Understanding the challenge of weight loss maintenance: a systematic review and synthesis of qualitative research on weight loss maintenance.
Behaviour change interventions can be effective in helping people to lose weight, but weight is often regained. Effective interventions are required to prevent this. We conducted a systematic review and synthesis of qualitative research on people's experiences of weight loss maintenance. We searched bibliographic databases for qualitative studies about the experience of currently or previously overweight adults trying to maintain weight loss. We thematically synthesised study findings to develop a model of weight loss maintenance. Twenty six studies from five countries with 710 participants were included. The model developed through our synthesis proposes that making the behaviour changes required for weight loss maintenance generates psychological 'tension' due to the need to override existing habits, and incompatibility of the new behaviours with the fulfilment of psychological needs. Successful maintenance involves management or resolution of this tension. Management of tension can be achieved through self-regulation, renewing of motivation and managing external influences, although this can require constant effort. Resolution may be achieved through changing habits, finding non-obesogenic methods for addressing needs, and potentially through change in self-concept. Implications for the development of weight loss maintenance interventions are explored.


Computed tomography assessment of three techniques for removal of filling material.
In this study, computed tomography (CT) was used to assess three techniques for root canal filling removal. Seventy-five roots of extracted human lower incisors were filled with zinc oxide-eugenol sealer and gutta-percha and separated into three groups before gutta-percha removal (group 1, Gates Glidden burs + K-type hand instrumentation; group 2, K-type reciprocating instrumentation + NSK TEP E16R; group 3, ProTaper rotary instrumentation + NSK NAC E16R). Specimens were CT-scanned before and after filling removal. The mean rate of filling removal was 94.88%. Reciprocating instrumentation was the most effective and manual instrumentation associated with Gates Glidden burs was the least effective technique. Removal rate was significantly different for the three groups according to one-way anova (P = 0.049). The Tukey test showed a significant difference between groups 1 and 2 (P = 0.039) only. CT proved to be a reliable method for assessing root filling removal techniques.


Impact of the Three Gorges project on ecological environment changes and snail distribution in Dongting Lake area.
The Three Gorges Dam (TGD) is a remarkable, far-reaching project in China. This study was conducted to assess the impact of TGD on changes in the ecological environment, snail distribution and schistosomiasis transmission in Dongting Lake area. Hydrological data were collected from 12 monitoring sites in Hunan section of Yangtze River before and after TGD was established. Data on snail distribution and human schistosomiasis infection were also collected. Correlation analyses were performed to detect the significance of snail distribution to changes in ecological environmental factors and human schistosomiasis infection. A series of ecological environmental factors have changed in Dongting Lake area following the operation of TGD. Volume of annual runoff discharged into Dongting Lake declined by 20.85%. Annual sediment volume discharged into the lake and the mean lake sedimentation rate decreased by 73.9% and 32.2%, respectively. From 2003 to 2015, occurrence rate of frames with living snails and mean density of living snails decreased overall by 82.43% and 94.35%, respectively, with annual decrements being 13.49% and 21.29%. Moreover, human infection rate of schistosomiasis had decreased from 3.38% in 2003 to 0.44% in 2015, with a reduction of 86.98%. Correlation analyses showed that mean density of living snails was significantly associated with water level (r = 0.588, p<0.001), as well as the mean elevation range of the bottomland (r = 0.374, p = 0.025) and infection rate of schistosomiasis (r = 0.865, p<0.001). Ecological environmental changes caused by the TGD were associated with distribution of snails, and might further affect the transmission and prevalence of schistosomiasis. Risk of schistosomiasis transmission still exists in Dongting Lake area and long-term monitoring is required.


Effects of hydrochlorothiazide on Na-K-ATPase activity along the rat nephron.
Na-K-ATPase activity was determined in seven nephron segments of five-week-old, spontaneously hypertensive rats (SHR) with or without continuous hydrochlorothiazide (HCTZ) treatment for seven days. For comparison, the effects of HCTZ treatment on Na-K-ATPase activity in the nephron segments of age-matched normotensive Wistar-Kyoto rats (WKY) were also determined. Na-K-ATPase activity in proximal convoluted tubule (PCT), medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), distal convoluted tubule (DCT) and cortical collecting duct (CCD) was significantly lower in HCTZ-treated SHR compared to control (untreated) SHR. However, there was no significant difference in Na-K-ATPase activity in proximal straight tubule (PST) and medullary collecting duct (MCD) between HCTZ-treated and control SHR. HCTZ treatment also produced a significant decrease in blood pressure (BP) and creatinine clearance (CCr) in SHR. On the other hand, HCTZ treatment did not produce a significant change in Na-K-ATPase activity in PCT, PST, MTAL, CTAL and MCD, in BP or in CCr in WKY. However, HCTZ treatment produced a decrease in the enzyme activity in the DCT and an increase in the enzyme activity in the CCD in WKY. The decrease in Na-K-ATPase activity in almost all nephron segments from SHR may be due to a significant decrease in CCr produced by HCTZ. On the other hand, a decrease in Na-K-ATPase activity in the DCT with an increase in the enzyme activity in the CCD from WKY suggest that renal compensation to the natriuretic effect of HCTZ occurs by an increase in Na+ reabsorption in the CCD.


Joint effects of self-fertilization and population structure on mutation load, inbreeding depression and heterosis.
Both the spatial distribution of organisms and their mode of reproduction have important effects on the change in allele frequencies within populations. In this article, we study the combined effect of population structure and the rate of partial selfing of organisms on the efficiency of selection against recurrent deleterious mutations. Assuming an island model of population structure and weak selection, we express the mutation load, the within- and between-deme inbreeding depression, and heterosis as functions of the frequency of deleterious mutants in the metapopulation; we then use a diffusion model to calculate an expression for the equilibrium probability distribution of this frequency of deleterious mutants. This allows us to derive approximations for the average mutant frequency, mutation load, inbreeding depression, and heterosis, the simplest ones being Equations 35-39 in the text. We find that population structure can help to purge recessive deleterious mutations and reduce the load for some parameter values (in particular when the dominance coefficient of these mutations is <0.2-0.3), but that this effect is reversed when the selfing rate is above a given value. Conversely, within-deme inbreeding depression always decreases, while heterosis always increases, with the degree of population subdivision, for all selfing rates.


Hexagonally ordered mesoporous ternary Li2O-TiO2-P2O5 oxides with high lithium content.
Hexagonally ordered mesoporous Li2O-TiO2-P2O5 oxides with high lithium content have been synthesized using surfactant-templated self-assembly; this ternary oxide has been specifically designed to yield a variety of mesoporous frameworks including a nanocomposite, amorphous multicomponent oxide, and almost fully nanocrystalline anatase.


Rapid identification of P-glycoprotein substrates and inhibitors.
Identifying molecules that interact with P-glycoprotein (P-gp) is important for drug discovery but is also generally reliant on time-consuming in vitro and in vivo studies. As an alternative approach, the current study applied pharmacophore models and database screening to rapidly retrieve molecules that bind as substrates or inhibitors for P-gp from commercial databases and then confirmed their affinity as inhibitors in vitro. Seven molecules (acitretin, cholecalciferol, misoprostol, nafcillin, repaglinide, salmeterol, and telmisartan) with no published details for P-gp affinity, one positive control inhibitor (miconazole), and two negative control molecules (phenelzine and zonisamide) were selected for testing. The MDCK-MDR1 in vitro cell model was used to confirm their inhibitory effect on [3H]digoxin transport, and the ATPase assay was used as an additional in vitro tool to indicate P-gp activation. All seven test drugs were confirmed to have P-gp affinity. Additionally, our experimental results provided plausible explanations for the published pharmacokinetic profiles of the tested drugs and their classification according to the biopharmaceutics and drug disposition classification system. In this study, we showed the successful application of pharmacophore models to accurately predict P-gp binding, which holds promise to anticipate drug-drug interactions from screening drug databases and a priori prediction of novel P-gp inhibitors or substrates.


Toll-like receptor 2-mediated NF-kappa B pathway activation in ocular surface epithelial cells.
Gram-positive bacteria stimulate Toll-like receptor (TLR) 2 and then activate the pro-inflammatory nuclear factor-kappa B (NF-κB) pathway. As the human ocular surface is heavily colonised by gram-positive cocci bacteria, a balance of activation/repression of NF-κB target genes is essential to avoid uncontrolled infection or autoimmune-related inflammation. It is advantageous to test NF-κB targeting molecules in an ocular surface culture system that allows assessment of temporal NF-κB activation in a longitudinal fashion without destruction of cells. Such initial testing under standardised conditions should reduce the number of molecules that progress to further evaluation in animal models. This study aims to establish an in-vitro cell culture system to assess NF-κB activation in the context of ocular surface cells. NF-κB activity was evaluated through a secretory alkaline phosphatase reporter assay (SEAP). Immunoblots and immunofluorescence were used to examine IκBα phosphorylation and p65/p50 nuclear localization. Monocyte chemoattractant protein-1 (MCP-1) transcripts were evaluated by real time PCR and protein levels were measured by ELISA. NF-κB activity in HCE-T cells treated with TLR2 activator Pam3CSK4 was higher than control cells at both 6 and 24 h. Pam3CSK4-stimulated NF-κB activation was inhibited by IκK inhibitors, Wedelolactone and BMS-345541. In Pam3CSK4 treated cells, active NF-κB subunits p50 and p65 increased in cell nuclear fractions as early as 1.5 h. Although the level of total IκB-α remained constant, phospho-IκB-α increased with treatment over time. In the culture media of Pam3CSK4-stimulated cells, MCP-1 protein level was increased, which was suppressed in the presence of IκK inhibitors. NF-κB pathway can be activated by the TLR2 ligand and inhibited by IκK inhibitors in the ocular surface cell culture system. This cell culture system may be used to evaluate TLR-related innate defences in ocular surface diseases.


