The site-specificity of supragingival calculus deposition on the lingual surfaces of the six permanent lower anterior teeth in humans and the effects of age, sex, gum-chewing habits, and the time since the last prophylaxis on calculus scores.
The hypotheses to be tested were: (i) that chewing sugar-free gum frequently and for long periods would be associated with higher amounts of supragingival calculus, and (ii) that there would be no site-specificity of calculus deposition on the lingual surfaces of the 6 lower anterior teeth. Subjects, 436 in Glasgow and 191 in Winnipeg, were scored for calculus at mesial, lingual, and distal sites on the lingual surface of each of the 6 lower anterior teeth, by the Volpe-Manhold method. They also answered questions on the time since the last prophylaxis, the frequency of gum chewing, the type of gum chewed, and the length of a typical gum-chewing episode. A subset (233) of the Glasgow subjects were scaled and re-scored for calculus 3 months later. When the data for the logarithmic transformations of the initial calculus scores were subjected to stepwise multiple-regression analysis, the only factor which correlated significantly with initial calculus scores in both cities was the time since the last prophylaxis. In the Glasgow subjects scored 3 months after a prophylaxis, there was a negative correlation between chewing sugar-free gum and calculus scores, whereas in the Winnipeg subjects, age and the chewing of sucrose-containing and sugar-free gum were positively correlated with calculus scores. Thus, the results were contradictory with respect to the first-tested hypothesis. The calculus distribution patterns were very similar in the subset of Glasgow subjects and the Winnipeg subjects, with the amounts on the lateral incisors and canines averaging 70.2% and 44.5%, respectively, of those on the central incisors. Thus, the second hypothesis was disproved.


Soft Material Approach to Induce Oxidative Stress in Mesenchymal Stem Cells for Functional Tissue Repair.
Biomimicking hydrogel-based cell culture platforms with physiologically relevant stiffness are powerful tools to modulate the behaviors of stem cells. Herein, the use of fibronectin-conjugated polyacrylamide (PAA) hydrogel biointerface is exploited to modulate the intracellular oxidative stress of human bone marrow derived mesenchymal stem cells (MSCs). We show that compliant culture surface with kPa range matrix stiffness can augment the expression level of reactive oxygen species (ROS) in MSCs by approximately 2-4 fold compared with cells grown on conventional FN coated glass control surface in a noncytotoxic manner. Via an unbiased proteomics approach and mechanistic studies, we show that the secretion level of a sub series of "mechano-sensitive" chemokines and trophic factors is heavily dependent on the PAA matrix stiffness mediated ROS level. Importantly, the secretome harvested from the cells that were grown on the PAA hydrogel was found to enhance wound healing in both in vitro and in vivo full thickness mouse excisional wound model. The devised "soft approach" to induce oxidative stress in MSCs is posited to pave the way for novel cell-free therapeutic interventions targeting a wide variety of diseases and to foster functional tissue repair.


Maintaining vector control during alveolar distraction osteogenesis: a technical note.
Distraction osteogenesis is a predictable method for restoring missing tissue prior to implant placement. However, pull from the soft tissue can alter the desired direction of the distraction. This article describes and illustrates techniques that are useful for maintaining the desired vector during alveolar distraction osteogenesis. These methods can prevent the need for further intervention and allow for ideal placement of endosseous dental implants without compromising results.


Improved liver preservation for transplantation due to calcium channel blockade.
Intracellular calcium is an important determinant for cell death in organ hypothermic preservation for transplantation. In this study, we show that prevention of calcium entry improves the result of liver cold storage in UW solution. The isolated perfused rabbit liver was used. After 48 hr of cold storage in UW solution, bile production was reduced by 70% (P less than 0.005). However, by adding the calcium channel blockers verapamil or nifedipine (40 microM) to the UW solution, this reduction was abolished, and the livers produced the same amount of bile as unpreserved livers. Furthermore, addition of the calcium channel activator, BAY K8644 (40 microM), to the UW solution, reduced bile production by 50% (P less than 0.01) already after preservation for 24 hr. We conclude that calcium entry is of importance for liver function after preservation and cold storage, and that including a calcium channel blocker to the preservation solution makes long-term liver preservation safer.


Multiparameter Optimization of Trypanocidal Cruzain Inhibitors With In Vivo Activity and Favorable Pharmacokinetics.
Cruzain, the main cysteine protease of Trypanosoma cruzi, plays key roles in all stages of the parasite's life cycle, including nutrition acquisition, differentiation, evasion of the host immune system, and invasion of host cells. Thus, inhibition of this validated target may lead to the development of novel drugs for the treatment of Chagas disease. In this study, a multiparameter optimization (MPO) approach, molecular modeling, and structure-activity relationships (SARs) were employed for the identification of new benzimidazole derivatives as potent competitive inhibitors of cruzain with trypanocidal activity and suitable pharmacokinetics. Extensive pharmacokinetic studies enabled the identification of metabolically stable and permeable compounds with high selectivity indices. CYP3A4 was found to be involved in the main metabolic pathway, and the identification of metabolic soft spots provided insights into molecular optimization. Compound 28, which showed a promising trade-off between pharmacodynamics and pharmacokinetics, caused no acute toxicity and reduced parasite burden both in vitro and in vivo.


Outcome of contralateral C7 nerve transferring to median nerve.
Contralateral C7 (cC7) transfer had been widely used in many organizations in the world, but the outcomes were significantly different. So the purpose of the study was to evaluate the outcome of patients treated with cC7 transferring to median nerve and to determine the factors affecting the outcome of this procedure. A retrospective review of 51 patients with total root avulsion brachial plexus injuries who underwent cC7 transfer was conducted. All of the surgeries were performed with two surgery stages and median nerve was the recipient nerve. The cC7 nerve was used in three different ways. The entire C7 root was used in 11 patients; the posterior division together with the lateral part of the anterior division was used in 15 patients; the anterior or the posterior division alone was used in 25 patients. The mean follow-up period was 6.9 years. The efficiency of the surgery in these 51 patients was 49.02% in motor and 62.75% in sensory function. The patients with entire C7 root transfer obtained significantly better recovery in both motor and sensory function than the patients with partial C7 transfer. The best function recovery could be induced if the interval between the two surgery stages was 4-8 months. cC7 transfer is an effective procedure in repairing median nerve. But using the entire C7 root transfer can obtain better recovery; so we emphasize using the entire root as the donor. The optimal interval between two surgery stages is 4-8 months.


Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy.
Current tumor regression grade (TRG) evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results. The recent six-tier system (JGCA2017-TRG) recommended by the Japanese Gastric Cancer Association (JGCA) is worth investigating, as four-tier TRG systems are favored in various parts of the world. To compare the predictive accuracies of five published TRG systems. Data were retrospectively collected from patients with locally advanced gastric cancer (LAGC) who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution. Outcomes were overall survival (OS) and disease-free survival (DFS), which were evaluated separately using the following TRG systems: JGCA2017, JGCA, Becker, AJCC/CAP, and Mandard. All five published TRG systems were independent predictors for OS and DFS. Concordance indices of the JGCA2017, JGCA, Becker, AJCC/CAP-TRG, and Mandard systems were 0.651/0.648 0.652/0.649, 0.693/0.695, 0.688/0.685, and 0.674/0.675 for OS and DFS, respectively. The four-tier Becker system showed the highest c-index, which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems (P < 0.05 in OS and DFS). When residual tumor percentages were reset as: "no residual tumor", < 10%, < 100%, and "no response", the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS, which was superior to the other five systems. The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification. The four-tier Becker system is more suitable for LAGC patients. A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.


Microscopic Nature of the First-Order Field-Induced Phase Transition in the Strongly Anisotropic Ferrimagnet HoFe_{5}Al_{7}.
We report on x-ray magnetic circular dichroism experiments in pulsed fields up to 30 T to follow the rotations of individual magnetic moments through the field-induced phase transition in the ferrimagnet HoFe_{5}Al_{7}. Near the ground state, we observe simultaneous stepwise rotations of the Ho and Fe moments and explain them using a two-sublattice model for an anisotropic ferrimagnet with weak intersublattice exchange interactions. Near the compensation point, we find two phase transitions. The additional magnetization jump reflects the fact that the Ho moment is no longer rigid as the applied field acts against the intersublattice exchange field.


The NIST High Accuracy Scale for Absolute Spectral Response from 406 nm to 920 nm.
We describe how the National Institute of Standards and Technology obtains a scale of absolute spectral response from 406 nm to 920 nm. This scale of absolute spectral response is based solely on detector measurements traceable to the NIST High Accuracy Cryogenic Radiometer (HACR). Silicon photodiode light-trapping detectors are used to transfer optical power measurements from the HACR to a monochromator-based facility where routine measurements are performed. The transfer also involves modeling the quantum efficiency (QE) of the silicon photodiode light-trapping detectors. We describe our planned quality system for these measurements that follows ANSI/NCSL Z540-1-1994. A summary of current NIST capabilities based on these measurements is also given.


Recurrent Tracheoinnominate Artery Fistula due to Stent Graft Fracture.
Tracheoinnominate artery fistula (TIF) is one of the most dangerous complications after tracheostomy, and fetal even after surgical repair. Recently, endovascular stent has been introduced as an option for the treatment of TIF. Unfortunately, endovascular stent repair could not replace the surgery due to rare clinical reports about the long-term follow-up and complications of stent graft. More collection of clinical data are necessary for the evaluation of long-term results. We report a rare case of recurrent TIF due to stent graft fracture after endovascular stent graft insertion in the treatment of TIF, and reviewed the world literature.


