). Newman-Keuls tests to compare themselves each groups. Anthropometric, demographic and clinical parameters were similar in the 3 groups. Energic intakes were less than 80% of basal energetic expenditures in 33%, 33 and 22% of patient, respectively (NS). Caloric and nitrogen intakes were less than recommended, respectively 19+/-6 (mean+/-SD), 21+/-7 and 21+/-8 kcal/kg/24 h and 102+/-32, 111+/-31 and 92+/-40 mg/kg/24 h (NS). However enteral nutrition was administered in 49, 40 and 100% of patients respectively (P<0.001). The glucid/lipid ratio improved from 0.47 in group 1 up to 0.68 in group 3 (P<0.0001). Vitamins, oligoelements and clinical and biological monitoring of artificial nutrition improved (P<0.001). A clinical audit demonstrated an improvement in artificial nutrition parameters but no significant change in others.


opp-lac Operon fusions and transcriptional regulation of the Escherichia coli trp-linked oligopeptide permease.
The transcriptional regulation of the Escherichia coli trp-linked opp operon that encodes the oligopeptide permease was investigated by using lambda plac Mu51-generated lac operon fusions. Synthesis of beta-galactosidase by strains harboring oppA-lac, oppB-lac, and oppD-lac fusions occurred at a basal level when the fusion-containing strains were grown in minimal medium. The addition of L-leucine or L-alanine to exponentially growing, aerobic cultures or shifting the aerobic fusion-containing strains to anaerobic growth medium increased the synthesis of beta-galactosidase from all opp-lac fusions. When transcription of the opp operon was induced by L-leucine, the differential rate of beta-galactosidase synthesis from each opp-lac fusion increased 8- to 10-fold; this increased rate of lacZ expression from the opp-lac fusions resulted in a 5- to 6-fold increase in total beta-galactosidase activity after maximum expression was achieved. Importantly, when F'123 derivatives harboring independently isolated E. coli opp-lac operon fusions were introduced into E. coli and Salmonella typhimurium, the data clearly demonstrated that the E. coli opp operon was expressed identically and responded to the same transcriptional regulatory signals in both E. coli and S. typhimurium. A comparison of beta-galactosidase synthesis by E. coli strains harboring an opp-lac operon fusion and either an oppE+ locus or an oppE mutation demonstrated that the reduction in peptide transport produced by the oppE mutation does not result from a decrease in the level of opp operon transcription.


[Mismatch negativity in the auditory event-related potentials in response to abrupt and smooth displacements of virtual sound source].
The work investigated event-related potentials, mismatch negativity (MMN), and P3a component under dichotic stimulation with deviant stimuli simulating abrupt or smooth displacement of auditory images to the left or to the right from the head midline by means of interaural time delay introduced into the deviant stimuli. Repetitive standard stimuli were localized near the head midline. All deviant stimuli elicited mismatch negativity and P3a component. It was shown the MMN for smooth deviant motion was lower than that for the abrupt deviant displacement. MMN amplitude for both deviant types obviously depended on interaural time delay, which confirms that MMN might be considered as a measure of the auditory system spatial discriminative ability. The P3a component demonstrated the same amplitude dependences as the MMN. The results obtained are discussed in respect to manifestation of the processes underlying the auditory motion detection in the event-related potentials.


Gene Silencing of Toll-like Receptor 2 Gene Expression as a Tactic to Control Mycobacterium Tuberculosis and Granuloma Formation.
Mycobacterium tuberculosis (MT) is the causative agent of tuberculosis (TB) in humans. Tuberculosis is one of the top 10 causes of mortality worldwide, resulting in 1.8 million deaths and 10.4 million new cases in 2016. Understanding the fundamental features of MT biology is critical to the eradication of MT in the future. Due to the increasing frequency of antimicrobial treatment resistance and problems in vaccine development, the pathogenesis of TB for its survival and growth is highly dependent on host lipids and stimulated-lipid droplets formation. Toll-like receptor 2 (TLR2) forms heterophilic dimers with TLR1 and TLR6, therefore, recognizing many MT components. Both of these receptors identify the invading antigen and activate downstream protein kinases. Some studies demonstrated that the cyclooxygenase-2 (COX-2) promoter-driven gene expression includes connecting sites for transcription factors, such as nuclear factor-kappa B, CREB, NFAT, and c/EBPβ. The current study aimed to investigate the role of the TLR2 receptor in positively regulating prostaglandin E2 production in M. bovis (BCG) infected macrophages in vivo using a human monocytic cell line THP-1. Our results revealed that MT infection triggers a time-dependent increase in COX-2 expression via pathways involving TLR2 receptor activation and enhances COX-2 expression, leading to an increase in lipid droplet formation and suppression of macrophage activation.


Glutathione homeostasis is significantly altered by quercetin via the Keap1/Nrf2 and MAPK signaling pathways in rats.
Previously, we showed that 0.5% quercetin simultaneously decreased serum homocysteine and glutathione (GSH) levels in rats. The aim of the present study was to investigate the effects of 0.5% quercetin on GSH metabolism, related enzymes and signal pathways in rats. Rats were fed the control diet and 0.5% quercetin-supplemented diet for 6 weeks. The results showed that quercetin reduced serum and hepatic content of GSH and the ratio of GSH and oxidized glutathione (GSSG), enhanced hepatic activity and mRNA expression of glutathione S-transferase (GST), inhibited hepatic activity and mRNA expression of glutamate cysteine ligase (GCL), and decreased hepatic glutathione reductase (GR) mRNA expression. Levels of phosphorylated p38 and extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinases (MAPKs) increased, while that of nuclear factor E2-like 2 (Nrf2) protein decreased after quercetin treatment. However, no significant hepatotoxicity was noted. We concluded that quercetin treatment altered hepatic GSH metabolism by modulating GSH metabolic enzyme activities and mRNA expression in rats, and p38, ERK1/2 MAPKs, and Nrf2 were involved in modulating GSH metabolism-related enzymes.