Spittlebugs as vectors of Xylella fastidiosa in olive orchards in Italy.
The recent introduction of Xylella fastidiosa in Europe and its involvement in the Olive Quick Decline Syndrome (OQDS) in Apulia (Salento, Lecce district, South Italy) led us to investigate the biology and transmission ability of the meadow spittlebug, Philaenus spumarius, which was recently demonstrated to transmit X. fastidiosa to periwinkle plants. Four xylem-sap-feeding insect species were found within and bordering olive orchards across Salento during a survey carried out from October 2013 to December 2014: P. spumarius was the most abundant species on non-olive vegetation in olive orchards as well as on olive foliage and was the only species that consistently tested positive for the presence of X. fastidiosa using real-time PCR. P. spumarius, whose nymphs develop within spittle on weeds during the spring, are likely to move from weeds beneath olive trees to olive canopy during the dry period (May to October 2014). The first X. fastidiosa-infective P. spumarius were collected in May from olive canopy: all the individuals previously collected on weeds tested negative for the bacterium. Experiments demonstrated that P. spumarius transmitted X. fastidiosa from infected to uninfected olive plants. Moreover, P. spumarius acquired X. fastidiosa from several host plant species in the field, with the highest acquisition rate from olive, polygala and acacia. Scanning electron microscopy (SEM) revealed bacterial cells resembling X. fastidiosa in the foreguts of adult P. spumarius. The data presented here are essential to plan an effective IPM strategy and limit further spread of the fastidious bacterium.


[Total cavopulmonary connection in complex heart defects with a single functional ventricle].
Nineteen children aged between 1.5 and 9.8 years (10 patients younger than 4 years) underwent total cavopulmonary connection (TCPC) for complex congenital heart defects other than tricuspid atresia. Diagnoses included double inlet left ventricle (n = 11), transposition of the great arteries with a large ventricular septal defect (n = 4), double outlet right ventricle (n = 2), congenitally corrected transposition of the great arteries with a large ventricular septal defect (n = 1) and criss-cross heart (n = 1). Two patients had situs ambiguous with polysplenia syndrome and four patients had anomalous systemic venous return. Thirty-six palliative procedures were performed in 15 patients before TCPC. The patients were selected according to the selection criteria of Choussat and Fontan. Four patients (21%) died between the 1st and 12th postoperative day because of low cardiac output syndrome (n = 2), supraventricular tachycardia unresponsive to treatment (n = 1), and cerebral edema (n = 1). In one patient take down of TCPC was performed for persistent low cardiac output syndrome. Four of these five patients were younger than 4 years old and had one or more additional risk factors. Postoperative complications were persistent pleural or pericardial effusions (n = 4), transient supraventricular tachycardia (n = 2), and low cardiac output syndrome (n = 1). There was no late death. Follow-up was available in 12 patients. At a mean follow-up of 15 +/- 9 months, nine patients are in NYHA-functional class I, two patients in class II, and one patient in class III. Postoperative cardiac catheterization revealed satisfactory results in seven of eight patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Biological and molecular properties of yellow venom of the Amazonian coral snake Micrurus surinamensis.
The coral snake Micrurus surinamensis, which is widely distributed throughout Amazonia, has a neurotoxic venom. It is important to characterize the biological and molecular properties of this venom in order to develop effective antitoxins. Toxins from the venom of M. surinamensis were analyzed by two-dimensional polyacrylamide gel electrophoresis and their neurotoxic effects in vivo were evaluated. Most proteins in the venom had masses < 14kDa, low phospholipase A2 activity, and no proteolytic activity. The toxins inhibited the coagulation cascade. The venom had neurotoxic effects in mice, with a median lethal dose upon intravenous administration of 700 µg/kg. Immunogenic studies revealed abundant cross-reactivity of antielapidic serum with 14kDa toxins and limited cross-reactivity with toxins < 10kDa. These results indicate that antielapidic serum against M. surinamensis venom has weak potency (0.35mg/ml) in mice.


Computing with networks of nonlinear mechanical oscillators.
As it is getting increasingly difficult to achieve gains in the density and power efficiency of microelectronic computing devices because of lithographic techniques reaching fundamental physical limits, new approaches are required to maximize the benefits of distributed sensors, micro-robots or smart materials. Biologically-inspired devices, such as artificial neural networks, can process information with a high level of parallelism to efficiently solve difficult problems, even when implemented using conventional microelectronic technologies. We describe a mechanical device, which operates in a manner similar to artificial neural networks, to solve efficiently two difficult benchmark problems (computing the parity of a bit stream, and classifying spoken words). The device consists in a network of masses coupled by linear springs and attached to a substrate by non-linear springs, thus forming a network of anharmonic oscillators. As the masses can directly couple to forces applied on the device, this approach combines sensing and computing functions in a single power-efficient device with compact dimensions.


Radiological and histological features of tumoral calcinosis of the dorsum of the foot.
Tumoral calcinosis is a rare condition characterized by large calcific masses occurring predominantly in the juxta-articular regions of the extremities. To our knowledge, occurrences in the foot, particularly in association with bone erosion, have been very rare. A 52-year-old Japanese man presented with a mass in the foot, the size of which increased over a period of 27 years. CT scan and MRI demonstrated a 6 cm x 3 cm x 2.5 cm sized mass. There was bone erosion of the dorsal side of the third metatarsal head. Marginal excision was made. Histopathologically, the mass was composed of amorphous calcification with inflammatory cell infiltration. X-ray diffraction method revealed that the pattern of the mass coincided with hydroxyapatite. The patients had no local recurrence at 5 years after operation.


Response sensitivity of barrel neuron subpopulations to simulated thalamic input.
Our goal is to examine the relationship between neuron- and network-level processing in the context of a well-studied cortical function, the processing of thalamic input by whisker-barrel circuits in rodent neocortex. Here we focus on neuron-level processing and investigate the responses of excitatory and inhibitory barrel neurons to simulated thalamic inputs applied using the dynamic clamp method in brain slices. Simulated inputs are modeled after real thalamic inputs recorded in vivo in response to brief whisker deflections. Our results suggest that inhibitory neurons require more input to reach firing threshold, but then fire earlier, with less variability, and respond to a broader range of inputs than do excitatory neurons. Differences in the responses of barrel neuron subtypes depend on their intrinsic membrane properties. Neurons with a low input resistance require more input to reach threshold but then fire earlier than neurons with a higher input resistance, regardless of the neuron's classification. Our results also suggest that the response properties of excitatory versus inhibitory barrel neurons are consistent with the response sensitivities of the ensemble barrel network. The short response latency of inhibitory neurons may serve to suppress ensemble barrel responses to asynchronous thalamic input. Correspondingly, whereas neurons acting as part of the barrel circuit in vivo are highly selective for temporally correlated thalamic input, excitatory barrel neurons acting alone in vitro are less so. These data suggest that network-level processing of thalamic input in barrel cortex depends on neuron-level processing of the same input by excitatory and inhibitory barrel neurons.


Surgical outcomes in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy.
Matched patients who test positive or negative for human immunodeficiency virus (HIV) who are undergoing comparable operations have similar complication rates and outcomes. A retrospective study of surgical outcomes in HIV-infected and matched HIV-noninfected patients. Baseline information including HIV-related laboratory results, complications, and mortality was collected from printed and electronic records through 12 postoperative months. Kaiser Permanente Medical Care Program-Northern California, an integrated health organization with more than 3 million members, including more than 5000 HIV-infected members. From July 1,1997, through June 30, 2002, HIV-infected members undergoing surgical procedures were matched 1:1 with HIV-noninfected patients undergoing surgical procedures by type, location, and year of surgery as well as by sex and age. Surgical procedures studied included appendectomy, arthrotomy or arthroscopy, bowel resection, cholecystectomy, cardiothoracic procedures, hernia repair, hysterectomy, hip or knee replacement, laparoscopy or laparotomy, and mammoplasty. Complications and mortality through 12 postoperative months, comparisons between HIV-infected and HIV-noninfected patients using matched-pair analyses, and HIV-infected cohort data were analyzed using the Fisher exact test and logistic regression. Of 332 HIV-infected-HIV-noninfected pairs (mean age, 46.7 years; male sex, 91%), more than 95.0% were followed up through 12 postoperative months or until their deaths. Pairs had similar comorbidities, length of hospital stay, and number of postoperative surgical visits (P>.05, all variables). Among HIV-infected patients, the median years with HIV infection was 8.4 years; median CD4 T-cell count was 379/microL; 61.5% of these patients had an HIV RNA level less than 500 copies per milliliter; and 68% were receiving highly active antiretroviral therapy. Various complications were no more frequent among HIV-infected than in HIV-noninfected patients (11.1% vs 10.2%; P = .79), except for pneumonia (P = .04). There were more deaths within the 12 postoperative months in HIV-infected patients (10/332 vs 2/332; P = .02); 2 patients died 30 days or less after being operated on. Among HIV-infected patients, viral load of 30 000 copies per milliliter or more was associated with increased complications (adjusted odds ratio, 2.95; P = .007), but a CD4 cell count less than 200/muL was not associated with poorer outcomes. The HIV-infected patients had more incidences of postoperative pneumonia and higher 12-month mortality, although other operative outcomes were comparable for HIV-infected and HIV-noninfected patients. Viral suppression to fewer than 30 000 copies per milliliter reduced surgical complications.


Comparison of physical and biological properties of CardioCel® with commonly used bioscaffolds.
Durability of bioscaffolds cross-linked with glutaraldehyde and used in cardiovascular surgery is limited by biomechanical instability, calcification and reduced biocompatibility. This study compares CardioCel®, a bovine pericardial scaffold engineered via the ADAPT® process to ensure optimized biostability and biocompatibility, with the commonly used bioscaffolds. Bovine pericardial scaffolds, cross-linked with 0.6% glutaraldehyde (XenoLogiX™, PeriGuard®), dye-mediated photo-oxidized (PhotoFix™) and a non-crosslinked porcine scaffold (CorMatrix®), were compared with CardioCel (decellularized, cross-linked with 0.05% monomeric glutaraldehyde, detoxified) by thermal stability and mechanical tests. Biocompatibility and calcification were assessed in a juvenile subcutaneous rat model at 6 and 12 weeks. CardioCel displayed significantly higher (P < 0.01) cross-link stability (77.99 ± 0.64 °C) than CorMatrix (57.88 ± 0.22 °C) and PhotoFix (53.96 ± 0.41 °C). Tensile strength of CardioCel (8.31 ± 3.36 MPa) was comparable with XenoLogiX (11.00 ± 5.43 MPa, P = 0.734), PeriGuard (16.44 ± 6.69 MPa, P = 0.136), PhotoFix (7.10 ± 6.11, P = 0.399) and CorMatrix (9.75 ± 2.61, P = 0.204). XenoLogiX and PeriGuard recorded the highest Young's modulus (67.01 ± 30.36 vs 95.67 ± 45.91 MPa), while CardioCel (50.21 ± 19.92 MPa) was comparable with CorMatrix (36.78 ± 10.47 MPa, P = 0.204) and PhotoFix (33.50 ± 10.24, P = 0.399). CorMatrix displayed a significantly (P < 0.05) greater stiffness (4.74 ± 0.77 MPa) at 10% strain than PeriGuard (3.73 ± 1.79 MPa), PhotoFix (1.59 ± 0.40 MPa) and CardioCel (3.39 ± 0.83 MPa). Differences in extractable calcium did not reach significance; however, the inorganic phosphorus content of PhotoFix (21.3 ± 9.0 µg/mg) was higher than CardioCel (11.35 ± 0.76 µg/mg, P = 0.004) or PeriGuard (10.7 ± 2.18 µg/mg, P = 0.002) at 12 weeks. CardioCel underwent a typical mild host-graft response with fibroblast infiltration and remodelling. Foreign body reactions were visible in both XenoLogiX and PeriGuard, with isolated fibroblast infiltration. PhotoFix showed severe inflammation and 2 implants were completely degraded at 12 weeks. CardioCel demonstrated optimized physical properties, minimal mineralization potential and superior biocompatibility. These results may benefit the long-term performance of this bioscaffold for cardiovascular surgery. The favourable characteristics of the comparator products were counterbalanced by less desirable features that may have negative implications on durability and performance when used in cardiovascular procedures.