Effects of ambient temperatures on evolutionary potential of reproductive timing in boreal passerines.
Many populations need to adapt to changing environmental conditions, such as warming climate. Changing conditions generate directional selection for traits critical for fitness. For evolutionary responses to occur, these traits need to be heritable. However, changes in environmental conditions can alter the amount of heritable variation a population expresses, making predictions about expected responses difficult. The aim of this study was to evaluate the effects of ambient temperatures on evolutionary potential and strength of natural selection on the timing of reproduction in two passerine birds breeding in boreal forests. Long-term data on individually marked Willow Tits Poecile montanus (1975-2018) and Great Tits Parus major (1969-2018) were analysed with random regression animal models to assess if spring temperatures affect the expressed amount of additive genetic variation (VA ) and heritability (h2 ) in the timing of breeding. We assessed if ambient temperatures of different seasons influenced the direction and strength of selection on breeding time. We also evaluated if the strength of selection covaried with evolutionary potential. Levels of VA or h2 expressed in laying date were unaffected by spring temperatures in both study species. Selection for earlier breeding was found in the Willow Tit, but not in the Great Tit. In the Willow Tit, selection for earlier breeding was more intense when the temperatures of following autumns and winters were low. Different measures of evolutionary potential did not covary strongly with the strength of selection in either species. We conclude that there is no or little evidence that climate warming would either constrain or promote evolutionary potential in timing of breeding through changes in amount of genetic variance expressed in boreal Willow and Great Tits. However, selection on the timing of breeding, a life-history event taking place in springtime, is regulated by temperatures of autumns and winters. Rapid warming of these periods have thus potential to reduce the rate of expected evolutionary response in reproductive timing.


Real-time process/quality control for HPC processing.
JACIE Standards (FACT Standards in the USA) have been implemented in Europe since 1999. An on-site accreditation inspection took place at our center in January 2004. The purpose of this work was to develop a real-time process/quality control system meeting the JACIE Standards for HPC release. Data from 194 HPC processing procedures for autologous transplantation performed over a 5-year period were analyzed. The results of different processing methods applied at our facility were compared: (1) cryopreservation without washing cells (n=50), (2) washing cells (n=87), (3) cell-density separation (n=12) and (4) positive CD34 selection (n=45). Four critical control points were set for the validation of HPC processing: (a) number of lost CD34(+) cells during processing, (b) contamination, (c) viability of the cells after thawing and (d) ability to reconstitute hematopoiesis after transplantation. On the basis of statistical analysis, ranges of acceptable values were defined for each critical control point and for each processing method. Those acceptable values were used for cell release and real-time quality control. This study describes a model for the validation of HPC processing and for a real-time process/quality control system for HPC release. Optimization of processing techniques, standardization of methods and comparison between facilities will open the way towards external quality controls and quality improvement.


[Therapy of candiduria by alkalinization of urine. Oral treatment with potassium-sodium-hydrogen citrate].
Eighteen hospitalized patients with candiduria were treated with oral potassium-sodium-hydrogen citrate to alkalinize the urine. The results obtained were compared with those observed in an untreated retrospective control group. Dosage was adjusted in accordance with the pH of the urine measured immediately before treatment with the aim of achieving a pH of 7 to 7.5. All patients had an indwelling catheter, which is a predisposing factor for candiduria. In 16 out of 18 patients (89%) treatment with potassium-sodium-hydrogen citrate raised pH and resulted in the disappearance of candiduria. Duration of treatment varied between two days and one month (mean: seven days). In four patients the urine became completely sterile; during treatment 12 out of 18 patients developed significant bacteriuria (in eight cases of these the indwelling catheter had been left in place). Alkalinization of the urine is a simple and effective method of treating candiduria in patients with an indwelling catheter. An additional advantage is the metaphylaxis and prophylaxis of renal stone formation in immobilized patients.


In Vivo Capillary Structure and Blood Cell Flux in the Normal and Diabetic Mouse Eye.
To characterize the early structural and functional changes in the retinal microvasculature in response to hyperglycemia in the Ins2Akita mouse. A custom phase-contrast adaptive optics scanning light ophthalmoscope was used to image retinal capillaries of 9 Ins2Akita positive (hyperglycemic) and 9 Ins2Akita negative (euglycemic) mice from postnatal weeks 5 to 18. A 15 kHz point scan was used to image capillaries and measure red blood cell flux at biweekly intervals; measurements were performed manually. Retinal thickness and fundus photos were captured monthly using a commercial scanning laser ophthalmoscope/optical coherence tomography. Retinal thickness was calculated using a custom algorithm. Blood glucose and weight were tracked throughout the duration of the study. Elevated blood glucose (>250 mg/dL) was observed at 4 to 5 weeks of age in Ins2Akita mice and remained elevated throughout the study, whereas euglycemic littermates maintained normal glucose levels. There was no significant difference in red blood cell flux, capillary anatomy, lumen diameter, or occurrence of stalled capillaries between hyperglycemic and euglycemic mice between postnatal weeks 5 and 18. Hyperglycemic mice had a thinner retina than euglycemic littermates (p < 0.001), but retinal thickness did not change with duration of hyperglycemia despite glucose levels that were more than twice times normal. In early stages of hyperglycemia, retinal microvasculature structure (lumen diameter, capillary anatomy) and function (red blood cell flux, capillary perfusion) were not impaired despite 3 months of chronically elevated blood glucose. These findings suggest that hyperglycemia alone for 3 months does not alter capillary structure or function in profoundly hyperglycemic mice.


7,8-Dihydroxy-4-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolinium bromide monohydrate, a dopamine agonist.
In the crystal structure of the title dopaminergic compound, C16H24NO2+.Br-.H2O, protonation occurs at the piperidine N atom. The piperidine ring adopts a chair conformation and the cyclohexene ring adopts a half-chair conformation; together with the planar benzene ring, this results in a relatively planar shape for the whole molecule. Classical hydrogen bonds (N-H...Br, O-H...Br and O-H...O) produce an infinite three-dimensional network. Hydrogen bonds between water molecules and Br- anions create centrosymmetric rings throughout the crystal structure. Structural comparison of the molecule with the ergoline dopamine agonist pergolide shows that it is the hydrogen-bond-forming hydroxy or imino group that is necessary for dopaminergic activity, rather than the presence of a phenyl or a pyrrole ring per se.


Physical training and noninvasive ventilation in COPD patients: a meta-analysis.
Exercise training improves both exercise tolerance and quality of life in patients with COPD. The intensity of exercise training is crucial to achieve a true physiologic effect. However, in COPD patients, exertional dyspnea and leg fatigue mean that the patient cannot maintain intensity of training for enough time to yield a physiologic training effect. The use of noninvasive ventilation (NIV) support has been proposed as an alternative strategy to improve exercise tolerance and respiratory and cardiovascular performances. The first aim of our meta-analysis was to evaluate exercise training with NIV in terms of physiologic effects after the completion of a pulmonary rehabilitation program. The second aim was to investigate the dose-response relationship between physical improvement and training intensity. Literature research was performed using MEDLINE, Embase, and CINAHL. Meta-analysis and meta-regressions were performed using random effects models. Eight studies provided a proper description of a training schedule in stable COPD patients. A similar effect between NIV and placebo was observed for the outcomes considered despite differences between studies. However, subjects experienced a relevant and statistically significant improvement after rehabilitation for almost all of the outcomes considered. Heart rate (6 beats/min [95% CI 0.94-11.01], P = .02), work load (9.73 W [95% CI 3.78-15.67], P < .001), and oxygen consumption (242.11 mL/min [95% CI 154.93-329.9], P < .001) significantly improved after training. Improvements in heart rate and work load were significantly correlated to training intensity. Given the small number of available studies, the small sample sizes, and the complete absence of power calculation, we think that this topic deserves a more in-depth investigation. Randomized clinical trials with larger sample sizes based on statistical power calculations and designed to investigate the effect of training duration and intensity on rehabilitation are needed to confirm results in this important field.


[Characteristics of anti-microbial agents and its clinical choice for H. pylori treatment].
Eradication of Helicobacter pylori (H. pylori) is now established as main treatment of upper-gastrointestinal diseases. Resistance to H. pylori and acid condition in the stomach were important factors which influenced H. pylori eradication. Recolonized H. pylori strains will be easily resistant to metronidazole and clarithromycin, whereas almost all of H. pylori strains are sensitive to amoxicillin. On the other hand, amoxicillin targets cell wall biosynthesis and clarithromycin inhibits protein synthesis of Helicobacter pylori mainly in the growth phase which induced high intragastric pH condition, however, metronidazole targets DNA and, therefore, is independent of the stationary or growth phase distribution. To established a optimal regimen for Helicobacter pylori treatment, several factors included them should be account according to the parmacokinetical standings.


Rare case of endometrioid adenocarcinoma arising from cystic adenomyosis.
Few reports on malignant transformation of adenomyosis are available, and endometrioid adenocarcinoma arising from cystic adenomyosis is further rarely reported. We report a case of a 67-year-old asymptomatic woman who was referred to our hospital for evaluation of a cystic lesion in the pelvis, which had been diagnosed as cystic degeneration of leiomyoma for 3 years. Magnetic resonance imaging revealed a cystic mass measuring 11 cm in diameter, which was contiguous with uterine myometrium. The lesion contained solid areas enhanced on gadolinium-enhanced T1 -weighted imaging. Transabdominal simple total hysterectomy with bilateral salpingo-oophorectomy was performed. Pathological examination revealed endometrioid adenocarcinoma arising from cystic adenomyosis. The patient underwent six courses of adjuvant combination chemotherapy with paclitaxel and carboplatin. No metastasis or recurrence has been demonstrated for 16 months following surgery. Our case demonstrates that cystic adenomyoma possesses the risk of malignant transformation, indicating the importance of long-term follow-up with imaging examination.