Comparison analysis of PD-1/PD-L1 inhibitors plus lenvatinib or gemcitabine/cisplatin as first-line treatment for patients with advanced intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive primary liver cancer, with increasing incidence worldwide. Effective first-line treatments for advanced ICC patients are currently limited. Therefore, our study aimed to assess the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in combination with gemcitabine/cisplatin (GC) and lenvatinib as first-line treatment in advanced ICC patients. This retrospective cohort study included 51 advanced ICC patients, among whom 25 patients were administered with PD-1/PD-L1 plus lenvatinib and 26 patients were administered with PD-1/PD-L1 plus GC. Baseline characteristics including demographic information, medical history, clinical characteristics, laboratory data, and imaging examination were collected. The primary endpoints were progression-free survival (PFS) and sixth- and ninth-month overall survival (OS) rate. Survival curve was plotted by the Kaplan-Meier method. A Cox proportion risk model was performed to investigate independent risk factors of PFS and OS. The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. The median age of advanced ICC patients in our study was 58.0 (95% confidence interval [95% CI] = 48.0-72.4) years, with 33 male and 18 female patients. Patients in the PD-1/PD-L1 inhibitors plus lenvatinib group were more likely to be in ECOG grade above 1, develop ascites, and have an elevated level of ALT. The ORR was 16.0% in the PD-1/PD-L1 inhibitors plus lenvatinib group and 23.1% in the GC group (p = 0.777). The DCR was 52.0% in the lenvatinib group and 46.2% in the GC group (p = 0.676). The combination treatment of PD-1/PD-L1 inhibitors plus lenvatinib was associated with longer PFS than the GC group; however, it was not statistically significant (lenvatinib: 9.5 months, GC: 5.1 months, p = 0.454). The sixth-month and ninth-month OS rates were 82.0% and 76.9% in the lenvatinib group and 87.4% and 71.5% in the GC group. After adjusting for confounders, multivariate Cox regression analysis showed that ECOG grade above 1 was an independent risk factor for PFS (hazard ratio [HR] = 3.388, 95% CI = 1.312-8.746, p = 0.012) and OS (HR = 4.220, 95% CI = 1.131-15.742, p = 0.032). PD-1/PD-L1 inhibitors in combination with lenvatinib or GC all demonstrated significant efficacy and safety as first-line treatment in patients with advanced ICC. As for patients who refuse or are intolerant to chemotherapy, PD-1/PD-L1 plus lenvatinib would be recommended.


Maintaining primacy of the patient perspective in the development of patient-centered patient reported outcomes.
The objectives of this study were to describe and demonstrate a new model of developing patient reported outcomes (PROs) that are patient-centered, and to test the hypothesis that following this model would result in a qualitatively different PRO than if the typical PRO development model were followed. The typical process of developing PROs begins with an initial list of signs or symptoms originating from clinicians or PRO developers; patient validation of this list ensures that the list (i.e., the new PRO) is interpretable by patients, but not that patient perspectives are central or even represented. The new model begins with elicitation from clinicians and patients independently and separately. These perspectives are formally analyzed qualitatively, and the results are iteratively integrated by researchers, supporting clinical relevance and patient centeredness. We describe the application of this new model to the development of a PRO for urinary signs and symptoms in individuals with neuropathic bladder, and test the hypothesis that the two processes generate qualitatively different instruments using a national validation sample of 300 respondents. Of its 29 items, the new instrument included 13 signs/symptoms derived from existing clinical practice guidelines, with 16 others derived from the patient/focus groups. The three most-endorsed items came from the patients, and the three least-endorsed items came from clinical guidelines. Thematic qualitative analysis of the elicitation process, as well as the results from our national sample, support the conclusion that the new model yields an instrument that is clinically interpretable, but more patient-centered, than the typical model would have done in this context.


Recent developments in Salvia miltiorrhiza polysaccharides: Isolation, purification, structural characteristics and biological activities.
In recent years, natural polysaccharides have attracted more and more attention and research because of their value in the medicine, beauty and food fields. Salvia miltiorrhiza is a traditional Chinese herb that has been used for thousands of years and has antidiabetic, antifibrotic, neuroprotective, antioxidation, anti-inflammatory and other effects. It mainly includes rosmarinic acid, tanshinone I, tanshinone IIA, tanshinone IIB, procatechualdehyde, polysaccharide and salvianolic acids. Salvia miltiorrhiza polysaccharide is a polysaccharide extracted and isolated from Salvia miltiorrhiza and has diverse biological functions, including antioxidation, anti-tumor, hepatoprotective, anti-inflammatory, immune regulatory and cardioprotective effect. In this review, the extraction, purification, structural characterization and biological activity of SMPs are summarized and new perspectives for the future work of SMPs were also proposed, we hope our research can provide a reference for further research on SMPs.


Effect of Thermozeaxanthins on Liposome Membranes in Acidic and Basic Conditions.
Thermozeaxanthins (TZS), a group of carotenoid-glucoside esters extracted from the lipids fraction of thermophilic bacterium, are amphiphilic compounds. The effects of TZS on membrane permeability were examined on large unilamellar liposomes (LUVs) in different pH buffers. The LUVs were composed of 0.01 molar of TZS and phosphatidylcholine (PC) of various lengths and saturation degrees of hydrocarbon chains. The results showed that the LUVs containing TZS were more stable than that liposomes without TZS in pH 5.0, and no significant effects in pH 8.2 and 9.0 buffer solutions. The liposomes composed of TZS and egg PC or E.coli PE were better than those DPPC or DOPC LUVs containing TZS at same experimental conditions. There was no observed difference in stability between the liposomes with or without TZS in pH 6.5 solution. Conclusions (1) Matching of rigid TZS in the lipid bilayer was important in stabilization effects on liposomes, (2)The TZS showed some stabilization effects on liposome membranes in acidic conditions and no significant effects in basic environment.


