[Effect of topical glaucoma medications on optic disc topography in normal tension glaucoma].
To investigate the effects of topical glaucoma medications on optic disc topography in patients with normal tension glaucoma (NTG) using confocal scanning laser ophthalmoscopy. We enrolled 39 NTG patients (39 eyes) who had not been treated for glaucoma. A combined medication of 0.005% latanoprost and 0.5% timolol gel was administered. Optic disc parameters were measured before and after the treatment using the Heidelberg Retina Tomograph (HRT). The treatment period was 20.2 +/- 6.4 days (mean +/- SD). Administration of these two drugs significantly decreased the intraocular pressure (IOP) from 16.7 +/- 1.9 mmHg to 12.3 +/- 1.9 mmHg (26.7 +/- 8.7% decrease). Cup area, cup/disk area ratio and cup volume decreased significantly, while the rim area increased significantly. Linear progression analysis showed a significant correlation between the percent decrease in the IOP and the topographic changes in the cup area, cup/disk area ratio, rim area, cup volume, rim volume, and height variation contour. When the subjects were divided into two groups: patients with high baseline IOP of more than 16 mmHg (HNTG group) and those with low baseline IOP below 15 mmHg (LNTG group), significant changes in several parameters were observed only in the HNTG group. These results suggest that the topographic changes in the optic disc were induced by the short-term topical glaucoma medications prescribed for the NTG patients, and the changes in several HRT parameters correlated with the percent decrease in the IOP.


Ghosts of dry seasons past: Legacy of severe drought enhances mangrove salinity tolerance through coordinated cellular osmotic and elastic adjustments.
The incidence and severity of global mangrove mortality due to drought is increasing. Yet, little is understood of the capacity of mangroves to show long-term acclimation of leaf water relations to severe drought. We tested for differences between mid-dry season leaf water relations in two cooccurring mangroves, Aegiceras corniculatum and Rhizophora stylosa before a severe drought (a heatwave combined with low rainfall) and after its relief by the wet season. Consistent with ecological stress memory, the legacy of severe drought enhanced salinity tolerance in the subsequent dry season through coordinated adjustments that reduced the leaf water potential at the turgor loss point and increased cell wall rigidity. These adjustments enabled maintenance of turgor and relative water content with increasing salinity. As most canopy growth occurs during the wet season, acclimation to the 'memory' of higher salinity in the previous dry season enables greater leaf function with minimal adjustments, as long-lived leaves progress from wet through dry seasons. However, declining turgor safety margins - the difference between soil water potential and leaf water potential at turgor loss - implied increasing limitation to water use with increasing salinity. Thus, plasticity in leaf water relations contributes fundamentally to mangrove function under varying salinity regimes.


Myeloid-Derived Suppressor Cells in Infection: A General Overview.
After initial infection, the immune response that serves to restrict the invading pathogen needs to be tightly calibrated in order to avoid collateral immunopathological damage. This calibration is performed by specialized suppressor mechanisms, which are capable of dampening overwhelming or unremitting inflammation in order to prevent tissue damage. Myeloid-derived suppressor cells (MDSC) are emerging as key players in counter-balancing inflammatory responses and pathogenesis during infection. However, some pathogens are able to exploit the suppressive activities of MDSC to favor pathogen persistence and chronic infections. In this article, we review the current knowledge about the importance of MDSC in the context of bacterial, virus, parasites, and fungal infections.


The Cumulative Burden of Mental, Substance Use, and General Medical Disorders and Rehospitalization and Mortality After an Injury.
Each year in the United States, 1.5-2.5 million individuals require hospitalization for an injury. Multiple mental, substance use, and chronic general medical disorders are endemic among injury survivors with and without traumatic brain injury (TBI), yet few studies have assessed the association between the cumulative burden of these conditions and health care outcomes. This study of patients hospitalized for an injury assessed associations between comorbid mental, substance use, and general medical disorders, TBI, and violent events or suicide attempts and the postinjury outcomes of recurrent hospitalization and death. Recurrent hospitalization and all-cause mortality were examined in this population-based retrospective cohort study. A total of 76,942 patients hospitalized for an injury in Washington State during 2006-2007 were followed for five years. ICD-9-CM codes identified conditions prior to or at the index injury admission. Index admissions related to injuries from firearms, assaultive violence, suicide attempts, and overdoses were identified through E-codes. Adjusted regression analyses demonstrated a significant, dose-response relationship between an increasing cumulative burden of disorders and an increasing risk of recurrent hospitalization (four or more conditions, relative risk=3.89, 95% confidence interval [CI]=3.66-4.14). Adjusted Cox proportional hazard regression demonstrated a similar relationship between increasing cumulative burden of disorders and all-cause mortality (four or more conditions, hazard ratio=5.33, CI=4.71-6.04). Increasing cumulative burden of disorders was associated with greater postinjury risk of recurrent hospitalization and death. Orchestrated investigative and policy efforts could introduce screening and intervention procedures that target this spectrum of comorbidity.


Wrist pain after a fall.
A 28-year-old right-handed man tripped down a flight of stairs, landing on his outstretched right hand. He developed immediate pain, swelling, and stiffness but did not seek medical attention. After 1 week without relief, he went to see his primary care provider. The patient did not have numbness or tingling, and he reported no previous injuries to the wrist. X-rays were obtained (figure 1), and the patient was referred to an orthopedist for further evaluation.


Time trends of incidence for cutaneous melanoma among the Japanese population: an analysis of Osaka Cancer Registry data, 1964-95.
Cutaneous malignant melanoma occurs much less frequently among non-white populations than among white populations. Little is known of the descriptive epidemiology of melanoma among Japanese. We investigated time trends of incidence of invasive cutaneous malignant melanoma using data from the Osaka Cancer Registry (Japan) among 321 men and 313 women diagnosed between 1964-95. Average, annual, age-standardized incidence rates per 1,000,000 population were 2.45 (95% confidence interval (CI): 2.17-2.72) for men and 2.04 (95% CI: 1.81-2.28) for women. The age-standardized rate ratio among men from 1964-71 as a reference was almost constant during the study period, whereas that among women increased up to 1.8 fold (95% CI: 1.25-2.56) in 1980-87 and seems to have reached a plateau recently. Among men, the ratio for head and neck lesions decreased to 0.5 fold (95% CI: 0.26-0.99) in 1988-95. Among women, the ratio for lesions of the extremities steeply increased up to 4.7 fold (95% CI: 2.68-8.35) in 1980-87 from the reference period of 1964-71, whereas a slight increase for trunk lesions and no increase for head and neck lesions were noted during the same period. Possible explanations for the subsite-specific time trends are discussed.


Comprehensive care improves health outcomes among elderly Taiwanese patients with hip fracture.
Few studies have investigated the effects of care models that combine interdisciplinary care with nutrition consultation, depression management, and fall prevention in older persons with hip fracture. The purpose of this study was to compare the effects of a comprehensive care program with those of interdisciplinary care and usual care for elderly patients with hip fracture. A randomized experimental trial was used to explore outcomes for 299 elderly patients with hip fracture receiving three treatment care models: interdisciplinary care (n = 101), comprehensive care (n = 99), and usual care (n = 99). Interdisciplinary care included geriatric consultation, continuous rehabilitation, and discharge planning with post-hospital services. Comprehensive care consisted of interdisciplinary care plus nutrition consultation, depression management, and fall prevention. Usual care included only in-hospital rehabilitation without geriatric consultation, in-home rehabilitation, and home environmental assessment. Participants in the comprehensive care group had better self-care ability (odds ratio, OR = 3.19, p < .01) and less risk of depression (OR = 0.48, p < .01) than those who received usual care. The comprehensive care group had less risk of depression (OR = 0.51, p < .05) and of malnutrition (OR = 0.48, p < .05) than the interdisciplinary care group during the first year following discharge. Older persons with hip fracture benefitted more from the comprehensive care program than from interdisciplinary care and usual care. Older persons with hip fracture benefitted more from comprehensive care including interdisciplinary care and nutrition consultation, depression management, and fall prevention than simply interdisciplinary care.


An unusual cribriform variant of salivary basal cell tumours: a clinicopathological study of 22 cases.
To clarify the clinicopathological characteristics of salivary basal cell tumours exhibiting cribriform architecture, and to discuss the differential diagnosis of these tumours with regard to adenoid cystic carcinoma (AdCC). Eighteen basal cell adenomas (BCAs) and four basal cell adenocarcinomas (BcACs) with at least a 10% area of cribriform morphology were collected, and the histological and immunohistochemical features were evaluated. The majority of tumours showed the typical histological patterns of basal cell tumours, in addition to cribriform architecture. In some areas, the periphery of cribriform nests had a palisade arrangement. Focal capsular infiltration, but not invasion of surrounding normal tissue, was detected in 14 of 18 BCAs. The capsules were absent or incomplete and mainly accompanied by focal invasion in BcACs. Cystic degeneration was observed in 12 of 22 tumours. The Ki67 labelling index of basal cell tumours was significantly lower than that of cribriform AdCCs (P = 0.001). All patients had a good outcome after a follow-up of 15-96 months. The cribriform variant shares most of the clinicopathological features of conventional basal cell tumours. Admixtures of cribriform and trabecular or tubulo-trabecular subtypes, peripheral palisading, cystic changes, non-invasive or low-grade invasive growth patterns and a low Ki67 labelling index may be useful for distinguishing basal cell tumours with a cribriform architecture from AdCCs.


17-α-Hydroxylase deficiency: An unusual case with primary amenorrhea and hypertension.
A 14-year-old girl presented with acute onset quadriparesis and newly detected hypertension. Parental consanguinity, delayed puberty with normal stature form the additional information. Hypokalemia with metabolic alkalosis, low cortisol, high ACTH and FSH pointed to the possibility of CAH with 17α hydroxylase deficiency. 46XX karyotype and high progesterone supported this. Normalization of hypokalemia and hypertension with glucocorticoid treatment confirmed the diagnosis. In summary, the possibility of 17 OHD should be suspected in patients with hypokalemic myopathy, Hypertension and hypogonadism so that appropriate therapy can be implemented.