Using ambulance attendances to recruit people who have experienced non-fatal heroin overdose.
To trial two novel methods of recruiting people who experience non-fatal heroin overdose through the ambulance service. Melbourne and Sydney, Australia. In Melbourne potential participants were given numbered contact cards by ambulance paramedics after revival, while in Sydney potential participants were approached after revival by a researcher who travelled with ambulance paramedics to the overdose scene. In Melbourne 281 cards were distributed during the period 1 June 1998-31 December 1998 and a subsequent contact rate of 24% was achieved with 14% attending a subsequent interview. In Sydney there were 170 initial contacts of which 139 (82%) answered a series of questions asked at the scene (the remainder either ineligible or incapable of answering questions) with 48 (35%) also attending for follow-up interviews. Recruitment through contact with ambulance services is a novel method of recruiting heroin users for research into non-fatal heroin overdose with advantages over other methods of sampling for research on non-fatal heroin overdose.


[Maternal blood intrauterine transfusions in the therapy of red-cell alloimmunization performed in three difficult cases].
Maternal alloimmunization can lead to hemolytic anemia, hydrops fetalis and even fetal or neonatal death. Intrauterine treatment is possible and effective even though it is associated with some risk. We present a rare method of maternal blood intrauterine transfusions in the therapy of three difficult cases of erythroblastosis fetalis. The aim of this report was to present an alternative to volunteer donors. In severe cases, i.e. in the absence of matching blood types from the donor in the presence of multiple alloantibodies in the pregnant woman or if multiple transfusions are required, this can be the only therapeutic option. To the best of our knowledge, this has been the first publication on maternal blood donation for intrauterine transfusion in the Polish literature.


Insulation Performance and Simulation Analysis of SiO2-Aramid Paper under High-Voltage Bushing.
The long-term safe and stable operation of oil-impregnated paper (OIP) bushings is of great significance to the operation of power systems. With the growth of OIP bushing, its internal insulation will gradually decay. Aramid insulation paper has excellent thermal aging characteristics and its insulation performance can be improved by using nano-modification technology. In this paper, the nano-SiO2 particles were used as the modified additives, and the modified aramid insulation paper was prepared through four steps: ultrasonic stirring, fiber dissociation, paper sample copying and superheated calendering. The microscopic physical morphology and chemical components of the insulation specimens before and after modification were analyzed by atomic force microscopy (AFM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), and an OIP bushing model based on the modified aramid insulation paper was constructed and its electric field distribution was analyzed. The simulation results show that the use of SiO2-modified aramid insulation paper can improve the electric field distribution of OIP bushings and increase the operating life of power transformers.


SARS-CoV antibody prevalence in all Hong Kong patient contacts.
A total of 1,068 asymptomatic close contacts of patients with severe acute respiratory (SARS) from the 2003 epidemic in Hong Kong were serologically tested, and 2 (0.19%) were positive for SARS coronavirus immunoglobulin G antibody. SARS rarely manifests as a subclinical infection, and at present, wild animal species are the only important natural reservoirs of the virus.


Future prospects of population-based mammographic screening.
Mammographic screening is one worthwhile way of reducing deaths from breast cancer among women diagnosed in ages 50-69. Our knowledge is less clear for women below 50 and above 70. Major research issues include whether by new approaches we can achieve a definitive mortality reduction in women under 50 and investigations of the efficacy of screening in the elderly. The optimal interval time has yet to be decided. When screening is taken to previously unscreened populations, effects on many parameters have to be followed, e.g., sensitivity, specificity, positive predictive value, gains, and costs. We do not as yet know what the implications of finding large numbers of women with in situ cancer are. Keeping high standards in population-based programs also means fighting potential drawbacks: minimizing the proportion of "unnecessary" biopsies and anxiety, avoiding over-treatment of cancers with excellent prognosis, preventing false reassurance or that women with suspicious findings are left without advice. Potential drawbacks of screening are best dealt with within a team of specialists on breast cancer diagnosis and treatment. Mammographic screening has become widely accepted as one important way of reducing breast cancer deaths, and this success has been dependent on the fact that its development has been science driven. To continue to develop, the tradition of critical evaluation and unsentimental bold testing of new ideas has to be carried on.


Embedded silver ions-containing liposomes in polyelectrolyte multilayers: cargos films for antibacterial agents.
A new antibacterial coating made of poly(L-lysine)/hyaluronic acid (PLL/HA) multilayer films and liposome aggregates loaded with silver ions was designed. Liposomes filled with an AgNO 3 solution were first aggregated by the addition of PLL in solution. The obtained micrometer-sized aggregates were then deposited on a PLL/HA multilayer film, playing the role of a spacer with the support. Finally, HA/PLL/HA capping layers were deposited on top of the architecture to form a composite AgNO 3 coating. Release of encapsulated AgNO 3 from this composite coating was followed and triggered upon temperature increase over the transition temperature of vesicles, found to be equal to 34 degrees C. After determination of the minimal inhibitory concentration (MIC) of AgNO 3 in solution, the antibacterial activity of the AgNO 3 coating was investigated against Escherichia coli. A 4-log reduction in the number of viable E. coli cells was observed after contact for 120 min with a 120 ng/cm (2) AgNO 3 coating. In comparison, no bactericidal activity was found for PLL/HA films previously dipped in an AgNO 3 solution and for PLL/HA films with liposome aggregates containing no AgNO 3 solution. The strong bactericidal effect could be linked to the diffusion of silver ions out of the AgNO 3 coating, leading to an important bactericidal concentration close to the membrane of the bacteria. A simple method to prepare antibacterial coatings loaded with a high and controlled amount of AgNO 3 is therefore proposed. This procedure is far superior to that soaking AgNO 3 or Ag nanoparticles into a coating. In principle, other small bactericidal chemicals like antibiotics could be encapsulated by this method. This study opens a new route to modify surfaces with small solutes that are not permeating phospholipid membranes below the phase transition temperature.


Functional dissection of the proton pumping modules of mitochondrial complex I.
Mitochondrial complex I, the largest and most complicated proton pump of the respiratory chain, links the electron transfer from NADH to ubiquinone to the pumping of four protons from the matrix into the intermembrane space. In humans, defects in complex I are involved in a wide range of degenerative disorders. Recent progress in the X-ray structural analysis of prokaryotic and eukaryotic complex I confirmed that the redox reactions are confined entirely to the hydrophilic peripheral arm of the L-shaped molecule and take place at a remarkable distance from the membrane domain. While this clearly implies that the proton pumping within the membrane arm of complex I is driven indirectly via long-range conformational coupling, the molecular mechanism and the number, identity, and localization of the pump-sites remains unclear. Here, we report that upon deletion of the gene for a small accessory subunit of the Yarrowia complex I, a stable subcomplex (nb8mΔ) is formed that lacks the distal part of the membrane domain as revealed by single particle analysis. The analysis of the subunit composition of holo and subcomplex by three complementary proteomic approaches revealed that two (ND4 and ND5) of the three subunits with homology to bacterial Mrp-type Na(+)/H(+) antiporters that have been discussed as prime candidates for harbouring the proton pumps were missing in nb8mΔ. Nevertheless, nb8mΔ still pumps protons at half the stoichiometry of the complete enzyme. Our results provide evidence that the membrane arm of complex I harbours two functionally distinct pump modules that are connected in series by the long helical transmission element recently identified by X-ray structural analysis.


Differential effects of pandemic (H1N1) 2009 on remote and indigenous groups, Northern Territory, Australia, 2009.
Pandemic (H1N1) 2009 influenza spread through the Northern Territory, Australia, during June-August 2009. We performed 2 cross-sectional serologic surveys on specimens from Northern Territory residents, with 445 specimens obtained prepandemic and 1,689 specimens postpandemic. Antibody titers were determined by hemagglutination inhibition against reference virus A/California/7/2009 on serum samples collected opportunistically from outpatients. All specimens had data for patients' gender, age, and address, with patients' indigenous status determined for 94.1%. Protective immunity (titer >40) was present in 7.6% (95% confidence interval [CI] 5.2%-10.1%) of prepandemic specimens and 19.5% (95% CI 17.6%-21.4%) of postpandemic specimens, giving a population-standardized attack rate of 14.9% (95% CI 11.0%-18.9%). Prepandemic proportion of immune persons was greater with increasing age but did not differ by other demographic characteristics. Postpandemic proportion of immune persons was greater in younger groups and around double in indigenous persons. Postpandemic proportion immune was geographically heterogeneous, particularly among remote-living and indigenous groups.


Body shaping with acoustic wave therapy AWT(®)/EPAT(®): randomized, controlled study on 14 subjects.
Reduction of localised adiposities by non invasive means is a very frequent request among the female and male population. The objective of this study is to demonstrate the efficacy and safety of AWT(®), combining two different mechanical waves, planar AWT and radial AWT during the same session, in volume reduction of saddle bags in women. Treatment was performed on the saddle bag areas of 14 female patients, with the CELLACTOR(®) SC1 (Storz Medical AG, Tägerwilen, Switzerland) using extracorporeal pulse activation technology, EPAT(®). This device includes two handpieces, the C-ACTOR(®) and the D-ACTOR(®). Within 4 weeks, eight AWT(®) treatment sessions have been performed with both applicators. Follow-up visits were performed 1, 4 and 12 weeks after the last treatment. Measurements with the ultrasound system clearly demonstrate a significant diminution in the subcutaneous fat layer thickness and a reduction of the averaged circumference of thighs. This study, although performed on a small number of patients, tends to show the safety and efficacy of AWT(®) in treating localized fat areas in a non-invasive way. There is also an additional benefit for patients in reducing the cellulite appearance and improving the skin firmness at the same time by using AWT(®).