Comparison of intelligence quotient in children surviving leukemia who received different prophylactic central nervous system treatments.
Neurocognitive deficits and decrease in intelligence quotient (IQ) is one of the complication of prophylactic central nervous system (CNS) treatment in acute lymphoblastic leukemia (ALL) patients. In this study, we compare the IQ in survivors of ALL that were treated with different prophylactic CNS treatments. We compared 43 long-term survivors of ALL: 21 survivors with intrathecal methotrexate (IT MTX) as CNS prophylaxis, 22 with IT MTX+1800-2400 rads cranial irradiation and 20 healthy controls. The IQ was measured using the Raven's test in these patients. Raven's test revealed significant differences in IQ between the survivors of ALL that were treated with IT MTX, IT MTX plus cranial irradiation and control group. There was no significant difference in the IQ with respect to sex, age and irradiation dose. We can that reveal that CNS prophylaxis treatment, especially the combined treatment, is associated with IQ score decline in ALL survivors. Therefore,a baseline and an annual assessment of their educational progress are suggested.


Modification of vectors for functional genomic analysis in plants.
Simple, efficient, and economical recombinant plant binary expression vectors for deciphering large-scale functional genomic research in plants and promoting crop improvement by genetically engineering and biotechnology is in great demand. In this research, using the pCHF3, pCAMBIA1301, pCAMBIA3300, pCAMBIA3301 vectors, we successfully constructed general plant binary expression vectors carrying CaMV35S and Arabidopsis rd29A promoters mediating multiple cloning sites ( SacI, KpnI, SmaI, BamHI, XbaI, SalI, and PstI). Meanwhile, a series of applicative binary expression vectors that can be utilized for subcellular localization were constructed by fusion of the MCS and eGFP. Subsequently, the recombinant vectors were successfully transferred into Arabidopsis thaliana and Nicotiana benthamiana for further investigation of functional elements in these plant binary expression vectors. Our results demonstrated that this system was a convenient and versatile vector system for phenotypic, functional, subcellular localization, and promoter activity analysis, and it provided a relatively high-efficiency and reliable platform for researchers in vector construction and may facilitate large-scale functional genomics analysis in plants.


Anti-influenza virus activities of 4-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)amino]-N-(4,6-dimethyl-2-pyrimidin-2-yl)benzenesulphonamide and its derivatives.
4-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)amino]-N-(4,6-dimethyl-2-pyrimidinyl)-benzenesulphonamide (SPIII-5H) and related compounds were tested for antiviral activity against influenza A (H1N1, H3N2, and H5N1) and B viruses in Madin Darby canine kidney (MDCK) cell culture. Among the compounds tested, SPIII-5H and four derivatives (5-chloro [SPill-5Cl], 5-bromo [SPIII-5Br], 5-methyl [SPIII-5Me] and N-acetyl [SPIII-NA]) showed similar antiviral potencies, with only the 5-fluoro (SPIII-5F) derivative being ineffective. Fifty percent effective concentration (EC50) values were determined in cytopathic effect (CPE) inhibition assays quantified by neutral red dye uptake. By this method, the active compounds were inhibitory to the H1N1 strain of influenza A at 2.7-5.2 microg/ml, to the H3N2 strain of influenza A at 13.8-26.0 microg/ml, to the H5N1 strain of influenza A at 3.1-6.3 microg/ml and to influenza B at 7.7-11.5 microg/ml. Confirmatory virus yield reduction studies against influenza A (H1N1) virus demonstrated antiviral activity (90% inhibition) at concentrations of 2-10 microg/ml. No cytotoxic effects were evident in actively growing uninfected cells or stationary monolayers at 100 microg/ml. Potencies of the compounds were similar to those of ribavirin, but much less than those of oseltamivir carboxylate against the various viruses. Time-of-addition studies indicated the compounds inhibited an early step in the virus replication cycle, probably virus adsorption/penetration, and no virucidal activity was evident. The basic molecule is amenable to diverse chemical modifications, which may improve water solubility and antiviral potency.


Temporal changes in liver tissue metabolome of lambs fed low-quality roughage.
Early experience with low-quality roughage may induce adaptations in ruminants' metabolism. This study was conducted to explore the variation in the hepatic metabolomes of lambs fed low-quality roughage beginning early in life. Five lambs were fed Sudan grass hay (crude protein (CP): 4.6% of the dry matter (DM), neutral detergent fiber, 68.5% of DM) for 6 months during time periods P1, P2 and P3, which consisted of 2 months each. The metabolizable energy (ME) and CP intake satisfied lambs' maintenance requirements in P1 and P2, but the ME intake was 78.5% of the maintenance ME requirement in P3. Liver metabolomics was carried out in P2 and P3 by the capillary electrophoresis and time-of-flight mass spectrometry system. Eight amino acids and six amino acid metabolism-related metabolites were altered between P2 and P3. Several intermediates of glycolysis/gluconeogenesis decreased, while nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate increased in P3. Taurocholic acid and taurine increased, while glycocholic acid decreased in P3. The results suggested that amino acid utilization and the efficiency of glycolysis/gluconeogenesis might be adjusted to accommodate the low-quality roughage fed to the lambs during early stages of life. The composition of bile acids might also be optimized to promote the efficiency of lipid absorption.