Polar pesticide contamination of an urban and peri-urban tropical watershed affected by agricultural activities (Yaoundé, Center Region, Cameroon).
Urban agriculture is crucial to local populations, but the risk of it contaminating water has rarely been documented. The aim of this study was to assess pesticide contamination of surface waters from the Méfou watershed (Yaoundé, Cameroon) by 32 selected herbicides, fungicides, and insecticides (mainly polar) according to their local application, using both grab sampling and polar organic compounds integrative samplers (POCIS). Three sampling campaigns were conducted in the March/April and October/November 2015 and June/July 2016 rainy seasons in urban and peri-urban areas. The majority of the targeted compounds were detected. The quantification frequencies of eight pesticides were more than 20% with both POCIS and grab sampling, and that of diuron and atrazine reached 100%. Spatial differences in contamination were evidenced with higher contamination in urban than peri-urban rivers. In particular, diuron was identified as an urban contaminant of concern because its concentrations frequently exceeded the European water quality guideline of 0.200 μg/L in freshwater and may thus represent an ecological risk due to a risk quotient > 1 for algae observed in 94% of grab samples. This study raises concerns about the impacts of urban agriculture on the quality of water resources and to a larger extent on the health of the inhabitants of cities in developing countries. Graphical abstract .


Effect of acute intravenous administration of isoproterenol on cardiorenal hemodynamics in man.
By the direct Fick, or the indocyanine-green or both, methods and by renal clearance of inulin and para-aminohippurate (PAH), simultaneous cardiorenal hemodynamic observations were made before and during isoproterenol infusion (0.9-2.6 micrograms/min) into three patients without, and 10 patients with, heart disease. Although a consistent increase in cardiac output (11 to 147%) was noted in all patients, no significant change in glomerular filtration rate or renal blood flow was observed. The percentage of the cardiac output delivered to the kidney during drug infusion decreased in all subjects. The renal extraction of PAH, measured in three patients, was not changed during isoproterenol administration. The infusion of isoproterenol to normovolemic and hypervolemic dogs (10 dogs) increased the cardiac output in all animals but produced no significant change in glomerular filtration rate or renal blood flow. Because the renal blood flow is not affected by the increased cardiac output produced by isoproterenol, the data suggest that there is either a weak or an absent beta-receptor response in the kidney in the dog and man.


Leaf senescence in rice plants: cloning and characterization of senescence up-regulated genes.
To identify senescence-associated genes (SAGs) in rice leaves, senescence was induced by transferring rice seedlings into darkness. Senescence up-regulated cDNAs were obtained by PCR-based subtractive hybridization. Among 14 SAG clones characterized, 11 were found to be associated with both dark-induced and natural leaf senescence. Three clones were associated only with dark-induced leaf senescence. The possible physiological roles of these SAGs during rice leaf senescence are discussed.


Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases.
Prostanoid synthesis in mammalian tissues is regulated at the level of prostaglandin H synthase (PGHS) cyclooxygenase catalysis by the availability and structure of substrate fatty acid and the availability of peroxide activator. Two major PGHS isoforms, with distinct pathophysiological functions and catalytic regulation, have been characterized in mammals; a functionally homologous PGHS isoform pair has been cloned from an evolutionarily distant vertebrate, brook trout. The cyclooxygenase activities of recombinant brook trout PGHS-1 and -2 were characterized to test the generality of mammalian regulatory paradigms for substrate specificity, peroxide activation, and product shifting by aspirin. Both trout cyclooxygenases had much more restrictive substrate specificities than their mammalian counterparts, with pronounced discrimination toward arachidonate (20:4n-6) and against eicosapentaenoate (20:5n-3) and docosahexaenoate (22:6n-3), the latter two prominent in trout tissue lipids. Aspirin treatment did not increase lipoxygenase-type catalysis by either trout enzyme. Both trout enzymes had higher requirements for peroxide activator than their mammalian counterparts, though the preferential peroxide activation of PGHS-2 over PGHS-1 seen in mammals was conserved in the fish enzymes. The divergence in cyclooxygenase characteristics between the trout and mammalian PGHS proteins may reflect accomodations to differences among vertebrates in tissue lipid composition and general redox state.


Characterization of the world's first nuclear explosion, the Trinity test, as a source of public radiation exposure.
The world's first atomic bomb was tested in New Mexico on 16 July 1945. From 1999 through 2008, scientists working for the Centers for Disease Control and Prevention gathered information relevant to past releases from Los Alamos activities, including the Trinity test. Detonation on a 30.5 m tower enhanced radioactive fallout, and terrain and wind patterns caused "hot spots" of deposition. Several ranchers reported that fallout resembling flour was visible for 4 to 5 d after the blast, and residents living as close as 19 km from ground zero collected rain water from metal roofs for drinking. Pressures to maintain secrecy and avoid legal claims led to decisions that would not likely have been made in later tests. Residents were not warned before the test or informed afterward about potential protective actions, and no evacuations were conducted. Occupied homes were overlooked on the day of the blast. Exposure rates in residential areas were recorded as high as 1.4 microC kg s (20 R h) using instruments that were crude, ill suited to field use, and incapable of effectively measuring alpha contamination from about 4.8 kg of unfissioned plutonium that was dispersed. Vehicle shielding and contamination were recognized but not corrected for. To date, the post-shot field team measurements have not been rigorously evaluated, cross-checked, adjusted, or subjected to uncertainty analysis. Evaluations of Trinity fallout published to date have not addressed internal doses to members of the public following intakes of contaminated air, water, or foods. The closing of these data gaps appears feasible with the information that has been assembled and would support placement of the Trinity event in perspective as a source of public radiation exposure and more defensible evaluation of the potential for human health effects.


Dual silencing of EGFR and HER2 enhances the sensitivity of gastric cancer cells to gefitinib.
Gefitinib exhibits very limited efficacy in gastric cancer (GC). Indeed, the limited clinical results obtained with gefitinib alone justify investigation of additional therapeutic strategies. Here, we demonstrate the importance of EGFR and HER2 in GC malignancy using RNA interference (RNAi). Additionally, we explored the ability of RNAi targeting EGFR and HER2 to enhance the sensitivity of GC cells to gefitinib. Specific small interfering RNAs (siRNAs) significantly inhibited mRNA and protein expression of target genes. EGFR-specific siRNA, EGFR/HER2 siRNAs, and gefitinib inhibited growth and induced apoptosis in GC cell lines in a dose-dependent manner. In contrast, resistance to HER2-siRNA-induced growth inhibition and apoptosis was linked to compensatory activation of EGFR. Moreover, gefitinib dramatically reduced p-EGFR and p-HER2 levels in the cell lines tested, and sensitivity to gefitinib was enhanced through dual silencing of EGFR and HER2 via suppression of AKT and ERK activation. These findings are in agreement with the profound inhibitory effect of gefitinib on activation of both EGFR and HER2. Overall, EGFR/HER2 knockdown by siRNAs further decreased the growth of GC cells treated with gefitinib alone, confirming that single-agent drug targeting does not achieve a maximal biological effect. The combination of gefitinib with EGFR/HER2 siRNAs should be further investigated as a new strategy for the treatment of GC and other EGFR/HER2-dependent cancers.


[Long-term care insurance system and osteoporosis].
The Long-term Care Insurance is the principal system that supports the Japanese elderly more than 24 million in number. The recipients of this system are increasing rapidly and get up to 3 million now. In Japan, hip fracture is one of the primary causes that make the elderly bedridden. In our study with the cases of hip fractures, 51.6% of the whole patients were self-reliant before fracture, but 25.6% one year after fracture. Keep it in mind that half of the self-reliant elderly will need support after fracture and encourage patients and their families to apply for certification of need for support.


Effect of initial position on the muscle activity of the hip extensors and amount of pelvic tilt during prone hip extension.
[Purpose] The aim of this study was to identify the effects of initial position of the hip joint with changes in the hip joint angle on the respective muscle activities of the bilateral erector spinae (ES), unilateral gluteus maximus (GM), and biceps femoris (BF) and the amount of pelvic anterior tilt during prone hip extension (PHE). [Subjects] Fifteen healthy volunteers were enrolled in this study. [Methods] The subjects performed PHE in three positions: neutral, 20°, and 45° flexed hip joint. The activities of the ES, GM, and BF were measured using surface electromyography, and kinematic values for pelvic anterior tilt were calculated using a motion capture system. [Results] There was a significant decrease in muscle activity of the contralateral ES at 45°, and an increase in the GM muscle activity and decrease in the BF muscle activity at 20°. The amount of pelvic anterior tilt was lower at 20°. [Conclusion] These results suggest that a hip flexion position of 20° would have an advantage over the other measured positions.


Single Chain Cationic Polymer Dot as a Fluorescent Probe for Cell Imaging and Selective Determination of Hepatocellular Carcinoma Cells.
This letter describes formation of single chain cationic polymer dots (Pdots) made of poly[1,4-dimethyl-1-(3-((2,4,5-trimethylthiophen-3-yl)oxy)propyl)piperazin-1-ium bromide] conjugated polyelectrolyte (CPE). The single chain Pdot formation relies on a simple process which is a rapid nanophase separation between CPE solution of ethylene glycol and water. Pdots show narrow monodisperse size distribution with a 3.6 nm in diameter exhibiting high brightness and excellent colloidal and optical stability. It has been demonstrated that photoluminescent Pdots provide selective nuclear translocation to hepatocellular carcinoma cells as compared to healthy liver cells. The Pdot labeling effectively discriminates cancer cells in the coculture media. Pdots hold great promise as a luminescent probe to diagnose cancer cells in histology and may guide surgeons during operations to precisely separate out cancerous tissue due to augmented fluorescence brightness.


Fatty acids and immune function: new insights into mechanisms.
Fatty acids are known to play diverse roles in immune cells. They are important as a source of energy, as structural components of cell membranes, as signaling molecules and as precursors for the synthesis of eicosanoids and similar mediators. Recent research has suggested that the localization and organisation of fatty acids into distinct cellular pools has a direct influence on the behaviour of a number of proteins involved in immune cell activation, including those associated with T cell responses, antigen presentation and fatty acid-derived inflammatory mediator production. This article reviews these studies and places them in the context of existing literature in the field. These studies indicate the existence of several novel mechanisms by which altered fatty acid availability can modulate immune responses and impact upon clinical outcomes.