Poverty and fatal accidental drug overdoses of cocaine and opiates in New York City: an ecological study.
This ecological study examines the association of the poverty status of urban communities in New York City with their mortality rates of accidental drug overdoses. Mean annual age-adjusted rates of drug overdoses involving cocaine, opiates, or both (n = 1,684) were calculated for each of 59 residential community districts in New York City for 1990-1992. A linear regression analysis was performed to test the association of the mortality rate with the poverty status of the district as measured by the proportion of the district living below the 1989 U.S. poverty line. Poverty status accounted for 69% of the variance in the drug overdose mortality rates of communities (p < .001). This study suggests that mortality rates of overdoses involving cocaine and optiates are significantly associated with the poverty status of communities in New York City.


Patient-specific modelling of whole heart anatomy, dynamics and haemodynamics from four-dimensional cardiac CT images.
There is a growing need for patient-specific and holistic modelling of the heart to support comprehensive disease assessment and intervention planning as well as prediction of therapeutic outcomes. We propose a patient-specific model of the whole human heart, which integrates morphology, dynamics and haemodynamic parameters at the organ level. The modelled cardiac structures are robustly estimated from four-dimensional cardiac computed tomography (CT), including all four chambers and valves as well as the ascending aorta and pulmonary artery. The patient-specific geometry serves as an input to a three-dimensional Navier-Stokes solver that derives realistic haemodynamics, constrained by the local anatomy, along the entire heart cycle. We evaluated our framework with various heart pathologies and the results correlate with relevant literature reports.


Extreme polarisation sensitivity in the retina of the corn borer moth Ostrinia.
The visual system of the European corn borer (Ostrinia nubilalis) was analysed with microscopy and electrophysiological methods (electroretinograms and single-cell recordings). Ostrinia nubilalis has a pair of mainly ultraviolet-sensitive ocelli and a pair of compound eyes, maximally sensitive to green light. The ommatidia contain a tiered, fused rhabdom, consisting of the rhabdomeres of 9-12 photoreceptor cells with sensitivity peak wavelengths at 356, 413, 480 and 530 nm. The photoreceptors in a large dorsal rim area have straight rhabdomeres and high polarisation sensitivity (PS1,2=3.4, 14). Elsewhere, in the main retina, the majority of photoreceptors have non-aligned microvilli and negligible PS, but each ommatidium contains one or two blue-sensitive distal photoreceptors with straight microvilli parallel to the dorsoventral axis, yielding extremely high PS (PS1,2,3=56, 63, 316). Rhabdoms containing distal cells with potentially high PS have evolved at least twice: in moths (Crambidae, Noctuidae, Saturniidae), as well as in dung beetles (Scarabaeidae). The distal photoreceptors with high PS, sensitive to vertically polarised light, represent a monopolatic system, which is unsuitable for the proper analysis of electric field vector (e-vector) orientation. However, the distal photoreceptors might be used in conjunction with polarisation-insensitive photoreceptors to detect objects that reflect polarised light with stereotyped orientation.


Effect of fenfluramine-induced increases in serotonin release on [18F]MPPF binding: a continuous infusion PET study in conscious monkeys.
[(18)F]MPPF is a selective and reversible antagonist to the serotonin-1A (5-HT(1A)) receptor. The aim of the present study was to investigate whether the binding of [(18)F]MPPF is sensitive to increases in 5-HT levels. We used the 5-HT releasing agent and reuptake inhibitor fenfluramine (FEN) to increase the concentration of 5-HT. [(18)F]MPPF binding was assessed using positron emission tomography (PET) in conscious monkeys. Possible effects of blood flow on ligand binding were excluded by using a bolus-infusion paradigm. Control scans were obtained to assess the state of ligand equilibrium. FEN (5 or 10 mg/kg, i.v.) was administered between 90 and 130 min after the start of the [(18)F]MPPF infusion. The binding potential (BP) was calculated for an early interval (30 min preceding FEN administration) and late interval (20-50 min after administration of FEN). Microdialyses results showed a 20- and 35-fold increase in extracellular 5-HT levels in the prefrontal cortex after injection of FEN at a dose of 5 mg/kg and 10 mg/kg respectively. However, despite these large increases in 5-HT levels, no differences in BP were found between the control and FEN scans. These results may imply that the majority of 5-HT(1A) receptors is in the low affinity state in the living brain.


Anammox biomass carrying efficiency of polyethylene non-woven sheets as a carrier material.
To access the effects of the surface modification and fabric structure of polyethylene (PE) non-woven fabric sheets on retaining the attachment efficiency of anammox biomass, three different non-woven sheets were prepared and inserted in an anammox reactor. The hydrophobic surface modification with 10% KMnO4 and gelatin did not improve the attachment efficiency of the anammox biomass on the surface of the PE non-woven fibers. Densely packed PE-755 having the highest specific surface area to volume ratio (SA/V) (755) retained 221.4 mg biomass per unit sheet, whereas PE-181 having the lowest SA/V (181) retained only 66.4 mg biomass per unit. Accordingly, the volumetric anammox activity of non-woven sheet PE-755 was the highest among the three PE non-woven sheets because of the strong positive relationship between the specific anammox activity and biomass amount (R = 0.835, P < .01). The specific surface area to volume ratio (cm2 cm-3) as well as the bulk density should be considered as important parameters for the selection of non-woven biocarriers for anammox biomass.


An eighth note.
Venous stenosis is the most common cause of arteriovenous fistula (AVF) failure in hemodialysis patients. For patients with AVF stenosis, the pressure over the antecedent part of the AVF stenotic lesion will increase if arterial inflow is sufficient. We report a chronic hemodialysis patient who received an angiographic examination for the juxta-anastomosis stenosis of his AVF. A unique feature of a collateral venous branch antecedent to the stenotic lesion was noted, resembling a musical sign as the "eighth note." After percutaneous transluminal angioplasty, the eighth note attenuated markedly at once. Of note, the eighth note sign is not seen frequently, and thus we postulate that the formation of an eighth note sign on the radiocephalic fistula should fulfill the following requirements, including a sufficient arterial inflow, an adjacent collateral branch close enough to the arteriovenous anastomosis, a severe juxta-anastomotic stenotic lesion, and an intact ulnar venous drainage system.


Body mass index, PAM50 subtype, recurrence, and survival among patients with nonmetastatic breast cancer.
Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype. This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013. Patients reported weight and height. Cox regression models were adjusted for age, menopause, race/ethnicity, stage, and chemotherapy. Over a median of 9 years (maximum, 19 years), 378 women developed recurrent disease, and 312 died from breast cancer. Overall, BMI was not associated with breast cancer recurrence or survival when controlling for subtype (eg, the hazard ratio per 5 kg/m2 of BMI was 1.05 [95% confidence interval, 0.95-1.15] for breast cancer-specific death). However, associations varied by subtype. Among women with luminal A cancers, those who had class II/III obesity, but not class I obesity or overweight, had worse outcomes. When women who had a BMI ≥35 kg/m2 were compared with those who had a BMI from 18.5 to <25 kg/m2 , the hazard ratio was 2.24 (95% confidence interval,1.22-4.11) for breast cancer-specific death and 1.24 (95% confidence interval, 1.00-1.54) for recurrence. There was no association within luminal B, basal-like or human epidermal growth factor over-expressing subtypes. Among patients who had accurately classified breast cancer subtypes based on gene expression, a BMI ≥35 kg/m2 was adversely associated with outcomes only among those who had luminal A cancers. Research is needed into whether tailoring recommendations for weight management to tumor characteristics will improve outcomes. Cancer 2017;123:2535-42. © 2017 American Cancer Society.


Dioxin effects on neonatal and infant thyroid function: routes of perinatal exposure, mechanisms of action and evidence from epidemiology studies.
Animal experiments suggest that thyroid function alterations in newborns and infants may represent one of the most sensitive markers of toxicity from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dioxin can be transferred from the mother to the offspring either in utero or through lactation. It has been suggested that thyroid-hormone alterations produced by dioxin in utero or shortly after birth may underlie long-term effects, such as cognitive-ability and neurodevelopment impairment. In the present review article, we appraise available evidence on the effects of perinatal exposure to dioxin on fetal and infant thyroid function. We summarized the routes of perinatal dioxin exposure and research results on possible mechanisms of dioxin toxic effects on thyroid function. We performed a systematic review of epidemiology studies conducted on mother-child pairs exposed to background environmental levels to investigate dioxin effects on neonatal and infant thyroid function. Toxicological and mechanistic data indicate that dioxin may impair thyroid function in exposed newborns and infants. Investigations on background-exposed children have not consistently demonstrated an association between perinatal TCDD exposure and thyroid function, although some of the studies suggest that sub-clinical hypothyroidism may be induced by perinatal dioxin exposure within 3 months from birth. Between studies inconsistencies may be related to lab method differences, mixed exposures, and small sample size of the populations evaluated. Epidemiology studies have as yet failed to demonstrate an association between perinatal TCDD exposure and thyroid function alterations in human subjects, although suggestive evidence from animal and in-vitro experimental data is available.


Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men.
Male testosterone levels decline by 1% per year from the age of 40 years. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin-54 and the pituitary response to gonadotropin-releasing hormone (GnRH) of older men with those of young men. Following 1 h of baseline sampling, healthy older men (n = 5, mean age 59.3 ± 2.9 years) received a 3-h intravenous infusion of either vehicle, kisspeptin-54 0.1, 0.3, or 1.0 nmol/kg/h or GnRH 0.1 nmol/kg/h, on five different study days. Serum gonadotropins and total testosterone were measured every 10 min and compared to those of young men (n = 5/group) (mean age 28.9 ± 2.0 years) with a similar body mass index (24 kg/m2) who underwent the same protocol. Kisspeptin-54 and GnRH significantly stimulated serum gonadotropin release in older men compared to vehicle (p < 0.001 for all groups). Gonadotropin response to kisspeptin-54 was at least preserved in older men when compared to young men. At the highest dose of kisspeptin-54 (1.0 nmol/kg/h), a significantly greater luteinising hormone (LH) (p = 0.003) response was observed in older men. The follicle-stimulating hormone (FSH) response to GnRH was increased in older men (p = 0.002), but the LH response was similar (p = 0.38). Serum testosterone rises following all doses of kisspeptin-54 (p ≤ 0.009) were reduced in older men. Our data suggest that healthy older men without late-onset hypo-gonadism (LOH) have preserved hypothalamic response to kisspeptin-54 and pituitary response to GnRH, but impaired testicular response. Further work is required to investigate the use of kisspeptin-54 to identify hypothalamic deficits in men with LOH.


Lower dietary concentrate level increases bacterial diversity in the rumen of Cervus elaphus yarkandensis.
The ruminal microbiota plays major roles in feed digestion. The composition and fermentation of the bacterial communities in 3 important ruminant species have been studied previously. Here, we extended this research to the effect of concentrate-to-forage ratios on ruminal bacterial communities in Tarim red deer (Cervus elaphus yarkandensis). Different concentrate-to-forage ratios (2:8, 3:7, 4:6, and 5:5) were fed to Tarim red deer for 20 days. Ruminal bacterial communities were elucidated by 16S ribosomal RNA gene sequencing on an Illumina HiSeq 2500 platform. The microbial composition and biodiversity at the different concentrate-to-forage ratio levels were analyzed using clustering of operational taxonomic units based on 97% sequence identity, taxonomic classification at the phylum and genus levels, α diversity, and β diversity. Rumen microorganisms of deer fed a diet with a concentrate-to-forage ratio of 2:8 had the highest species diversity, followed by ratios of 3:7, 4:6, and 5:5. The community structure of the A1 and A2 samples and the A3 and A4 samples was similar. The bacterial composition appeared to be affected by diet, with a lower dietary concentrate level tending to increase the richness and diversity of ruminal bacteria in the rumen of Tarim red deer.


Accuracy of a Fourth-Generation Subcutaneous Continuous Glucose Sensor.
This study evaluated the accuracy and performance of a fourth-generation subcutaneous glucose sensor (Guardian™ Sensor 3) in the abdomen and arm. Eighty-eight subjects (14-75 years of age, mean ± standard deviation [SD] of 42.0 ± 19.1 years) with type 1 or type 2 diabetes participated in the study. Subjects wore two sensors in the abdomen that were paired with either a MiniMed™ 640G insulin pump, or an iPhone® or iPod® touch® running a glucose monitoring mobile application (Guardian Connect system) and a third sensor in the arm, which was connected to a glucose sensor recorder (GSR). Subjects were also asked to undergo in-clinic visits of 12-14 h on study days 1, 3, and 7 for frequent blood glucose sample testing using a Yellow Springs Instrument (YSI) reference. The overall mean absolute relative difference (MARD ± SD) between abdomen sensor glucose (SG) and YSI reference values was 9.6% ± 9.0% and 9.4% ± 9.8% for the MiniMed 640G insulin pump and Guardian Connect system, respectively; and 8.7% ± 8.0% between arm SG and YSI reference values. The percentage of SG values within 20% agreement of the YSI reference value (for YSI >80 mg/dL) was 90.7% with the MiniMed 640G insulin pump, 91.8% with the Guardian Connect system, and 93.1% for GSR-connected arm sensors. Mean functional sensor life, when calibrating 3-4 times/day, was 145.9 ± 39.3 h for sensors paired with the MiniMed 640G insulin pump, 146.1 ± 41.6 h for sensors paired with the Guardian Connect system, and 147.6 ± 40.4 h for sensors connected to the GSR. Responses to survey questions regarding sensor comfort and ease of use were favorable. The Guardian Sensor 3 glucose sensor, whether located in abdomen or the arm, provided accurate glucose readings when compared with the YSI reference and demonstrated functional life commensurate with the intended 7-day use. ClinicalTrials.gov : NCT02246582.


Pediatric Ramsay Hunt Syndrome: Analysis of Three Cases.
Ramsay Hunt syndrome (RHS) is a disorder characterized by herpetic eruptions on the auricle, facial paralysis, and vestibulocochlear dysfunction and is attributed to varicella zoster virus (VZV) infection in the geniculate ganglion. Although it is a common cause of acute peripheral facial paralysis, children are not usually affected. The diagnosis is based on history and physical findings. Treatment of RHS uses a combination of high-dose corticosteroids and acyclovir. This paper presents three cases diagnosed as RHS in the pediatric age group in association with the literature review. The aim of this paper is to emphasize the importance of careful examination and early initiation of therapy in suspected cases of RHS.


[Human Y chromosome: structure and biological role].
Y chromosome differs from other human chromosomes. It is found in cells of the male persons only. Different human phenotypes are associated with non-recombinant region of Y chromosome. This chromosome is of great significance in the human sex determination and the development of male gametes (spermatogenesis). Testes develop in embryos which have the Y chromosome, and ovaries develop in embryos which have no Y chromosome. SRY (sex-determining region of the Y chromosome) gene determines the male phenotype. Translocation of this gene determines sex reversal. The aim of this article was to review the structure and biological functions of the human Y chromosome.


Pancreatic somatostatinoma presenting with chronic intestinal pseudo-obstruction syndrome.
A case of pancreatic somatostatinoma in a patient with long-standing symptoms of intestinal pseudo-obstruction is reported. Diagnosis was made incidentally following an exploratory laparotomy for an episode of acute intestinal obstruction. After surgical excision of the endocrine neoplastic tissue there was a decrease in plasma somatostatin levels, associated with a striking improvement of symptoms related to gut motility dysfunction. Delayed intestinal transit and gastric emptying and impaired gallbladder contraction persisted after surgery during a follow-up of 9 years in association with a positive calcium-pentagastrin test, suggestive of residual tumoral somatostatin secretion. This case report shows that a chronic intestinal pseudo-obstruction syndrome can be associated with a somatostatin-producing endocrine neoplasm and confirms the clinical heterogeneity of somatostatinoma patients.


Severe plexiform facial neurofibromatosis, type 1 with underdeveloped eyes and a novel NF1 mutation.
A Thai woman, who was affected with neurofibromatosis type 1, was followed up and re-evaluated at ages 45, 61, and 67 years. Her mother and her three brothers were also affected. The proposita was very severely affected. She was born blind with underdeveloped eyeglobes and had large plexiform neurofibromas on her face. Her eyelids were gigantic and tears drained from the orifice between them. Cutaneous neurofibromas were observed all over her body. A novel mutation c.4821delA was identified in NF1 gene, which predicted truncation of neurofibromin (p.Leu1607fs).


A patient resource program--strengthening primary nursing.
A patient resource program addresses fragmentation of care, duplication and blurred accountability. This centralized referral service uses experts such as clinical nurse specialists, enterostomal therapists and pain management nurses to improve the primary nursing care model.


Amino Acid transporter-targeted radiotracers for molecular imaging in oncology.
Amino acids are required for sustenance of continuous uncontrolled growth of tumor cells, and upregulation of amino acid transporter expression has often been observed in tumor cells to facilitate their accelerated rates of amino acid uptake. Therefore, amino acid transporters have promise as ideal targets for tumor imaging. In fact, many natural and artificial amino acids have been radiolabeled for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging of tumor. In this article, we review the classification, molecular biology, and pharmacological relevance of amino acid transport systems. In addition, we discuss the chemistry, radiochemistry, current clinical applications, and future prospects for the use of radiolabeled amino acid-based probes for PET and SPECT imaging in oncology for each category of radionuclide.


[Effects of pH on the surface characteristics and molecular structure of extracellular polymeric substances from activated sludge].
To understand the mechanisms of extracellular polymeric substances (EPS) influencing sludge characteristics, change in constituents of extractable EPS from municipal wastewater and beverage wastewater sludge at various pH was investigated. Fourier transform infrared (FTIR) spectrophotometry was used to analyze the effect of pH on the functional groups in EPS. Surface charge was measured by colloid titration. Finally, surface charge measurements and molecular structure analysis were evidenced by Scanning Electron Microscopy (SEM) observation of the sludge samples before and after EPS extraction at different pH. The results show that at strong acid condition (pH 3), the extractable EPS are lower than those at neutral condition by about 50% including 30% decreasing in polysaccharides and 65% - 70% in protein. At strong alkali condition (pH 11), the extractable EPS are higher than those at neutral condition by 20% - 30% including about 15% increasing in polysaccharides and 20% - 50% in protein. Hydroxyl changes both at alkali and acid condition. Carboxyl acid, polysaccharides, phenolic groups, and amino groups in protein disappear at acid condition (pH 3). Negative surface charge of EPS from both of the sludges increases with pH. Observation of sludge by SEM indicates that compared with alkali condition, acid condition is more effective in making the bacterial cell broken. The results suggest that pH changes the constituents, concentration and functional groups in EPS, consequently the surface charge of EPS. As a result, sludge characteristics are changed.


Phosphine-Catalyzed [3+2] and [4+3]Annulation Reactions of C,N-Cyclic Azomethine Imines with Allenoates.
Phosphine-catalyzed [3+2] and [4+3]annulation reactions of C,N-cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways, [3+2] and [4+3]cyclization, depend on the nature of the nucleophilic phosphine and the allenoate. Generally, for α-alkylallenoates, the reactions always proceed with [3 +2]cyclization as the major pathway no matter what phosphine was used; for α-ArCH2-substituted allenoates, the reaction pathway was controlled by the phosphine catalyst used.


On the limitations of automated restriction mapping.
Eight important restriction mapping programs, developed between 1978 and 1993, are analyzed and their performance evaluated. The analyses concentrate on the practical value of the programs to molecular biologists who do restriction mapping on a daily basis, rather than on theoretical efficiency. Although all of the programs could find maps consistent with the data, none were able to discriminate reliably the true map from the other consistent maps, given realistic levels of error. To alleviate this problem, we propose an expert mapping system which utilizes the same inferences and mapping techniques used by expert human mappers to reduce the number of false maps found.