Genomic Identity of Fluoroquinolone-Resistant blaCTX-M-15-Type ESBL and pMAmpC β-Lactamase Producing Klebsiella pneumoniae from Buffalo Milk, India.
We investigated the occurrence of extended-spectrum β-lactamase (ESBL) and AmpC-type β-lactamase (ACBL) producing quinolone-resistant Klebsiella pneumoniae (KP) in milk samples of apparently healthy buffaloes (n = 348) and buffaloes (n = 19) with evidence of subclinical mastitis from seven districts of West Bengal, India. In total, 12 ESBL producing KP were isolated with blaCTX-M-15 gene and 7 of them were ACBL producers, as well. The blaCTX-M-15 genes were carried by transposable element ISEcp1. The plasmid-mediated quinolone resistance genes-qnrS, qnrA, qnrB, qepA, and aac(6')-Ib-cr were detected in five, one, three, four, and one isolate (s), respectively. In addition, eight isolates carried mutation in gyrase (gyrA) and six in topoisomerase IV (parC). Resistance markers/genes for sulfonamide (sul1), tetracycline [tet(A) and tet(B)], and aminoglycoside (aacC2) were also detected in eight, four, and one isolate(s), respectively. The class I integrons identified in five isolates carried aad2/aad5 and dfrA12/dfrA17 gene cassettes. The enterobacterial repetitive intergenic consensus-PCR revealed that all the isolates were genetically diverse and comprised a heterogeneous population. Isolation of multidrug-resistant KP, a typical nosocomial pathogen from buffalo milk, reiterates the need to monitor farm animals for ESBL producing Enterobacteriaceae and emphasizes on judicious use of antibiotics in animal husbandry sector.


Autonomy, consent, and medical paternalism: legal issues in medical intervention.
Patients are increasingly questioning their relationships with their doctors during a time when use of alternative health care approaches is rising, paternalistic models of health care are waning, and police powers related to health care are expanding. Focusing on the topics of mandatory vaccination and forced medical treatment of children with cancer, this paper reviews issues related to autonomy, informed consent, medical paternalism, forced medical treatment, the police powers of the state, and related legal issues. Based upon this review, it becomes clear that the fight over personal autonomy and paternalism in health care is far from over.


Nonconventional yeasts: their genetics and biotechnological applications.
To date, more than 500 species of yeasts have been described. Most of the genetic and biochemical studies have, however, been carried out with Saccharomyces cerevisiae. Although a considerable amount of knowledge has been accumulated on fundamental processes and biotechnological applications of this industrially important yeast, the large variety of other yeast genera and species may offer various advantages for experimental study as well as for product formation in biotechnology. The genetic investigation of these so-called unconventional yeasts is poorly developed and information about corresponding data is dispersed. It is the aim of this review to summarize and discuss the main results of genetic studies and biotechnological applications of unconventional yeasts and to serve as a guide for scientists who wish to enter this field or are interested in only some aspects of these yeasts.


Synergy between Th1 and Th2 responses during Mycobacterium tuberculosis infection: A review of current understanding.
Induction of Th1 (cell-mediated) immunity and associated production of IFN-γ by CD4+ T cells has been widely used as a marker of protective immunity against tuberculosis (TB). This is based on two assumptions. The first is the widely accepted view that Mycobacterium tuberculosis (Mtb), the causative agent of TB is an obligate intracellular pathogen, and the second is based on the Th1/Th2 paradigm, which posits that polarization of CD4+ T cells into type1 (cell-mediated) and type 2 (humoral) is central for proper induction of protective immunity against pathogens. However, almost all licensed vaccines currently in use are primarily anti-body based whether intracellular or extra-cellular. In addition, converging data from both animal models and humans indicate that the production of IFN-γ alone is not sufficient to confer protection against TB. In addition, a substantial body of the literature suggests that, in addition to Th1 cells, antibody classes and sub-classes are protective against TB. In a recent study, we have shown that there is a synergy between IFN-γ (cell-mediated) and IgA (humoral) in human population in an endemic setting. In this review, current data from both animal and human studies that support mixed Th1 and Th2 responses that are protective against Mtb and other pathogens are presented.


Breath biopsy for early detection and precision medicine in cancer.
Breath biopsy enables the non-invasive collection and analysis of volatile organic compounds (VOCs) in exhaled breath, providing valuable information about disease processes occurring in the body. Metabolic changes occur in cancer cells at the earliest stages of disease. We discuss progress in the use of breath biopsy for discovery of breath-based biomarkers for early detection of cancer, and potential applications for breath biopsy in enabling precision medicine in cancer.


Effect of calf-raise training on rapid force production and balance ability in elderly men.
This study examined whether home-based, high-speed calf-raise training changes the rate of torque development (RTD) during plantar flexion contractions and balance performance in elderly men. Thirty-four healthy elderly men (73 ± 5 yr) were randomly assigned to a training or control group (n = 17 in each group). The subjects in the training group completed 8 wk (3 times/wk) of home-based bilateral calf-raise training using body mass. Before and after the intervention, RTD during plantar flexion contractions and center-of-pressure (COP) displacement during single-leg standing were measured. Surface electromyographic amplitude of the triceps surae and tibialis anterior during the strength and single-leg standing was measured. Clinical magnitude-based inferences were used to interpret the training effect, with the smallest worthwhile effect assumed to be 0.2 of the baseline SD. The peak RTD increased 21% (90% confidence limits, ±19%) relative to the control group, which was accompanied by corresponding changes of the medial gastrocnemius (MG) and soleus (SOL) activations. The effect on COP displacement was possibly trivial (0%, ±13%), whereas substantial reduction in the MG (-19%, ±15%) and SOL (-25%, ±13%) activations during standing was observed. Our findings indicate that calf-raise training at home, performed without special equipment or venue, induces a substantial increase in the plantar flexors' rapid force-generating capability and triceps surae activations. Although the training effect on standing balance performance was not substantial, observed changes in the triceps surae activations during standing are expected to contribute to future balance performance improvement.NEW & NOTEWORTHY Calf-raise training with the intent to move rapidly, without special equipment or venue, induces an improvement of explosive plantar flexion force, which is attributable to neuromuscular rather than musculotendinous adaptations. Although the training effect on balance performance was trivial, we found a sign of improvement (i.e., neuromuscular adaptations during standing). In conclusion, functional neuromuscular capacity can be enhanced by home-based calf-raise exercise in elderly men, which may protect against mobility loss with aging.


Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population.
The main objective of this study was to investigate whether patients with chronic myeloid leukemia (CML) in treatment with long-term therapy imatinib have a different health-related quality-of-life (HRQOL) profile compared with the general population. In total, 448 CML patients were enrolled, and the SF-36 Health Survey was used to compare generic HRQOL profiles. Symptoms were also assessed. HRQOL comparisons were adjusted for key possible confounders. The median age of patients was 57 years and the median time of imatinib treatment was 5 years (range 3-9 years). The largest HRQOL differences were found in younger patients. In particular, patients aged between 18 and 39 years had marked impairments in role limitations because of physical and emotional problems, respectively: -22.6 (P < .001), -22.3 (P < .001). Patients with CML age 60 or older had a HRQOL profile very similar to that reported by the general population. Women had a worse profile than men when each were compared with their peers in the general population. Fatigue was the most frequently reported symptom. The HRQOL of CML patients is comparable with that of population norms in many areas, however, younger and female patients seem to report the major limitations.


Characterization of X chromosome inactivation using integrated analysis of whole-exome and mRNA sequencing.
In females, X chromosome inactivation (XCI) is an epigenetic, gene dosage compensatory mechanism by inactivation of one copy of X in cells. Random XCI of one of the parental chromosomes results in an approximately equal proportion of cells expressing alleles from either the maternally or paternally inherited active X, and is defined by the XCI ratio. Skewed XCI ratio is suggestive of non-random inactivation, which can play an important role in X-linked genetic conditions. Current methods rely on indirect, semi-quantitative DNA methylation-based assay to estimate XCI ratio. Here we report a direct approach to estimate XCI ratio by integrated, family-trio based whole-exome and mRNA sequencing using phase-by-transmission of alleles coupled with allele-specific expression analysis. We applied this method to in silico data and to a clinical patient with mild cognitive impairment but no clear diagnosis or understanding molecular mechanism underlying the phenotype. Simulation showed that phased and unphased heterozygous allele expression can be used to estimate XCI ratio. Segregation analysis of the patient's exome uncovered a de novo, interstitial, 1.7 Mb deletion on Xp22.31 that originated on the paternally inherited X and previously been associated with heterogeneous, neurological phenotype. Phased, allelic expression data suggested an 83∶20 moderately skewed XCI that favored the expression of the maternally inherited, cytogenetically normal X and suggested that the deleterious affect of the de novo event on the paternal copy may be offset by skewed XCI that favors expression of the wild-type X. This study shows the utility of integrated sequencing approach in XCI ratio estimation.


Information retrieval and knowledge discovery utilising a biomedical Semantic Web.
Although various ontologies and knowledge sources have been developed in recent years to facilitate biomedical research, it is difficult to assimilate information from multiple knowledge sources. To enable researchers to easily gain understanding of a biomedical concept, a biomedical Semantic Web that seamlessly integrates knowledge from biomedical ontologies, publications and patents would be very helpful. In this paper, current research efforts in representing biomedical knowledge in Semantic Web languages are surveyed. Techniques are presented for information retrieval and knowledge discovery from the Semantic Web that extend traditional keyword search and database querying techniques. Finally, some of the challenges that have to be addressed to make the vision of a biomedical Semantic Web a reality are discussed.


Cochlear Histopathology as Observed in Two Patients With a Cochlear Implant Electrode With Positioner.
This study reports the cochlear histopathology of two patients who during life underwent cochlear implantation with a positioner. A silastic positioner introduced by the Advanced Bionics Corporation in 1999 was designed to position the electrode of the cochlear implant close to the modiolus. The positioner was recalled in the United States in July 2002 because of an apparent higher incidence of bacterial meningitis in patients in whom the positioner had been placed. Four celloidin-embedded temporal bones from two patients with cochlear implants with a positioner from the temporal bone collection of the Massachusetts Eye and Ear Infirmary were included in the study. In a previous study, we reported histopathologic findings in Patient 1, and in this report, we present the findings in a second case in a 94-year-old woman (Patient 2), and the similarities and differences between the two patients. All four specimens were prepared for histologic study by conventional techniques and 2-D reconstruction. Evidence of insertion trauma was observed in all three implanted specimens. More significant trauma was found in Patient 2 than in Patient 1 including disruption of the osseous spiral lamina and the basilar membrane. In addition, there was more new fibrous tissue and bone in Patient 2 than in Patient 1. There was a large fluid space in all three implanted temporal bones around the electrode and positioner. The findings observed in the two patients may help to explain the increased risk of meningitis in patients implanted with a positioner.


The Use of CAD/CAM Technology for Fabricating Cast Gold Survey Crowns under Existing Partial Removable Dental Prosthesis. A Clinical Report.
The fabrication of a survey crown under an existing partial removable dental prosthesis (PRDP) has always been a challenge to many dental practitioners. This clinical report presents a technique for fabricating accurate cast gold survey crowns to fit existing PRDPs using CAD/CAM technology. The report describes a technique that would digitally scan the coronal anatomy of a cast gold survey crown and an abutment tooth under existing PRDPs planned for restoration, prior to any preparation. The information is stored in the digital software where all the coronal anatomical details are preserved without any modifications. The scanned designs are then applied to the scanned teeth preparations, sent to the milling machine and milled into full-contour clear acrylic resin burn-out patterns. The acrylic resin patterns are tried in the patient's mouth the same day to verify the full seating of the PRDP components. The patterns are then invested and cast into gold crowns and cemented in the conventional manner.