The Renner-Teller effect in HCCCl(+)(X̃(2)Π) studied by zero-kinetic energy photoelectron spectroscopy and ab initio calculations.
The spin-vibronic energy levels of the chloroacetylene cation up to 4000 cm(-1) above the ground state have been measured using the one-photon zero-kinetic energy photoelectron spectroscopic method. The spin-vibronic energy levels have also been calculated using a diabatic model, in which the potential energy surfaces are expressed by expansions of internal coordinates, and the Hamiltonian matrix equation is solved using a variational method with harmonic basis functions. The calculated spin-vibronic energy levels are in good agreement with the experimental data. The Renner-Teller (RT) parameters describing the vibronic coupling for the H-C≡C bending mode (ε4), Cl-C≡C bending mode (ε5), the cross-mode vibronic coupling (ε45) of the two bending vibrations, and their vibrational frequencies (ω4 and ω5) have also been determined using an effective Hamiltonian matrix treatment. In comparison with the spin-orbit interaction, the RT effect in the H-C≡C bending (ε4) mode is strong, while the RT effect in the Cl-C≡C bending mode is weak. There is a strong cross-mode vibronic coupling of the two bending vibrations, which may be due to a vibronic resonance between the two bending vibrations. The spin-orbit energy splitting of the ground state has been determined for the first time and is found to be 209 ± 2 cm(-1).


The effects of aerobic training and age on plasma sICAM-1.
Chronic low-grade systemic inflammation plays a role in the development of cardiovascular (CV) disease. Habitual endurance exercise training reduces the risk of CV disease in part through anti-inflammatory mechanisms. The purpose of this study was to investigate the effects of age, endurance training status, and their interaction on pro-inflammatory plasma cytokines involved in the pathogenesis of CV disease. Subjects were BMI-matched young (25±3 years; endurance trained: n=9, sedentary: n=11) and older (62±5 years; endurance-trained: n=12, sedentary: n=11) men. Plasma cytokine concentrations were determined by multiplex cytometric bead assay. Soluble intercellular adhesion molecule-1 (sICAM-1) levels were 40% higher in sedentary older men compared to young sedentary subjects (P=0.048), but they were not different between the young and older trained men. Furthermore, sICAM-1 levels were negatively correlated with maximal oxygen uptake (V˙O2max; r= - 0.38, P=0.01) across all subjects. There were no significant differences among the groups in plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), soluble tumor necrosis-α receptor (sTNFR), soluble CD40 ligand (sCD40L), or resistin. We conclude that habitual endurance training is associated with an attenuated age-related increase in plasma sICAM-1.


The tolerability and efficacy of entacapone over 3 years in patients with Parkinson's disease.
The long-term safety and efficacy of the catechol-O-methyltransferase (COMT) inhibitor entacapone was investigated in a 3-year open-label extension of the 6-month double-blind placebo-controlled Nordic (NOMECOMT) study. After a wash-out following this study, 132 patients with Parkinson's disease (PD) experiencing motor fluctuations treated with levodopa/dopa decarboxylase (DDC) inhibitor received additional therapy with entacapone 200 mg, administered with each dose of levodopa. The most common adverse events (AEs) were insomnia (30%), dizziness (20%), nausea (20%), aggravated parkinsonism (17%) and hallucinations (14%). Only 19 (14%) patients discontinued because of AEs. Most dopaminergic AEs occurred shortly after initiation of entacapone, and these could be managed by levodopa down-adjustment. The mean duration of benefit of a single dose of levodopa increased significantly from 2.1 to 2.8 h (P < 0.01) at 3 months and remained prolonged for the whole study. At the end of the study, the mean daily dose of levodopa was significantly decreased from baseline (from 737 to 696 mg; P < 0.05). The patients' global assessment indicated that 69% of patients improved when given entacapone and this proportion was maintained until the end of the study (64%). There was a significant worsening of disability upon withdrawal of entacapone. In conclusion, entacapone given in combination with levodopa, has a good long-term safety profile and a sustained beneficial effect in patients with PD with motor fluctuations.


Development and Characterisation of Joints with Novel Densified and Wood/Cork Composite Substrates.
The automotive industry, driven by the desire to decrease the environmental impact of vehicles, is permanently seeking to develop lightweight structural components, which lead to lower gas emissions and energy consumption, reducing their carbon footprint. In parallel, adopting innovative, constructive solutions, which dispense non-recyclable and energy-intensive materials, can increase the footprint reduction. Thus, an increase in the use of renewable materials for structural applications, including wood and its by-products, has been observed over the last few decades. Furthermore, composite materials are often joined by using petroleum-based synthetic adhesives, which should be progressively replaced by eco-friendly bio-adhesives. In this study, novel densified wood and wood/cork composites, joined with a bio-adhesive, are proposed and characterised. The densification of the wood aims to enhance the mechanical properties of the natural material, with the purpose of improving the energy absorption of the wood/bio-adhesive joint. To mitigate delamination and the brittle behaviour of wood/cork agglomerates were introduced between the wood substrate and the bio-adhesive. Different configurations of single lap joints (SLJ) were manufactured to study the effect of the overlap length and loading rate on the performance of the joints, both in terms of failure load and energy absorption. Afterward, the joints were numerically simulated. The densification process was successful, although it represents an additional challenge in terms of surface flatness, because the bio-adhesive requires zero bondline thickness. The increase of the overlap had a positive impact on the energy absorption of the joint, and the addition of cork resulted in a more consistent failure mode and higher strain to failure. The numerical models developed had a good correlation with the experimental results.


Successful treatment of invasive mucormycosis with isavuconazole in pediatric patients.
Invasive mold infections (IMIs) are a leading cause of mortality among immunocompromised patients. Isavuconazole is a new drug that shows promise in the adult population for the treatment of IMIs. No data regarding the use of isavuconazole in pediatric patients have been published. Patients with a diagnosis of IMI from our pediatric hemato-oncology division, treated with isavuconazole between 2010 and 2016, were identified using the hospital's computerized database. Data including demographics, clinical course, and outcome were collected. Pharmacokinetic samples were obtained from two younger patients to guide dosing. In total, three patients (4.5, 5, and 19 years of age) with invasive mucormycosis who were treated with isavuconazole were identified. All patients were treated with isavuconazole as a second line therapy and experienced improvement following the initiation of this treatment. Based on our limited clinical experience, isavuconazole may be a safe and effective treatment option for children and adolescents afflicted by IMI. Prospective clinical trials should be performed in order to evaluate the pharmakokinetics and safety of isavuconazole in the pediatric population.


Private sector healthcare in Bangladesh: Implications for social justice and the right to healthcare.
Based on a brief examination of private sector healthcare in Bangladesh, this article examines two questions: (a) the compatibility of social justice and the right to healthcare with the private provision of healthcare, (b) the implication of the private sector's role in realising social justice and the right to healthcare. It is based on an extensive review of both published and unpublished documents including journal articles, government reports, policy and planning documents, as well as reports of United Nations, the World Health Organisation and the World Bank. Different search engines and databases were used to collect the documents. Thematic data analysis techniques were used in developing the text. Private provision of healthcare services raises concerns about social justice and the right to healthcare. This sector to some extent is unable to fulfil its obligation to realise social justice and the right to healthcare in the provision of healthcare. An expanding private sector role creates complexities in promoting and protecting the right to health and social justice. The study emphasised the role of the government to engage its political will and make changes in policy and governance to engage private sector in realising right to healthcare and social justice.


Synthesis of Thymoquinone-Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents.
A series of hybrid compounds based on the natural products artemisinin and thymoquinone was synthesized and investigated for their biological activity against the malaria parasite Plasmodium falciparum 3D7 strain, human cytomegalovirus (HCMV), and two leukemia cell lines (drug-sensitive CCRF-CEM and multidrug-resistant subline CEM/ADR5000). An unprecedented one-pot method of selective formation of C-10α-acetate 14 starting from a 1:1 mixture of C-10α- to C-10β-dihydroartemisinin was developed. The key step of this facile method is a mild decarboxylative activation of malonic acid mediated by DCC/DMAP. Ether-linked thymoquinone-artemisinin hybrids 6a/b stood out as the most active compounds in all categories, while showing no toxic side effects toward healthy human foreskin fibroblasts and thus being selective. They exhibited EC50 values of 0.2 μM against the doxorubicin-sensitive as well as the multidrug-resistant leukemia cells and therefore can be regarded as superior to doxorubicin. Moreover, they showed to be five times more active than the standard drug ganciclovir and nearly eight times more active than artesunic acid against HCMV. In addition, hybrids 6a/b possessed excellent antimalarial activity (EC50 = 5.9/3.7 nM), which was better than that of artesunic acid (EC50 = 8.2 nM) and chloroquine (EC50 = 9.8 nM). Overall, most of the presented thymoquinone-artemisinin-based hybrids exhibit an excellent and broad variety of biological activities (anticancer, antimalarial, and antiviral) combined with a low toxicity/high selectivity profile.


The Influence of Using a Footstool during a Prolonged Standing Task on Low Back Pain in Office Workers.
While many office workers experience low back pain (LBP), little is known about the effect of prolonged standing on LBP symptoms. This repeated-measures within-subjects study aimed to determine whether office workers with LBP are able to work at a standing workstation for one hour without exacerbating symptoms and whether using a footstool affects LBP severity. Sixteen office workers with LBP performed computer work at a standing workstation for one hour under the following two conditions, one week apart: with a footstool and without a footstool. The intensity of LBP was recorded at 10 min intervals. Maximal severity of LBP pain and change in LBP severity throughout the standing task were not different between the footstool and no footstool conditions (p > 0.26). There was a trend for more participants to have an increase in their pain between the start and end of the task when not using a footstool compared to using a footstool (p = 0.10). Most office workers with LBP are able to use a standing workstation without significant exacerbation of symptoms, but a proportion will experience a clinical meaningful increase in symptoms. Using a footstool does not change the severity of LBP experienced when using a standing workstation in individuals with a history of LBP.