Acute-on-chronic liver failure in a multi-ethnic Asian city: A comparison of patients identified by Asia-Pacific Association for the Study of the Liver and European Association for the Study of the Liver definitions.
To explore the applicability of the Asia-Pacific Association for the Study of the Liver (APASL) and European Association for the Study of the Liver (EASL) guidelines for acute-on-chronic liver failure (ACLF) in profiling patients and determining the outcome. Patients admitted to a tertiary hospital in Singapore with acute decompensation of liver disease from January 2004 to July 2014 are screened for ACLF according to the APASL and EASL criteria. The patients' data (including basic demographics, information about existing chronic liver disease, information about the acute decompensation, relevant laboratory values during admission, treatment, and outcome) are retrospectively analyzed to determine the background, precipitating factors and outcome. A total of 458 liver patients is analyzed, and 78 patients with ACLF are identified. Sixty-three patients (80.8%) meet the APASL criteria, 64 patients (82.1%) meet the EASL criteria, and 49 patients (62.8%) fulfilled both criteria. The most common causes of acute liver injury are bacterial infections (59.0%), hepatitis B flare (29.5%), and variceal bleeding (24.4%). The common aetiologies of the underlying chronic disease included hepatitis B (43.6%), alcoholic (20.5%) and cryptogenic (11.5%) liver disease. The overall mortality rate is 61.5%. Increased age, the number of organ failures (as per CLIF-SOFA score), peak creatinine, INR, and amylase levels are associated with increased mortality or the need for liver transplantation. 14.3% of patients undergo liver transplantation with a 100% 1-year survival rate. Both APASL and EASL criteria have identified ACLF patients with high three-month mortality, but those who fulfill APASL criteria alone have a better survival.


Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization.
The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.


Localized Hypertrichosis Following Vaccination in an Infant.
Hypertrichosis is characterized by increased hair growth independent of androgen excess. There are various causes of acquired localized hypertrichosis including chronic irritation and inflammation. Localised hypertrichosis following pentavalent vaccine has not been described previously in Indian literature. We hereby report a case of a 4-month-old healthy infant presenting with focal circumscribed areas of hypertrichosis over anterolateral aspect of bilateral thighs at the site of vaccination.


Predicting scores of the Halstead Category Test with the WAIS-III.
The Halstead Category Test (HCT) and the Wechsler Adult Intelligence Scale (WAIS) are two of the most widely used neuropsychological tests. Often assessment conclusions are dependent upon the comparison of these measures. Therefore, it is crucial for clinicians to know how they relate to one another. This study examined the relationship between the HCT and the WAIS-III with undergraduate psychology students. Correlational analyses were conducted between HCT scores and WAIS-III subtests, Verbal and Performance IQ, and Full Scale IQ scores. Additionally, the new WAIS-III scales (Letter-Number Sequencing, Matrix Reasoning, and Symbol Search) were further examined. Regression analyses were run to develop predictor equations for the HCT using VIQ, PIQ, and FSIQ. Finally, predictor tables were generated between the HCT and VIQ, PIQ, and FSIQ to provide assessment of brain dysfunction for clinical use.


Evaluation of pseudoseizures. A psychiatric perspective.
Two subgroups of patients with psychogenic pseudoseizures were identified among 20 neurology patients referred for consultation to rule out pseudoseizures. Patients with pseudo complex partial seizures were found to have primarily dissociative symptoms with guilt-laden bereavement as an important precursor. Patients with pseudo grand mal type seizures appeared to have developed their illness in the context of longstanding personality traits. Diagnostic and prognostic implications of these findings are discussed.


Suppressed patterns alter vision during binocular rivalry.
Binocular rivalry occurs when incongruent patterns are presented to corresponding regions of the retinas, leading to fluctuations of awareness between the patterns . One attribute of a stimulus may rival whereas another may combine between the eyes , but it is typically assumed that the dominant features are perceived veridically. Here, we show this is not necessarily the case and that a suppressed visual feature can alter dominant perception. The cortical representations of oriented gratings can interact even when one of them is perceptually suppressed, such that the perceived orientation of the dominant grating is systematically biased depending on the orientation of the suppressed grating. A suppressed inducing pattern has the same qualitative effect as a visible one, but suppression reduces effective contrast by a factor of around six. A simple neural model quantifies and helps explain these illusions. These results demonstrate that binocular rivalry suppression operates in a graded fashion across multiple sites in the visual hierarchy rather than truncating processing at a single site and that suppressed visual information can alter dominant vision in real-time.


Assessing clinical significance of apnea exceeding fifteen seconds with event recording.
Using event recording, we determined how often apnea exceeding 15 seconds in duration was associated with bradycardia and how often patients with apnea resumed breathing spontaneously. Of 1306 documented apnea events exceeding 15 seconds (54 patients), 926 lasted 16 to 20 seconds, 262 lasted 21 to 25 seconds, and 118 exceeded 25 seconds. Of these episodes, 75.3% were isolated and 14.9% were associated with pulse deceleration, 4.4% with irregular transthoracic impedance, and 5.4% with bradycardia. Event recording provided data supporting discontinuation of monitoring in 50 of 54 patients: 36 spontaneously resumed breathing before the auditory alarm and 14 had a decreased incidence of apnea with maturation. Follow-up of 51 patients (three not located) showed that none had subsequent apparent life-threatening events or sudden infant death syndrome. Our results in these older infants and children (median age 6.7 months) provide substantiation that such patients with apnea of less than 20 seconds without bradycardia do not require continued monitoring. Further, these data suggest that in selected older infants, longer isolated apnea may be well tolerated; however, hemoglobin saturation during sleep and the ability to resume breathing after the apnea alarm delay is prolonged should be verified. Our patient population had a wide age range and heterogeneity of diagnoses, and was typically free of symptoms, so these results should not be extrapolated uncritically to premature infants, infants with chronic lung disease, and patients with symptomatic apnea.


Calcium differentially alters behavioral and electrophysiological responses to ethanol in selectively bred mouse lines.
Sensitivity to the hypnotic action of ethanol has been found to increase in SS/Ibg (SS) but not in LS/Ibg (LS) mice after intracerebroventricular (icv) administration of calcium. In the present investigation, a correlation was found between calcium-induced changes in behavioral sensitivity and in the sensitivity of cerebellar Purkinje neurons to the depressant effects of locally applied ethanol. Cerebellar Purkinje neuron sensitivity was measured as the dose of ethanol pressure ejected from a multibarreled micropipette required to produce a 50% depression of spontaneous firing rate of single neurons. Administration of 0.2-0.4 mumol calcium chloride into the lateral ventricle of the brain increased the sensitivity of SS but not LS mice to the hypnotic behavioral effect of systemically administered ethanol. Similarly, Purkinje neuron sensitivity to locally applied ethanol was also enhanced in SS but not in LS mice 15 min following administration of calcium (0.25 mumol) icv. Furthermore, locally applied ethanol was more effective in depressing spontaneous Purkinje neuron discharge in SS mice when a 1 mM calcium solution was concomitantly pressure ejected with ethanol from the micropipette. Magnesium chloride did not mimic the effects of calcium on either behavioral or electrophysiological effects of ethanol, suggesting that the action of calcium is not a nonspecific effect of divalent cations. These data suggest that calcium-dependent processes may be involved in behavioral and electrophysiological effects associated with ethanol intoxication. Further research will be required to determine if the genetically selected difference in ethanol sensitivity expressed in LS and SS mice is regulated by calcium mechanisms.


Pharmacological inhibition of Akt and downstream pathways modulates the expression of COX-2 and mPGES-1 in activated microglia.
Microglia are considered a major target for modulating neuroinflammatory and neurodegenerative disease processes. Upon activation, microglia secrete inflammatory mediators that contribute to the resolution or to further enhancement of damage in the central nervous system (CNS). Therefore, it is important to study the intracellular pathways that are involved in the expression of the inflammatory mediators. Particularly, the role of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and glycogen synthase kinase-3 (GSK-3) pathways in activated microglia is unclear. Thus, in the present study we investigated the role of Akt and its downstream pathways, GSK-3 and mTOR, in lipopolysaccharide (LPS)-activated primary rat microglia by pharmacological inhibition of these pathways in regard to the expression of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1) and to the production of prostaglandin (PG) E2 and PGD2. We show that inhibition of Akt by the Akt inhibitor X enhanced the production of PGE2 and PGD2 without affecting the expression of COX-2, mPGES-1, mPGES-2 and cytosolic prostaglandin E synthase (cPGES). Moreover, inhibition of GSK-3 reduced the expression of both COX-2 and mPGES-1. In contrast, the mTOR inhibitor rapamycin enhanced both COX-2 and mPGES-1 immunoreactivity and the release of PGE2 and PGD2. Interestingly, NVP-BEZ235, a dual PI3K/mTOR inhibitor, enhanced COX-2 and reduced mPGES-1 immunoreactivity, albeit PGE2 and PGD2 levels were enhanced in LPS-stimulated microglia. However, this compound also increased PGE2 in non-stimulated microglia. Taken together, we demonstrate that blockade of mTOR and/or PI3K/Akt enhances prostanoid production and that PI3K/Akt, GSK-3 and mTOR differently regulate the expression of mPGES-1 and COX-2 in activated primary microglia. Therefore, these pathways are potential targets for the development of novel strategies to modulate neuroinflammation.


Toward a core nutraceutical program for cancer management.
As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroombeta-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, beta-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and beta-hydroxy-beta-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-B activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.


Short-term outcomes following intrauterine transfusion in Scotland.
To describe neonatal outcomes following intrauterine transfusion (IUT) for severe Rhesus isoimmunisation from 1993 to 2004. 116 neonates who had undergone 457 IUTs (median 4, range 1-9) were identified. Three neonates died, all before 1995 (two because of hypoxic ischaemic multiorgan failure and one because of overwhelming Escherichia coli sepsis). 13 neonates (11%) were delivered by emergency Caesarean section following either IUT complication or spontaneous onset of preterm labour. They were more likely to require intubation (p<0.0001), on-going respiratory support (p=0.0007) and an exchange transfusion (p=0.007). 23 (20%) required an exchange transfusion and 63 (54%) at least one top-up transfusion. Management of severe Rhesus disease is associated with encouraging neonatal outcomes and most infants can be managed with phototherapy and a few top-up transfusions. IUT complications are rare but significantly increase neonatal mortality and morbidity. Antenatal counselling should address the likely postnatal course for these infants.


Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer.
Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression. The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was potently cytotoxic to cancer cells highly expressing GPC1. There were no inhibitory effects on cancer cells with low expression of GPC1. In a murine xenograft model, GPC1-ADC also had significant and potent tumor growth inhibition. GPC1-ADC-mediated G2/M phase cell cycle arrest was detected, indicating that the dominant antitumor effect in vivo was MMAF-mediated. The toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our data showed that GPC1-ADC has potential as a promising therapy for uterine cervical cancer.


Three-Dimensional Microstructure of ε-Fe2O3 Crystals in Ancient Chinese Sauce Glaze Porcelain Revealed by Focused Ion Beam Scanning Electron Microscopy.
Ancient Chinese sauce glaze porcelain has recently received growing attention for the discovery of epsilon iron oxide (ε-Fe2O3) crystals in glaze. In this work, we first confirm the presence of ε-Fe2O3 microcrystals, in large quantiteis, in sauce glaze porcelain fired at the Qilizhen kiln in Jiangxi province during the Southern Song dynasty. We then employed focused ion beam scanning electron microscopy (FIB-SEM) to investigate the three-dimensional microstructure of ε-Fe2O3 microcrystals, which revealed three well-separated layers (labeled, respectively, as LY1, LY2, and LY3 from the glaze surface to inside) under the glaze surface. Specifically, LY1 consists of well-defined dendritic fractal structure with high ordered branches at micrometers scale, LY2 has spherical or irregular-shaped particles at nanometers scale, while LY3 consists of dendrites with four, six, or eight primary branches ranging from several nanometers to around 1 μm. Given these findings, we proposed a process for the possible growth of ε-Fe2O3 microcrystals in ancient Chinese sauce glaze.


Crassicaudiasis in three geographically and chronologically distant Cuvier's beaked whales (Ziphius cavirostris) stranded off Brazil.
The Cuvier's beaked whale (CBW; Ziphius cavirostris) is a cosmopolitan marine mammal found in deep tropical and temperate waters of all oceans. CBW strandings have been recorded sporadically in Brazil; however, there is lack of information available regarding their causes of stranding and/or death. Herein, we report the epidemiologic, pathologic, morphologic parasitologic features and molecular identification of arterial and renal crassicaudiasis by Crassicauda sp. in three geographically and chronologically distant CBW stranded off Brazil. CBW-1 was an adult male stranded dead in Rio Grande do Sul State. CBW-2 was an adult female that stranded alive in Sergipe State and died shortly after. CBW-3 was and adult male that stranded dead in Santa Catarina State. The most relevant pathologic findings in these three CBW were severe, chronic proliferative mesenteric and caudal aortic endarteritis and chronic granulomatous and fibrosing interstitial nephritis with renicular atrophy and loss, and numerous intralesional Crassicauda sp. nematodes. Furthermore, CBW-1 had concomitant gram-negative bacterial pneumonia and pulmonary and hepatic thromboembolism. Morphologic analysis of renal adult nematodes identified Crassicauda sp. in the three CBW. Molecular analyses targeting the 18S and ITS-2 ribosomal loci of renal nematodes in CBW-2 and CBW-3 identified C. anthonyi. It is believed that severe arterial and renal crassicaudiasis likely resulted or contributed significantly to morbidity and death of these animals. These results expand the known geographical range of occurrence of crassicaudiasis in CBW. Specifically, the present study provides the first accounts of arterial and renal crassicaudiasis in CBW off the southern hemisphere, specifically in CBW off Brazil, and to the authors' knowledge, it is the first record of C. anthonyi in the southern Atlantic Ocean.


Reunifying families, cutting costs: housing-child welfare partnerships for permanent supportive housing.
In the absence of an adequate supply of affordable, quality housing, child welfare agencies are placed in the unenviable position of separating families to protect children from the debilitating effects of homelessness. This article presents recommendations for costeffective housing-child welfare partnerships that will shift the burden of providing adequate housing back to housing agencies. These partnerships have the potential to move child welfare agencies closer to achieving permanence and well-being for all children.


[A comparative study of 4 diagnostic strategies in coronary artery disease. A theoretical approach].
The prognosis of patients with coronary artery disease is constantly improving mainly due to better control of risk factors, to improved methods of myocardial revascularisation and better follow-up. For effective management, the diagnosis of coronary disease has to be established. The authors used a statistical model to study the efficacy of 4 diagnostic strategies used in daily practice: (i) three investigations in two stages: exercise stress testing, stress echocardiography or stress scintigraphy followed by coronary angiography when positive (EE, ECHO, SCINTI): (ii) one stage investigation: coronary angiography of first indication (CORO). When the a priori probability is low or moderate (less than 0.5) the efficacy of EE, ECHO and SCINTI is excellent as there are few false negative results. When the a priori probability of coronary disease is high (0.7 or more), the percentage of false negative results (patients with undetected significant coronary disease) becomes very high. At this level of risk the CORO strategy avoids the false negatives without increasing the costs with respect to the other strategies. In conclusion, the choice of diagnostic strategy of coronary artery disease should take into account the "a priori" risk of the patient. When high (> 0.7), coronary angiography of first intention seems to be statistically justified.


Roles of cutaneous versus spinal TRPA1 channels in mechanical hypersensitivity in the diabetic or mustard oil-treated non-diabetic rat.
Previous results indicate that intaperitoneal administration of a TRPA1 channel antagonist attenuates diabetic hypersensitivity. We studied whether the antihypersensitivity effect induced by a TRPA1 channel antagonist in diabetic animals is explained by action on the TRPA1 channel in the skin, the spinal cord, or both. For comparison, we determined the contribution of cutaneous and spinal TRPA1 channels to development of hypersensitivity induced by topical administration of mustard oil in healthy controls. Diabetes mellitus was induced by streptozotocin in the rat. Hypersensitivity was assessed by the monofilament- and paw pressure-induced limb withdrawal response. Intrathecal (i.t.) administration of Chembridge-5861528 (CHEM, a TRPA1 channel antagonist) at doses 2.5-5.0 microg/rat markedly attenuated diabetic hypersensitivity, whereas 20 microg of CHEM was needed to produce a weak attenuation of diabetic hypersensitivity with intraplantar (i.pl.) administrations. In controls, i.pl. administration of CHEM (20 microg) produced a weak antihypersensitivity effect at the mustard oil-treated site. I.t. administration of CHEM (10 microg) in controls produced a strong antihypersensitivity effect adjacent to the mustard oil-treated area (site of secondary hyperalgesia), while it failed to influence hypersensitivity at the mustard oil-treated area (site of primary hyperalgesia). A reversible antagonism of the rat TRPA1 channel by CHEM was verified using in vitro patch clamp recordings. The results suggest that while cutaneous TRPA1 channels contribute to mechanical hypersensitivity induced by diabetes or topical mustard oil, spinal TRPA1 channels, probably on central terminals of primary afferent nerve fibers, play an important role in maintenance of mechanical hypersensitivity in these conditions.


Should a borderline negative HER2 result in a core biopsy of invasive carcinoma of the breast have HER2 assessment repeated in the excision specimen?
The 2015 UK guidelines for HER2 assessment in breast cancer recommended repeat assessment if the core biopsy was scored as 2+ on HER2 immunohistochemistry (IHC) with borderline negative in situ hybridisation (ratio of number of HER2 to chromosome 17 centromere copies of 1.8-1.99). This case series aimed to assess the value of such repeat assessment in the surgical specimen, in particular the proportion that were HER2 positive. Details of biopsies with 2+ IHC and borderline negative in situ hybridisation were extracted from a database. The results of repeat HER2 testing in the surgical specimen for this cohort study were then obtained. 112 patients with no preoperative treatment had repeat assessment: 4 were 3+ and 16 were 2+ amplified. Of 14 with preoperative chemotherapy, 1 was 3+ and 4 were 2+ amplified. All the 2+ amplified carcinomas had a HER2 to chromosome 17 ratio less than 4, in 50% the ratio was between 2.0 and 2.2, and in 50% the HER2 copy number was less than 4. Repeat assessment yielded 4% 3+ results and 14% 2+ amplified carcinomas but with low level amplification. These results suggest that retesting of borderline negative HER2 cases should be optional and no longer mandatory.


Freezing injuries in the embryos of Piaractus mesopotamicus.
Cryopreservation of mammal embryos has been technically feasible for many years, but morphological injuries still persist in fish embryos during cryopreservation. Thus, the objective of the present study was to describe these freezing injuries in Piaractus mesopotamicus embryos. Two hundred and twenty-five embryos were collected at the post-gastrula stage and assigned into four treatments of sucrose at 8.5, 17.0, 25.0 or 34.0% plus 9.0% methanol. The control was prepared with distilled water only. The gradual decrease in the temperature was 0.5°C/min. After the seeding stage, the fish embryos were stored in liquid nitrogen at -33°C. Thereafter, they were thawed for evaluating per cent hatching, and the samples collected from every treatment were submitted to scanning electron microscopy for morphological analysis. The micrographic images showed that there was substantial alterations in embryo morphology under the highest concentrations of sucrose. These solutions did not prevent the formation of ice crystals, which lead to deformities and killed the embryos, but the observed reduced level of morphological structure in these embryos when treated with 17.0% sucrose plus 9.0% methanol is a compelling argument for additional studies.