Decisional Balance of Smoking and Planning to Quit Smoking: A Moderated Mediation Model among Chinese Male Smokers.
Decisional balance in quitting smoking involves positive and negative attitudes toward smoking. This study explored the relationship between the decisional balance of smoking and planning to quit smoking, and examined the mediating role of willingness to quit smoking and the moderating role of social support. A questionnaire survey was conducted among 326 daily male smokers from China in 2016, including the decisional balance of smoking, willingness to quit smoking, social support, planning to quit, and nicotine dependence. The results showed: (1) willingness to quit smoking mediated the relationship between the decisional balance of smoking and planning to quit smoking; (2) the relationship between the decisional balance of smoking and planning to quit smoking was moderated by emotional support rather than instrumental support. Smokers with a higher level of emotional support for quitting smoking were more likely to progress to planning to quit smoking, while this relationship was not found among smokers with a lower level of emotional support. These findings suggested that smokers' willingness to quit smoking would be key to promoting their planning to quit. Meanwhile, the dynamic process of planning to quit smoking was moderated by emotional support from others.


Organ culture of craniopharyngioma and its cellular effects induced by colloidal chromic phosphate.
Since a marked clinical improvement has been reported following chromic phosphate treatment in recurrent craniopharyngioma, we have attempted to study the in vitro cellular changes of two craniopharyngiomas maintained in organ culture system and subsequently treated with colloidal chronic phosphate. When incubated for 24 and 48 hours respectively, at a concentration of 10 muCi/ml. of colloidal 32P, only vacuolar degeneration and hyperchromasia of the tumor cells have been observed. When incubated with 50 muCi/ml. for 24 hours, further cellular degeneration and focal necrosis begin to appear. Up to 48 hours after 50 muCi/ml. obvious necrosis and extensive degeneration become apparent. Autoradiography confirms the fact that radioactive material is absorbed by the tumor cells. Brain tumors when maintained in an organ culture system may serve as a useful model for the evaluation of the effects of various chemotherapeutic and radiotherapeutic agents in vitro.


Ruptured organosilica nanocapsules immobilized acetylcholinesterase coupled with MnO2 nanozyme for screening inhibitors from Inula macrophylla.
Abnormal expression of acetylcholinesterase (AChE) causes Alzheimer's disease (AD). Inhibiting AChE is a common strategy for reducing the degradation of neurotransmitter acetylcholine, in order to treat early-stage AD. Therefore, it is crucial to screen and explore AChE inhibitors which are safer and cause fewer side effects. Our research is focused on establishing a platform of ruptured organosilica nanocapsules (RONs) immobilized AChE coupled with an MnO2-OPD colorimetric assay, which could monitor AChE activity and screen AChE inhibitors. The fabricated RONs immobilized AChE possessed excellent pH and thermal stability. Huperzine A was introduced into the established platform to evaluate the inhibition kinetics of the immobilized AChE, which promoted its application in the screening of AChE inhibitors. The satisfactory results of enzyme inhibition kinetics proved the feasibility and applicability of the established method. Thus, the proposed platform was applied to screen AChE inhibitors from 14 compounds isolated from Inula macrophylla, and β-cyclocostunolide (compound 4) demonstrated the best AChE inhibitory activity among these compounds. This work confirms the existence of chemical components that inhibit AChE activity in Inula macrophylla, and provides a new idea for the application of immobilized enzyme-nanozyme in the field of enzyme inhibitor screening.


Assessment of trans-scleral iontophoresis delivery of lutein to the human retina.
The efficacy of novel scleral iontophoresis device for in situ delivery of lutein to the human retina was assessed by Resonance Raman spectroscopy (RRS) technique. Eight human donor eye globes were used for experiments, 6 of which underwent trans-scleral iontophoresis delivery of lutein and the other 2 were used as controls. The scleral iontophoresis applicator was filled with liposome-enriched 0.1% lutein solution and the generator's current was set at 2.5 mA and delivered for 4 min. A custom RRS setup was used for detecting lutein in the inner sclera, choroid, retinal periphery and macula of treated samples and controls. Forty minutes after iontophoresis, the inner sclera, choroid and retinal periphery were greatly enriched with lutein (P < .05); no lutein was found in the same ocular regions of non-treated samples. In the same period, the average concentration of lutein in the macula (4.8 ± 1.7 ng/mm2 ) of treated samples was 1.3 times greater than controls (3.7 ± 1.0 ng/mm2 ; P = .4). Scleral iontophoresis was shown to be effective in delivering lutein to the human retina. Future studies will aim at assessing if this therapeutic strategy is valuable to enrich the macular pigment in human subjects.


The association of SHANK3 gene polymorphism and autism.
Autism spectrum disorder (ASD) and Autism are both general terms for a group of complex disorders of brain development. These disorders are characterized by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. Many genes have been shown to be involved in Autism. SHANK3 (SH3 and multiple ankyrin repeat domain 3) is a member of the highly conserved Shank/ProSAP family of synaptic scaffolding proteins. SHANK3 is suggested as a strong candidate gene for the pathogenesis of Autism and its loss results in disruption of synaptic function. The rs9616915 SNP, which directly affects SHANK3 gene function of splicing regulation and protein structure damage, is a non-synonymous SNP (T>C) that found in exon 6, leads to substitution of Isoleucine to Threonine. The present study was aimed to evaluate whether rs9616915 polymorphism of SHANK3 are related with the susceptibility to Autism. Samples were obtained from 90 patients diagnosed with Autism and 100 controls subjects and genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The results of this study showed that there is a significant association in genotype distribution between cases and controls (P=0.0001). Our findings revealed that individuals with TC genotypes were associated with increased risk of Autism disorder (OR=4.35, 95% CI: 2.15-8.80, P=0.0001) but no significant differences were found in allele distributions (P=0.1). Our results indicated that the SHANK3 rs9616915 polymorphism is associated with increased risk of Autism. Larger studies with more patients and controls are needed to confirm the results.


Organ chemiluminescence: noninvasive assay for oxidative radical reactions.
In situ and perfused rat livers showed a spontaneous chemiluminescence of 7-12 counts/sec . cm2 (corresponding to 7-12 x 10(3) photons/sec . cm2); chemiluminescence was increased up to 30 times by infusion of exogenous hydroperoxides. The chemiluminescence of the perfused liver was oxygen dependent. Ethyl, t-butyl, and cumene hydroperoxides were almost equally effective in inducing light emission in the perfused liver. Glutathione release and chemiluminescence showed a parallel increase upon hydroperoxide supply to the perfused liver. A partial spectral analysis of the chemiluminescence of the perfused liver showed a predominance of red-light-emitting species, presumably arising from the singlet oxygen dimol-emission peaks. Many side reactions derived from the complex free radical sequence of lipid peroxidation could afford the chemistry leading to light emission, which represents only about 10(-14) of the utilization of peroxide.


The nucleoside and nucleotide mixture (OG-VI) rescues intestinal-like epithelial cells from the cytotoxicity of chemotherapeutic agents.
Immune cells and cells undergoing rapid turn-over can obtain exogenous nucleotides via salvage synthesis. We evaluated whether or not the balanced nucleoside and nucleotide mixture OG-VI, could rescue intestinal epithelial-like Caco-2 cells from the cytotoxic effects of several chemotherapeutic agents, in the presence and absence of glutamine (Gln). Cells were exposed to 5-fluorouracil (5FU), methotrexate (MTX) or 6-mercaptopurine (6MP), after which proliferation and cell cycle analyses were performed. Following exposure to the chemotherapeutic agents, we observed that cells treated with OG-VI proliferated well, whereas those without the supplement did not proliferate. Furthermore, following treatment with either 5FU or MTX, we observed that the number of cells in the G0/G1 phase decreased and those in the S phases increased. However, these cell cycle alterations were prevented by the addition of OG-VI. With the exception of 6MP-treated cells, we did not observe any effects on proliferation or cell cycle regulation that could be ascribed to the presence of Gln. Thus, we have demonstrated that OG-VI rescues cells from the cytotoxic effects of several chemotherapeutic agents.


[Diagnostic imagings and embolotherapy for the superior mesenteric vein-inferior vena cava shunt].
Diagnostic imaging and embolization therapy for the uncommon portal and mesenteric vein-inferior vena cava shunt (PV.SMV-IVC shunt) are reported. As the frequency of clinical symptoms such as hematemesis, melena and confusion caused by gastrointestinal varices, or hepatoencephalopathy was about 40%, it was important for this disease entity to be diagnosed with noninvasive diagnostic images. The careful examination of the area around the right renal vein was able to overcome the low diagnostic rate of 20-40% obtained with US and CT images. In cases of simple PV.SMV-IVC shunt without gastrointestinal varices, embolization therapy using steel coils and done by the intravenous approach is easy and noninvasive. On the other hand, in cases of complex PV-SMV-IVC shunt with gastrointestinal varices, dual balloon occluded embolization therapy using a liquid sclerosing agent and done by the intravenous and portal approaches is preferable.


[QTL mapping for "pre-summer boll, summer boll and autumn boll" traits in cotton].
"Pre-summer boll, summer boll and autumn boll" have long been regarded as an important index for prematurity and high-yield in cotton. In this study, the prematurity and high-yield cotton cultivar, Baimian 2, was used as the central parent to cross separately with the middle-late-matury lines TM-1 and CIR12, and then two populations of F2 and F2:3 family lines were obtained, which was used to construct two genetic linkage maps. These maps were comprised of 269 and 127 marker loci with the total length 1837.8 cM and 1244.3 cM, respectively. Results of QTL location showed that a total of 29 QTLs were detected in the two combinations, including 16 suggestive QTLs and 13 significant QTLs, of which 5 significant QTLs had higher LOD values that was not only greater than 3 but also greater than the threshold calculated by permutation test. The contribution rate of 16 QTLs explained 10.9%-44.5% of the phenotypic variations. Four common QTLs, qPSB-17 for pre-summer boll, qSB-17 (qSB-17a/17b) for summer boll, and qAB-17 and qAB-12/26 for autumn boll, were detected close to common markers of the same chromosome in the two combinations, which could be applied in marker-assisted selection. Moreover, the contribution rate of qSB-17 (qSB-17a/17b) for summer boll in the two combinations was greater than 10%, and that of qAB-17, qAB-12/26 for autumn boll in one combination were greater than 10%. These common QTLs with greater contribution rates should take into consideration firstly in marker-assisted selection.