Experimental investigation of NIRS spatial sensitivity.
Near infrared spectroscopy (NIRS) is regarded as a potential medical diagnostic technique for investigation of hemodynamic changes. However, uncertainties pertaining to the origin of NIRS signals have hampered its clinical interpretation. The uncertainities in NIRS measurements especially in case of living tissues are due to lack of rigorous combined theoretical-experimental studies resulting in clear understanding of the origin of NIRS signals. For their reliable interpretation it is important to understand the relationship between spatial changes in optical properties and corresponding changes in the NIRS signal. We investigated spatial sensitivity of near infrared optical measurements using an experimental approach. It uses a liquid optical phantom as tissue equivalent, which is explored under robot-control by a small, approximately point like perturbation of desired optical properties, and a NIRS instrument for trans-illumination/reflection measurements. The experimentally obtained sensitivity has been analyzed and compared with numerical simulations. In preliminary experiments we investigated the influence of various optical properties of the medium and of source/detector distances on the spatial sensitivity distribution. The acquired sensitivity maps can be used to define characteristic parameters. As an example, we used a 25% threshold to define a penetration depth measure which provides values in good accordance with published ones. To the best of our knowledge this is the first experimental study of NIRS spatial sensitivity. The presented method will allow in depth experimental investigation of the influence of various conditions pertaining to medium such as optical properties of tissue (scattering and absorption) and of the source/detector configuration.


Identification of the Coenzyme A (CoA) Ester Intermediates and Genes Involved in the Cleavage and Degradation of the Steroidal C-Ring by Comamonas testosteroni TA441.
Comamonas testosteroni TA441 degrades steroids aerobically via aromatization of the A-ring accompanied by B-ring cleavage, followed by D- and C-ring cleavage. We previously revealed major enzymes and intermediate compounds in A,B-ring cleavage, the β-oxidation cycle of the cleaved B-ring, and partial C,D-ring cleavage. Here, we elucidate the C-ring cleavage and the β-oxidation cycle that follows. ScdL1L2, a 3-ketoacid coenzyme A (CoA) transferase which belongs to the SugarP_isomerase superfamily, was thought to cleave the C-ring of 9-oxo-1,2,3,4,5,6,10,19-octanor-13,17-secoandrost-8(14)-ene-7,17-dioic acid-CoA ester, the key intermediate compound in the degradation of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid (3aα-H-4α [3'-propionic acid]-7aβ-methylhexahydro-1,5-indanedione; HIP)-CoA ester in our previous study; however, the present study suggested that ScdL1L2 is the isomerase of the derivative with a hydroxyl group at C-14 which cleaves the C-ring. The subsequent ring-cleaved product was indicated to be converted to 4-methyl-5-oxo-octane-1,8-dioic acid-CoA ester mainly by ORF33-encoded CoA-transferase (named ScdJ), followed by dehydrogenation by ORF21- and 22-encoded acyl-CoA dehydrogenase (named ScdM1M2). Then, a water molecule is added by ScdN for further degradation by β-oxidation. ScdN is proposed to catalyze the last reaction in C,D-ring degradation by the enzymes encoded in the steroid degradation gene cluster tesB to tesR. IMPORTANCE Studies on bacterial steroid degradation were initiated more than 50 years ago primarily to obtain materials for steroid drugs. Steroid-degrading bacteria are globally distributed, and the role of bacterial steroid degradation in the environment, as well as in humans, is attracting attention. The overall degradation process of the four steroidal rings has been proposed; however, there is still much to be revealed to understand the complete degradation pathway. This study aimed to uncover the whole steroid degradation process in C. testosteroni, which is one of the most studied representative steroid-degrading bacteria and is suitable for exploring the degradation pathway because the involvement of degradation-related genes can be determined by gene disruption.


Factors affecting the catch-up growth of preterm infants after discharge in China: a multicenter study based on the health belief model.
The purpose of this study was to analyze the growth status and to identify the risk factors that influence the catch-up growth of preterm infants after discharge and to provide evidence for feeding strategies and the need for further research. A descriptive correlational analysis was applied. The sample consisted of 309 preterm infants and their caregivers selected from June to August 2017 from five women's and children's hospitals. Self-designed questionnaires based on knowledge, attitude and practice and the Health Belief Model (HBM) were used to measure the catch-up growth status of preterm infants after discharge. Logistic regression was used to determine the risk factors for the catch-up growth of preterm infants. The results showed that of 309 preterm infants, only 14 (4.5%) were underweight, and 52 (17.4%) did not meet the criteria for catch-up growth at 12 months of actual age. The logistic regression analysis showed that gestational age, regular health care, caregivers' educational background, mothers' daily contact with the baby, monthly average family income, the addition of a breast milk supplement, and daily milk volume were risk factors that affected the catch-up growth of preterm infants after discharge. The rate of catch-up growth of preterm infants is still not high. We should pay much more attention to preterm infants of small gestational age and guide their child care on a regular basis to detect and correct risk factors in a timely fashion, especially those involving lower daily milk volume, lower degree of culture and family economic difficulties. Second, we suggest that the government publish relevant policy that appropriately increases the length of maternity leave for preterm mothers. Future studies should have larger sample sizes and explore other important factors influencing the catch-up growth of preterm infants.


Aortic mineralisation in children with congenital cardiac disease.
Congenital cardiac diseases are the most frequent congenital malformations. In adult patients, the mineralisation of the aorta due to cardiovascular disease is very common, but vascular mineralisation in paediatric cardiopathies is a topic less studied. This study shows that children with a complex congenital cardiopathy show a high degree of vascular mineralisation in the ascending aorta. This can be part of the cardiac failure pathophysiology due to congenital cardiopathies. The aim of this study was to determine the presence and degree of vascular mineralisation in samples of the ascending and descending aorta of children with complex congenital cardiopathies. We conducted a cross-sectional study. We obtained 34 vascular tissues from the autopsies of 17 children with congenital cardiac disease. We used a scanning electron microscope with an energy-dispersive X-ray spectroscopy in order to analyse the vascular tissues. The amount of minerals was two times higher in the ascending aorta than in the descending aorta of children with congenital cardiac disease. The study provides evidence that vascular mineralisation can start at an early age, and that it is higher in the ascending aorta than in the descending aorta.


Effect of aminoacyl-tRNA synthetase mutations on susceptibility to ciprofloxacin in Escherichia coli.
Chromosomal mutations that reduce ciprofloxacin susceptibility in Escherichia coli characteristically map to drug target genes (gyrAB and parCE), and genes encoding regulators of the AcrAB-TolC efflux pump. Mutations in RNA polymerase can also reduce susceptibility, by up-regulating the MdtK efflux pump. We asked whether mutations in additional chromosomal gene classes could reduce susceptibility to ciprofloxacin. Experimental evolution, complemented by WGS analysis, was used to select and identify mutations that reduce susceptibility to ciprofloxacin. Transcriptome analysis, genetic reconstructions, susceptibility measurements and competition assays were used to identify significant genes and explore the mechanism of resistance. Mutations in three different aminoacyl-tRNA synthetase genes (leuS, aspS and thrS) were shown to reduce susceptibility to ciprofloxacin. For two of the genes (leuS and aspS) the mechanism was partially dependent on RelA activity. Two independently selected mutations in leuS (Asp162Asn and Ser496Pro) were studied in most detail, revealing that they induce transcriptome changes similar to a stringent response, including up-regulation of three efflux-associated loci (mdtK, acrZ and ydhIJK). Genetic analysis showed that reduced susceptibility depended on the activity of these loci. Broader antimicrobial susceptibility testing showed that the leuS mutations also reduce susceptibility to additional classes of antibiotics (chloramphenicol, rifampicin, mecillinam, ampicillin and trimethoprim). The identification of mutations in multiple tRNA synthetase genes that reduce susceptibility to ciprofloxacin and other antibiotics reveals the existence of a large mutational target that could contribute to resistance development by up-regulation of an array of efflux pumps.


Kinetic Model of Photoautotrophic Growth of Chlorella sp. Microalga, Isolated from the Setúbal Lagoon.
In this work, a kinetic expression relating light availability in the culture medium with the rate of microalgal growth is obtained. This expression, which is valid for low illumination conditions, was derived from the reactions that take part in the light-dependent stage of photosynthesis. The kinetic expression obtained is a function of the biomass concentration in the culture, as well as of the local volumetric rate of absorption of photons, and only includes two adjustable parameters. To determine the value of these parameters and to test the validity of the hypotheses made, autotrophic cultures of the Chlorella sp. strain were carried out in a modified BBM medium at three CO2 concentrations in the gas stream, namely 0.034%, 0.34% and 3.4%. Moreover, the local volumetric rate of photon absorption was predicted based on a physical model of the interaction of the radiant energy with the suspended biomass, together with a Monte Carlo simulation algorithm. The proposed intrinsic expression of the biomass growth rate, together with the Monte Carlo radiation field simulator, are key to scale up photobioreactors when operating under low irradiation conditions, independently of the configuration of the reactor and of its light source.


Spinal cord injury: prognosis for ambulation based on sensory examination in patients who are initially motor complete.
The purpose of this retrospective study was to document that patients with motor complete injury, but preserved pin appreciation, in addition to light touch, below the zone of injury have better prognoses with regard to ambulation than patients with only light touch preserved. Medical records were examined of all spinal cord injury (SCI) patients admitted between 1982 and 1988. Twenty-seven Frankel B patients with upper motor neuron lesions admitted within 72 hours of injury were identified. These patients were divided into two groups (B-1 and B-2). Group B-1 (n = 18) were patients who had touch sensation but no pin appreciation below the zone of injury. Group B-2 (n = 9) were patients who had partial or complete pin appreciation and light touch below the zone of injury. The charts were examined for the patient's ability to walk independently using a reciprocal gait for at least 200 feet. The data were analyzed by the Fisher Exact test. Eight of the nine Group B-2 patients ambulated as compared to two of the 18 Group B-1 patients (p less than .0002). Frankel B SCI patients with only touch preserved below the zone of injury had poor prognoses for ambulation; those with preserved pin appreciation below the zone of injury had excellent prognoses to regain functional ambulation.


Effects of an S84E mutation of bovine growth hormone in transgenic mice.
The ability of mutant bovine growth hormones (bGH) to serve as either agonist or antagonist has been demonstrated in transgenic mice. We have prepared two transgenic strains of FVB/N mice, one expressing wild-type bGH and a second with a glutamic acid mutation at serine 84 in helix 2. Comparison of their phenotypes to those of nontransgenic littermates indicates that wild-type bGH induces a previously described phenotype for hyper-somatotrophic mice. In contrast, the replacement of the side chain hydroxyl at serine 84 with acetic acid produced a phenotype that expressed bGH at appreciable concentrations, but failed to elicit the phenotype observed with either an agonist or an antagonist of bGH. These results indicate that serine 84 is crucial for the activity of bGH despite this site being distal to the receptor binding surfaces.