Insect photoreceptor adaptations to night vision.
Night vision is ultimately about extracting information from a noisy visual input. Several species of nocturnal insects exhibit complex visually guided behaviour in conditions where most animals are practically blind. The compound eyes of nocturnal insects produce strong responses to single photons and process them into meaningful neural signals, which are amplified by specialized neuroanatomical structures. While a lot is known about the light responses and the anatomical structures that promote pooling of responses to increase sensitivity, there is still a dearth of knowledge on the physiology of night vision. Retinal photoreceptors form the first bottleneck for the transfer of visual information. In this review, we cover the basics of what is known about physiological adaptations of insect photoreceptors for low-light vision. We will also discuss major enigmas of some of the functional properties of nocturnal photoreceptors, and describe recent advances in methodologies that may help to solve them and broaden the field of insect vision research to new model animals.This article is part of the themed issue 'Vision in dim light'.


Physiological Changes of Parachlorella Kessleri TY02 in Lipid Accumulation under Nitrogen Stress.
In order to study the effects of nitrogen stress on the lipid synthesis of Parachlorella kessleri TY02 and to understand the changes in growth, photosynthetic pigments, total protein and total carbohydrate contents during lipid accumulation, the cells of the strain were cultured in nitrogen-deficient (N-) and nitrogen-rich (N⁺) media for one week. Changes in cell growth, chlorophyll content, chlorophyll fluorescence parameters, neutral lipid and total lipid content, total protein content and total carbohydrate content were measured and analyzed. The results showed that, under nitrogen stress, the algal strain grew slowly, and chlorophyll and total protein contents decreased, while total carbohydrate and total lipid contents increased. This indicated that, under nitrogen stress, most of the carbon flowed to the synthesis of lipids and carbohydrates. Meanwhile, reducing the nitrogen content was a relatively economical and easy to operate method of promoting lipid accumulation.


Maternal obesity and fetal programming: effects of a high-carbohydrate nutritional modification in the immediate postnatal life of female rats.
Our earlier studies have shown that the artificial rearing of newborn rat pups [first generation high carbohydrate (1-HC)] on an HC milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Offspring [second-generation HC (2-HC)] of 1-HC female rats spontaneously acquired the HC phenotype in the postweaning period. In this study, we have characterized the development of the abnormal intrauterine environment in the 1-HC female rats and the effects on fetal development under such pregnancy conditions for the offspring. 1-HC female rats demonstrated hyperphagia on laboratory chow and increased body weight gain beginning from the immediate postweaning period along with hyperinsulinemia and hyperleptinemia. During pregnancy, 1-HC female rats showed several metabolic alterations including increased body weight gain and increased plasma levels of insulin, leptin, proinflammatory markers, and lipid peroxidation products. Although there were no significant changes in the body weights or litter size of term 2-HC fetuses, the plasma levels of insulin and leptin were significantly higher compared with those of control term fetuses. Quantitation of mRNA levels by real-time RT-PCR indicated significant increases in the mRNA levels of orexigenic neuropeptides in the hypothalamus of 2-HC term fetuses. Collectively, these results indicate that the HC diet in infancy results in an adverse pregnancy condition in female rats with deleterious consequences for the offspring.


Tuning Physical Crosslinks in Hybrid Hydrogels for Network Structure Analysis and Mechanical Reinforcement.
Hydrogels with high mechanical strength are needed for a variety of industrial applications. Here, a series of hydrogels was prepared by introducing hybrid particles as hydrophobic association points to toughen the hydrogels. These toughened hydrogels were able to transfer an external mechanical force via the reorganization of the crosslinking networks. They exhibited an extraordinary mechanical performance, which was the result of the coordination between hydrophobic segments and hybrid particles. Herein, the connection between the dissipated energy of the inner distribution structure (on a small scale) and the mechanical properties (on a large scale) was conducted. Specifically, we inspected hydrogels of latex particles (LPs) with different chain lengths (C4, C12, C18) and studied their inner structural parameters, namely, the relationship between the density and molecular weight of crosslinking points to the mechanical strength and energy dissipation. Favorable traits of the hydrogels included compact internal structures that were basically free from defects and external structures with puncture resistance, high toughness, etc. Based on the experimental results that agreed with the theoretical results, this study provides a profound understanding of the internal structure of hydrogels, and it offers a new idea for the design of high-strength hybrid hydrogels.


Characterization of protein in old myocardial infarction by FTIR micro-spectroscopy.
The aim of the present study was to assess whether Fourier transform infrared spectrometry (FTIR) micro-spectroscopy could produce distinct spectral information on protein of old myocardial infarction (OMI) and to set them as molecular markers to diagnose atypical OMI. Paraffin-embedded heart samples were derived from victims dying of OMI. In combination with histological stain, FTIR and infrared micro-spectroscopy, the characteristics of OMI were analyzed morphologically and molecularly. The most relevant bands identified were the amide A, B, I and, II showing crucial spectral differences between apparent normal region and OMI region, including the peak position blue shift and the increased intensity of OMI, moreover relative increase in alpha-helix and decrease in beta-sheet of protein secondary structures in OMI. Comparing to single spectral band, the I1650/I1550 ratio was increased and rationally used as a molecular marker for diagnosing OMI. These novel preliminary findings supported further exploration of FTIR molecular profiling in clinical or forensic study, and were in accordance with histopathology.


Functional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation cascade from an uncultured archaeon.
The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. Although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. Encoded in operons, these components are likely representative of the progenitor apparatus that founded the modern eukaryotic ubiquitin modification systems. Here we report that these proteins from the archaeon Candidatus 'Caldiarchaeum subterraneum' operate together as a bona fide ubiquitin modification system, mediating a sequential ubiquitylation cascade reminiscent of the eukaryotic process. Our observations support the hypothesis that complex eukaryotic ubiquitylation signalling pathways have developed from compact systems originally inherited from an archaeal ancestor.


Breed-specific values for vertebral heart score (VHS), vertebral left atrial size (VLAS), and radiographic left atrial dimension (RLAD) in pugs without cardiac disease, and their relationship to Brachycephalic Obstructive Airway Syndrome (BOAS).
This prospective study aims to establish reference ranges for vertebral heart score (VHS), vertebral left atrial size (VLAS), and radiographic left atrial dimension (RLAD) in pugs. The impact of clinical severity of Brachycephalic Obstructive Airway Syndrome (BOAS), gender, body condition score, and body weight on VHS, VLAS, and RLAD were investigated. Intra- and interobserver correlation was determined. Correlation of radiographic scores to echocardiographic left atrial dimension was inspected. Additionally, for VLAS and RLAD, correlation to VHS was examined. Additionally, an assessment of thoracic and vertebral malformations was performed. Forty-seven privately owned pugs underwent physical examination, echocardiography, and thoracic radiography to determine cardiac health. Thirty-two pugs were eligible for establishing reference ranges for VHS in right lateral radiographs, which was 11.25 ± 0.62 (95% range, 10.1-12.8). Reference ranges for VHS in left lateral, and for VLAS and RLAD in right lateral radiograph were determined in 30 pugs. The VHS in left lateral radiograph was 11.01 ± 0.70 (95% range, 9.4-12.6), VLAS was 1.96 ± 0.38 (95% range, 1.1-2.8), and RLAD was 1.59 ± 0.34 (95% range, 0.7-2.4). Clinical severity of BOAS did not show any impact on radiographic measurements. For VLAS, a significant correlation to VHS was detected by all observers. No other variables had a consistent influence on the radiographic scores given by all observers. Interobserver agreement was almost perfect for VHS (0.89 on right lateral and 0.91 on left lateral image), moderate for VLAS (0.49), and fair for RLAD (0.22). More than one third of the entire study population (18 of 47 pugs) showed at least one thoracic cavity or spine abnormality, often leading to considerable changes in vertebral body shape and size.


Crushed sunflower, flax, or canola seeds in lactating dairy cow diets: effects on methane production, rumen fermentation, and milk production.
The objective of this study was to investigate the potential of reducing enteric methane production from dairy cows by incorporating into the diet various sources of long-chain FA varying in their degree of saturation and ruminal availability. The experiment was conducted as a crossover design with 16 lactating dairy cows maintained in 2 groups and fed 4 dietary treatments in four 28-d periods. Eight ruminally cannulated primiparous cows (96 +/- 18 d in milk) were assigned to group 1 and 8 multiparous cows (130 +/- 31 d in milk) were assigned to group 2. The dietary treatments were: 1) a commercial source of calcium salts of long-chain fatty acids (CTL), 2) crushed sunflower seeds (SS), 3) crushed flaxseed (FS), and 4) crushed canola seed (CS). The oilseeds added 3.1 to 4.2% fat to the diet (DM basis). All 3 oilseed treatments decreased methane production (g/d) by an average of 13%. When corrected for differences in dry matter intake (DMI), compared with CTL, methane production (g/kg of DM intake) was decreased by feeding FS (-18%) or CS (-16%) and was only numerically decreased (-10%) by feeding SS. However, compared with the CTL, feeding SS or FS lowered digestible DMI by 16 and 9%, respectively, because of lowered digestibility. Thus, only CS lowered methane per unit of digestible DM intake. Feeding SS and CS decreased rumen protozoal counts, but there were no treatment effects on mean ruminal pH or total volatile fatty acid concentration. Milk efficiency (3.5% fat corrected milk/DMI), milk yield, and component yield and concentrations were not affected by oilseed treatments. The study shows that adding sources of long-chain fatty acids to the diet in the form of processed oilseeds can be an effective means of reducing methane emissions. However, for some oilseeds such as SS or FS, the reduction in methane can be at the expense of diet digestibility. The use of crushed CS offers a means of mitigating methane without negatively affecting diet digestibility, and hence, milk production.