Aminobenzofuran-containing analogues of proximicins exhibit higher antiproliferative activity against human UG-87 glioblastoma cells compared to temozolomide.
A new series of proximicin analogues containing a benzofuran moiety as the replacement of the di-furan scaffold of the parent compound were synthesised and evaluated for their anti-proliferative activities against human glioblastoma cells U-87 MG. Proximicins A, B, and C are secondary metabolites produced by Verrucosispora Fiedleri MG-37, a Gram-positive actinomycete isolated from deep-sea sediment. Proximicins exhibit significant cytotoxic and apoptotic effects in a number of tumour cell lines, although further investigations on these natural products biological activity are hampered by the challenging synthesis of their constitutive di-furan unit. Therefore, the easily-synthesisable benzofuran ring was elected as a replacement of the di-furan platform, and a library of proximicin analogues was prepared in which different substituents were introduced at both the N-terminus and C-terminus of the benzofuran core unit. The novel compounds were tested against U-87 MG, as it was previously found that proximicins targeted this cancerous cell line, and the human healthy cell line WI-38. Temozolomide, the chemotherapeutic agent of choice for the treatment of glioblastoma, was used as a control. Analysis of growth inhibitory concentration values revealed that a number of furan-benzofuran-containing proximicin analogues, including 23(16) (IC50 U-87 MG = 6.54 μg mL-1) exhibited higher antiproliferative activity against glioblastoma cells compared to both proximicins A-C and temozolomide (IC50 U-87 MG = 29.19 μg mL-1) in U-87 MG.


Molecular interactions of the inclusion complexes of hinokitiol and various cyclodextrins.
The aim of this study was to prepare inclusion complexes of hinokitiol (HT)/α-cyclodextrin (α-CD) and HT/β-cyclodextrin (β-CD) by cogrinding and to evaluate the differences in their formation. The physical properties of the preparation were evaluated by Job's plot, phase solubility studies, differential scanning calorimetry, powder X-ray diffraction, solid fluorescence spectra, and infrared absorption spectra. Intermolecular interaction in the solid state was confirmed to be in the ratios HT/α-CD = 1/2 and HT/β-CD = 1/1. Results indicated that the dissolution property of HT was improved by inclusion in the complexes HT/α-CD and HT/β-CD compared with HT crystals. The 1H-1H ROESY NMR spectrum of HT/α-CD showed that part of the seven-membered ring of HT and the isopropyl group of HT was linked to the wider edges of the two α-CDs. In HT/β-CD, the seven-membered ring of HT interacted with the narrower edge of β-CD and the isopropyl group of HT interacted with the wider edges. This structure of inclusion complexes was attributed to the difference in the cavity diameter of the CD and was thought to influence the dissolution properties.


Effects of a herbal ergogenic drink on cycling performance in young cyclists.
It is essential to replace fluids lost so as to remain well hydrated during exercise. The intake of fluids is considered a physiological ergogenic aid to enhance exercise performance. There are currently several products in the market that are believed to have ergogenic properties which act as fluid replacement drinks during exercise. One such drink available in the Malaysian market is 'AgroMas®' herbal drink whose efficacy is yet to be proven. The purpose of this study was, therefore, to evaluate the effects of acute ingestion of this herbal drink (H) or a coloured water placebo (P) on cycling performance. Nine healthy and trained young male cyclists (age: 16.2 ± 0.5 years) exercised on a cycle ergometer at 71.9 ± 0.7% of maximal oxygen consumption (VO2max) until exhaustion on two occasions at 1-week intervals. During each exercise bout, subjects received 3ml kg-1 body weight of H or P every 20 min in a double-blind randomised study design. There was no significant difference between H and P trials in the total work time to exhaustion (83.7 ± 4.6 and 81.5 ± 5.0 min respectively). Changes in oxygen consumption, heart rate and perceived rate of exertion were similar for both types of drinks. These results demonstrate that the herbal drink and the placebo elicited similar physiological responses and exercise performance during endurance cycling. It is therefore concluded that AgroMas? herbal drink and water ingestion resulted in a similar ergogenic response on cycling performance in young cyclists.


Case Report: TFE3 Positive Xp11.2 Translocation Renal Cell Carcinoma (TRCC) - A Case Study and Review of the Literature.
Microphthalmia-associated transcription factor renal cell cancer, also known as translocation renal cell cancer, belongs to the group of extremely rare non-clear-cell kidney neoplasms. Their incidence is lower in adulthood than in childhood. The only known risk factor for the development of this tumor is prior chemotherapy. In the operable stage of the disease, the prognosis depends on the status of regional lymph nodes. Interestingly lymph node positivity worsens the prognosis only in the adult patient population. Radical surgical excision is the best therapy in the early stage. The optimal treatment strategy for locally advanced and metastatic disease has not been established, given the lack of evidence in such a rare disease. We present the case of a patient with an aggressive course of this neoplasm treated with temsirolimus, who achieved 10-month control of this neoplasm accompanied by a discussion on other therapeutic possibilities.


Retinopathy of incontinentia pigmenti: a case report with thirteen years follow-up.
A spectrum of retinal features has been recognised in association with incontinentia pigmenti. The majority of reported cases describe a rapidly progressive proliferative retinopathy, often leading to retinal detachment, emphasizing the potentially blinding nature of the disease. In some instances, the retinopathy has been noted to be less severe but follow-up has been short. We describe a young girl with incontinentia pigmenti in whom the retinopathy has shown a fluctuating but stable course over 13 years without treatment.


Dispelling misconceptions in the management of familial adenomatous polyposis.
Patients with familial adenomatous polyposis require surgical intervention at some point in their lives. The diagnosis is often apparent from their phenotype and family history, however, this is not always the case. Many factors can influence the surgical strategy although the polyposis burden and distribution remain the main consideration. While prophylactic removal of the rectum and colon is often required, sparing the rectum at the index surgery is safe in select patients. This article aims to dispel misconceptions in the diagnosis and treatment of patients with familial adenomatous polyposis.


Soft Bite Appliance for Teething Infants.
Mother's milk is a biological secretion that provides the best nutritional source with numerous benefits to the infant, which include somatic growth, modulation of post-natal intestinal function, brain development, and immune ontogeny. As per WHO, exclusive breastfeeding is recommended for the first six months and continuation up to two years of age as both mother and the infant are mutually benefitted. Breast milk contains more nutritional, hormonal, and growth factors which are mandatory for the baby to attain the highest standards of health. Many mothers encounter bite injuries in their nipples and areola while feeding due to the teething process, which usually starts six months after birth. This may cause injury to the mother's skin causing inconvenience in feeding. This can be avoided by fabricating a "soft bite appliance" for the infant, which prevents bite injuries and makes both the baby and mother feel comfortable during feeding. This device can be used as a temporary device during the teething process, thereby enhancing nursing mothers to continue the feeding process without anxiety.


#Neurosurgery: A Temporal and Content Analysis of Academic Neurosurgery on Twitter.
Social media has become ubiquitous in modern medicine. Academic neurosurgery has increased adoption to promote individual and departmental accomplishments, engage with patients, and foster collaboration. We sought to quantitatively evaluate the adoption of one of the most used social media platforms, Twitter, within academic neurosurgery. A quantitative and qualitative analysis of Twitter use across 118 academic neurosurgery departments with residency programs in the United States was performed in March 2019 and March 2021. We collated Twitter handles, Doximity residency ranking (a peer-determined ranking system), geographic location, and Twitter demographics (tweets, followers, likes, and tweet content) from before and after the coronavirus disease 2019 (COVID-19) pandemic. Tweet content was characterized by reviewers over a predetermined 6-month period. Linear regression and parametric/nonparametric tests were used for analysis. Departmental accounts grew 3.7 accounts per year between 2009 and 2019 (R2 = 0.96), but 43 accounts (130%) were added between 2019 (n = 33) and 2021 (n = 76). This growth, coinciding with the COVID-19 pandemic, changed the model from linear to exponential growth (R2 = 0.97). The highest-ranking programs based on Doximity were significantly more likely to have an account (P < 0.001) and have more followers (P < 0.0001). Tweet content analysis revealed prioritization of faculty/resident activity (mean 49.9%) throughout the quartiles. We demonstrate rapid uptake in Twitter use among U.S. academic neurosurgical departments, accelerated by COVID-19. With the impact of COVID-19, it is clear that there will be continued rapid adoption of this platform within neurosurgery, and future studies should explore the outcomes of peer collaboration, patient engagement, and dissemination of medical information.


Diagnostic Value of the Serum Anti-Toxocara IgG Titer for Ocular Toxocariasis in Patients with Uveitis at a Tertiary Hospital in Korea.
This study evaluated the prevalence of ocular toxocariasis (OT) in patients with uveitis of unknown etiology who visited a tertiary hospital in South Korea and assessed the success of serum anti-Toxocara immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) as a diagnostic test for OT. The records of consecutive patients with intraocular inflammation of unknown etiology were reviewed. All participants underwent clinical and laboratory investigations, including ELISA for serum anti-Toxocara IgG. OT was diagnosed based on typical clinical findings. Clinical characteristics, seropositivity, and IgG titers were compared between patients diagnosed with OT and non-OT uveitis. The seropositivity and the diagnostic value of anti-Toxocara IgG was investigated among patients with different types of uveitis. Of 238 patients with uveitis of unknown etiology, 71 (29.8%) were diagnosed with OT, and 80 (33.6%) had positive ELISA results for serum anti-Toxocara IgG. The sensitivity and specificity of the ELISA test were 91.5% (65 / 71) and 91.0% (152 / 167), respectively. The positive predictive value of the serum anti-Toxocara IgG assay was 81.3%. Among patients with anterior, intermediate, posterior, and panuveitis, the prevalence rates of OT were 8.3%, 47.1%, 44.8%, and 7.1%, respectively; the seropositivity percentages were 18.1%, 47.1%, 43.7%, and 17.9%; and the positive predictive values were 38.5%, 95.8%, 92.1%, and 40.0%. The serum anti-Toxocara IgG titer also significantly decreased following albendazole treatment. OT is a common cause of intraocular inflammation in the tertiary hospital setting. Considering that OT is more prevalent in intermediate and posterior uveitis, and that the positive predictive value of the anti-Toxocara IgG assay is high, a routine test for anti-Toxocara IgG might be necessary for Korean patients with intermediate and posterior uveitis.