Systems Pharmacology and Microbiome Dissection of Shen Ling Bai Zhu San Reveal Multiscale Treatment Strategy for IBD.
Generally, inflammatory bowel disease (IBD) can be caused by psychology, genes, environment, and gut microbiota. Therefore, IBD therapy should be improved to utilize multiple strategies. Shen Ling Bai Zhu San (SLBZS) adheres to the aim of combating complex diseases from an integrative and holistic perspective, which is effective for IBD therapy. Herein, a systems pharmacology and microbiota approach was developed for these molecular mechanisms exemplified by SLBZS. First, by systematic absorption-distribution-metabolism-excretion (ADME) analysis, potential active compounds and their corresponding direct targets were retrieved. Then, the network relationships among the active compounds, targets, and disease were built to deduce the pharmacological actions of the drug. Finally, an "IBD pathway" consisting of several regulatory modules was proposed to dissect the therapeutic effects of SLBZS. In addition, the effects of SLBZS on gut microbiota were evaluated through analysis of the V3-V4 region and multivariate statistical methods. SLBZS significantly shifted the gut microbiota structure in a rat model. Taken together, we found that SLBZS has multidimensionality in the regulation of IBD-related physiological processes, which provides new sights into herbal medicine for the treatment of IBD.


Cranial Osteopathy: Obscurantism and Enlightenment.
The application of cranial osteopathic manipulative medicine (OMM) is always controversial in the literature. Primary respiration related to the movement of spheno-basilar synchondrosis in the adult goes against the knowledge of complete ossification that occurs at this articulation after the pubertal phase. The idea that the operator's hands can communicate with the meninges is difficult to accept. The anatomy shows us that the fascial system involves the meninges and that from the microcellular point of view there are no layers that divide one tissue from another. The backing of new sciences, such as quantum physics, suggest that cranial palpation allows the osteopath to come into contact with the meninges. Recent scientific evidence shows that meningeal afferents can affect extracranial areas and that the pericranial musculature itself is able to influence these afferents. The article highlights some reflections in support of cranial osteopathy, based on scientific information that could help the osteopath to improve clinical work.


Characteristics and Research Progress of Legume Nodule Senescence.
Delaying the nodule senescence of legume crops can prolong the time of nitrogen fixation and attenuate the lack of fertilizer in the later stage of legume crop cultivation, resulting in improved crop yield and reduced usage of nitrogen fertilizer. However, effective measures to delay the nodule senescence of legume crops in agriculture are relatively lacking. In the present review, we summarized the structural and physiological characteristics of nodule senescence, as well as the corresponding detection methods, providing technical support for the identification of nodule senescence phenotype. We then outlined the key genes currently known to be involved in the regulation of nodule senescence, offering the molecular genetic information for breeding varieties with delayed nodule senescence. In addition, we reviewed various abiotic factors affecting nodule senescence, providing a theoretical basis for the interaction between molecular genetics and abiotic factors in the regulation of nodule senescence. Finally, we briefly prospected research foci of nodule senescence in the future.


Semen extenders: An evaluative overview of preservative mechanisms of semen and semen extenders.
Reproduction is fundamental for all living things as it ensures the continued existence of a species and an improved economy in animal husbandry. Reproduction has developed since history, and diverse processes, such as artificial insemination and in vitro fertilization, have been developed. Semen extenders were discovered and developed to protect sperm from harmful factors, such as freeze and osmotic shock, oxidative stress, and cell injury by ice crystals. Semen extenders preserve sperm by stabilizing its properties, including sperm morphology, motility, and viability and membrane, acrosomal, and DNA integrity. Therefore, semen extenders must provide a favorable pH, adenosine triphosphate, anti-cooling and anti-freeze shock, and antioxidant activity to improve semen quality for fertilization. Hence, this review provides precise data on different semen extenders, preservative mechanisms, and essential additives for semen extenders in different animals.


Baseline Level and Reduction in PaCO2 are Associated with the Treatment Effect of Long-Term Home Noninvasive Positive Pressure Ventilation in Stable Hypercapnic Patients with COPD: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
The evidence of long-term home noninvasive positive pressure ventilation (LTHNIPPV) in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD) is controversial. In this meta-analysis study, we sought to establish whether a baseline level and reduction in partial pressure of arterial carbon dioxide (PaCO2) were associated with the treatment effect of LTHNIPPV in these patients. Six electronic databases were comprehensively searched from January 1980 until June 2020. Randomized clinical trials (RCTs) comparing LTHNIPPV with control treatment were included. Two authors independently extracted data, assessed the study quality, and used the GRADE approach to evaluate evidence quality. The main outcome was mortality. Nineteen studies involving 1482 patients (LTHNIPPV, n = 730; control, n = 752) were included. LTHNIPPV significantly reduced mortality (relative risk [RR] = 0.76; 95% confidence interval [CI]: 0.61-0.95; p = 0.02; I2 = 14%), the frequency of hospital admissions, PaCO2, and improved partial pressure of oxygen (PaO2) compared to control treatment. LTHNIPPV also relieved dyspnea and improved exercise capacity and health-related quality of life (HRQL) but showed no significant benefit for improving the forced expiratory volume in one second in predicted (FEV1% pred). Subgroup analysis revealed that the baseline level and reduction in PaCO2 were associated with decreased mortality (baseline PaCO2 ≥ 55 mmHg RR = 0.69, P = 0.02; vs baseline PaCO2 < 55 mmHg RR = 0.87, P = 0.32; and higher dPaCO2 RR = 0.42, P < 0.0001; vs lower dPaCO2 RR = 0.91, P = 0.38). LTHNIPPV significantly reduced mortality. The baseline level and reduction in PaCO2 were associated with the treatment effect of LTHNIPPV in patients with stable hypercapnic COPD. Large-scale, multicenter RCTs are needed to confirm our results.


Understanding and evaluating historical sources in nursing history research.
All nurse researchers need to address, in the manner most appropriate to their research methodology, issues of quality related to their research material. This concern is not about the care needed in generating data, rather it relates to understanding and evaluating material that already exists. This article describes four historical sources relevant to the history of nursing in New Zealand and uses them to explain how nurse researchers can evaluate their research material. The dimensions of this evaluation are the provenance, purpose, context, veracity and usefulness of the historical sources. The article explains the questions that need to be addressed in each dimension of the evaluation. The different kinds of information available in the four historical sources are illustrated by references to individual nurses.


The M locus and ethylene-controlled sex determination in andromonoecious cucumber plants.
Sex determination in cucumber (Cucumis sativus L.) plants is genetically controlled by the F and M loci. These loci interact to produce three different sexual phenotypes: gynoecious (M-F-), monoecious (M-ff), and andromonoecious (mmff). Gynoecious cucumber plants produce more ethylene than do monoecious plants. We found that the levels of ethylene production and the accumulation of CS-ACS2 mRNA in andromonoecious cucumber plants did not differ from those in monoecious plants and were lower than the levels measured in gynoecious plants. Ethylene inhibited stamen development in gynoecious cucumbers but not in andromonoecious ones. Furthermore, ethylene caused substantial increases in the accumulation of CS-ETR2, CS-ERS, and CS-ACS2 mRNA in monoecious and gynoecious cucumber plants, but not in andromonoecious one. In addition, the inhibitory effect of ethylene on hypocotyl elongation in andromonoecious cucumber plants was less than that in monoecious and gynoecious plants. These results suggest that ethylene responses in andromonoecious cucumber plants are reduced from those in monoecious and gynoecious plants. This is the first evidence that ethylene signals may influence the product of the M locus and thus inhibit stamen development in cucumber. The andromonoecious line provides novel material for studying the function of the M locus during sex determination in flowering cucumbers.


Physical activity self-efficacy mediates the effect of symptom distress on exercise involvement among adolescents undergoing cancer treatment.
The objective of this study was to examine whether physical activity self-efficacy mediated the adverse effect of symptom distress on exercise involvement among adolescents undergoing cancer treatment. A secondary data analysis approach was used to analyse a pooled sample of 97 adolescents who were undergoing cancer treatment in paediatric oncology/haematology wards and ambulatory settings in northern Taiwan. Mediation analysis was performed to examine the mediation relationship among physical activity self-efficacy, symptom distress and exercise involvement. The total effect (path c) (p < 0.001), the indirect effect (paths a and b) (p < 0.05 and p < 0.01) and the direct effect (path c') (p < 0.001) were significant. The bootstrapping test was significant (95% CI: -0.356 to -0.016), indicating that physical activity self-efficacy partially mediated the adverse effect of symptom distress on exercise involvement after adjusting for age, gender and cancer diagnosis. Physical activity self-efficacy partially mediates the relationship between symptom distress and exercise involvement for adolescents undergoing cancer treatment. There is an imperative need for healthcare professionals to design interventions to enhance these adolescents' physical activity self-efficacy, increase their exercise involvement and thus improve their quality of life.


Report of a patient with complex composites of hepatitis B virus, allergic asthma and diabetes.
HBV is a non-cytopathic virus and cell mediated immune response against this. Humoral mediated immune response are responsible for allergic diseases. Balance between these two subsets of Th CD4+ cells are result of the immune system response. A 56 year old woman presented with chronic HBV infection, allergic asthma, type 2 diabetes mellitus and high blood pressure and high blood lipid. Patients should be followed for the allergic and autoimmune diseases along with their viral reactivation.


Aggregated and free bacteria as food sources for heterotrophic microflagellates.
Laboratory evidence for the selective grazing of aggregated bacteria by a Bodo sp. and free bacteria by a Paraphysomonas sp. is presented. The relevance of different microflagellate feeding mechanisms with respect to prey distribution in the natural environment is discussed.


Purkinje cell axonal swellings enhance action potential fidelity and cerebellar function.
Axonal plasticity allows neurons to control their output, which critically determines the flow of information in the brain. Axon diameter can be regulated by activity, yet how morphological changes in an axon impact its function remains poorly understood. Axonal swellings have been found on Purkinje cell axons in the cerebellum both in healthy development and in neurodegenerative diseases, and computational models predicts that axonal swellings impair axonal function. Here we report that in young Purkinje cells, axons with swellings propagated action potentials with higher fidelity than those without, and that axonal swellings form when axonal failures are high. Furthermore, we observed that healthy young adult mice with more axonal swellings learn better on cerebellar-related tasks than mice with fewer swellings. Our findings suggest that axonal swellings underlie a form of axonal plasticity that optimizes the fidelity of action potential propagation in axons, resulting in enhanced learning.