Automatic control of the artificial heart.
An automatic control system has been developed to balance and control the output of an artificial heart. The system consisted of 2 linked negative feedback loops. The left ventricle was controlled by a Servo-Stroke Optimizer, which insured complete filling and full stroke operation of the left pump with each beat and changed the beat rate in accord with changes in aortic pressure. The right ventricle was controlled by a Servo-Variable Systolic Duration unit, which changed the stroke of the right ventricle to maintain the left atrial pressure within a preset band. In the initial animal studies, control pressures (aortic and left atrial pressure) were obtained from implanted transducers. More recently, a method has been devised whereby the control pressures were obtained from specific points on the left air line pressure wave, obviating the need for implanted transducers. The control system has been evaluated in a mock circulatory loop and in 9 calves with implanted artificial hearts. The system has provided balance of the 2 implanted ventricles and changes in flow rate in response to changes in peripheral resistance. The need for an operator to make manual adjustment to the power units has been considerably reduced. Further studies are indicated to evaluate the function of the control system in animals performing moderate-to-maximal exercise. Furthermore, the ultimate benefits of full stroke operation vs fill limited mode operation remain to be delineated.


Feedback control of glucosamine-6-phosphate synthase GlmS expression depends on the small RNA GlmZ and involves the novel protein YhbJ in Escherichia coli.
Amino sugars are essential precursor molecules for the biosynthesis of bacterial cell walls. Their synthesis pathway is initiated by glucosamine-6-phosphate (GlcN-6-P) synthase (GlmS) which catalyses the rate limiting reaction. We report here that expression of the Escherichia coli glmS gene is negatively feedback regulated by its product GlcN-6-P at the post-transcriptional level. Initially, we observed that mutants defective for yhbJ, a gene of the rpoN operon, overproduce GlmS. Concomitantly, a glmS mRNA accumulates that is derived from processing of the primary glmUS transcript at the glmU stop codon by RNase E. A transposon mutagenesis screen in the yhbJ mutant identified the small RNA GlmZ (formerly RyiA or SraJ) to be required for glmS mRNA accumulation. GlmZ, which is normally processed, accumulates in its full-length form in the yhbJ mutant. In the wild type, a decrease of the intracellular GlcN-6-P concentration induces accumulation of the glmS transcript in a GlmZ-dependent manner. Concomitantly, GlmZ accumulates in its unprocessed form. Hence, we conclude that the biological function of GlmZ is to positively control the glmS mRNA in response to GlcN-6-P concentrations and that YhbJ negatively regulates GlmZ. As in yhbJ mutants GlcN-6-P has no effect, YhbJ is essential for sensing this metabolite.


Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia.
To evaluate the usefulness of serum prostate specific antigen in the preoperative staging of prostate cancer we examined tumor volume and differentiation, as well as benign prostatic hyperplasia volume to determine their influence on serum antigen levels. Serum prostate specific antigen was measured in 350 men with clinically localized prostate cancer and preoperatively in 72 men with documented benign prostatic hyperplasia. Although the mean antigen levels increased with advancing pathological stage, the usefulness of prostate specific antigen to predict pathological stage for an individual patient was limited: 1 of 102 men (0.9%) with prostate specific antigen levels of less than 2.8 ng./ml. had positive lymph nodes and 5 of 5 men with levels of greater than 100 ng./ml. had either seminal vesicle or lymph node involvement. However, for the majority of men (greater than 70%) with prostate specific antigen values between these 2 extremes the antigen levels did not accurately predict pathological stage. Because serum prostate specific antigen levels correlated with morphometrically determined tumor volume (r equals 0.535, p less than 0.01) they should, in fact, be predictive of pathological stage. However, most men with prostate cancer also have varying degrees of benign prostatic hyperplasia tissue in the gland producing prostate specific antigen. We have found that serum prostate specific antigen does not correlate with the volume of benign hyperplasia within the gland (r equals 0.21, p greater than 0.05). In addition, immunohistochemical studies have suggested that the lack of correlation between pathological stage and serum prostate specific antigen might be explained by a decrease in the production of antigen with increasing histological grade. Our findings of a negative correlation (r equals -0.37, p less than 0.01) between serum prostate specific antigen levels and Gleason score adjusted for tumor volume confirmed this suggestion. Consequently, serum prostate specific antigen levels do not reflect tumor burden and pathological stage accurately in individual patients for 2 reasons: 1) the unpredictable contribution from the benign prostatic hyperplasia component of the gland and 2) the decreasing production of prostate specific antigen by higher grade lesions as tumor volume increases.


Epidemiology of lung cancer and approaches for its prediction: a systematic review and analysis.
Owing to the use of tobacco and the consumption of alcohol and adulterated food, worldwide cancer incidence is increasing at an alarming and frightening rate. Since the last decade of the twentieth century, lung cancer has been the most common cancer type. This study aimed to determine the global status of lung cancer and to evaluate the use of computational methods in the early detection of lung cancer. We used lung cancer data from the United Kingdom (UK), the United States (US), India, and Egypt. For statistical analysis, we used incidence and mortality as well as survival rates to better understand the critical state of lung cancer. In the UK and the US, we found a significant decrease in lung cancer mortalities in the period of 1990-2014, whereas, in India and Egypt, such a decrease was not much promising. Additionally, we observed that, in the UK and the US, the survival rates of women with lung cancer were higher than those of men. We observed that the data mining and evolutionary algorithms were efficient in lung cancer detection. Our findings provide an inclusive understanding of the incidences, mortalities, and survival rates of lung cancer in the UK, the US, India, and Egypt. The combined use of data mining and evolutionary algorithm can be efficient in lung cancer detection.