Return to work among patients with small cell lung cancer.
Forty-four patients with small cell lung cancer (SCLC), who were working in some kind of profession when they were taken ill, were studied with regard to return to work during or after cancer treatment. All patients received combination chemotherapy without chest radiotherapy or prophylactic brain irradiation. Twelve patients, referred to as W, returned to work during some period (14-83 weeks) after commencement of treatment, and 32 did not (NW). The stage of the disease prior to treatment and the type of profession seemed to be major prognostic factors. Patients with limited disease or "light" occupations more often returned to work than did patients with extensive disease or "heavy" occupations (P = 0.027 and 0.037, respectively). Age, sex and performance status were less important factors. Long-term survival was not a necessary condition for return to work, and overall survival was not prolonged in W patients compared with NW patients. It is concluded that increased occupational activity is an important palliative gain from chemotherapy in SCLC, and that this gain is not confined to a specific subgroup of patients, but is most likely to occur in patients with limited disease.


Post-partum complete acute uterine inversion: A coordinated multi-disciplinary approach ameliorates an obstetric nightmare, a case report.
Acute uterine inversion is a rare life-threatening complication of third stage of labour. In majority of cases, exact aetiology is unknown. It should be strongly suspected when the triad of haemorrhage, shock and severe abdominal pain with bearing down sensation is present after delivery of placenta. It can occur even after active management of third stage of labour. Diagnosis is essentially clinical. Expeditious manual repositioning of uterus and simultaneous liberal use of uterotonics is the management of choice. This was successfully attempted in the present case where a 26-year-old multiparous woman, without any identifiable risk factors, developed acute puerperal uterine inversion after active management of labour. It was observed that quick and accurate clinical judgement and timely intervention can prevent maternal mortality. The role of a multidisciplinary team including primary health care provider, obstetrician, anaesthesiologist and critical care experts has significant effects on outcome especially in intractable cases.


The Liberty Mutual manual materials handling (LM-MMH) equations.
We summarise more than 40 years of Liberty Mutual psychophysical research on lifting, lowering, pushing, pulling and carrying, including the 7 studies used to develop the 1991 Liberty Mutual Tables and 12 subsequent studies. Predictive equations were developed based on 612 mean maximum acceptable loads (MALs), representing 388 unique conditions from 123 female and 149 male participants, starting with a maximum reference load that is scaled based on frequency, height, distance (vertical for lift & lower, horizontal for push, pull and carry tasks) and horizontal reach (for lift & lower tasks). Representative coefficients of variation are provided to allow for the calculation of MALs for any percentile. Each equation performed well and, overall, they explained 90% of the variance in MAL values, with RMS differences of 6.7% and 4.8% of the full range for females and males, respectively. We propose that these equations replace the 1991 Liberty Mutual Tables. Practitioner summary: We propose predictive equations to replace the 14 manual materials handling tables in Snook and Ciriello (1991). These equations are based on 12 more publications, matched the empirical data well, are easier to use and allow for both a wider range and more specific inputs than the tables.


Nitric oxide and β(2)-adrenoceptor activation attenuate pulmonary vasoconstriction during anaphylactic hypotension in anesthetized BALB/c mice.
Systemic anaphylaxis accompanies pulmonary vasoconstriction and bronchoconstriction, which may contribute to increased right heart afterload, and finally anaphylactic hypotension. However, the pulmonary response to anaphylaxis is not known in mice. We determined the pulmonary vascular and bronchial response to systemic anaphylaxis in anesthetized BALB/c mice. We also clarified the roles of β-adrenoceptors, nitric oxide, and cyclooxygenase metabolites in these responses. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen into open-chest artificially ventilated sensitized mice. Mean arterial pressure, systolic pulmonary arterial pressure, central venous pressure, airway pressure, and aortic blood flow were continuously measured. In sensitized control mice, mean arterial pressure, and aortic blood flow substantially decreased soon after the antigen injection, while systolic pulmonary arterial pressure and airway pressure did not increase. In contrast, in mice pretreated with either the β(2)-adrenoceptor antagonist ICI 118,551 (0.2 mg/kg; n = 6), or L-NAME (50 mg/kg; n = 6), but not with the β(1)-adrenoceptor antagonist atenolol (2 mg/kg; n = 6) or indomethacin (5 mg/kg; n = 6), systolic pulmonary arterial pressure increased by 7 mmHg at 1.5 min after antigen. In L-NAME pretreated mice, pulmonary hypertension was sustained over 30 min of the experimental period. Airway pressure did not significantly change after antigen in any mice studied. In conclusion, pulmonary response to systemic anaphylaxis does not increase the right heart afterload and, therefore, may not contribute to the initial decrease in venous return and anaphylactic hypotension in anesthetized mice. β(2)-adrenoceptor activation and nitric oxide, but not β(1)-adrenoceptor activation or cyclooxygenase metabolites, attenuate the antigen-induced pulmonary vasoconstriction.


A Public Health Analysis on Gaps in Disease Monitoring and Opportunities for Improved Care for the Management of Hepatitis B and C.
Hepatitis B and Hepatitis C have been major disease-causing agents among humans since they were discovered in the 1960s. Both cause jaundice-like symptoms initially but their prognosis and treatment are somehow different and depend upon many demographic details, such as the age and susceptibility of the patients and any other comorbid conditions. They clinically present primarily with hepatitis and can have many adverse effects or even be life-threatening at times, if not treated properly. However, their epidemiological background and findings in terms of morbidity, mortality, and case fatality rates are different. The disease burden, impact on the healthcare system, and prevention of the two diseases are quite different. The treatment and management options along with the prevention and control measures share unique strategies for handling the two diseases. The purpose of this review is to highlight the gaps in disease monitoring and to find ways and opportunities that can lead to improved care and better management of Hepatitis B and C locally and globally. Online databases were searched and peer-reviewed articles were selected. Key issues identified were lack of education globally in resource-limited settings, leading to a decreased understanding of the potential hazards associated with needle sharing and lack of access to healthcare because of a lack of insurance. The failure of compliance with vaccination leads to an increase in mother-to-child transmission (MTCT)-related infections. Increased global travel demands a systematic program in most immigrant-receiving countries to screen for hepatitis B virus (HBV)/hepatitis c virus (HCV) infections. Delayed U.S. Food and Drug Administration (FDA) licensing for new drugs hampers the treatment of chronic Hepatitis-B (CHB) among children. With the advancement in science, an effective vaccine against HCV will definitely help in eradicating the infection.


Postauricular pull-through transpositional flap: an option for one-stage reconstruction of anterior auricle defects.
The reconstruction of anterior-superior defects of the auricle is usually a challenging task. We describe three patients with non-melanoma skin cancer localized in the upper portion of the antihelix. Tumour sizes ranged from 0.6 cm to 1.3 cm. All patients underwent a postauricular pull-through transpositional flap to repair the primary defect. The donor sites were closed using a T-plasty. The final results were aesthetically good. The main advantages as well as disadvantages of this one-stage reconstruction of anterior auricle defects are discussed.


PATH: a task for the inference of phylogenies.
Phylogenetic Analysis Task in Husar (PATH) is a task for the inference of phylogenies. It executes three phylogenetic methods and automatically chooses the evolutionary model for each set of data. The output of the tasks shows the consensus trees together with full results obtained from all executed methods. PATH is available at the German EMBnet node after registration via www at http://genome.dkfz-heidelberg.de


Three-dimensional spatiotemporal tracking of fluorine-18 radiolabeled yeast cells via positron emission particle tracking.
A method for Positron Emission Particle Tracking (PEPT) based on optical feature point identification techniques is demonstrated for use in low activity tracking experiments. A population of yeast cells of approximately 125,000 members is activated to roughly 55 Bq/cell by 18F uptake. An in vitro particle tracking experiment is performed with nearly 20 of these cells after decay to 32 Bq/cell. These cells are successfully identified and tracked simultaneously in this experiment. This work extends the applicability of PEPT as a cell tracking method by allowing a number of cells to be tracked together, and demonstrating tracking for very low activity tracers.


Coronary artery aneurysms: the chest pain "zebra".
Coronary artery aneurysms (CAAs) are defined as entire wall dilatation to 1.5 times the size of the adjacent normal vessel. They can present as chest pain with electrocardiogram (ECG) changes, mass effects or rupture with tamponade. This case describes the presentation of a patient with a ST elevation myocardial infarction and concurrent end stage renal failure, and the options for treatment in this rare condition.


Neuropeptides in the seminal vesicles: locations, binding sites and functional implications.
The importance of neuronal factors in the normal physiology of the seminal vesicles has been traditionally underestimated when compared to the trophic role of androgens. Immunohistochemical, autoradiographical and pharmacological experiments have, however, raised the possibility that neuropeptides, such as vasoactive intestinal polypeptide (VIP), neuropeptide tyrosine (NPY) and calcitonin gene-related peptide (CGRP), are necessary for full seminal vesicle function and development. These neuropeptides may be involved in the regulation of secretion, smooth muscle tone and blood flow. Furthermore, neuropeptides may have functional interactions with androgens affecting, probably, androgen receptor-dependent gene expression in these glands. It is now timely to focus attention on the biological relevance of neuropeptides in the seminal vesicles.


Faecal Microbiota Analysis of Piglets During Lactation.
Antimicrobial use in animals and the potential development of antimicrobial resistance is a global concern. So, non-antimicrobial techniques for animal disease control are needed. This study aimed to determine whether neonatal ceftiofur (CF) treatment affects piglet faecal microbiomes and whether faecal microbiome transplantation (FMT) can correct it. Two focal piglets per sow were assigned to treatments as follows: cffresh (n = 6) received CF (3 mg/kg intramuscular) at 7 d and fresh FMT at 13 d; cffrozen (n = 7) received CF at 7 d and frozen FMT at 13 d; CF (n = 8) received CF at 7 d and no FMT; and no CF (n = 5) received no CF or FMT. DNA was extracted from faecal samples collected on days 7, 13, and 18 for 16S rRNA amplicon analysis. All faecal blends used for the FMT consisted of pooled donor pig faeces at 1:2 ratio with saline, delivered orally at 3 mL/kg. Alpha and beta diversity metrics increased with age (p < 0.05). However, no effect of antibiotic or FMT treatment was evident in 13 and 18 d old piglets (p > 0.05). Although no effect of treatment was observed, information regarding microbial membership during lactation was gained.