Giant ecchordosis physaliphora in an adolescent girl: case report.
The authors describe a rare case of giant ecchordosis physaliphora (EP) in a 16-year-old female patient who presented with diplopia. Magnetic resonance imaging of the brain with Gd contrast revealed a 3.0 × 1.7 × 1.8-cm nonenhancing, extraaxial epidural mass along the dorsal aspect of the clivus that was T2 hyperintense and T1 isointense with intermediate signal on diffusion sequences. Resection via a transnasal transsphenoidal approach to the ventral clival wall resulted in a stable tumor size with no evidence of interval growth after 30 months. Although this case features a strictly extradural EP, this tumor more commonly occurs in the subdural space and requires differentiation from intradural chordoma. Unlike EP, intradural chordoma may enhance with Gd contrast, is more likely to be associated with cranial nerve palsies and brainstem symptoms, and will occasionally have an elevated MIB-1 index. In this paper the authors highlight the different possible midline locations for both EP and chordoma, the difficulty in distinguishing between intradural giant EP and intradural chordoma, and the potential occurrence of these lesions in young people despite their typically slow rate of growth, while also underscoring the need for further investigation into the tumors' cytogenetic behavior.


Neuropathies associated with IgG and IgA monoclonal gammopathy.
Neuropathy has been frequently reported in patients with monoclonal gammopathy, particularly those with monoclonal gammopathy of undetermined significance (MGUS). While the neuropathy associated with IgM-MGUS is well characterized and is often associated with a reactivity of the monoclonal protein with neural antigens, the relationship between the neuropathy and IgG and IgA MGUS is less clear. We review here the clinical, electrophysiological and pathogenetic features of neuropathies associated with IgG and IgA M-proteins in order to determine whether they represent distinct clinical entities and, most importantly, whether the finding of an IgG or IgA monoclonal gammopathy in a patient with neuropathy should led to different diagnostic or therapeutical approaches. This review will mainly focus on neuropathies associated with MGUS since the disclosure of a malignant monoclonal gammopathy, including multiple or osteosclerotic myeloma, lymphoma or primary amyloidosis, in a patient with neuropathy usually divert the therapeutical decisions to the hematologist for an appropriate therapy of the underlying life threatening condition.


Weight reduction in obese hypertensive patients.
This study tested the feasibility of a low-technology office-based approach to weight reduction in obese hypertensive patients. Family practice residents were randomly assigned to either an experimental or a control group. Physicians in the experimental group were instructed in methods of weight reduction, which they then passed on to their patients. Patients of experimental physicians were seen monthly, their diets were discussed, and improvements were suggested. The control group patients received their usual care. After six months the experimental patients had lost significantly more weight than the controls and had significantly reduced the number of antihypertensive drugs while maintaining blood pressure control. After 12 months there was no significant difference between the two groups with respect to weight loss, blood pressure, or number of antihypertensive drugs. Experimental and control patients who lost weight had visited their physicians more frequently than those who did not and had reduced the number of antihypertensive medications they were taking. This educationally oriented intervention trial is an example of the type of research that is practical to perform in a family practice center and is applicable in family physicians' offices.


Baicalein inhibits pancreatic cancer cell proliferation and invasion via suppression of NEDD9 expression and its downstream Akt and ERK signaling pathways.
Baicalein, a flavone ingredient of Scutellaria baicalensis Georgi, is a promising anti-cancer agent. However, its potential anti-pancreatic cancer effects and the underlying mechanisms are still unclear. In this study, we showed that Baicalein not only induced apoptosis, but also suppressed proliferation, migration and invasion of two pancreatic cancer cell lines BxPC-3 and PANC-1 in a dose- and time-dependent manner. Notably, Baicalein exhibited low toxicity to normal human liver or kidney cells. We further discovered that Baicalein suppressed BxPC-3 and PANC-1 cell proliferation and invasion through targeting the expression of NEDD9, a Cas scaffolding protein, to decrease Akt and ERK activities. Especially, Baicalein decreased Akt phosphorylation at T-308 via lowering NEDD9-dependent PDK1 expression. Overexpression of NEDD9 effectively rescued proliferation and invasion of BxPC-3 and PANC-1 cells dampened by Baicalein. Taken together, our findings suggest that Baicalein is a potent remedy applied to pancreatic cancer treatment in the future.


Analysis of the clinical utility of a predictive chemosensitivity assay.
We present an elementary statistical analysis for quantifying the clinical utility of a predictive chemosensitivity assay based on retrospective data. An assay predictive of patient response could possibly improve response rates and reduce morbidity by individualizing chemotherapy for each patient. An analysis of retrospective data can suggest appropriate patient populations and sample sizes for study in prospective trials using the chemosensitivity assay. We provide an example with data from a clonogenic assay collected on melanoma patients.


Identification and clearance involved in the formation of glucuronides of RT-3003, a new peripheral blood flow enhancer, and its metabolite in rats.
Glucuronides of RT-3003 and its metabolite (9-OH-RT-3003), which was hydroxylated at the 9 position on the benzene ring, were separated by HPLC and identified by liquid chromatography (LC)/MS/MS and NMR. The conjugation sites of these glucuronides were determined by nuclear Overhauser effects (NOE) irradiation; RT-3003 was conjugated at an alcoholic hydroxyl group of the hydroxymethyl moiety, and 9-OH-RT-3003 at a phenolic hydroxyl group on a benzene ring and at an alcoholic hydroxyl group of a hydroxymethyl moiety. On a reversed-phase HPLC of 9-OH-RT-3003, alcoholic glucuronide was eluted later than phenolic glucuronide, indicating the high hydrophobicity of alcoholic glucuronide. Clearance for the glucuronidation (ClG) of RT-3003 was lower than the summation of ClG for two types of glucuronidation of 9-OH-RT-3003. ClG of 9-OH-RT-3003 was high in phenolic glucuronide. The activity of UDP-glucuronyltransferase (UDPGT) for RT-3003 was 9.63 times that for 9-OH-RT-3003, and the activity ratio of the two types of glucuronidation of 9-OH-RT-3003 was similar to the ratio of the corresponding ClG. The difference between ClG and UDPGT activity is discussed in association with clearance for the hydroxylation and interaction of substrates with UDPGT.


Perforation of a Peptic Ulcer in a Hiatal Hernia Into the Left Ventricle With Systemic Air and Food Embolism.
Perforation of a peptic ulcer into the ventricle is uncommon, and the definitive diagnosis is difficult in living patients. We herein report a case of perforation of a peptic ulcer in a hiatal hernia into the left ventricle with systemic air and food embolism. This is the first case report of the perforation diagnosed by computed tomography and confirmed by autopsy. Computed tomography was useful for the diagnosis of perforation into the ventricle.


Product versus additive model for studying artificial insemination results in several livestock populations.
Two models can be used for studying binary results of AI. The additive threshold model proposes an underlying variable as summing the environmental and genetic effects from the 2 individuals involved in the mating, and the product threshold model assumes that the conditional probability of AI success is the product of the probabilities of success of 2 unobserved binary phenotypes (one is the male fertility; the other is the female fertility). The purpose of this paper is to compare the predictive ability of the product and the additive threshold models for studying AI results and to compare results obtained with the 2 models in 3 different species: cattle, sheep, and rabbits. Results showed that the predictive ability of the product model is similar to the additive model in sheep and rabbits but worst in cattle (percentage of wrong prediction = 42, 27, and 35% in the additive model; 43, 28, and 47% in the product model in sheep, rabbits, and cattle, respectively). Even when the 2 models have similar performance, they differed in their EBV (for instance, Pearson correlation between EBV predicted with the 2 models = 0.46 in sheep for male fertility). The product model can determine which sex is responsible for an AI failure. In sheep, the female was the responsible in 94% of the cases and male in 2% of them; in rabbits, the female was the responsible in 54% of the cases and the male in 39% of them. Different estimates of probabilities for male and female fertility success obtained with the product model in the 3 species suggest that male and female fertilities behave differently depending on the species and the uniqueness of the data sets. Although product model seems to provide additional information in the fertility process, further research is needed to understand the worst performance of the product model in cattle.


Co3O4-SiO2 nanocomposite: a very active catalyst for CO oxidation with unusual catalytic behavior.
A high surface area Co(3)O(4)-SiO(2) nanocomposite catalyst has been prepared by use of activated carbon as template. The Co(3)O(4)-SiO(2) composite, the surface of which is rich in silica and Co(II) species compared with normal Co(3)O(4), exhibited very high activity for CO oxidation even at a temperature as low as -76 °C. A rather unusual temperature-dependent activity curve, with the lowest conversion at about 80 °C, was observed with a normal feed gas (H(2)O content ~3 ppm). The U-shape of the activity curve indicates a negative apparent activation energy over a certain temperature range, which has rarely been observed for the heterogeneously catalyzed oxidation of CO. Careful investigation of the catalytic behavior of Co(3)O(4)-SiO(2) catalyst led to the conclusion that adsorption of H(2)O molecules on the surface of the catalyst caused the unusual behavior. This conclusion was supported by in situ diffuse reflectance Fourier transform infrared (DRIFT) spectroscopic experiments under both normal and dry conditions.


The protective role of silicon in the Arabidopsis-powdery mildew pathosystem.
The role and essentiality of silicon (Si) in plant biology have been debated for >150 years despite numerous reports describing its beneficial properties. To obtain unique insights regarding the effect of Si on plants, we performed a complete transcriptome analysis of both control and powdery mildew-stressed Arabidopsis plants, with or without Si application, using a 44K microarray. Surprisingly, the expression of all but two genes was unaffected by Si in control plants, a result contradicting reports of a possible direct effect of Si as a fertilizer. In contrast, inoculation of plants, treated or not with Si, altered the expression of a set of nearly 4,000 genes. After functional categorization, many of the up-regulated genes were defense-related, whereas a large proportion of down-regulated genes were involved in primary metabolism. Regulated defense genes included R genes, stress-related transcription factors, genes involved in signal transduction, the biosynthesis of stress hormones (SA, JA, ethylene), and the metabolism of reactive oxygen species. In inoculated plants treated with Si, the magnitude of down-regulation was attenuated by >25%, an indication of stress alleviation. Our results demonstrate that Si treatment had no effect on the metabolism of unstressed plants, suggesting a nonessential role for the element but that it has beneficial properties attributable to modulation of a more efficient response to pathogen stress.