Electrophile affinity: quantifying reactivity for the bromination of arenes.
Electrophile affinity (Ealpha), a recently proposed theoretical construct based on computed energies of arenium ion formation, rationalizes the substrate reactivity and regioselectivity of S(E)Ar bromination of three sets of available experimental arene data where closely related conditions had been employed uniformly. The Ealpha parameters (computed at B3LYP/6-311+G(2d,2p)) correlated very well (r = 0.987) with the partial rate factors (log f) for 18 regiospecific brominations of benzene and various methyl benzenes. Analysis of the bromination reactivities of 32 mono- and polysubstituted benzenes including various polar groups gave similar results (r = 0.982). The electrophile affinity treatment also accounted satisfactorily (r = 0.957) for bromination reactivities of polybenzenoid hydrocarbons. Conversely, comparisons with NBO-based charges and the electrostatic potential at nuclei (EPN) were not generally successful. The uniform effectiveness of Ealpha treatments for the cases analyzed with regard both to relative substrate reactivity (e.g., benzene vs toluene) and to regiospecificity (e.g., the positional reactivity of toluene) supports the "limiting case" conventional interpretation of the electrophilic aromatic substitution mechanism as being governed by the energy of sigma-complex formation. Although other mechanisms are possible under different conditions, the computed energies of arene-dibromine pi-complex formation for the polysubstituted benzene set examined correlated poorly with experimental reactivity data (r = 0.714) and only varied from 1.8 (for benzene) to 3.5 kcal/mol, in contrast to the 10(12) range in reactivity measured experimentally.


Strong Hot Carrier Effects in Single Nanowire Heterostructures.
We use transient Rayleigh scattering to study the thermalization of hot photoexcited carriers in single GaAs0.7Sb0.3/InP nanowire heterostructures. By comparing the energy loss rate in single core-only GaAs0.7Sb0.3 nanowires which do not show substantial hot carrier effects with the core-shell nanowires, we show that the presence of an InP shell substantially suppresses the longitudinal optical phonon emission rate at low temperatures which then leads to strong hot carrier effects.


Porous Mn-Doped FeP/Co3 (PO4 )2 Nanosheets as Efficient Electrocatalysts for Overall Water Splitting in a Wide pH Range.
Development of highly active and stable electrocatalysts for overall water splitting is important for future renewable energy systems. In this study, porous Mn-doped FeP/Co3 (PO4 )2 (PMFCP) nanosheets on carbon cloth are utilized as a highly efficient 3 D self-supported binder-free integrated electrode for the oxygen evolution and hydrogen evolution reactions (OER and HER) over a wide pH range. Specifically, overpotentials of 27, 117, 85 mV are required for the PMFCP nanosheets to attain 10 mA cm-2 for HER in 0.5 m H2 SO4 , 1.0 m phosphatebuffered saline (PBS), and 1.0 m KOH, respectively. In addition to the excellent performance for HER electrocatalysis, PMFCP nanosheets were also efficient electrocatalysts for the OER. Thus, the PMFCP nanosheets can serve as anodes and cathodes for overall water splitting (OWS). The OWS working voltages to attain 10 mA cm-2 are found to be 1.75, 1.82, and 1.61 V in acid, neutral, and alkaline electrolytes, respectively. Chronopotentiometric tests show that the PMFCP electrode can maintain its excellent pH-universal OWS activity for more than 30 000 s. This work also provides new insights into developing high-performance electrocatalysts for water splitting over a wide pH range. The improvement in electrochemical performance by introduction of Mn dopant and nano-holes offers new opportunities in the development of effective electrodes for other energy-related applications.


Identification of novel VHL targets that are associated with the development of renal cell carcinoma.
von Hippel-Lindau (VHL) disease is a dominantly inherited family cancer syndrome characterized by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC) and phaeochromocytoma. Specific germline VHL mutations may predispose to haemangioblastomas, RCC and phaeochromocytoma to a varying extent. Although dysregulation of the hypoxia-inducible transcription factor-2 and JunB have been linked to the development of RCC and phaeochromocytoma, respectively, the precise basis for genotype-phenotype correlations in VHL disease have not been defined. To gain insights into the pathogenesis of RCC in VHL disease we compared gene expression microarray profiles in a RCC cell line expressing a Type 1 or Type 2B mutant pVHL (RCC-associated) to those of a Type 2A or 2C mutant (not associated with RCC). We identified 19 differentially expressed novel VHL target genes linked to RCC development. Eight targets were studied in detail by quantitative real-time polymerase chain reaction (three downregulated and five upregulated by wild-type VHL) and for six genes the effect of VHL inactivation was mimicked by hypoxia (but hypoxic-induction of smooth muscle alpha-actin 2 was specific for a RCC cell line). The potential role of four RCC-associated VHL target genes was assessed in vitro. NB thymosin beta (TMSNB) and proteinase-activated receptor 2 (PAR2) (both downregulated by wt pVHL) increased cell growth and motility in a RCC cell line, but aldehyde dehydrogenase (ALDH)1 and ALDH7 had no effect. These findings implicate TMSNB and PAR2 candidate oncogenes in the pathogenesis of VHL-associated RCC.


GRAND: An Integrated Genome, Transcriptome Resources, and Gene Network Database for Gossypium.
With the increasing amount of cotton omics data, breeding scientists are confronted with the question of how to use massive cotton data to mine effective breeding information. Here, we construct a Gossypium Resource And Network Database (GRAND), which integrates 18 cotton genome sequences, genome annotations, two cotton genome variations information, and also four transcriptomes for Gossypium species. GRAND allows to explore and mine this data with the help of a toolbox that comprises a flexible search system, BLAST and BLAT suite, orthologous gene ID, networks of co-expressed genes, primer design, Gbrowse and Jbrowse, and drawing instruments. GRAND provides important information regarding Gossypium resources and hopefully can accelerate the progress of cultivating cotton varieties.