Reversal of age-associated oxidative stress in mice by PFT, a novel kefir product.
Oxidative stress is a key contributor to aging and age-related diseases. In the present study, we examine the protective effects of PFT, a novel kefir product, against age-associated oxidative stress using aged (10-month-old) mice. Mice were treated with PFT orally at a daily dose of 2 mg/kg body weight over 6 weeks, and antioxidant status, protein oxidation, and lipid peroxidation were studied in the brain, liver, and blood. PFT supplementation significantly reduced the oxidative stress biomarkers malondialdehyde (MDA) and nitric oxide; reversed the reductions in glutathione (GSH) levels, total antioxidant capacity (TAC), and anti-hydroxyl radical (AHR) content; enhanced the antioxidant enzyme activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD); inhibited the liver enzyme levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT); significantly reduced triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL) levels; and significantly elevated high density lipoprotein (HDL) levels. Interestingly, PFT supplementation reversed the oxidative changes associated with aging, thus bringing levels to within the limits of the young control mice in the brain, liver, and blood. We also note that PFT affects the redox homeostasis of young mice and that it is corrected post-treatment with PFT. Our findings show the effectiveness of dietary PFT supplementation in modulating age-associated oxidative stress in mice and motivate further studies of PFT's effects in reducing age-associated disorders where free radicals and oxidative stress are the major cause.


Ammonium Polyphosphate Intercalated Layered Double Hydroxide and Zinc Borate as Highly Efficient Flame Retardant Nanofillers for Polypropylene.
We found in our previous study that layered double hydroxides (LDHs) which undergo aqueous miscible organic solvent treatment (AMOST) can tune the hydrophobicity surface of LDHs to be hydrophobic, and then the solvent mixing method can be used to prepare polymer/LDH nanocomposites. However, flame retardant property is not very high if LDHs are only used. In this present work, ammonium polyphosphate (APP) intercalated LDHs and zinc borate (ZB) was incorporated into a polypropylene (PP) matrix using the solvent mixing method. The structures, morphologies, and performance of the composites were characterized carefully. The peak heat release rate (PHRR) reduction of PP containing 10 and 20 wt % APP-LDH reached 27% and 55%, respectively, which increased up to 63% compared with PP/CO₃-LDH. After incorporating 2 wt % ZB in the PP/APP-LDH system, the flame retardant property was further improved. Polypropylene composites with 20 wt % APP-LDH and 2 wt % ZB showed a 58% PHRR reduction. In addition, thermogravimetric analyzer (TGA) results indicated that the addition of APP-LDH and ZB improved the temperature at 50% weight loss (T50%) and the char formation of the materials significantly.


Role of genetic polymorphisms in ACE and TNF-alpha gene in sarcoidosis: a meta-analysis.
A great number of association studies have been performed to identify the genes involved in the etiology and prognosis of sarcoidosis. We performed a systematic review of case-control studies through the PubMed database and evaluated them for a possible inclusion into a meta-analysis in order to assess whether the reported genetic polymorphisms are the risk factors of sarcoidosis. Case-control studies with clear diagnostic criteria and interventions were included. Only investigations of a single polymorphism/gene involvement in sarcoidosis reported more than five times were selected. Aggregating data from 12 studies on ID/ACE polymorphisms, the odds ratio (OR) for sarcoidosis, if the polymorphism was considered under the dominant genetic model, was not significantly increased: 1.19 (95% CI 0.98-1.43); OR under the recessive model was 1.20 (95% CI 0.98-1.46). In seven case-control studies on -308/TNF-alpha polymorphism, the OR for sarcoidosis if the polymorphism considered under the dominant genetic model was significantly increased at 1.47 (95% CI 1.03-2.08); the OR under the recessive model was 1.39 (95% CI 0.67-2.90). In conclusion, the results showed that the TNF-alpha genotype could be a significant risk factor for sarcoidosis, whereas the risk of sarcoidosis due to the ACE genotype was not substantially elevated.


Two-Dimensional Gold Halides: Novel Semiconductors with Giant Spin-Orbit Splitting and Tunable Optoelectronic Properties.
We introduce a new family of 2D materials with unique structure and optoelectronic properties, namely, single-layer gold(I) halides (AuHals). We propose their stability as well as structural, electronic, and optical properties using first-principles calculations. The cleavage energy is found to be similar to that of graphene from graphite, indicating the possibility for mechanical exfoliation. We show that AuHals are stable and have tunable direct (AuBr) and indirect (AuI) band gaps depending on the number of layers. We discuss the possible origin of the giant spin-orbit coupling (SOC) induced conduction band splitting in terms of orbital-decomposed band structure to guide future investigations on the design of materials with highly effective SOC. Exceptionally high excitonic binding energy, high hole mobility, and tunable band gaps indicate that AuHals are promising candidates for optoelectronic devices with excellent performance.


A population-based analysis of health behaviours, chronic diseases and associated costs.
Health behaviours influence the future incidence of certain common chronic diseases and thus have an impact on health status and utilization of health care services and costs. We analyzed person-level data of the Albertan adult population from the Canadian Community Health Survey, Cycle 1.1 (2000) to determine health care costs associated with specific health behaviours (smoking, sub-optimal diet, physical inactivity) and chronic disease states (heart disease, diabetes, COPD). We found that 74.7 percent of the population exhibited one or more risk behaviours, while 10.5 percent had one or more of the chronic diseases of interest. Greater health care utilization and costs were noted in groups exhibiting risk behaviour and chronic disease states. Approximately 31 percent of health care costs in Alberta were attributable to people having one or more of the three chronic diseases. Our findings of higher health care costs incurred by those exhibiting unhealthy behaviour prior to development of disease, as well as by those with multiple co-existent diseases, are important indicators to guide future prevention and treatment strategies of chronic illness.


Risk and Protective Factors for Postoperative Complications in Elderly Patients With Colorectal Cancer.
This study aimed to evaluate perioperative factors, including nutritional status and sarcopenia on short-term postoperative complications, determine the risk factors for postoperative complications, and clarify potential preoperative interventions and optimal surgical procedures to improve short-term outcomes in elderly patients with colorectal cancer (CRC). This retrospective, single-centre cohort study analysed the factors and short-term postoperative complications of CRC in a cohort of 101 patients aged ≥80 years who underwent radical resection between 2013 and 2020. Nutritional status was evaluated by calculating the controlling nutritional status. The median age was 83 years, and the frequency of sarcopenia was 39.6%. Short-term postoperative complications occurred in 24 patients. Risk factors for short-term postoperative complications in multivariate analysis were sarcopenia combined with nutritional disorders and open surgical approach. The status of nutrition and sarcopenia must be considered in order to predict and improve postoperative outcomes. If possible, a laparoscopic approach should be selected to prevent poor postoperative outcomes.


Highly efficient near-infrared-emitting lanthanide(III) complexes formed by heterogeneous self-assembly of Ag(I), Ln(III), and thiacalix[4]arene-p-tetrasulfonate in aqueous solution (Ln(III) = Nd(III), Yb(III)).
Heterogeneous self-assembly of thiacalix[4]arene-p-tetrasulfonate (TCAS), Ag(I), and Ln(III) (= Nd(III), Yb(III)) in aqueous solutions conveniently afforded ternary complexes emitting Ln(III)-centered luminescence in the near-infrared (NIR) region. A solution-state study revealed that the Ag(I)-Nd(III)-TCAS system gave a complex Ag(I)(4)·Nd(III)·TCAS(2) in a wide pH range of 6-12. In contrast, the Ag(I)-Yb(III)-TCAS system gave Ag(I)(2)·Yb(III)(2)·TCAS(2) at a pH of around 6 and Ag(I)(2)·Yb(III)·TCAS(2) at a pH of approximately 9.5. The structures of the Yb(III) complexes were proposed based on comparison with known Ag(I)-Tb(III)-TCAS complexes that show the same self-assembly behavior. In Ag(I)(2)·Yb(III)(2)·TCAS(2), two TCAS ligands sandwiched a cyclic array of a Ag(I)-Ag(I)-Yb(III)-Yb(III) core. In Ag(I)(2)·Yb(III)·TCAS(2), Yb(III) was accommodated in an O(8) cube consisting of eight phenolate O(-) groups from two TCAS ligands linked by two S-Ag-S linkages. Crystallographic analysis of Ag(I)(4)·Nd(III)·TCAS(2) revealed that the structure was similar to Ag(I)(2)·Yb(III)·TCAS(2) but that it had four instead of two S-Ag-S linkages. The number of water molecules coordinating to Ln(III) (q) estimated on the basis of the luminescent lifetimes was as follows: Ag(I)(4)·Nd(III)·TCAS(2), 0; Ag(I)(2)·Yb(III)(2)·TCAS(2), 2.4; and Ag(I)(2)·Yb(III)·TCAS(2), 0. These findings were compatible with the solution-state structures. The luminescent quantum yield (Φ) for Ag(I)(4)·Nd(III)·TCAS(2) was 4.9 × 10(-4), which is the second largest value ever reported in H(2)O. These findings suggest that the O(8) cube is an ideal environment to circumvent deactivation via O-H oscillation of coordinating water. The Φ values for Ag(I)(2)·Yb(III)(2)·TCAS(2) and Ag(I)(2)·Yb(III)·TCAS(2) were found to be 3.8 × 10(-4) and 3.3 × 10(-3), respectively, reflecting the q value. Overall, these results indicate that the ternary systems have the potential for a noncovalent strategy via self-assembly of the multidentate ligand, Ln(III), and an auxiliary metal ion to obtain a highly efficient NIR-emissive Ln(III) complex that usually relies on elaborate covalent linkage of a chromophore and multidentate ligands to expel coordinating water.