Potential role of MRN-100, an iron-based compound, in upregulating production of cytokine IL-10 in human dendritic cells to promote an anti-inflammatory response in vitro.
The hydroferrate fluid MRN-100, an iron-based compound with potent antioxidant characteristics, was examined to identify its possible anti-inflammatory effects on human dendritic cells (DCs) in vitro. Human monocyte-derived DCs were treated with MRN-100 at two concentrations (50 and 100 μL/mL) for 24 h and then stimulated with or without lipopolysaccharides (LPS). The expression of DC maturation markers was assessed by flow cytometry and the production of cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Functional assay was performed by co-culturing MRN-100-treated and untreated DCs with allogeneic naïve CD4+ T cells and assaying the T cells' cytokine production. Results show that treatment with MRN-100 significantly upregulated the co-stimulatory molecules CD80 and CD86 and increased human leukocyte antigen-DR (HLA-DR) though not significantly. MRN-100 treatment also significantly increased the production of the anti-inflammatory cytokine interleukin (IL)-10. On the other hand, MRN-100 significantly induced the secretion of pro-inflammatory cytokines such as IL-6 only at high concentrations. Furthermore, DCs pretreated with MRN-100 and either stimulated or not with LPS were able to prime CD4+ T cells to secrete significant amounts of IL-10 while inhibiting the secretion of pro-inflammatory cytokine tumor necrosis factor (TNF)-α. These results indicate that MRN-100 is a powerful anti-inflammatory agent that promotes the generation of an anti-inflammatory immune response in vitro. MRN-100 could be beneficial for treating patients with inflammatory diseases, including arthritis and type 1 diabetes, and its potential benefits should be examined in clinical trials.


Non-Invasive Buccal Swab Gene Testing for Skin Cancer Risk
Background: Studies have identified numerous genetic polymorphisms associated with increased risk of melanoma and non-melanoma skin cancer (NMSC). In this pilot study, we aimed to examine whether previously identified melanoma and non-melanoma associated single nucleotide polymorphisms (SNPs) which were found to be associated with cutaneous malignancy were also present in a relatively heterogeneous population with a history of skin cancer versus an age and environmental matched controls. The undertaking of this project serves to further the current understanding of the genetic profile for those at higher risk for developing skin cancer. Methods: Nineteen NMSC patients and their age-matched and environmental controls underwent genotyping of 7 previously discovered SNPs associated with melanoma and NMSC. Results: In a random, heterogeneous population in Southern California, SNP's Chr1, PAD16, PIGU, TDG had a similar association with NMSC previously reported in prior studies. Due to small trial size, no conclusions or observable associations could be drawn from the SNPs MC1R, TP53, and XRCC1. Conclusion: This data supports that 4 of the 7 SNP's studied had similar associations and could potentially be predictive tool of NMSC risk in this patient population. The remaining three SNP's did not have a definitive association with malignancy. Larger studies are needed to further elucidate the specific roles of these SNPs collectively and ultimately to develop a genetic profile for those patients at increased risk of developing skin cancer. J Drugs Dermatol. 2019;18(5):448-453.


Dynamic control of nucleic-acid-sensing Toll-like receptors by the endosomal compartment.
Nucleic-acid (NA)-sensing Toll-like receptors (TLRs) are synthesized in the endoplasmic reticulum and mature with chaperones, such as Unc93B1 and the protein associated with TLR4 A (PRAT4A)-gp96 complex. The TLR-Unc93B1 complexes move to the endosomal compartment, where proteases such as cathepsins activate their responsiveness through proteolytic cleavage of the extracellular domain of TLRs. Without proteolytic cleavage, ligand-dependent dimerization of NA-sensing TLRs is prevented by the uncleaved loop in the extracellular domains. Additionally, the association of Unc93B1 inhibits ligand-dependent dimerization of TLR3 and TLR9 and, therefore, Unc93B1 is released from these TLRs before dimerization. Ligand-activated NA-sensing TLRs induce the production of pro-inflammatory cytokines and act on the endosomal compartment to initiate anterograde trafficking to the cell periphery for type I interferon production. In the endosomal compartment, DNA and RNA are degraded by DNases and RNases, respectively, generating degradation products. DNase 2A and RNase T2 generate ligands for TLR9 and TLR8, respectively. In this mechanism, DNases and RNases control innate immune responses to NAs in endosomal compartments. NA-sensing TLRs and the endosomal compartment work together to monitor environmental cues through endosomes and decide to launch innate immune responses.


High-Pressure Synthesis and Crystal Structure of Ce4B14O27.
Ce4B14O27 was synthesized under conditions of 2.6 GPa and 750 °C in a Walker-type multianvil apparatus. The crystal structure was determined on the basis of single-crystal X-ray diffraction data, collected at room temperature, revealing that Ce4B14O27 is isotypic to La4B14O27. Ce4B14O27 crystallizes monoclinically with four formula units in the space group C2/c (No. 15) and the lattice parameters a = 1117.8(2), b = 640.9(2), c = 2531.7(5) pm, and β = 100.2(1)°. The three-dimensional boron-oxygen framework consists of [BO4]5- tetrahedra and trigonal-planar [BO3]3- groups. The structure contains two crystallographically different cerium ions. Furthermore, Raman spectroscopy was performed on single crystals of Ce4B14O27.


Respiratory adaptation to chronic hypercapnia in newborn rats.
We asked 1) whether newborn rats respond to chronic hypercapnia with a persistent increase in ventilation and 2) whether changes in lung mass were accompanying the respiratory adaptation to chronic hypercapnia, as previously observed during neonatal chronic hypoxia. Five litters of rats were kept in 7% CO2 (with 21% O2) from day 1 to 7 after birth (CO2exp) and compared with six litters of control rats growing in normocapnia-normoxia (C). Body weight was similar between the two groups. Ventilation, measured by flow plethysmography, increased in CO2exp from day 2 and remained steadily elevated, and at day 7 it almost doubled (174%) the C value because of the large increase in tidal volume and mean inspiratory flow (192 and 189%, respectively) with no changes in respiratory frequency. Two days after return to normocapnia, ventilation was still 33% higher than in C; at this time, acute exposure to hypercapnia increased ventilation relatively less in the CO2exp than in C because of a lower increase in tidal volume. Neither the lung weight-to-body weight nor the heart weight-to-body weight ratios increased in CO2exp. We conclude that 1) chronic hypercapnia in newborn rats induces a steady increase in ventilation, which persists at least 2 days after return to normocapnia with a reduction in the acute response to CO2, and 2) hyperventilation per se is not the cause of the increased lung mass observed during chronic neonatal hypoxia.


Erythroid differentiation and the Na+,K+-pump in ouabain-sensitive and ouabain-resistant Friend erythroleukemia cell lines.
The selection and biochemical characterization of ouabain-resistant erythroleukemia cell lines are described. Treatment of ouabain-resistant Friend erythroleukemia cell (FLC) lines with 1 mM ouabain demonstrated a reduced ouabain-sensitive 86Rb+-uptake after Na+-preloading in comparison with ouabain-sensitive cells. The ouabain- and diuretic (piretanide)-insensitive component of the 86Rb+-uptake (residual influx) was significantly enhanced in the ouabain-resistant FLC clones. Measurements of the Na+,K+-ATPase activity (E.C. 22.214.171.124) in plasma membrane preparations of the ouabain-resistant FLC clone B6/2 indicated that a ouabain-resistant Na+,K+-ATPase activity of about 20% of the total enzyme activity existed in the presence of 1 mM ouabain. Further experiments showed that the Na+,K+-ion-gradient in ouabain-resistant B6/2 cells was unaffected by ouabain exposure whereas the gradient collapsed in wild type 12 N cells. Another property of the ouabain-resistant cell lines was a decrease of the 86Rb+-uptake due to the Na+,K+, 2Cl(-)-cotransport system measured as piretanide-sensitive 86Rb+-uptake. The data on ion transport mechanisms in QuaR and QuaS FLC are discussed with respect to mutagen-induced and spontaneous cellular ouabain resistance. In addition, the role of altered ion transport mechanisms is considered for induced erythroid differentiation.


Role of N defects on thermally induced atomic-scale structural changes in transition-metal nitrides.
Transition-metal nitrides (TMN) have exceptional stability, which underlies their use in various applications. Here, we study the role of N point defects on the stability of prototype TMNs using first-principles calculations. We find that distinct regimes for TMN changes relate to specific atomic-scale mechanisms, namely, diffusion of N interstitials (I(N)), of I(N) pairs, and of N vacancies. The activation of these processes occurs sequentially as the temperature is raised in a range of several hundreds of degrees, accounting for observed TMN changes under widely different conditions.


Circadian variation of stroke onset in Hong Kong Chinese: a hospital-based study.
Circadian variation of onset of transient ischaemic attack (TIA) or stroke during four 6-hourly periods starting from midnight was studied in Hong Kong Chinese patients admitted to a regional hospital between October 1996 and July 1999. The onset was classifiable into one of the 6-hourly periods in 832 of 905 patients; patients with unclassifiable onset were more likely to have lacunar infarct and less likely to have intracerebral haemorrhage (ICH). There was a significant circadian variation of onset in all strokes and TIA, TIA alone, ischaemic stroke (IS), ICH and different IS subtypes. The risk of onset was greatest between 6 a.m. and noon for IS or TIA, but between noon and 6 p.m. for ICH. There was no difference in the circadian variation between patients with and without prior TIA or stroke. This hospital-based study revealed a significant circadian variation of onset in different types and subtypes of stroke.


Cardiac Epithelioid PEComa: Report of Two Cases and Review of the Literature.
Cardiac PEComa is very rare. We reported two cases of epithelioid PEComas, one in an adult and one in a 2-year-old child. Both tumors were composed of sheets of epithelioid cells with coagulation necrosis. In addition, the adult case showed marked nuclear atypia and high mitotic activity with atypical mitosis and the pediatric case showed unusual clear cell features. Immunohistochemically, both tumors were positive for HMB-45 and SMA and negative for S100 and cytokeratin. Electron microscopy was performed in the pediatric case and showed premelanosomes. The adult patient developed extensive metastasis indicating malignant behavior. Prior to the two cases, only 5 other cases of cardiac PEComa were reported and the literatures are reviewed.