Dosimetric comparison of volumetric modulated arc therapy with robotic stereotactic radiation therapy in hepatocellular carcinoma.
To compare volumetric modulated arc therapy of RapidArc with robotic stereotactic body radiation therapy (SBRT) of CyberKnife in the planning and delivery of SBRT for hepatocellular carcinoma (HCC) treatment by analyzing dosimetric parameters. Two radiation treatment plans were generated for 29 HCC patients, one using Eclipse for the RapidArc plan and the other using Multiplan for the CyberKnife plan. The prescription dose was 60 Gy in 3 fractions. The dosimetric parameters of planning target volume (PTV) coverage and normal tissue sparing in the RapidArc and the CyberKnife plans were analyzed. The conformity index was 1.05 ± 0.02 for the CyberKnife plan, and 1.13 ± 0.10 for the RapidArc plan. The homogeneity index was 1.23 ± 0.01 for the CyberKnife plan, and 1.10 ± 0.03 for the RapidArc plan. For the normal liver, there were significant differences between the two plans in the low-dose regions of V1 and V3. The normalized volumes of V60 for the normal liver in the RapidArc plan were drastically increased when the mean dose of the PTVs in RapidArc plan is equivalent to the mean dose of the PTVs in the CyberKnife plan. CyberKnife plans show greater dose conformity, especially in small-sized tumors, while RapidArc plans show good dosimetric distribution of low dose sparing in the normal liver and body.


In vivo skin penetration and metabolic path of quantum dots.
The skin is the largest organ of the body and is a potential route of exposure to sunscreens and cosmetics containing nanoparticles; however, the permeability of the skin to these nanoparticles is currently unknown. In this paper, we studied the transdermal delivery capacity through mouse skin of water-soluble CdSeS quantum dots (QDs) and the deposition of these QDs in the body. QD solution was coated onto the dorsal hairless skin of male ICR mice. Fluorescence microscopy and transmission electron microscopy (TEM) were used to observe the distribution of QDs in the skin and organs, and inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure the (111)Cd content to indicate the concentration of QDs in plasma and organs. Experimental results indicate that QDs can penetrate into the dermal layer and are limited to the uppermost stratum corneum layers and the hair follicles. Through blood circulation, QDs deposit mostly in liver and kidney and are difficult to clear. (111)Cd concentration was greater than 14 ng g(-1) in kidney after 120 h after 0.32 nmol QDs was applied to a mouse. These results suggest that QDs have in vivo transdermal delivery capacity through mouse skin and are harmful to the liver and kidney.


Shape-Adaptive, Self-Healable Triboelectric Nanogenerator with Enhanced Performances by Soft Solid-Solid Contact Electrification.
The viable application of soft electronics/robotics relies on the development of power devices which are desired to be flexible, deformable, or even self-healable. We report here a shape-adaptive, self-healable triboelectric nanogenerator (SS-TENG) for harvesting biomechanical energies. The use of a viscoelastic polymer, normally known as Silly Putty, as the electrification material and as the matrix of a carbon-nanotube-filled composite (CNT-putty) electrode endows the SS-TENG the capability of adapting to arbitrary irregular surfaces and instantaneous healing from mechanical damage (almost completely recovered in 3 min without extra stimuli). Furthermore, the output performances of the SS-TENG have also been significantly improved because (i) the ideal soft contact is achieved at the solid-solid interfaces for more effective contact electrification and (ii) the introduced cation dopants make the putty even more tribo-negative than polytetrafluoroethylene. The SS-TENG can be adhered to any curvy surface, tailored, and reshaped into arbitrary configurations and utilized as a power supply for small electronics, suggesting promising applications in soft electronics/robotics in the future.


Excision of a Large Complex Left Middle Cerebral Artery Aneurysm With a Middle Cerebral Artery-Middle Cerebral Artery and Superficial Temporal Artery-Middle Cerebral Artery Bypass: 2-Dimensional Operative Video.
Revascularization techniques for microsurgical manage-ment of middle cerebral artery (MCA) bifurcation aneurysms are often necessary for treatment of fusiform or giant aneurysms. Augmentation of the standard pterional approach to include an extended orbitozygomatic or modified orbitozygomatic approach provides a wider and more favorable approach to the MCA when attempting revascularization. Direct excision of a giant aneurysm (aneurysmectomy) with mobilization and reanastomosis of the MCA afterward has been reported. This patient had a giant MCA bifurcation aneurysm for which aneurysmectomy and distal reanastomosis were performed between the M1 and two M2 branches via a modified orbitozygomatic craniotomy. A second bypass between a third M2 branch at the ipsilateral superficial temporal artery was performed. Postoperative angiography confirmed patency of the bypasses. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.


Thomas G Orr Memorial Lecture. Pathogenesis, prophylaxis, and treatment of stress gastritis.
In the last decade, significant progress has been made in understanding the basic mechanisms involved in the development of acute stress gastritis. Many of the experimental observations have been applied in our clinical approaches to patients at high risk. A strong impression exists among investigators that efforts to improve ventilatory support, correct abnormalities in cardiac output and intravascular volume, and maintain adequate nutrition in critically ill patients may have contributed to the decreased incidence and prevalence of stress gastritis over the past decade. In addition, reduction of intragastric acidity, either by titration with antacids or administration of H2 antagonists, further prevented stress gastritis in these patients. We have every reason to believe that progress will continue at the same rate in the decades before us in this area of investigation.


Effect of pH on Cr(III) accumulation, biomass production, and phenolic profile in 2 Salvinia species.
We analyzed the effect of pH on Cr(III) accumulation, biomass production, and phenolic profile of Salvinia rotundifolia and Salvinia minima plants grown in the presence of increasing concentrations of CrCl3 . Biomass accumulation, metal tolerance index, and photosynthetic pigment contents indicate that Salvinia rotundifolia seems to be more tolerant of Cr(III) than S. minima at different pHs. Increased metal accumulation by Salvinia species under increasing pH could be explained by changes of the protonation status of cell wall functional groups because both the highest and the lowest pH values used in the present study were outside of the levels at which Cr(III) species start to precipitate. The metal translocation factor indicates that in buffered conditions S. rotundifolia tend to retain more Cr(III) in lacinias than S. minima, probably through the involvement of insoluble phenolics. The results of the present study could be useful to the management of solution pH to maximize the removal of Cr(III) by aquatic plants. Environ Toxicol Chem 2019;38:167-176. © 2018 SETAC.