Validation of glomerular filtration rate-estimating equations in Chinese children.
Glomerular filtration rate (GFR) is essential for renal function evaluation and classification of chronic kidney disease (CKD), while the reference method in children are cumbersome. In the Chinese children, there was no data about GFR measured through plasma or renal clearance of the exogenous markers, and therefore no validated GFR-estimating tools in this population. We measured GFR with double-sample plasma clearance of 99mTc-DTPA (mGFR) in 87 hospitalized children with renal injury. Using mGFR as the golden standard, we evaluate the efficiency of four different GFR estimation equations (the original and update Schwartz equation, the Filler equation, the CKiD equation) by statistical parameters of correlation, precision and accuracy. In our population, mGFR was 97.0± 31.9 mL/min/1.73m2. The updated Schwartz equation, the Filler equation and the CKiD equation, produced eGFR with strong correlation with mGFR, strong explanation capacity of variance in mGFR, small bias, satisfactory performance in Bland-Altman analysis, high intra-class correlation coefficients, high ratio of eGFR within mGFR±10% and eGFR within mGFR±30%, good agreement in CKD staging between eGFR and mGFR. The original Schwartz equation produced eGFR with large bias, poor precision and accuracy. The validated equations to estimate GFR in our patients are the updated Schwartz equation, which is simple for bedside use, the Filler equation and the CKiD equation, which provide more accurate eGFR. The original Schwartz equation should not be applied to estimate GFR in Chinese children with kidney injuries.


Socioeconomic background and road traffic injuries: a study of young car drivers in Sweden.
The aim of this study is to explore the manner in which different measures of original socioeconomic position (SEP) influence road traffic injuries (RTIs) among young car drivers in Sweden. The study consists of young people age 16-23. Subjects were taken from the Swedish Population and Housing Census of 1990 (n=727,995), and followed up by a search for cases of injury to car drivers in Sweden's National Hospital Discharge Register over the years 1991-96 (n=1,599). Household SEP was measured using social class, education, and disposable income. Relative risks were estimated by Poisson regression and population attributable risks were computed for each measure of SEP. Children of unskilled workers, of the self-employed, and of farmers, as well as children of parents with compulsory education only showed an increased risk of injury as car drivers compared to children in the highest socioeconomic group and children of highly educated parents. By contrast, level of household disposable income was found not to vary with RTI among young drivers. Twenty-five percent of the injuries could be avoided if all young people had the injury rate of the highest socioeconomic group, and 29% if all young people had the injury rate of those with highly educated parents. The reduction of risk differences based on household SEP calls for consideration of factors related to both differential exposure and differential susceptibility, which may be addressed in driver education.


Repetitive immunoadsorption cycles for treatment of severe atopic dermatitis.
The purpose of the study was to investigate the clinical efficacy of repetitive IgE immunoadsorption (IA) cycles in severe atopic dermatitis (AD) with high serum IgE levels. A total of seven patients with severe AD with a history of no significant or longterm Scoring Atopic Dermatitis (SCORAD) reduction and total serum IgE levels >700 IU/mL were enrolled. The patients received one to five series of IA (Ig-Therasorb adsorber columns; Miltenyi Biotec, Teterow, Germany) each consisting of five consecutive treatments which were performed on a monthly regimen. Overall, one patient received one, two patients two, one patient three, two patients four and one patient five cycles of IA. IA was well tolerated in all the studied AD patients and led to a significant decrease of SCORAD and IgE levels during each IA cycle in all the patients. The relative decrease of SCORAD and serum IgE levels after treatment was 11.1% and 80%, respectively, after five immunoadsorption series, 24.1% and 83.6%, respectively, after four series, 37.6% and 75.9%, respectively, after three series, 27.9% and 74.2%, respectively, after two series, and 25.1% and 74.8% after the 1st IA cycle. One of the patients exhibited a long lasting clinical benefit over more than 12 months after the 5th IA cycle. Repetitive IA with more than two cycles at intervals of 4 weeks induces a profound and persisting IgE reduction which is remarkable clinical efficacy improving SCORAD in severe AD with high serum IgE levels.


Utility of Bedside Ultrasound Measurement of Optic Nerve Sheath Diameter as a Screening Tool for raised Intracranial Pressure in Neurocritical Care Prospective Observational Study.
Intracranial pressure (ICP) needs to be monitored in neurocritical patients. There is a need for portable bedside optic nerve ultrasound (ONUS) for early diagnosis to initiate the measures to reduce ICP Objective: To find the utility of bedside ONUS to diagnose raised ICP in neurocritical care. Materials and methods: After approval from the ethical committee, a prospective observational study was conducted. Optic nerve sheath diameter (ONSD) was measured in two groups: control group patients with neurological symptoms but computed tomography (CT)/magnetic resonance imaging (MRI) not suggestive of raised ICP, and second was study group patients with neurological symptoms and CT/MRI suggestive of elevated ICP Result: In patients with normal ICP, the mean ONSD in females was 4.47mm, and in males was 4.66mm. In patients with raised ICP, the mean ONSD in females was 6.45 ± 0.78 mm, and in males was 6.33 ± 0.70 mm. Regarding the correlation between Glasgow coma scale (GCS) and mean ONSD parameters, the coefficient of correlation (R) is 0.14; thus, there is a weak negative correlation. In our study, no difference was observed in raised mean ONSD in patients with different diagnoses. At a cut-off value of >4.8 mm, the sensitivity and specificity are 100% to diagnose raised ICP. Conclusion: Optic nerve sheath diameter (ONSD) is a reliable, rapid bedside screening tool in the Emergency Department/Critical Care/Operation Theatre to diagnose raised ICP. In order to keep a record of trends in ICP, we need to measure ONSD frequently. There was no correlation between GCS and ONSD measurement.


Lysinuric protein intolerance.
Lysinuric protein intolerance (LPI), an autosomal recessive defect of diamino acid transport, is characterized chemically by renal hyperdiaminoaciduria, especially lysinuria, and by impaired formation of urea with hyperammonemia after protein ingestion. Our 20 patients thrived during breast-feeding, but ingestion of cow's milk caused diarrhea and vomiting. When able to select their diet, they rejected all protein-rich foods. They were short staturated and had weak atrophic muscles, osteoporosis, hepatomegaly and often splenomegaly. Four patients were mentally retarded. Fifteen patients had leukocyte counts below 4,000/mm3, and 17 patients had platelet counts below 150,000/mm3. Serum lactate dehydrogenase activity was constantly increased, and transaminase and aldolase activities were often increased. In the infants' livers, changes were only revealed by electron microscopy: increased and vesicular smooth endoplasmic reticulum, and abundance of glycogen particles in the hepatocytes. In the older patients, light microscopy demonstrated clearly limited areas where hepatocytes had large pale cytoplasm and small pyknotic nuclei. The diamino acids lysine, arginine and ornithine had plasma concentrations only one-third to one-half the normal mean; the renal clearances were clearly increased. Oral diamino acid loading tests suggested impaired intestinal absorption. Urea is built in the liver through transformation of ornithine to arginine, and cleavage of arginine to ornithine and urea. The addition of ornithine to an intravenous I-alanine loading prevented the hyperammonemia and normalized the urea production. Therefore, the diet has been supplemented with arginine, and more protein has been added. This therapy has lead to a remarkable catch-up growth in some patients. The pathophysiology of LPI is explained. Because of defective intestinal absorption and incrased renal loss, the diamino acids have a low plasma concentration. Their transport from plasma to hepatocytes is also impaired, and the liver becomes deficient in ornithine. This retards the urea cycle, and leads to postprandial hyperammonemia and protein aversion. The presence of the transport defect in the hepatocytes distinguishes LPI from other hyperdibasicaminoacidurias.


A comparison of several methods for analyzing data from thorough QT studies.
Currently, the intersection-union test (IUT) is the standard method of analysis of the data from a thorough QT (TQT) study. In this current work, we compared the methods proposed in three recent publications (Boos et al., 2007; Cheng et al., 2008; Eaton et al., 2006) to IUT using a simulation study. The methods proposed by Cheng and Eaton did not produce a considerable improvement over IUT in the power and size of the test. The power of the Boos et al. method was a substantial improvement over IUT, but the size of the test was found to be greater than 5%.


Pharmacokinetics and safety of the anti-human cytomegalovirus drug letermovir in subjects with hepatic impairment.
Human cytomegalovirus constitutes a prevalent and serious threat to immunocompromised individuals and requires new treatments. Letermovir is a novel viral-terminase inhibitor that has demonstrated prophylactic/pre-emptive activity against human cytomegalovirus in Phase 2 and 3 transplant trials. As unchanged letermovir is primarily excreted via the liver by bile, this trial aimed to assess the effect of hepatic impairment on letermovir pharmacokinetics. Phase 1, open-label, parallel-group pharmacokinetic and safety comparison of multiple once-daily oral letermovir in female subjects with hepatic impairment and healthy matched controls. For 8 days, subjects with moderate hepatic impairment (n = 8) and their matched healthy controls (n = 9) received 60 mg letermovir/day and those with severe hepatic impairment (n = 8) and their matched healthy controls (n = 8) received 30 mg letermovir/day. Pharmacokinetic parameters were determined from blood samples. For subjects with moderate hepatic impairment, maximal observed concentration at steady state (Css,max ) and the area under the concentration vs. time curve over a dosing interval at steady state (AUCτ,ss ) for total letermovir were 1.37-fold (90% confidence interval: 0.87, 2.17) and 1.59-fold (0.98, 2.57) higher, respectively, than in healthy subjects. For subjects with severe hepatic impairment, Css,max and AUCτ,ss values of total letermovir were 2.34-fold (1.91, 2.88) and 3.82-fold (2.94, 4.97) higher, respectively, compared with healthy subjects. Moderate hepatic impairment increased exposure to letermovir <2-fold, while severe hepatic impairment increased letermovir exposure approximately 4-fold as compared with healthy subjects. Letermovir 60/30 mg/day was generally well-tolerated in subjects with hepatic impairment.


Eccentricity dependent auditory enhancement of visual stimulus detection but not discrimination.
Sensory perception is enhanced by the complementary information provided by our different sensory modalities and even apparently task irrelevant stimuli in one modality can facilitate performance in another. While perception in general comprises both, the detection of sensory objects as well as their discrimination and recognition, most studies on audio-visual interactions have focused on either of these aspects. However, previous evidence, neuroanatomical projections between early sensory cortices and computational mechanisms suggest that sounds might differentially affect visual detection and discrimination and differentially at central and peripheral retinal locations. We performed an experiment to directly test this by probing the enhancement of visual detection and discrimination by auxiliary sounds at different visual eccentricities and within the same subjects. Specifically, we quantified the enhancement provided by sounds that reduce the overall uncertainty about the visual stimulus beyond basic multisensory co-stimulation. This revealed a general trend for stronger enhancement at peripheral locations in both tasks, but a statistically significant effect only for detection and only at peripheral locations. Overall this suggests that there are topographic differences in the auditory facilitation of basic visual processes and that these may differentially affect basic aspects of visual recognition.