Enhancement of dissolution rate and bioavailability of sulfamethoxazole by complexation with β-cyclodextrin.
The purpose of this study was to improve the solubility and dissolution rate of sulfamethoxazole (SMZ) with inclusion compound of β-cyclodextrin (β-CD). The interaction between SMZ and β-CD in solution was studied by the phase-solubility method. The phase-solubility studies revealed the formation of inclusion complexes with poor solubility with an inclusion complex of 1:1 molar ratio and a stability constant of 122.3 M(-1). The solid complexes of SMZ with β-CD were prepared by using kneading and coprecipitation methods. The physical mixture of these chemicals was also prepared for comparison. Inclusion complexation was confirmed by the results from the studies of infrared spectoroscopy (IR) and differential scanning calorimetry (DSC). The effect of water-soluble polymers i.e., polyethylene glycol 20000 and non-ionic surfactants i.e., polysorbate 20 on the complexation of SMZ with β-CD was also investigated by the same methods. The rates of release of the active material from the complexes were determined from dissolution studies using USP XXII paddle method. The formulation, that provided delivery of active material near to the target value in six healthy volunteers and in vivo tests, clearly revealed that the bioavailability of active material was found to be enhanced by preparing ternary mixtures.


Serine one-carbon catabolism with formate overflow.
Serine catabolism to glycine and a one-carbon unit has been linked to the anabolic requirements of proliferating mammalian cells. However, genome-scale modeling predicts a catabolic role with one-carbon release as formate. We experimentally prove that in cultured cancer cells and nontransformed fibroblasts, most of the serine-derived one-carbon units are released from cells as formate, and that formate release is dependent on mitochondrial reverse 10-CHO-THF synthetase activity. We also show that in cancer cells, formate release is coupled to mitochondrial complex I activity, whereas in nontransformed fibroblasts, it is partially insensitive to inhibition of complex I activity. We demonstrate that in mice, about 50% of plasma formate is derived from serine and that serine starvation or complex I inhibition reduces formate synthesis in vivo. These observations transform our understanding of one-carbon metabolism and have implications for the treatment of diabetes and cancer with complex I inhibitors.


Inhibitory effects of hydrogen on in vitro platelet activation and in vivo prevention of thrombosis formation.
Hydrogen (H2) has antioxidant effects. The pharmacologic function of H2 in platelets is not yet clear. Therefore, in this study we sought to investigate the inhibitory effects of H2 on in vitro platelet activation and in vivo prevention of thrombus formation. After platelets were incubated with H2-rich saline (HRS), platelet adhesion in whole human blood was assessed in fibrinogen-coated perfusion chambers, while rat platelet aggregation induced by ADP, collagen and H2O2 was detected through light transmission aggregometry. The level of P-selectin, thromboxane B2, nitric oxide (NO), malondialdehyde, reactive oxygen species (ROS), cGMP, extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), and fibrinogen binding to platelets were evaluated in vitro. Besides, the in vivo effects were examined in arterio-venous shunt thrombosis, FeCl3-induced artery thrombus formation, and tail bleeding time in mice and rats. HRS prolonged tail bleeding time in mice and rats, decreased thrombus weight and prolonged the time to occlusion in rat and mouse thrombosis models in vivo and inhibited platelet adhesion as well as aggregation in vitro. Additionally, HRS decreased P-selectin expression, release of thromboxane B2, ROS, and fibrinogen binding, but enhanced NO levels in H2O2-exposed platelets. HRS also decreased malondialdehyde levels in plasma of the rat arterial thrombosis or H2O2-exposed platelet model. Moreover, HRS increased cGMP level, decreased p-ERK1/2 (diminished with KT5823) in the platelets stimulated by H2O2. These results suggest that H2 has antithrombotic effects, which may be due to its antioxidant property and subsequent inhibition of platelet activation via NO/cGMP/PKG/ERK pathway.


Electrochemical carbon nanotube filter oxidative performance as a function of surface chemistry.
An electrochemical carbon nanotube filter has been reported to be effective for the removal and electrooxidation of aqueous chemicals and microorganisms. Here, we investigate how carbon nanotube (CNT) chemical surface treatments including calcination to remove amorphous carbon, acid treatment to remove internal residual metal oxide, formation of surficial oxy-functional groups, and addition of Sb-doped SnO(2) particles affect the electrooxidative filter performance. The various CNT samples are characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) and electrochemically evaluated by cyclic voltammetry, open circuit potential versus time analysis, and electrochemical impedance spectroscopy. Voltammetry results indicate that the near CNT surface pH is at least two units lower than the bulk pH. The electrooxidative performance of the various CNT samples is evaluated with 1 mM of methyl orange (MO) in 100 mM sodium sulfate at a flow rate of 1.5 mL min(-1). At both 2 and 3 V, the efficacy of electrochemical filtration is observed to be function of CNT surface chemistry. The samples with the greatest electrooxidation were the calcinated then HCl-treated CNTs, i.e., the CNTs with the most surficial sp(2)-bonded carbon, and the Sb-SnO(2)-coated CNTs, i.e., the CNTs with the most electrocatalytic surface area. At 3 V applied voltage, these CNT samples are able to oxidize 95% of the influent MO within the liquid residence time of <1.2 s. The broader applicability of electrochemical filtration is evaluated by challenging the C-CNT-HCl and C-CNT-HNO(3) networks with various organics including methylene blue, phenol, methanol, and formaldehyde. At 3 V applied voltage, both CNTs are able to degrade a fraction of all the organics with the extent organic degradation dependent on both CNT and organic properties. The C-CNT-HCl network generally had the better oxidative performance than the C-CNT-HNO(3) network with an exception being the positively charged methylene blue. The extent of MO degradation, steady-state current, anode potential, effluent pH, and back pressure are also measured as a function of applied voltage (1-3 V) and CNT surface chemistry. Mass spectrometry of electrochemical CNT filter effluent at 2 and 3 V is utilized to evaluate plausible electrooxidation products. Energy consumption as compared to state-of-the-art electrodes and strategies to tailor the CNT surface for a specific target molecule are discussed.


Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferation in vitro.
The therapeutic benefits of platelet-rich plasma (PRP) for the promotion of healing and regeneration of periodontal tissues are thought to result from enrichment in growth factors released from platelets. The aim of this study was to evaluate the effects of specific growth factors released from PRP on endothelial cell proliferation. The levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in supernatants of calcium- and thrombin-activated PRP samples from five donors were quantified by enzyme-linked immunosorbent assay. Supernatants were treated with neutralizing antibodies specific to each growth factor, and the effects of these treatments on human umbilical vein endothelial cell (HUVEC) proliferation in vitro were determined. The effect of removing EGF from PRP supernatants with antibody-coated beads on HUVEC proliferation was also tested. Average concentrations of VEGF, PDGF-BB, bFGF and EGF in PRP supernatants were 189, 27,190, 39.5 and 513 pg/mL, respectively. The addition of EGF neutralizing antibodies to the PRP supernatants significantly reduced HUVEC proliferation (up to 40%), while such an inhibition was not observed following neutralization of the other growth factors. Removal of EGF from PRP supernatants by treatment with antibody-coated beads also resulted in a significant decrease in HUVEC proliferation. Recombinant EGF increased HUVEC proliferation in vitro in a dose-dependent manner. This study showed that PRP supernatants are highly mitogenic for endothelial cells and provided evidence that this effect may be due, at least in part, to the presence of EGF. In vivo experiments are needed to confirm the roles of specific growth factors released from PRP in the healing of oral surgical and/or periodontal wounds.


Cell-cell interactions in the T cell proliferative response. I. Analysis of the cell types involved and evidence for nonspecific T cell recruitment.
In the antigen-induced T cell proliferative response, it has been firmly established that antigen-specific T cell activation signals are provided by a specialized antigen-presenting cell (APC). However, the number of responding T cell populations involved has not been clearly delineated. This problem can be analyzed by plotting the logarithm of the number of cultured cells against the logarithm of the response. This yields a straight line, the slope of which indicates the minimum number of interacting cell populations that are required to give the response. In the antigen-induced T cell proliferative response, this number is 3. Based on their ability to shift the slopes of the log cell number-log response line, two of the populations were identified to be T cells. The third cell, which was present in irradiated spleens, possessed certain properties of the APC. Of the two T cells, one was antigen-specific and the other could come from normal unprimed animals. The frequency of antigen-specific proliferating T cells in primed animals was estimated to be only 1 in 1.3 x 10(3), and a large proportion of the proliferation was shown to be due to unprimed cells. Furthermore, without the need to use antigen-pulsed macrophages, this slope analysis demonstrated convincingly that the successful interaction between APCs and proliferating T lymphocytes is determined by products of the I-region immune response genes.


Enhanced photoelectrochemical activity of the TiO2 /ITO nanocomposites grown onto single-walled carbon nanotubes at a low temperature by nanocluster deposition.
High-resolution transmission electron microscopy (HRTEM) is used to observe a TiO2/ITO-coated composite nanostructure grown onto single-walled carbon nanotubes (SWCNTs). The SWCNTs, indium tin oxide (ITO), and TiO2 mixtures of anatase (A) and rutile (R) are clearly distinguished in the HRTEM images. The thickness of the SWCNT was about 3 nm, and the TiO2 shell included different polycrystalline structures.


[Advance of heterologous expression study of eukaryote-origin laccases].
Laccases are enzymes belonging to the group of multi-copper oxidases. These enzymes are widely distributed in insects, plants, fungi and bacteria. In general, laccases can oxidize an exceptionally high number of substrates, so they have broad applications in textile, pulp, food and the degradation of lignin. However, low yield, low activity and thermo-instability of laccase in nature limit the application of laccase. High efficient heterologous expression of the protein is an effective way for solving this problem. Here, we summarize the research advances of heterologous expression of eukaryote-origin laccases. We focus on the overexpression of eukaryote-origin laccases using different expression system and the method for improving the production yield and enzyme activity in yeast cells. Information provided in this review would be helpful for researchers in the field.


Atmospheric turbulence parameters from visual resolution.
Direct visual observations of image blurring by atmospheric turbulence are used to obtain line averages of the refractive index structure function coefficient C(n)(2) along lines of sight in the lower atmosphere. Good agreement with meteorological point measurements is obtained both above a dry land surface, where temperature fluctuations cause most of the image degradation, and above a pond, where humidity fluctuations are also important. No optical saturation effects are found, and a simplified formula for determining longexposure, limiting-resolution angles is verified.