Source of cigarettes among youth smokers in Malaysia: Findings from the tobacco and e-cigarette survey among Malaysian school adolescents (TECMA).
Understanding how and where youth obtain tobacco products are major factors in the development of suitable intervention programs to reduce youth smoking. This study aimed to determine the source of cigarettes and the associated factors among Malaysian school adolescent smokers. Our sample consisted of 1348 youth aged 10-17 years who were current smokers (having smoked at least once in the last 30 days). The source of cigarettes (commercial, over-the-counter purchases; or social, borrowing or obtaining from someone else) was the dependent variable, and multivariable logistic regression was employed to determine its association with independent variables (i.e. sociodemographics, smoking behavior, and knowledge of laws prohibiting sales of cigarettes to youth). Over half (54.3%) of current smokers obtained cigarettes from commercial sources, with a proportion nearly two times higher (84.2% vs 43.7%) among frequent smokers (i.e. those smoking more than 20 days per month) compared to less-frequent smokers, and among young males (56.5% vs 32.0%) compared young females. Multivariable logistic regression indicated that in urban areas, young females (AOR=12.5, 95% CI: 1.38-99.8) frequent smokers (AOR=4.41, 95% CI: 2.05-9.46), and those studying in lower (AOR=3.76, 95% CI: 1.41-10.02) and upper secondary (AOR=4.74, 95% CI: 1.72-13.06) school students were more likely to obtain cigarettes from a commercial source. On the other hand, in rural areas, only frequent smokers were more likely to get their cigarettes from commercial sources, whilst other variables were not significant. The proportion of youth smokers who obtained cigarettes from commercial sources appeared to be high, suggesting that law enforcement and health promotion activities should be enhanced to reduce the rate of smoking among Malaysian youth.


Diagnosis and metaphylaxis of stone disease. Consensus concept of the National Working Committee on Stone Disease for the upcoming German Urolithiasis Guideline.
This review draws the recent state of the art in metabolic diagnosis and metaphylaxis of stone disease. It is the basis for the consensus approval with the other medical societies and institutions in Germany involved in the guideline process of the new "Urolithiasis Guideline". The German Working Committee on Stone Disease reviewed critically the current literature in the field of urolithiasis-including the existing German and EAU-Guidelines as well as the Conference Book of the First International Consultation on Stone Disease. As far as possible the references were rated according to the EBM criteria. On this basis the expert group discussed all pathways and statements regarding the management of stone disease. The present review coincides with the consented guideline draft of the German Working Committee on Stone Disease. Occurrence of stone disease in the western world increases seriously. Modern lifestyle, dietary habits and overweight-problems of the affluent societies-emerge to be the important promoters of the "stone-boom" in the new millennium. This even affects children, whose stone prevalence is otherwise significantly less than that of adults. Criteria for the high risk group of stone formers were clearly defined. A diagnostic standard is formulated for the basic and the elaborate metabolic evaluation of a stone patient. Approximately 75% of all stone patients could anticipate stone recurrence with elementary reorientation of their lifestyle and dietary habits, summarized as general metaphylaxis. About 25% of the stone formers require additional pharmacological intervention to normalize their individual biochemical risk, precisely compiled for each stone type as specific metaphylaxis.


Leading causes of cardiovascular hospitalization in 8.45 million US veterans.
We sought to determine the leading causes of cardiovascular (CV) hospitalization, and to describe and compare national rates of CV hospitalization by age, gender, race, ethnicity, region, and year, among U.S. veterans. We evaluated the electronic health records of all veterans aged ≥18 years who had accessed any healthcare services at either a VA healthcare facility or a non-VA healthcare facility that was reimbursed by the VA, between January 1 2010 and December 31 2014. Among these 8,452,912 patients, we identified the 5 leading causes of CV hospitalization and compared rates of hospitalization by age, gender, race, ethnicity, region, year and type of VA healthcare user. The top 5 causes of CV hospitalization were: coronary atherosclerosis, heart failure, acute myocardial infarction, stroke and atrial fibrillation. Overall, 297,373 (3.5%) veterans were hospitalized for one or more of these cardiovascular conditions. The percentage of veterans hospitalized for one or more of these CV conditions decreased over time, from 1.23% in 2010 to 1.18% in 2013, followed by a slight increase to 1.20% in 2014. There was significant variation in rates of CV hospitalization by gender, race, ethnicity, geographic region, and urban vs. rural zip code. In particular, older, male, Black, non-Hispanic, urban and Continental region veterans experienced the highest rates of CV hospitalizations. Among 8.5 million patients enrolled in the VA healthcare system from 2010 to 2014, there was substantial variation in rates of CV hospitalization by age, gender, race, geographical distribution, year, and use of non-VA (vs. VA only) healthcare care facilities.


Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease.
Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods. A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54). MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa). Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.


Molecular interactions on single-walled carbon nanotubes revealed by high-resolution transmission microscopy.
The close solid-state structure-property relationships of organic π-aromatic molecules have attracted interest due to their implications for the design of organic functional materials. In particular, a dimeric structure, that is, a unit consisting of two molecules, is required for precisely evaluating intermolecular interactions. Here, we show that the sidewall of a single-walled carbon nanotube (SWNT) represents a unique molecular dimer platform that can be directly visualized using high-resolution transmission electron microscopy. Pyrene is chosen as the π-aromatic molecule; its dimer is covalently linked to the SWNT sidewalls by aryl addition. Reflecting the orientation and separation of the two molecules, the pyrene dimer on the SWNT exhibits characteristic optical and photophysical properties. The methodology discussed here—form and probe molecular dimers—is highly promising for the creation of unique models and provides indispensable and fundamental information regarding molecular interactions.


Geographic Financial Analysis of Craniosynostosis Surgery in the United States.
The purpose of this study was to investigate the financial implications of demographic and socioeconomic factors upon the cost of surgical procedures for craniosynostosis. A retrospective cohort study was conducted of admissions for craniosynostosis surgery in the United States from 2015 through 2020 using the Pediatric Health Information System. Patient demographics, case volume, and surgical approach were analyzed in context of hospital charges. During the study interval, 3869 patients were admitted for surgery for craniosynostosis. In multivariate regression accounting for demographic and socioeconomic factors, hospital admission charges were significantly higher in patients with longer hospital length of stay ( P < 0.001), longer ICU length of stay ( P < 0.001), living in an underserved area ( P = 0.046), preoperative risk factors ( P = 0.016), and those undergoing open procedures ( P < 0.001); hospital admission charges were significantly lower in patients with White race ( P = 0.020) and those treated at high-volume centers ( P < 0.001). In multivariate regression, ICU length of stay was significantly higher in patients with preoperative risk factors ( P < 0.001), undergoing open procedures ( P < 0.001), government insurance ( P = 0.018), and not treated at high-volume centers ( P = 0.005). There were significant differences in admission charges ( P < 0.001), charge-to-cost ratios ( P < 0.001), and likelihood of being treated at high-volume craniofacial centers ( P < 0.001) across geographic regions of the country. In the United States, there is significant sociodemographic variability in charges for craniosynostosis care, with increased hospital charges independently associated with non-White race, preoperative risk factors, and living in an underserved area.


Milk ejection bursts of supraoptic oxytocin neurones during bilateral and unilateral suckling in the rat.
Extracellular recordings of the electrical activity of oxytocin neurones were made from the supraoptic nuclei (SON) of lactating rats, and the milk-ejection bursts and the background activity of oxytocin neurones were investigated during unilateral and bilateral suckling. When application of pups was limited to the nipples on either the same side (ipsilateral suckling) or the side opposite (contralateral suckling) to the oxytocin neurone recorded, the burst amplitude and background firing rate were significantly (P < 0.05) lower and the inter-burst interval was significantly (P < 0.05) longer than during bilateral suckling. Furthermore, the burst amplitude was significantly (P < 0.05) lower during ipsilateral suckling than during contralateral suckling. The majority of the oxytocin neurones showed a gradual increase in the burst amplitude during bilateral (88.9%) and contralateral (77.3%) suckling, but during ipsilateral suckling only 40% of the neurones did. The inter-burst interval became shorter with the progress of the milk ejection reflex during any mode of suckling. Three pairs of oxytocin neurones recorded simultaneously from both SON were successfully tested for the effect of bilateral and unilateral suckling on the electrical activity, and the results showed the same direction of change in the burst amplitude, background activity and burst interval as shown in single side recordings. These findings indicate that the burst amplitude mainly depends on the amount of afferent suckling signals arising from the nipples on the side opposite to the recording side, and that there may exist bilateral summation centres coordinating with the synchronization mechanism of milk-ejection bursts of oxytocin neurones.


Mitral valve perforation, a hole-in-one for 3-dimensional echocardiography.
Mitral valve perforation is an uncommon aetiology of mitral regurgitation in the paediatric population. We present a case where 3-dimensional echocardiography assisted in the diagnosis of the source of mitral regurgitation and the surgical correlation.


Change in Domain-specific but not General Psychological Flexibility Relates to Greater Weight Loss in Acceptance-Based Behavioral Treatment for Obesity.
Acceptance-based approaches have demonstrated promise for improving outcomes in behavioral treatments for obesity, but few studies have examined processes of change in these treatments. It is critical to identify mechanisms of action in treatment to further optimize this approach, refine theory, and inform future research. This study examined change in several domain-specific and general measures of psychological flexibility in a randomized controlled trial of an acceptance-based behavioral weight loss treatment. The relationships between change in these measures and weight loss outcomes were also examined. Adults (N = 283) were randomized to receive 12 months of acceptance-based (ABT) or non-acceptance-based (non-ABT) behavioral treatment and completed measures of general and weight control-specific psychological flexibility at months 0, 6, and 12. Participants in ABT demonstrated greater increases in psychological flexibility related to eating and physical activity experiences during treatment compared to participants in non-ABT, and changes in these processes were correlated with better weight loss. Parallel mediation analyses further revealed that psychological flexibility related to eating and physical activity experiences partially mediated the relationship between treatment condition and 12-month weight loss. Participants across conditions also experienced small increases in general psychological flexibility, but general psychological flexibility was not meaningfully related to weight loss outcomes. These findings indicate that domain-specific (versus general) psychological flexibility may be most impacted by ABT and most relevant to weight loss outcomes. Results also provide partial support for the theoretical model of ABT for weight management.